US 2011 01 05519A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0105519 A1 Mendla et al. (43) Pub. Date: May 5, 2011

(54) PHARMACEUTICAL COMPOSITIONS FOR Publication Classification THE TREATMENT OF SEXUAL DISORDERS (51) Int. Cl. A63/496 (2006.01) (76) Inventors: Klaus Mendla, (US); Thomas A6IP 5/00 (2006.01) Friedl. (US); Wolfram Eisenreich, A6IP 25/00 (2006.01) (US); Robert Pyke, (US) (21) Appl. No.: 12/987,388 (52) U.S. C...... 514/252.16; 514/254.06; 514/253.07; 9 514/254.04 (22) Filed: Jan. 10, 2011 Related U.S. Application Data (57) ABSTRACT (63) goE.E.N.E. R The invention relates to new pharmaceutical compositions for No 1 f 10.4 49 filed on Apr. 20, 2005 E. aban- the treatment of sexual disorders and methods for the prepa doned s - s pr. ZU, s ration thereof. In a preferred embodiment, the instant inven tion is directed to ppharmaceutical combinations comprisinpr1S1ng (60) Provisional application No. 60/564,662, filed on Apr. as one active ingredient in combination with at 22, 2004, provisional application No. 60/631,800, least one additional active ingredient for the treatment of filed on Nov.30, 2004. sexual disorders and methods for the preparation thereof. US 2011/O 105519 A1 May 5, 2011

PHARMACEUTICAL COMPOSITIONS FOR D4 antagonist, 5-HT-2A/C antagonists, selective THE TREATMENT OF SEXUAL DISORDERS receptor modulators (SARMs), selective receptor modulators (SERMs), , and C.-adrenergic receptor antagonists. RELATED APPLICATIONS 0007. The compositions according to the invention may 0001. This application is a continuation of U.S. applica contain flibanserin 1 and the one or more additional active tion Ser. No. 11/110,449 filed Apr. 20, 2005 which claims ingredient 2 in a single formulation or in separate formula priority benefit, as does the present application, to U.S. Pro tions. If flibanserin and the one or more additional active visional Application Ser. No. 60/564,662 filed Apr. 22, 2004 ingredient are present in separate formulations these separate and U.S. Provisional Application Ser. No. 60/631,800 filed formulations may be administered simultaneously or sequen Nov.30, 2004. tially. 0008. A preferred embodiment according to the invention BACKGROUND OF THE INVENTION is directed to pharmaceutical compositions comprising a therapeutically effective amount offilibanserin 1 and a thera 0002 The invention relates to new pharmaceutical com peutically effective amount of one or more, preferably one positions for the treatment of sexual disorders and methods 2a, optionally in combination with a for the preparation thereof. In a preferred embodiment, the pharmaceutically acceptable excipient. instant invention is directed to pharmaceutical combinations comprising flibanserin as one active ingredient in combina 0009 Examples of suitable melanocortin include tion with at least one additional active ingredient for the PT-141, MCL-0129. PG-917, and Ro-27-3225, optionally in treatment of sexual disorders and methods for the preparation form of the pharmaceutically acceptable acid addition salts, thereof. in form of the hydrates and/or solvates and optionally in the 0003. The invention relates to new pharmaceutical com form of the individual optical isomers, mixtures of the indi positions for the treatment of sexual disorders and methods vidual enantiomers or racemates thereof. for the preparation thereof. In a preferred embodiment, the 0010. Another preferred embodiment according to the instant invention is directed to pharmaceutical combinations invention is directed to pharmaceutical compositions com comprisingatherapeutically effective amount offilibanserin 1 prising a therapeutically effective amount offilibanserin 1 and as one active ingredient in combination with a therapeutically a therapeutically effective amount of one or more, preferably effective amount of at least one additional active ingredient 2 one agonist 2b, optionally in combination for the treatment of sexual disorders and methods for the with a pharmaceutically acceptable excipient. Examples of preparation thereof. Suitable prostaglandin E1 agonists, include ornoprostil, 0004. The compound 1-2-(4-(3-trifluoromethyl-phenyp limaprost, alprostadil, gemeprost, liprostin, NMI-775, pros piperazin-1-yl)ethyl-2,3-dihydro-1H-benzimidazol-2-one taglandin E (PGE-1), , dioxyline, ethaverine, (flibanserin) is disclosed inform of its hydrochloride in Euro , , minoxidil, nitroglycerin, alpha pean Patent Application EP-A-526434 and has the following blockers, nitric oxide donors, and peptides (e.g., VIP), option chemical structure: ally in form of the pharmaceutically acceptable salts, inform of the hydrates and/or solvates and optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof. 0011 Preferred compounds 2b include ornoprostil, limaprost, alprostadil, gemeprost, liprostin and NMI-775, HN 4. CF from which ornoprostil, limaprostandalprostadil are particu larly preferred, optionally in form of the pharmaceutically \-O-CS\ / acceptable salts, in form of the hydrates and/or Solvates and optionally in the form of the individual optical isomers, mix tures of the individual enantiomers or racemates thereof. 1 X HC 0012 Another preferred embodiment according to the invention is directed to pharmaceutical compositions com 0005 Flibanserin shows affinity for the 5-HT, and prising a therapeutically effective amount offilibanserin 1 and 5-HT-receptor. It is therefore a promising therapeutic agent a therapeutically effective amount of one or more, preferably for the treatment of a variety of diseases, for instance depres one elevator of c(GMP , preferably a coMP phosphodi Sion, , Parkinson, anxiety, sleep disturbances, esterase (cGMP PDE) inhibitor, more preferably a selective sexual and mental disorders and age associated memory PDE V inhibitor, optionally in combination with a pharma impairment. ceutically acceptable excipient. Examples of elevators of cGMP in particular examples for suitable PDE V inhibitors include , , , NCX-911, Sch DETAILED DESCRIPTION OF THE INVENTION 444877, FR-229934, 4-bromo-5-(pyridylmethylamino)-6- 0006 A preferred embodiment of the invention is directed 3-(4-chlorophenyl)-propoxy-3(2H)pyridaZinone, 1-4-(1, to pharmaceutical compositions comprising atherapeutically 3-benzodioxol-5-ylmethyl)amiono-6-chloro-2- effective amount offilibanserin 1 in combination with athera quinozolinyl-4-piperidine-carboxylic acid, monosodium peutically effective amount of one or more, preferably one salt, (+)-cis-5,6a, 7.9.9.9a-hexahydro-2-4-(trifluoromethyl)- active ingredient 2 selected from the group consisting of phenylmethyl-5-methyl-cyclopent-4.5imidazo[2,1-bpurin melanocortin agonists, prostaglandin E1 agonists, elevators 4(3H)one, furazlocillin, cis-2-hexyl-5-methyl-3,4,5,6a,7,8,9, of cyclic guanosine 3',5'-monophosphate (cGMP) (preferably 9a-octahydrocyclopent4.5-imidazo[2.1-bpurin-4-one, PDE V inhibitors), 5-HT-1A agonists, dopamine agonists, 3-acetyl-1-(2-chlorobenzyl)-2 propylindole-6-carboxylate,

US 2011/O 105519 A1 May 5, 2011

0026. Another preferred embodiment according to the invention is directed to pharmaceutical compositions com prising a therapeutically effective amount offilibanserin 1 and a therapeutically effective amount of one or more, preferably one 5-HT1A agonist 2d, optionally in combination with a pharmaceutically acceptable excipient. Examples of Suitable 5-HT-1A agonists include , , , attached to the rest of the molecule via one of the benzene , , , , ring carbon atoms and wherein the fused ring A is a 5- or , , , hydrochlo 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and option ride, , AP-521, SUN-N4057, , MKC ally one or two heteroatoms selected from oxygen, Sulphur 242, OPC-14523, maleate, SLV-308, BTS-79018, and nitrogen; and R-137696, F-13640, SSR-181507, SLV-314, SLV-319, 0019 R represents hydrogen or Calkyl, or R' and R' 7-OH-DPAT, VN-2222, PD-158771, RS-30199, WAY together represent a 3- or 4-membered alkyl or alkenyl 100012, A-74283, , Org-13011, B-8805-033, chain, optionally in form of the pharmaceutically accept AP-159, AZ-16596, Anpirtoline, , , able acid addition salts, in form of the hydrates and/or MDL-72832, RU-24969, Bay-r-1531, , BIMG 80, solvates and optionally in the form of the individual optical BMS-181100, BMS-181101, BMS-181970, BMY-7378, isomers, mixtures of the individual enantiomers or race BW-1205U90, B-20991, HAT-90B, Nerisopam, LY-175644, mates thereof. LY-178210, LY-228729, LY-274600, LY-274601, 0020. The aforementioned compounds of formula 2c. 1 are LY-293284, LY-301317, LY-315535, E-4414, E-6265 citrate, known in the art (WO95/19978). , RGH-1756, RGH-1757, 1192U90, HP-236, 0021. Another preferred genus of compounds 2c appli FG-5938, LEK-8804, LB-50016, RWJ-25730, EMD-56551, cable within the scope of the instant invention are compounds EMD-67478, EMD-77697, , , BP-554, of formula 2c.2 CGP-50281, CGS-12066B, CGS-18102, SDZ-MAR-327, CL-870801, CP-110330, CP-146662, CP-291952, FCE 23892, FG-5865, FG-5893, OSU-191, ,

U-67413B, U-86170, U-86192A, U-92016A, U-93385, Eptapirone, succinate, SL-870765, SL-880338, SR-59026, , , S-14506, S-14671, S-15535, S-15931, S-16924, S-213571, S-215521, Elopipra Zole, , , , SUN-8399, S-23751, PM-1000, LY 41, , WY-48723, and MDL-73975, optionally inform of the phar maceutically acceptable acid addition salts, in form of the hydrates and/or solvates and optionally in the form of the individual optical isomers, mixtures of the individual enanti wherein omers or racemates thereof. 0022) R' represents hydrogen, halogen or Calkyl: 0027 Preferred examples of suitable 5-HT1A agonists 2d 0023 R' represents hydrogen, Calkyl, haloCalkyl, include Urapidil, Buspirone, Aripiprazole, Ziprasidone, Naf Cs-scycloalkyl, CascycloalkyCisalkyl, arylC-alkyl or topidil, Tandospirone, Nemonapride, Gepirone, Repinotan, heteroarylC-alkyl; and Sumanirole, Xaliproden hydrochloride, Bifeprunox, AP-521, 0024 R represents an optionally substituted monocyclic SUN-N4057, Sarizotan, MKC-242, OPC-14523, Eptapirone aromatic ring selected from benzene, thiophene, furan and maleate, SLV-308, BTS-79018, R-137696, F-13640, SSR pyridine or an optionally Substituted bicyclic ring 181507, SLV-314, SLV-319, 7-OH-DPAT, VN-2222, PD-158771, RS-30199 and WAY-100012, optionally in form of the pharmaceutically acceptable acid addition salts, in form of the hydrates and/or solvates and optionally in the form of the individual optical isomers, mixtures of the indi vidual enantiomers or racemates thereof. 0028. Another preferred embodiment according to the invention is directed to pharmaceutical compositions com attached to the rest of the molecule via one of the benene prising a therapeutically effective amount offilibanserin 1 and ring carbon atoms and wherein the fused ring A is a 5- or a therapeutically effective amount of one or more, preferably 6-membered ring which may be saturated or partially or one 2e, optionally in combination with a fully unsaturated and comprises carbon atoms and option pharmaceutically acceptable excipient. Examples of Suitable ally one or two heteroatoms selected from oxygen, Sulphur dopamine agonists 2e include ABT-724, CP-226269, bro and nitrogen, optionally in form of the pharmaceutically mocriptin, cabergolin, alpha-dihydroergocryptin, , acceptable acid addition salts, in form of the hydrates and/ , pramipexol, roXindol, ropinirol, Sopirinol, tal or solvates and optionally in the form of the individual ipexol, and optionally in form of the optical isomers, mixtures of the individual enantiomers or pharmaceutically acceptable acid addition salts, in form of racemates thereof. the hydrates and/or solvates and optionally in the form of the 0025. The aforementioned compounds of formula 2c.2 are individual optical isomers, mixtures of the individual enanti known in the art (WO95/19978). omers or racemates thereof. US 2011/O 105519 A1 May 5, 2011

0029 Preferred examples of suitable dopamine agonist 2e LUR-2366, NEO-376, NGB-4420, NGD-941, NRA-0045, include pramipexol, bupropion roXindol, and talipexol. NRA-0074, NRA-0154, NRA-0160, NRA-0161, NRA optionally in form of the pharmaceutically acceptable acid 0215, NRA-0219, NRA-0544, PD-089232, PD-108306, addition salts, in form of the hydrates and/or solvates and PD-165167, PD-167063, PD-168306, PD-172760, optionally in the form of the individual optical isomers, mix PD-172760, PD-172938, PD-35680, PD-82011, PNU tures of the individual enantiomers or racemates thereof. 106161, PNU-106675, QF-1003B, QF-1004B, Ro-62-4599, 0030. Another preferred embodiment according to the S-16924, S-17828, Sch-71450, , U-101958, invention is directed to pharmaceutical compositions com U-103073E, U-96415E andYM-43611, optionally inform of prising atherapeutically effective amount offilibanserin 1 and the pharmaceutically acceptable acid addition salts, in form a therapeutically effective amount of one or more, preferably of the hydrates and/or solvates and optionally in the form of one 5-HT2A/2C antagonist 2f, optionally in combination the individual optical isomers, mixtures of the individual with a pharmaceutically acceptable excipient. Examples of enantiomers or racemates thereof. suitable 5-HT2A/2C antagonists 2f include Aripiprazole, , , , , Sarpogre 0033 Preferred examples of suitable dopamine D4 late, Ziprasidone, , , , Ilo antagonist 2g include , Ziprasidone, MDL peridone, , , M 100907, Netamiftide, 814608A, NRA-0562, S-18126, SPI-376 and YM-50001, in , S-20098, Abaperidone, ACP-103, EMD particular olanzapine and Ziprasidone, optionally in form of 281014, EMR 62218, LU-31-130, SL 650472, EGIS-10037, the pharmaceutically acceptable acid addition salts, in form LEK-8829, , QF-2004B, R-107500, S 35120, of the hydrates and/or solvates and optionally in the form of S-14297, , , AT 1015, Balaperidone, the individual optical isomers, mixtures of the individual BIMG 80, , EGIS 8465, EGIS 9933, Fan enantiomers or racemates thereof. anserin, FG 5803, FG 5893, FG-5938, FG-5974, GMC 1169, 0034. Another preferred embodiment according to the GMC 283, GMC 306, GMC 6139, ICI-169369, Irindalone, IT invention is directed to pharmaceutical compositions com 657, JL-13, , LY 215840, LY-367265, NRA prising a therapeutically effective amount offilibanserin 1 and 0045, Org-38457, PNU-96415E, QF 0510B, QF 1003B, QF a therapeutically effective amount of one or more, preferably 1004B, RO 600946, Ro-60-0759, RP 71602, RS-102221, S one selective modulator (SARM) 2h, 16924, S 213571, S 35031, S-17828, S-21357-1, SB optionally in combination with a pharmaceutically accept 200646A, SB 206553, SB 221284, SB 228357, SB 242084, able excipient. Examples of suitable SARMs 2h include SB 243213, SDZ SER 082, TY 12283, TY-11223 and LGD2226, LGD1331, (both available from Pharma ZD-3638 optionally in form of the pharmaceutically accept ceuticals (San Diego, Calif.), , able acid addition salts, in form of the hydrates and/or sol acetate, , , 4-(trifluorom vates and optionally in the form of the individual optical ethyl)-2(1H)-pyrrolidone3.2-gquinolinone and its deriva isomers, mixtures of the individual enantiomers or racemates tives, 1,2-dihydropyridono.5,6-glquinoline and its deriva thereof. tives and piperidino3.2-gquinolinone and its derivatives, 0031 Preferred 5-HT2A/2C antagonist N include Arip optionally in form of the pharmaceutically acceptable acid iprazole, Fluoxetine, Nefazodone, Pizotifen, Risperidone, addition salts, in form of the hydrates and/or solvates and , Ziprasidone, Agomelatine, Asenapine, Epli optionally in the form of the individual optical isomers, mix vanserin, , M 100907, Netamiftide, Ocaperidone, tures of the individual enantiomers or racemates thereof. S-20098, Abaperidone, ketanserin, ritanserin, ACP-103. 0035. Preferred examples of suitable SARMs 2h include EMD 281014, EMR 62218, LU-31-130, SL 650472, EGIS LGD2226 and/or LGD1331, bicalutamide, cyproterone 10037, LEK-8829, Nantenine, QF-2004B, R-107500, S acetate, hydroxyflutamide and spironolactone, in particular 35120 and S-14297 optionally in form of the pharmaceuti LGD2226, optionally inform of the pharmaceutically accept cally acceptable acid addition salts, in form of the hydrates able acid addition salts, in form of the hydrates and/or sol and/or solvates and optionally in the form of the individual vates and optionally in the form of the individual optical optical isomers, mixtures of the individual enantiomers or isomers, mixtures of the individual enantiomers or racemates racemates thereof. Particular preferred 5-HT2A/2C antago thereof. nist2fare selected from the group consisting of Aripiprazole, 0036) Another preferred embodiment according to the Fluoxetine, Nefazodone, Pizotifen, Risperidone, Sarpogre invention is directed to pharmaceutical compositions com late and Ziprasidone optionally in form of the pharmaceuti prising a therapeutically effective amount offilibanserin 1 and cally acceptable acid addition salts, in form of the hydrates a therapeutically effective amount of one or more, preferably and/or solvates and optionally in the form of the individual one estrogen 2 k, optionally in combination with a pharma optical isomers, mixtures of the individual enantiomers or ceutically acceptable excipient. Examples of Suitable estro racemates thereof. gens 2 k include synthetic and natural estrogens such as 0032. Another preferred embodiment according to the (i.e. 1,3,5-estratriene-3,17 B-diol, or “ 17 B-estra invention is directed to pharmaceutical compositions com diol) and its esters, including , Valerate, prising atherapeutically effective amount offilibanserin 1 and cypionate, heptanoate, decanoate, acetate and diacetate, 17C.- a therapeutically effective amount of one or more, preferably estradiol, (i.e. 17C.-ethynylestradiol) and one dopamine D4 antagonist 2g, optionally in combination esters and ethers thereof, including ethinylestradiol 3-acetate with a pharmaceutically acceptable excipient. Examples of and ethinylestradiol 3-benzoate, and , Suitable dopamine D4 antagonists 2g include olanzapine, polyestrol phosphate, and its esters and derivatives, ziprasidone, MDL-814608A, NRA-0562, S-18126, SPI-376, including , , and YM-50001, 1192U90, ALX-D4, Balaperidone, BIMG 80, estrone sulfate, , , and conjugated equine CI-1030, CP-293,019, , JL-13, L-741742, estrogens, optionally in form of the pharmaceutically accept L-745870, L-751852, L-772620, L-800892, LU-35138, able acid addition salts, in form of the hydrates and/or sol US 2011/O 105519 A1 May 5, 2011

vates and optionally in the form of the individual optical prising a therapeutically effective amount offilibanserin 1 and isomers, mixtures of the individual enantiomers or racemates a therapeutically effective amount of one or more, preferably thereof. one C.-adrenergic 2m, optionally in com 0037 Preferred examples of suitable estrogens 2 k include bination with a pharmaceutically acceptable excipient. estradiol and 17C.-estradiol, in particular estradiol, optionally Examples of Suitable C-adrenergic receptor antagonists 2m in form of the pharmaceutically acceptable acid addition include phentolamine mesylate, HMP-12, REC-15/2615 and salts, inform of the hydrates and/or Solvates and optionally in MPV 1248 (atipamezole), optionally in form of the pharma the form of the individual optical isomers, mixtures of the ceutically acceptable acid addition salts, in form of the individual enantiomers or racemates thereof. hydrates and/or solvates and optionally in the form of the 0038 Another preferred embodiment according to the individual optical isomers, mixtures of the individual enanti invention is directed to pharmaceutical compositions com omers or racemates thereof. prising atherapeutically effective amount offilibanserin 1 and 0041 Preferred examples of suitable C.-adrenergic recep a therapeutically effective amount of one or more, preferably tor antagonists 2m include phentolamine mesylate and REC one androgen 21, optionally in combination with a pharma 15/2615, optionally in form of the pharmaceutically accept ceutically acceptable excipient. Examples of Suitable andro able acid addition salts, in form of the hydrates and/or gens 21 include, but are not limited to the naturally occurring solvates and optionally in the form of the individual optical androgens and derivatives thereof, including , isomers, mixtures of the individual enantiomers or racemates androsterone acetate, androsterone propionate, androsterone thereof. benzoate, , androstenediol-3-acetate, andros 0042 Another preferred embodiment according to the tenediol-17-acetate, androstenediol-3,17-diacetate, andros invention is directed to pharmaceutical compositions com tenediol-17-benzoate, androstenediol-3-acetate-17-ben prising a therapeutically effective amount offilibanserin 1 and Zoate, , , , a therapeutically effective amount of one or more, preferably phenpropionate, , nan one selective modulator (SERM) 2n, drolone furylpropionate, nandrolone cyclohexane-propi optionally in combination with a pharmaceutically accept onate, nandrolone benzoate, nandrolone cyclohexanecar able excipient. Examples of suitable SERMs 2n include boxylate, , dromoStanolone, dromostanolone , , , N-butyl-3,17-dihy propionate, , (“praster droxy-N-methyl-estra-1,3,5(10)-triene-7-undecanamide one’), sodium dehydroepiandrosterone Sulfate, and 4-dihy (ICI 164.384), (ICI 182,780), 19-nor-progester drotestosterone (“stanolone” and 5C-); one and its derivatives, and 19-nor-testosterone and its deriva pharmaceutically acceptable esters of testosterone and 4-di tives, (6-hydroxy-3-4-2-(1-piperidinyl)ethoxy hydrotestosterone, typically esters formed from the hydroxyl phenoxy-2-(4-hydroxyphenyl)benzobthiophene group present at the C-17 position, including, but not limited hydrochloride), and derivatives thereof, including —S , to, the enanthate, propionate, cypionate, phenylacetate, NH , —NCH —SO and —CH-substituted ral acetate, isobutyrate, buciclate, heptanoate, decanoate, penta oxifene, as described in Schmid et al. (1999) Bioorg. & Med. decanoate, undecanoate, pelargonate, tridecanoate, palmi Chem. Lett. 9:523-528), trans-2,3-dihydroraloxifene and its tate, caprate, isocaprate, C.-methylcaprate, B-methylcaprate, derivatives as disclosed in Grese, et al., (J. Med. Chem. laurate, a-methylpelargonate, B-methylpelargonate, B.B-dim (1997) Vol. 40, pp. 146-167) such as 4 halo-raloxifene and ethylpelargonate, B-(p-methyl-cyclohexyl)propionate, ethyl 2-(alkyl, cycloalkyl or naphthyl)raloxifene, benzothiophenes cyclohexyl)-propionate, B-(cycloheptyl)-propionate, C.-me as disclosed in U.S. Pat. No. 5,962,475, such as 6-methoxy thyl-cyclohexyl-propionate, B-methyl-f-cyclohexyl 2-(4-methoxyphenyl)-3-(4-nitrobenzoyl)-benzob. propionate, cyclododecyl-carboxylate, adamantine-1- thiophene, (LY353381), 2-(4-methoxyphenyl)-3- carboxylate, adamant-1-yl-acetate, methyl-O-cyclohexyl (4-(2-(1-piperidinyl)ethoxy)-phenoxybenzobthiophene-6- propionate, and C-(bicyclo-2.2.2-oct-1-yl)-propionate ol); LY 1 17018 (6-hydroxy-2-(4-hydroxyphenyl)benzob. esters, as well as the alkyl-substituted, preferably C-C, thien-3-yl)(4-(2-(1-pyrrolidinyl)ethoxy)phenyl)- alkyl-substituted cyclic esters, such as the 3-n-hexylcyclobu methanone), and baZedoxifen (TSE-424), (1-2-4- tanecarboxylate, 3-n-butylcyclopentanecarboxylate, 4-n-bu (1E)-1-(4-Iodophenyl)-2-phenyl-1-butenylphenoxyethyl tylcyclohexanecarboxylate, 4-n-pentylcyclohexanecarboxy pyrrolidine) (3-(1E)-1-4-2-(Dimethylamino) late and n-hexylcyclohexanecarboxylate esters; and ethoxyphenyl-2-phenyl-1-butenylphenol), pharmaceutically acceptable derivatives of testosterone Such ((Z)-244-(1,2-Diphenyl-1-butenyl)phenoxy-N,N-dimethyl as methyl testosterone, , , flu ethanamine), (2-4-(17)-4-Chloro-1,2-diphenyl , optionally in form of the pharmaceutically 1-butenyl)phenoxy-N,N-dimethylethanamine), clomi acceptable acid addition salts, in form of the hydrates and/or phene, (2-4-(2-Chloro-1,2-diphenylethenyl)phenoxy-N,N- solvates and optionally in the form of the individual optical diethylethanamine), meproxifene ((4-(1-(4-(2- isomers, mixtures of the individual enantiomers or racemates (dimethylamino)ethoxy)phenyl)-2-(4-(1-methylethyl) thereof. phenyl)-1-butenyl)-phenol) or TAT-59), , 0039 Preferred examples of suitable androgens 21 include , , , halogenated triph testosterone, methyl testosterone, testolactone, enylethylene derivatives as disclosed in U.S. Patent Applica oxymetholone, , in particular testosterone, tion Publication No. 2002/0013297, such as 3-4-1-(4-fluo optionally in form of the pharmaceutically acceptable acid rophenyl)-2-phenyl-but-1-enylphenylacrylic acid and addition salts, in form of the hydrates and/or solvates and 3-4-(1,2-diphenyl-but-1-enyl)-phenylacrylic acid; substi optionally in the form of the individual optical isomers, mix tuted naphthalenes and isoquinolines, including, for example tures of the individual enantiomers or racemates thereof. cis-6-phenyl-5-(4-(2-pyrrolidin-1-yl-ethoxy)phenyl)-5,6,7, 0040 Another preferred embodiment according to the 8-tetrahydronaphthalene-2-ol, cis-644-fluorophenyl)-5-4- invention is directed to pharmaceutical compositions com (2-piperidin-1-yl-ethoxy)-phenyl-5,6,7,8-tetrahydronaph US 2011/O 105519 A1 May 5, 2011

thalene-2-ol. cis-1-6'-pyrrolidinoethoxy-3-pyridyl-2- sium salts; and salts formed with Suitable organic ligands, phenyl-6-hydroxy-1,2,3,4-tetrahydronaphthalene, cis-6-(4'- e.g., quaternary ammonium salts. hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl-5, 0048. The compounds 2 may have chiral centers and occur 6,7,8-tetrahydronaphthalen-2-ol, 6-(4-hydroxyphenyl)-5-4- as racemates, racemic mixtures and as individual diastere (2-piperidin-1-yl-ethoxy)-benzyl-naphthalen-2-ol. 1-(4'- omers, or enantiomers with all isomeric forms being included pyrrolidinoethoxyphenyl)-2-(4"-fluorophenyl)-6-hydroxy in the present invention. Therefore, where a compound is 1,2,3,4-tetrahydroisoquinoline, 1-(4'- chiral, the separate enantiomers, Substantially free of the pyrrolidinoethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4- other, are included within the scope of the invention. Further tetrahydroisoquinoline, and other compounds disclosed in included are all mixtures of the two enantiomers. Also U.S. Pat. No. 5,916,916, U.S. Pat. No. 5,552,412 and in EP included within the scope of the invention are polymorphs 1004306 A2, optionally in form of the pharmaceutically and hydrates of the compounds of the instant invention. acceptable acid addition salts, in form of the hydrates and/or 0049. The present invention includes within its scope pro solvates and optionally in the form of the individual optical of the compounds 1 and 2. In general, such isomers, mixtures of the individual enantiomers or racemates will be functional derivatives of the compounds of this inven thereof. tion which are readily convertible in vivo into the required 0043 Preferred examples of a suitable SERMs 2n are compound. tibolone and lasofoxifene, optionally in form of the pharma 0050. The term “therapeutically effective amount” shall ceutically acceptable acid addition salt, inform of the hydrate mean that amount of a or pharmaceutical agent that will and/or solvate and optionally in the form of the individual elicit the biological or medical response of a tissue, system, optical isomers, mixtures of the individual enantiomers or animal or human that is being sought by a researcher or racemates thereof. clinician. 0044. In the present invention the term “modulator” as 0051. As used herein, the term “composition' is intended used in the terms “selective androgen ” or to encompass a product comprising the specified ingredients 'selective estrogen receptor modulator” means a compound in the specified amounts, as well as any product which results, that produces tissue specific effects that can be agonistic or directly or indirectly, from combination of the specified antagonistic to the effects of estrogen or androgen. ingredients in the specified amounts. 0045 Flibanserin 1 may be used in form of the free base, 0052. In the combination of the present invention, the optionally in form of its pharmaceutically acceptable acid components 1 and 2 may be administered separately or addition salts and/or optionally inform of the hydrates and/or together in one pharmaceutical composition. In addition, the solvates thereof. Suitable acid addition salts include for administration of one element of the combination of the example those of the acids selected from, Succinic acid, present invention may be prior to, concurrent to, or Subse hydrobromic acid, acetic acid, fumaric acid, maleic acid, quent to the administration of the other element of the com methaneSulphonic acid, lactic acid, phosphoric acid, hydro bination. chloric acid, Sulphuric acid, tartaric acid and citric acid. Mix 0053. The elements of the combination of 1 and 2 may be tures of the abovementioned acid addition salts may also be administered by oral, parenteral (e.g., intramuscular, intrap used. From the aforementioned acid addition salts the hydro eritoneal, intravenous or Subcutaneous injection, or implant), chloride and the hydrobromide, particularly the hydrochlo buccal, nasal, vaginal, rectal, Sublingual, or topical (e.g. ocu ride, are preferred. If flibanserin 1 is used in form of the free lar eyedrop) routes of administration and may be formulated, base, it is preferably used in form offilibanserin polymorph A alone or together, in Suitable dosage unit formulations con as disclosed in WO 03/O14079. taining conventional non-toxic pharmaceutically acceptable 0046. The active ingredients 2 which are suitable to be carriers, adjuvants and vehicles appropriate for each route of combined with flibanserin within the teaching of the instant administration. invention and which are mentioned hereinbefore may also be 0054 The pharmaceutical compositions for the adminis capable of forming acid addition salts with pharmaceutically tration of the components 1 and 2 of this invention may acceptable acids. Representative salts include the following: conveniently be presented in dosage unit form and may be Acetate, Benzenesulfonate, Benzoate, Bicarbonate, Bisul prepared by any of the methods well known in the art of fate, Bitartrate, Borate, Bromide, Camsylate, Carbonate, pharmacy. All methods include the step of bringing the active Chloride, Clavulanate, Citrate, Dihydrochloride, Edetate, ingredient into association with the carrier which is consti Edisylate, Estolate, Esylate, Fumarate, Gluceptate, Glucon tuted of one or more accessory ingredients. In general, the ate, Glutamate, Glycolylarsanilate, Hexylresorcinate, pharmaceutical compositions are prepared by uniformly and Hydrabamine, Hydrobromide, Hydrochloride, Hydrox intimately bringing the active ingredients into association ynaphthoate, Iodide, Isothionate, Lactate, Lactobionate, Lau with a liquid carrier or a finely divided solid carrier or both, rate, Malate, Maleate, Mandelate, Mesylate, Methylbromide, and then, if necessary, shaping the product into the desired Methylnitrate, Methylsulfate. Mucate, Napsylate, Nitrate, dosage form. In the pharmaceutical compositions the active N-methylglucamine ammonium salt, Oleate, Oxalate, Pamo compounds are included in an amount Sufficient to produce ate (Embonate), Palmitate, Pantothenate, Phosphate/diphos the desired pharmacologic effect. phate, Polygalacturonate, Salicylate, Stearate, Sulfate, Sub 0055. The pharmaceutical compositions containing the acetate. Succinate, Tannate, Tartrate, Teoclate, Tosylate, active ingredients 1 and 2, separately or together, that are Triethiodide and Valerate. suitable for oral administration may be in the form of discrete 0047. Furthermore, where the compounds 2 carry an units such as hard or soft capsules, tablets, troches or loZ acidic moiety, Suitable pharmaceutically acceptable salts enges, each containing a predetermined amount of the active thereof may include alkali metal salts, e.g., Sodium or potas ingredients; in the form of a dispersible powder or granules; sium salts; alkaline earth metal salts, e.g., or magne in the form of a solution or a Suspension in an aqueous liquid US 2011/O 105519 A1 May 5, 2011 or non-aqueous liquid; in the form of syrups or elixirs; or in 0063. Oily suspensions may be formulated by suspending the form of an oil-in-water emulsion or a water-in-oil emul the active ingredients 1 and 2, separately or together, in a Sion. Vegetable oil, for example arachis oil, olive oil, sesame oil or 0056 Dosage forms intended for oral use may be prepared coconut oil, or in a mineral oil such as liquid paraffin. The oily according to any method known in the art for the manufacture Suspensions may contain a thickening agent, for example of pharmaceutical formulations and Such compositions. beeswax, hard paraffin or cetyl . Sweetening agents 0057 The excipients used may be for example, (a) inert and flavoring agents may be added to provide a palatable oral diluents such as mannitol, Sorbitol, calcium carbonate, prege preparation. These compositions may be prepared by the latinized starch, lactose, calcium phosphate or sodium phos addition of an antioxidant Such as ascorbic acid. phate; (b) granulating and disintegrating agents. Such as povi 0064 Dispersible powders and granules are suitable for done, copovidone, hydroxypropylmethylcellulose, corn the preparation of an aqueous Suspension. They provide the starch, alginic acid, crospovidone, Sodiumstarchglycolate, active ingredients 1 and 2, separately or together, in admix croScarmellose, or polacrilin potassium; (c) binding agents ture with a dispersing or wetting agent, a suspending agent Such as microcrystalline cellulose or acacia; and (d) lubricat and one or more preservatives. Suitable dispersing or wetting ing agents such as Stearate, Stearic acid, fumaric agents and Suspending agents are exemplified by those acid or talc. already mentioned above. Additional excipients, for example, 0058. In some cases, formulations for oral use may be in those Sweetening, flavoring and coloring agents described the form of hard gelatin or HPMC capsules wherein the active above may also be present. ingredient 1 or 2, separately or together, is mixed with an inert 0065. The pharmaceutical compositions of the invention Solid diluent, for example pregelatinized starch, calcium car may also be in the form of oil-in-water emulsions. The oily bonate, calcium phosphate or kaolin, or dispensed via a pellet phase may be a vegetable oil such as olive oil or arachis oils, formulation. They may also be in the form of soft gelatin or a mineral oil such as liquid paraffin or a mixture thereof. capsules wherein the active ingredient is mixed with water or 0.066 Suitable emulsifying agents may be (a) naturally an oil medium, for example peanut oil, liquid paraffin, occurring gums such as gum acacia and gum tragacanth, (b) medium chain triglycerides or olive oil. naturally-occurring phosphatides such as Soybean and leci 0059. The tablets, capsules or pellets may be uncoated or thin, (c) esters or partial esters derived from fatty acids and they may be coated by known techniques to delay disintegra hexitol anhydrides, for example, Sorbitan monooleate, (d) tion and absorption in the gastrointestinal tract and thereby condensation products of said partial esters with ethylene provide a delayed action or sustained action over a longer oxide, for example polyoxyethylene sorbitan monooleate. period. For example, a time delay material Such as cellulose The emulsions may also contain Sweetening and flavoring acetate phtalate or hydroxypropylcellulose acetate Succinate agents. or Sustained release material Such as ethylcellulose or ammo 0067 Syrups and elixirs may be formulated with Sweet niomethacrylate copolymer (type B) may be employed. ening agents, for example, glycerol, propylene glycol, Sorbi 0060 Liquid dosage forms for oral administration include tol or Sucrose. Such formulations may also contain a preser pharmaceutically acceptable emulsions, Solutions, Suspen Vative and flavoring and coloring agents. sions, syrups, and elixirs containing inert diluents commonly 0068. The pharmaceutical compositions containing 1 and used in the art, such as water. Besides such inert diluents, 2, separately or together, may be in the form of a sterile compositions can also include adjuvants, such as wetting injectable aqueous or oleagenous Suspension or Solution. The agents, emulsifying and Suspending agents, and Sweetening, Suspension may be formulated according to known methods flavoring, perfuming and preserving agents. using those Suitable dispersing or wetting agents and Sus 0061 Aqueous Suspensions normally contain the active pending agents which have been mentioned above. The sterile materials 1 and 2, separately or together, in admixture with injectable preparation may also be a sterile injectable solution excipients Suitable for the manufacture of aqueous Suspen or Suspension in a non-toxic parenterally-acceptable diluent sions. Such excipients may be (a) Suspending agents such as or solvent, for example as a solution in 1,3-butane-diol. hydroxy ethylcellulose, sodium carboxymethylcellulose, Among the acceptable vehicles and solvents that may be methylcellulose, hydroxypropylmethylcellulose, sodium employed are water, Ringer's Solution and isotonic sodium alginate, polyvinylpyrrolidone, gum tragacanthandgum aca chloride solution. In addition, sterile, fixed oils are conven cia; (b) dispersing or wetting agents which may be (b. 1) a tionally employed as a solvent or Suspending medium. For naturally-occurring phosphatide such as lecithin, (b.2) a con this purpose any bland fixed oil may be employed including densation product of an alkylene oxide with a fatty acid, for synthetic mono- or diglycerides. In addition, fatty acids Such example, polyoxyethylene Stearate, (b.3) a condensation as oleic acid find use in the preparation of injectables. product of ethylene oxide with a long chain aliphatic alcohol, 0069 Preparations according to this invention containing for example heptadecaethyleneoxycetanol, (b.4) a condensa 1 and 2, separately or together, for parenteral administration tion product of ethylene oxide with a partial ester derived include sterile aqueous or non-aqueous Solutions, Suspen from a fatty acid and a hexitol Such as polyoxyethylene Sor Sion, or emulsions. bitol monooleate, or (b.5) a condensation product of ethylene 0070. Examples of non-aqueous solvents or vehicles are oxide with a partial ester derived from a fatty acid and a propylene glycol, polyethylene glycol, vegetable oils, such as hexitol anhydride, for example polyoxyethylene sorbitan olive oil and corn oil, gelatin, and injectable organic esters monooleate. Such as ethyl oleate. Such dosage forms may also contain 0062. The aqueous Suspensions may also contain one or adjuvants such as preserving, wetting, emulsifying, and dis more preservatives, for example, ethyl or n-propyl p-hy persing agents. They may be sterilized by, for example, fil droxybenzoate; one or more coloring agents; one or more tration through a bacteria-retaining filter, by incorporating flavoring agents; and one or more Sweetening agents, such as sterilizing agents into the compositions, by irradiating the Sucrose or saccharin. compositions, or by heating the compositions. They can also US 2011/O 105519 A1 May 5, 2011

be manufactured in the form of sterile solid compositions invention may be administered in a single daily dose, or the which can be reconstituted in sterile water, or some other total daily dosage may be administered in divided doses of sterile injectable medium immediately before use. The com two, three or four times daily. bination of this invention may also be administered in the 0076. Within the instant invention the elevator of c(GMP2c form of Suppositories for rectal administration. This compo is preferably administered in Such an amount that per day sition can be prepared by mixing the drugs with a Suitable between 0.1 to 200 mg of 2c are applied. Preferred are ranges non-irritating excipient which is solid at ordinary tempera of between 1 to 150 mg, particular preferred 5 to 100 mg of 2c. tures, e.g., room temperature, but liquid at the rectal tempera (0077. In case of the preferred elevator of c(GMP 2c ture and will therefore melt in the rectum to release the drug. sildenafil particularly preferred doses per day are in the range Such materials are cocoa butter, hard fat, and polyethylene of about 25 to 100 mg. In case of the preferred elevator of glycols. Compositions for buccal, nasal or Sublingual admin cGMP2c tadalafil particularly preferred doses per day are in istration are also prepared with standard excipients well the range of about 10 to 20 mg. In case of the preferred elevator of c(GMP 2c Vardenafil particularly preferred doses known in the art. per day are in the range of about 5 to 20 mg. Suitable dosage 0071. For topical administration the combinations of this forms may contain for instance 5, 10, 15, 20, 25, 30, 35, 40, invention containing 1 and 2, separately or together, may be 45, 50, 55, 60, 65, 70, 75, 80, 85,90, 95 or 100 mg of 2c. formulated in liquid or semi-liquid preparations such as lini Advantageously, the compounds 2c of the present invention ments, lotions, applications; oil-in-water or water-in-oil may be administered in a single daily dose, or the total daily emulsions such as creams, ointments, jellies or pastes, includ dosage may be administered in divided doses of two, three or ing tooth-pastes; or solutions or Suspensions such as drops, four times daily. and the like. 0078. Within the instant invention the 5-HT1A agonist 2d 0072 The dosage of the active ingredients in the compo is preferably administered in Such an amount that per day sitions of this invention may be varied. However, it is neces between 1 to 200 mg of 2d are applied. Preferred are ranges of sary that the amount of the active ingredients 1 and 2 be such between 5 to 150 mg, particular preferred 10 to 100 mg of 2d. that a suitable dosage form is obtained. The selected dosage 0079. In case of the preferred 5-HT-1A agonist 2d arip and the dosage form depend upon the desired therapeutic iprazole particularly preferred doses per day are in the range effect, on the route of administration and on the duration of of about 10 to 30 mg. In case of the preferred 5-HT1A agonist the treatment. Dosage ranges in the combination are approxi 2d Ziprasidone particularly preferred doses per day are in the mately one tenth to one times the clinically effective ranges range of about 20 to 80 mg. Suitable dosage forms may required to induce the desired therapeutic effect, respectively contain for instance 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, when the compounds are used singly. 65,70, 75,80, 85,90, 95 or 100 mg of 2d. Advantageously, the 0073. Within the instant invention flibanserin 1 is prefer compounds 2d of the present invention may be administered ably administered in Such an amount that per single dosage in a single daily dose, or the total daily dosage may be admin between 5 to 200 mg offilibanserin 1 areapplied. Preferred are istered in divided doses of two, three or four times daily. ranges of between 10 to 150 mg, particular preferred 20 to 100 0080 Within the instant invention the dopamine agonist mg of flibanserin 1. Suitable dosage forms may contain for 2e is preferably administered in Such an amount that per day instance 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, between 0.01 to 600 mg of 2e are applied. Preferred are 90, 95 or 100 mg offilibanserin1. The aforementioned values ranges of between 0.025 to 500 mg, particular preferred 0.05 are based on flibanserin 1 in form of the free base. If fli to 450 mg of 2e. In case of the preferred dopamine agonist 2e banserin 1 is applied in form of one of its acid addition salts, particularly preferred doses per day are in the the corresponding values are readily calculable from the range of about 0.375 to 4.5 mg. In case of the preferred aforementioned values. dopamine agonist 2e particularly preferred doses 0074. Within the instant invention the melanocortin ago per day are in the range of about 0.75 to 3 mg. In case of the nist 2a is preferably administered in a range of between about preferred dopamine agonist 2e bupropion particularly pre 0.001 mg per kg of bodyweight per day (mg/kg/day) to about ferred doses per day are in the range of about 100 to 450 mg. 100 mg/kg/day, preferably 0.01 to 10 mg/kg/day, and most In case of the preferred dopamine agonist 2e pergolide par preferably 0.1 to 5.0 mg/kg/day. Intravenously, the most pre ticularly preferred doses per day are in the range of about 0.05 ferred doses will range from about 0.1 to about 10 mg/kg/ to 3 mg. Suitable dosage forms may contain for instance 0.05. minute during a constant rate infusion. Advantageously, the 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6,0.65, compounds 2a of the present invention may be administered 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, in a single daily dose, or the total daily dosage may be admin 1.35, 14, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, istered in divided doses of two, three or four times daily. 1.95, 2, 2.05, 2.1, 2.15, 2.2, 2.25, 2.3, 2.35, 2.4, 2.45, 2.5, 0075 Within the instant invention the prostaglandin E1 2.55, 2.6, 2.65, 2.7, 2.75, 2.8, 2.85, 2.9, 2.95, 3, 3.05, 3.1, agonist 2b is preferably administered in Such an amount that 3.15, 3.2, 3.25, 3.3, 3.35, 3.4, 3.45, 3.5, 3.55, 3.6, 3.65, 3.7, per day between 0.1 to 150 lug are applied. Preferred are 3.75, 3.8, 3.85, 3.9, 3.95, 4, 4.05, 4.1, 4.15, 4.2, 4.25, 4.3, ranges of between 0.5 to 100 ug, particular preferred 1 to 50 4.35, 4.4, 4.45, 4.5, 4.55, 4.6, 4.65, 4.7, 4.75, 4.8, 4.85, 4.9, ug of the prostaglandin E1 agonist 2b. In case of the preferred 4.95, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, prostaglandin E1 agonist 2b limaprost particularly preferred 80, 85,90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, doses per day are in the range of about 15 to 30 Jug. In case of 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, the preferred prostaglandin E1 agonist 2b alprostadil particu 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, larly preferred doses per day are in the range of about 1.25 to 265, 270,275, 280, 285,290, 295,300, 305,310,315, 320, 20 ug. Suitable dosage forms may contain for instance 1, 5. 325, 330, 335, 340, 345, 350, 355, 360,365, 370, 375, 380, 10, 15, 20, 25, 30,35, 40, 45 or 50 ug of the prostaglandin E1 385, 390, 395,400, 405, 410, 415, 420, 425, 430, 435, 440, agonist 2b. Advantageously, the compounds 2b of the present 445 or 450 mg of 2e. Advantageously, the compounds 2e of US 2011/O 105519 A1 May 5, 2011

the present invention may be administered in a single daily 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6,0.65, 0.7, 0.75, 0.8, 0.85, dose, or the total daily dosage may be administered in divided 0.9, 0.95, 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, 1.35, 14, 1.45, 1.5, doses of two, three or four times daily. 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 19, 1.95, 2, 2.05, 2.1, 0081. Within the instant invention the 5-HT2A/2C antago 2.15, 2.2, 2.25, 2.3, 2.35, 2.4, 2.45, 2.5, 2.55, 2.6, 2.65, 2.7, nist 2f is preferably administered in Such an amount that per 2.75, 2.8, 2.85, 2.9, 2.95, 3, 3.05, 3.1, 3.15, 3.2, 3.25, 3.3, day between 0.1 to 200 mg of 2fare applied. Preferred are 3.35, 3.4, 3.45, 3.5, 3.55, 3.6, 3.65, 3.7, 3.75, 3.8, 3.85, 3.9, ranges of between 0.5 to 150 mg, particular preferred 1 to 100 3.95, 4, 4.05, 4.1, 4.15, 4.2, 4.25, 4.3, 4.35, 4.4, 4.45, 4.5, mg of 2f. In case of the preferred 5-HT2A/2C antagonist 2f 4.55, 4.6, 4.65, 4.7, 4.75, 4.8, 4.85, 4.9, 4.95, 5, 10, 15, 20, 25, fluoxetine particularly preferred doses per day are in the range 30, 35, 40, 45, 50,55, 60, 65,70, 75,80, 85,90, 95, 100,105, of about 20 to 60 mg. In case of the preferred 5-HT2A/2C 110, 115, 120, 125, 130, 135, 140, 145, 150, 155, 160, 165, antagonist2frisperidone particularly preferred doses per day 170, 175, 180, 185, 190, 195, 200, 210, 220, 230, 250, 260, are in the range of about 1 to 8 mg. Suitable dosage forms may 270, 280,290, 300, 310,320,330, 350,375,400, 425,450, contain for instance 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 475,500, 550, 600, 650, 700, 750 ug of the estrogen 2 k. 35, 40, 45, 50, 55, 60, 65,70, 75,80, 85,90, 95 or 100 mg of I0087 Advantageously, the compounds 2% of the present 2f. Advantageously, the compounds 2f of the present inven invention may be administered in a single daily dose, or the tion may be administered in a single daily dose, or the total total daily dosage may be administered in divided doses of daily dosage may be administered in divided doses of two, two, three or four times daily. three or four times daily. I0088. Within the instant invention the androgen 21 is pref 0082. Within the instant invention the dopamine D4 erably administered in Such an amount that per day between antagonist 2g is preferably administered in Such an amount 0.01 to 600 mg of 21 are applied. Preferred are ranges of that per day between 0.1 to 100 mg of 2g are applied. Pre between 0.025 to 500 mg, particular preferred 0.05 to 450 mg ferred is are ranges of between 1 to 75 mg, particular preferred of 21. In case of the preferred androgen 21 testosterone par 5 to 50 mg of 2g. In case of the preferred dopamine D4 ticularly preferred doses per day are in the range of about 100 antagonist2g, olanzapine particularly preferred doses per day ug to 10 mg, more preferrably in the range of 500 ug to 5 mg. are in the range of about 5 to 15 mg. Suitable dosage forms Suitable dosage forms may contain for instance 0.05, 0.1, may contain for instance 5, 10, 15, 20, 25, 30,35, 40, 45 or 50 0.15, 0.2,0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6,0.65, 0.7, mg of 2g. Advantageously, the compounds 2g of the present 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.05, 1.1, 1.15, 1.2, 1.25, 1.3, invention may be administered in a single daily dose, or the 1.35, 14, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 1.85, 1.9, total daily dosage may be administered in divided doses of 1.95, 2, 2.05, 2.1, 2.15, 2.2, 2.25, 2.3, 2.35, 2.4, 2.45, 2.5, two, three or four times daily. 2.55, 2.6, 2.65, 2.7, 2.75, 2.8, 2.85, 2.9, 2.95, 3, 3.05, 3.1, 0083. Within the instant invention the selective androgen 3.15, 3.2, 3.25, 3.3, 3.35, 3.4, 3.45, 3.5, 3.55, 3.6, 3.65, 3.7, receptor modulator (SARM) 2his preferably administered in 3.75, 3.8, 3.85, 3.9, 3.95, 4, 4.05, 4.1, 4.15, 4.2, 4.25, 4.3, such an amount that per day between 0.01 to 600 mg of 2h are 4.35, 4.4, 4.45, 4.5, 4.55, 4.6, 4.65, 4.7, 4.75, 4.8, 4.85, 4.9, applied. Preferred are ranges of between 0.025 to 500 mg. 4.95, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, particular preferred 0.05 to 100 mg of 2h. 80, 85,90, 95, 100, 105, 110, 115, 120, 125, 130, 135, 140, 0084 Suitable dosage forms may contain for instance 145, 150, 155, 160, 165, 170, 175, 180, 185, 190, 195, 200, 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 260, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.05, 1.1, 1.15, 1.2, 265, 270,275, 280, 285,290, 295,300, 305,310,315, 320, 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 325, 330, 335, 340, 345, 350, 355, 360,365, 370, 375, 380, 1.85, 1.9, 1.95, 2, 2.05, 2.1, 2.15, 2.2, 2.25, 2.3, 2.35, 2.4, 385, 390, 395,400, 405, 410, 415, 420, 425, 430, 435, 440, 2.45, 2.5, 2.55, 2.6, 2.65, 2.7, 2.75, 2.8, 2.85, 2.9, 2.95, 3, 445 or 450 mg of 21. 3.05, 3.1, 3.15, 3.2, 3.25, 3.3, 3.35, 3.4, 3.45, 3.5, 3.55, 3.6, I0089 Advantageously, the compounds 21 of the present 3.65, 3.7, 3.75, 3.8, 3.85, 3.9, 3.95, 4, 4.05, 4.1, 4.15, 4.2, invention may be administered in a single daily dose, or the 4.25, 4.3, 4.35, 4.4, 4.45, 4.5, 4.55, 4.6, 4.65, 4.7, 4.75, 4.8, total daily dosage may be administered in divided doses of 4.85, 4.9, 4.95, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50,55, 60, 65, two, three or four times daily. 70, 75, 80, 85,90, 95, 100,105,110, 115, 120, 125, 130, 135, 0090. Within the instant invention the C-adrenergic recep 140, 145, 150, 155, 160, 165,170, 175, 180, 185, 190, 195, tor antagonist 2m is preferably administered in Such an 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, amount that per day between 0.01 to 600 mg of 2m are 260, 265, 270,275, 280, 285,290, 295,300, 305,310,315, applied. Preferred are ranges of between 0.025 to 500 mg. 320, 325, 330, 335, 340, 345,350, 355, 360, 365, 370, 375, particular preferred 0.05 to 450 mg of 2m. In case of the 380, 385, 390, 395, 400, 405, 410, 415, 420, 425, 430, 435, C.-adrenergic receptor antagonist 2m phentolamine mesylate 440, 445 or 450 mg of 2h. preferred doses per day are in the range of about 1 to 70 mg. 0085 Advantageously, the compounds 2h of the present particularly preferred doses per day are in the range of 30 to invention may be administered in a single daily dose, or the 50 mg. total daily dosage may be administered in divided doses of 0091 Suitable dosage forms may contain for instance two, three or four times daily. 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, I0086. Within the instant invention the estrogen 2 k is pref 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.05, 1.1, 1.15, 1.2, erably administered in Such an amount that per day between 1.25, 1.3, 1.35, 14, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, 0.1 to 3000 ug are applied. Preferred are ranges of between 1.85, 1.9, 1.95, 2, 2.05, 2.1, 2.15, 2.2, 2.25, 2.3, 2.35, 2.4, 0.5 to 1500 ug, particular preferred 1 to 750 g of estrogen 2 2.45, 2.5, 2.55, 2.6, 2.65, 2.7, 2.75, 2.8, 2.85, 2.9, 2.95, 3, k. In case of the preferred estrogen 2 k estradiol particularly 3.05, 3.1, 3.15, 3.2, 3.25, 3.3, 3.35, 3.4, 3.45, 3.5, 3.55, 3.6, preferred doses per day are in the range of about 1 lug to 500 3.65, 3.7, 3.75, 3.8, 3.85, 3.9, 3.95, 4, 4.05, 4.1, 4.15, 4.2, ug, more preferrably in the range of 5 to 250 g. Suitable 4.25, 4.3, 4.35, 4.4, 4.45, 4.5, 4.55, 4.6, 4.65, 4.7, 4.75, 4.8, dosage forms may contain for instance 0.1, 0.15, 0.2, 0.25, 4.85, 4.9, 4.95, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50,55, 60, 65, US 2011/O 105519 A1 May 5, 2011

70, 75, 80, 85,90, 95, 100,105,110, 115, 120, 125, 130, 135, optionally in form of the hydrates and/or solvates thereof, in 140, 145, 150, 155, 160, 165,170, 175, 180, 185, 190, 195, combination with a therapeutically effective amount of 2, 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, optionally in form of the pharmaceutically acceptable acid 260, 265, 270,275, 280, 285,290, 295,300, 305,310,315, addition salts, in form of the hydrates and/or solvates and 320, 325, 330, 335, 340, 345,350, 355, 360, 365, 370, 375, optionally in the form of the individual optical isomers, mix 380, 385, 390, 395, 400, 405, 410, 415, 420, 425, 430, 435, tures of the individual enantiomers or racemates thereof, 440, 445 or 450 mg of 2m. separately or together within one pharmaceutical composi 0092 Advantageously, the compounds 2m of the present tion. In another preferred embodiment the invention relates to invention may be administered in a single daily dose, or the a method for the treatment of disorders selected from the total daily dosage may be administered in divided doses of group consisting of Hypoactive Sexual Desire Disorder and two, three or four times daily. loss of sexual desire, preferably Hypoactive Sexual Desire 0093. Within the instant invention the selective androgen Disorder, comprising the administration of a therapeutically receptor modulator (SERM) 2n is preferably administered in effective amount of 1 optionally in form of its pharmaceuti such an amount that per day between 0.01 to 600 mg of 2n are cally acceptable acid addition salts and/or optionally in form applied. Preferred are ranges of between 0.025 to 500 mg. of the hydrates and/or solvates thereof, in combination with a particular preferred 0.05 to 450 mg of 2n. In case of the therapeutically effective amount of 2, optionally in form of preferred SERM 2nlasofoxifene particularly preferred doses the pharmaceutically acceptable acid addition salts, in form per day are in the range of about 0.5 to 50 mg. In case of the of the hydrates and/or solvates and optionally in the form of preferred compound 2ntibolon preferred doses per day are in the individual optical isomers, mixtures of the individual the range of about 0.5 to 10 mg, particularly preferred doses enantiomers or racemates thereof, separately or together per day are in the range of 1 to 5 mg. within one pharmaceutical composition. 0094 Suitable dosage forms may contain for instance 0097. In another preferred embodiment the invention 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, relates to a method for the treatment of premenstrual disor 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1, 1.05, 1.1, 1.15, 1.2, ders, comprising the administration ofatherapeutically effec 1.25, 1.3, 1.35, 1.4, 1.45, 1.5, 1.55, 1.6, 1.65, 1.7, 1.75, 1.8, tive amount of 1 optionally in form of its pharmaceutically 1.85, 1.9, 1.95, 2, 2.05, 2.1, 2.15, 2.2, 2.25, 2.3, 2.35, 2.4, acceptable acid addition salts and/or optionally inform of the 2.45, 2.5, 2.55, 2.6, 2.65, 2.7, 2.75, 2.8, 2.85, 2.9, 2.95, 3, hydrates and/or solvates thereof, in combination with a thera 3.05, 3.1, 3.15, 3.2, 3.25, 3.3, 3.35, 3.4, 3.45, 3.5, 3.55, 3.6, peutically effective amount of 2, optionally in form of the 3.65, 3.7, 3.75, 3.8, 3.85, 3.9, 3.95, 4, 4.05, 4.1, 4.15, 4.2, pharmaceutically acceptable acid addition salts, in form of 4.25, 4.3, 4.35, 4.4, 4.45, 4.5, 4.55, 4.6, 4.65, 4.7, 4.75, 4.8, the hydrates and/or solvates and optionally in the form of the 4.85, 4.9, 4.95, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50,55, 60, 65, individual optical isomers, mixtures of the individual enanti 70, 75, 80, 85,90, 95, 100,105,110, 115, 120, 125, 130, 135, omers or racemates thereof, separately or together within one 140, 145, 150, 155, 160, 165,170, 175, 180, 185, 190, 195, pharmaceutical composition. 200, 205, 210, 215, 220, 225, 230, 235, 240, 245, 250, 255, 0098. In another preferred embodiment the invention 260, 265, 270,275, 280, 285,290, 295,300, 305,310,315, relates to a method for the treatment of premenstrual disor 320, 325, 330, 335, 340, 345,350, 355, 360, 365, 370, 375, ders, selected from the group consisting of premenstrual dys 380, 385, 390, 395, 400, 405, 410, 415, 420, 425, 430, 435, phoria, premenstrual syndrome and premenstrual dysphoric 440, 445 or 450 mg of 2n. disorder, in particular premenstrual dysphoric disorder, com 0095 Advantageously, the compounds 2n of the present prising the administration of a therapeutically effective invention may be administered in a single daily dose, or the amount of 1 optionally in form of its pharmaceutically total daily dosage may be administered in divided doses of acceptable acid addition salts and/or optionally inform of the two, three or four times daily. hydrates and/or solvates thereof, in combination with a thera 0096. In another preferred embodiment the invention peutically effective amount of 2, optionally in form of the relates to a method for the treatment of disorders selected pharmaceutically acceptable acid addition salts, in form of from the group consisting of Hypoactive Sexual Desire Dis the hydrates and/or solvates and optionally in the form of the order, loss of sexual desire, lack of sexual desire, decreased individual optical isomers, mixtures of the individual enanti sexual desire, inhibited sexual desire, loss of libido, libido omers or racemates thereof, separately or together within one disturbance, and frigidity, comprising the administration of a pharmaceutical composition. therapeutically effective amount of 1 optionally inform of its 0099. In another preferred embodiment the invention pharmaceutically acceptable acid addition salts and/or relates to a method for the treatment of sexual aversion dis optionally in form of the hydrates and/or solvates thereof, in order in females, comprising the administration of a thera combination with a therapeutically effective amount of 2, peutically effective amount of 1 optionally in form of its optionally in form of the pharmaceutically acceptable acid pharmaceutically acceptable acid addition salts and/or addition salts, in form of the hydrates and/or solvates and optionally in form of the hydrates and/or solvates thereof, in optionally in the form of the individual optical isomers, mix combination with a therapeutically effective amount of 2, tures of the individual enantiomers or racemates thereof, optionally in form of the pharmaceutically acceptable acid separately or together within one pharmaceutical composi addition salts, in form of the hydrates and/or solvates and tion. In another preferred embodiment the invention relates to optionally in the form of the individual optical isomers, mix a method for the treatment of disorders selected from the tures of the individual enantiomers or racemates thereof, group consisting of Hypoactive Sexual Desire Disorder, loss separately or together within one pharmaceutical composi of sexual desire, lack of sexual desire, decreased sexual tion. desire, inhibited sexual desire, comprising the administration 0100. In another preferred embodiment the invention of a therapeutically effective amount of 1 optionally in form relates to a method for the treatment of disor of its pharmaceutically acceptable acid addition salts and/or der in females, comprising the administration of a therapeu US 2011/O 105519 A1 May 5, 2011 tically effective amount of 1 optionally in form of its phar inhibitors), 5-HT-1A agonists, dopamine agonists, dopamine maceutically acceptable acid addition salts and/or optionally D4 antagonists, 5-HT-2A/C antagonists, selective androgen in form of the hydrates and/or solvates thereof, in combina receptor modulators (SARMs), selective estrogen receptor tion with atherapeutically effective amount of 2, optionally in modulators (SERMs), estrogens, androgens and C.-adrener form of the pharmaceutically acceptable acid addition salts, gic receptor antagonists. in form of the hydrates and/or solvates and optionally in the 0.107 Another embodiment of the invention relates to the form of the individual optical isomers, mixtures of the indi use of the combinations of 1 and 2, optionally inform of their vidual enantiomers or racemates thereof, separately or pharmaceutically acceptable acid addition salts for the prepa together within one pharmaceutical composition. ration of a medicament for the treatment of the aforemen 0101. In another preferred embodiment the invention tioned disorders, wherein 2 is selected from the group con relates to a method for the treatment of orgasmic disorder in sisting of the aforementioned melanocortin agonists, females, comprising the administration of a therapeutically prostaglandin E1 agonists, elevators of cyclic guanosine 3',5'- effective amount of 1 optionally in form of its pharmaceuti monophosphate (cGMP) (preferably PDE V inhibitors), cally acceptable acid addition salts and/or optionally in form 5-HT-1A agonists, dopamine agonists, dopamine D4 antago of the hydrates and/or solvates thereof, in combination with a nists, 5-HT2A/C antagonists, selective androgen receptor therapeutically effective amount of 2, optionally in form of modulators (SARMs), selective estrogen receptor modula the pharmaceutically acceptable acid addition salts, in form tors (SERMs), estrogens, androgens and C.-adrenergic recep of the hydrates and/or solvates and optionally in the form of tor antagonist. the individual optical isomers, mixtures of the individual 0108. Another preferred embodiment of the invention is enantiomers or racemates thereof, separately or together directed to a method for the treatment of one of the aforemen within one pharmaceutical composition. tioned disorders, comprising the administration of a thera 0102. In another preferred embodiment the invention peutically effective amount of one or more, preferably one of relates to a method for the treatment of sexual pain disorders the aforementioned melanocortin agonists 2a, optionally in in females, comprising the administration ofatherapeutically form of the pharmaceutically acceptable acid addition salts, effective amount of 1 optionally in form of its pharmaceuti in form of the hydrates and/or solvates and optionally in the cally acceptable acid addition salts and/or optionally in form form of the individual optical isomers, mixtures of the indi of the hydrates and/or solvates thereof, in combination with a vidual enantiomers or racemates thereof. therapeutically effective amount of 2, optionally in form of 0.109 Another embodiment of the invention relates to the the pharmaceutically acceptable acid addition salts, in form use of a therapeutically effective amount of one or more, of the hydrates and/or solvates and optionally in the form of preferably one of the aforementioned melanocortin agonists the individual optical isomers, mixtures of the individual 2a, optionally inform of the pharmaceutically acceptable acid enantiomers or racemates thereof, separately or together addition salts, in form of the hydrates and/or solvates and within one pharmaceutical composition. optionally in the form of the individual optical isomers, mix 0103) In a particular preferred embodiment the invention tures of the individual enantiomers or racemates thereof, for relates to a method for the treatment of sexual pain disorders the preparation of a medicament for the treatment of the selected from the group consisting of dyspareunia, Vaginis aforementioned disorders. mus, noncoital sexual pain disorder, due 0110. Another preferred embodiment of the invention is to a general medical condition and Substance-induced sexual directed to a method for the treatment of one of the aforemen dysfunction, comprising the administration of a therapeuti tioned disorders, comprising the administration of a thera cally effective amount of 1 optionally in form of its pharma peutically effective amount of one or more, preferably one of ceutically acceptable acid addition salts and/or optionally in the aforementioned prostaglandin E1 agonists 2b, optionally form of the hydrates and/or solvates thereof, in combination in form of the pharmaceutically acceptable acid addition with a therapeutically effective amount of 2, optionally in salts, inform of the hydrates and/or Solvates and optionally in form of the pharmaceutically acceptable acid addition salts, the form of the individual optical isomers, mixtures of the in form of the hydrates and/or solvates and optionally in the individual enantiomers or racemates thereof. form of the individual optical isomers, mixtures of the indi 0111. Another embodiment of the invention relates to the vidual enantiomers or racemates thereof, separately or use of a therapeutically effective amount of one or more, together within one pharmaceutical composition. preferably one of the aforementioned prostaglandin E1 ago 0104. The beneficial effects of the compositions according nists 2b, optionally in form of the pharmaceutically accept to the invention can be observed regardless of whether the able acid addition salts, in form of the hydrates and/or sol disturbance existed lifelong or was acquired, and independent vates and optionally in the form of the individual optical of etiologic origin (organic—both, physically and drug isomers, mixtures of the individual enantiomers or racemates induced-, psychogen, a combination of organic—both, physi thereof, for the preparation of a medicament for the treatment cally and drug induced-, and psychogen, or unknown). of the aforementioned disorders. 0105. Another embodiment of the invention relates to the 0112 Another preferred embodiment of the invention is use of the combinations of 1 and 2, optionally inform of their directed to a method for the treatment of one of the aforemen pharmaceutically acceptable acid addition salts for the prepa tioned disorders, comprising the administration of a thera ration of a medicament for the treatment of the aforemen peutically effective amount of one or more, preferably one of tioned disorders. the aforementioned elevators of cyclic guanosine 3',5'-mono 010.6 Another preferred embodiment of the invention is phosphate (cGMP) 2c, optionally in form of the pharmaceu directed to the aforementioned methods wherein 2 is selected tically acceptable acid addition salts, in form of the hydrates from the group consisting of the aforementioned melanocor and/or solvates and optionally in the form of the individual tin agonists, prostaglandin E1 agonists, elevators of cyclic optical isomers, mixtures of the individual enantiomers or guanosine 3',5'-monophosphate (cGMP) (preferably PDEV racemates thereof. US 2011/O 105519 A1 May 5, 2011

0113 Another embodiment of the invention relates to the I0120 Another preferred embodiment of the invention is use of a therapeutically effective amount of one or more, directed to a method for the treatment of one of the aforemen preferably one of the aforementioned elevators of cyclic gua tioned disorders, comprising the administration of a thera nosine 3',5'-monophosphate (cGMP) 2c, optionally in form peutically effective amount of one or more, preferably one of of the pharmaceutically acceptable acid addition salts, in the aforementioned dopamine D4 antagonists 2g, optionally form of the hydrates and/or solvates and optionally in the form of the individual optical isomers, mixtures of the indi in form of the pharmaceutically acceptable acid addition vidual enantiomers or racemates thereof, for the preparation salts, inform of the hydrates and/or Solvates and optionally in of a medicament for the treatment of the aforementioned the form of the individual optical isomers, mixtures of the disorders. individual enantiomers or racemates thereof. 0114. Another preferred embodiment of the invention is 0.121. Another embodiment of the invention relates to the directed to a method for the treatment of one of the aforemen use of a therapeutically effective amount of one or more, tioned disorders, comprising the administration of a thera preferably one of the aforementioned dopamine D4 antago peutically effective amount of one or more, preferably one of nists 2g, optionally in form of the pharmaceutically accept the aforementioned 5-HT1A agonists 2d, optionally in form able acid addition salts, in form of the hydrates and/or sol of the pharmaceutically acceptable acid addition salts, in vates and optionally in the form of the individual optical form of the hydrates and/or solvates and optionally in the isomers, mixtures of the individual enantiomers or racemates form of the individual optical isomers, mixtures of the indi thereof, for the preparation of a medicament for the treatment vidual enantiomers or racemates thereof. of the aforementioned disorders. 0115. Another embodiment of the invention relates to the use of a therapeutically effective amount of one or more, I0122) Another preferred embodiment of the invention is preferably one of the aforementioned 5-HT-1A agonists 2d. directed to a method for the treatment of one of the aforemen optionally in form of the pharmaceutically acceptable acid tioned disorders, comprising the administration of a thera addition salts, in form of the hydrates and/or solvates and peutically effective amount of one or more, preferably one of optionally in the form of the individual optical isomers, mix the aforementioned selective androgen receptor modulators tures of the individual enantiomers or racemates thereof, for (SARMs) 2h, optionally in form of the pharmaceutically the preparation of a medicament for the treatment of the acceptable acid addition salts, in form of the hydrates and/or aforementioned disorders. solvates and optionally in the form of the individual optical 0116. Another preferred embodiment of the invention is isomers, mixtures of the individual enantiomers or racemates directed to a method for the treatment of one of the aforemen thereof. tioned disorders, comprising the administration of a thera (0123. Another embodiment of the invention relates to the peutically effective amount of one or more, preferably one of use of a therapeutically effective amount of one or more, the aforementioned dopamine agonists 2e, optionally inform preferably one of the aforementioned selective androgen of the pharmaceutically acceptable acid addition salts, in receptor modulators (SARMs) 2h, optionally in form of the form of the hydrates and/or solvates and optionally in the pharmaceutically acceptable acid addition salts, in form of form of the individual optical isomers, mixtures of the indi the hydrates and/or solvates and optionally in the form of the vidual enantiomers or racemates thereof. individual optical isomers, mixtures of the individual enanti 0117. Another embodiment of the invention relates to the use of a therapeutically effective amount of one or more, omers or racemates thereof, for the preparation of a medica preferably one of the aforementioned dopamine agonists 2e. ment for the treatment of the aforementioned disorders. optionally in form of the pharmaceutically acceptable acid 0.124. Another preferred embodiment of the invention is addition salts, in form of the hydrates and/or solvates and directed to a method for the treatment of one of the aforemen optionally in the form of the individual optical isomers, mix tioned disorders, comprising the administration of a thera tures of the individual enantiomers or racemates thereof, for peutically effective amount of one or more, preferably one of the preparation of a medicament for the treatment of the the aforementioned estrogens 2 k, optionally in form of the aforementioned disorders. pharmaceutically acceptable acid addition salts, in form of 0118. Another preferred embodiment of the invention is the hydrates and/or solvates and optionally in the form of the directed to a method for the treatment of one of the aforemen individual optical isomers, mixtures of the individual enanti tioned disorders, comprising the administration of a thera omers or racemates thereof. peutically effective amount of one or more, preferably one of 0.125. Another embodiment of the invention relates to the the aforementioned 5-HT2A/C antagonists 2f, optionally in use of a therapeutically effective amount of one or more, form of the pharmaceutically acceptable acid addition salts, preferably one of the aforementioned estrogens 2 k, option in form of the hydrates and/or solvates and optionally in the ally in form of the pharmaceutically acceptable acid addition form of the individual optical isomers, mixtures of the indi vidual enantiomers or racemates thereof. salts, inform of the hydrates and/or Solvates and optionally in 0119) Another embodiment of the invention relates to the the form of the individual optical isomers, mixtures of the use of a therapeutically effective amount of one or more, individual enantiomers or racemates thereof, for the prepara preferably one of the aforementioned 5-HT-2A/Cantagonists tion of a medicament for the treatment of the aforementioned 2f optionally inform of the pharmaceutically acceptable acid disorders. addition salts, in form of the hydrates and/or solvates and 0.126 Another preferred embodiment of the invention is optionally in the form of the individual optical isomers, mix directed to a method for the treatment of one of the aforemen tures of the individual enantiomers or racemates thereof, for tioned disorders, comprising the administration of a thera the preparation of a medicament for the treatment of the peutically effective amount of one or more, preferably one of aforementioned disorders. the aforementioned androgens 21, optionally in form of the US 2011/O 105519 A1 May 5, 2011 13 pharmaceutically acceptable acid addition salts, in form of Example 1 the hydrates and/or solvates and optionally in the form of the Combination 1 with 2c individual optical isomers, mixtures of the individual enanti omers or racemates thereof. 0135) 0127. Another embodiment of the invention relates to the use of a therapeutically effective amount of one or more, preferably one of the aforementioned androgens 21, option Constituents mg tablet ally in form of the pharmaceutically acceptable acid addition salts, inform of the hydrates and/or Solvates and optionally in Core the form of the individual optical isomers, mixtures of the Flibanserin (free base) SO.OOO individual enantiomers or racemates thereof, for the prepara Sildenafil citrate 70.225 tion of a medicament for the treatment of the aforementioned Anhydrous dibasic calcium phosphate 1OO.OOO Microcrystalline cellulose 2O3.090 disorders. HPMC (Methocel E5) 6.615 Croscarmellose sodium 8.82O 0128. Another preferred embodiment of the invention is Magnesium stearate 2.2SO directed to a method for the treatment of one of the aforemen Coating tioned disorders, comprising the administration of a thera HPMC (Methocel E5) 4.32O peutically effective amount of one or more, preferably one of Polyethylene Glycol 6000 1260 the aforementioned C.-adrenergic receptor antagonist 2m, Titanium dioxide 1800 optionally in form of the pharmaceutically acceptable acid Talc 1542 addition salts, in form of the hydrates and/or solvates and Iron oxidered O.078 optionally in the form of the individual optical isomers, mix Total Film coated tablet tures of the individual enantiomers or racemates thereof. 0129. Another embodiment of the invention relates to the use of a therapeutically effective amount of one or more, Example 2 preferably one of the aforementioned C.-adrenergic receptor antagonist 2m, optionally in form of the pharmaceutically Combination 1 with 2d acceptable acid addition salts, in form of the hydrates and/or 0.136 solvates and optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates thereof, for the preparation of a medicament for the treatment of the aforementioned disorders. Constituents mg tablet 0130. Another preferred embodiment of the invention is Core directed to a method for the treatment of one of the aforemen Flibanserin (free base) SO.OOO tioned disorders, comprising the administration of a thera Aripiprazole 1.O.OOO peutically effective amount of one or more, preferably one of Lactose monohydrate 133.750 Microcrystalline cellulose 40.OOO the aforementioned selective estrogen receptor modulators Hydroxypropylcellulose 2. SOO (SERMs) 2n, optionally in form of the pharmaceutically Corn starch 12.SOO acceptable acid addition salts, in form of the hydrates and/or Magnesium stearate 1.2SO solvates and optionally in the form of the individual optical Coating isomers, mixtures of the individual enantiomers or racemates HPMC (e.g. Pharmacoat 606) 2.400 thereof. Polyethylene Glycol 6000 O.7OO Titanium dioxide 1.OOO 0131. Another embodiment of the invention relates to the Talc 0.857 use of a therapeutically effective amount of one or more, Iron oxide yellow O.043 preferably one of the aforementioned selective estrogen receptor modulators (SERMs) 2n, optionally in form of the Total Film coated tablet pharmaceutically acceptable acid addition salts, in form of the hydrates and/or solvates and optionally in the form of the individual optical isomers, mixtures of the individual enanti Example 3 omers or racemates thereof, for the preparation of a medica Combination 1 with 2e ment for the treatment of the aforementioned disorders. 0132) The present invention is further described in the 0.137 following examples which are provided for illustrative pur poses only and are not to be construed as limiting. Indeed, other variants of the invention will be readily apparent to one Constituents mg tablet of ordinary skill in the art. C 0.133 All publications and patents cited herein are incor- Oe porated by reference in their entireties. Flibanserin (free base) SO.OOO Pramipexole dihydrochloride monohydrate 1.OOO 0134. The following examples demonstrate possible phar Lactose monohydrate 143.490 maceutical compositions comprising flibanserin in combina- Microcrystalline cellulose 47.810 tion with one of the aforementioned combination partners 2. US 2011/O 105519 A1 May 5, 2011 14

-continued -continued Constituents mg tablet Constituents mg tablet HPMC (e.g. Pharmacoat 606) 2.SOO Carboxymethylcellulose sodium S.OOO Titanium dioxide Mannitol 6O.OOO Talc Corn starch 36.500 Povidone 1.OOO Iron oxidered Colloidal silicon dioxide 1.OOO Magnesium stearate 1.700 Coating Total Film coated tablet 128.OOO HPMC (e.g. Methocel E5) 3.360 Polyethylene Glycol 6000 O.980 Titanium dioxide 1400 Example 6 Talc 1200 Iron oxidered O.O60 Composition Total Film coated bilayer tablet 357.OOO 0141 Example 4 Combination of 1 with 2f Constituents mg tablet 0138 Core Flibanserin (free base) SO.OOO Lactose monohydrate 143.440 Microcrystalline cellulose 47.810 Constituents mg tablet HPMC (e.g. Pharmacoat 606) 2. SOO Carboxymethylcellulose sodium S.OOO Final Mixture Magnesium stearate 1.2SO Coating Flibanserin (free base) SO.OOO Ziprasidone hydrochloride monohydrate 40.OOO HPMC (e.g. Pharmacoat 606) 2.400 Lactose monohydrate 2OOOOO Polyethylene Glycol 6000 O.7OO Pregelatinized starch 108.OOO Titanium dioxide 1.OOO Magnesium stearate 2.OOO Talc 0.857 Capsule Iron oxidered O.043

Final Mixture 4OOOOO Total Film coated tablet Capsule (size 1) 82.OOO Total weight of Capsule 482.OOO Example 7 0.139. The following examples show preferred pharma ceutical compositions of flibanserin, if the combinations Composition according to the invention are administered in separate dos age units. 0142 Example 5 Composition Constituents mg tablet 0140 Core Flibanserin (free base) 1OO.OOO Lactose monohydrate 171.08O Microcrystalline cellulose 57.02O Constituents mg tablet HPMC (e.g. Methocel E5) 3.400 Carboxymethylcellulose sodium 6.8OO Core Magnesium stearate 1.700 Coating Flibanserin (free base) 2S.OOO Lactose monohydrate 71.720 HPMC (e.g. Methocel E5) 3.360 Microcrystalline cellulose 23.905 Polyethylene Glycol 6000 O.980 HPMC (Methocel E5) 1.2SO Titanium dioxide 1400 Carboxymethylcellulose sodium 2.500 Talc 1200 Magnesium Stearate O.625 Iron oxidered O.O60 Coating Total Film coated tablet 347.OOO HPMC (Methocel E5) 1.440 Polyethylene Glycol 6000 O42O US 2011/O 105519 A1 May 5, 2011 15

Example 8 Composition -continued Constituents mg tablet 0143 Sodium Starch Glycolate 4.OOO Magnesium stearate 1.OOO Coating Constituents mg tablet HPMC (e.g. Methocel E5) 2.400 Core Polyethylene Glycol 6000 O.7OO Titanium dioxide 1.043 Flibanserin (free base) 2.OOO Talc 0.857 Dibasic Calciumphosphate, anhydrous 61010 Microcrystalline cellulose 61010 Total Film coated tablet 2OS.OOO HPMC (Methocel E5) 1.9SO Carboxymethylcellulose sodium 2.600 Colloidal silicon dioxide O.6SO What is claimed is: Magnesium Stearate O.78O Coating 1. A pharmaceutical composition comprising a therapeuti cally effective amount offilibanserin as one active ingredient HPMC (Methocel E5) 1.440 in combination with a therapeutically effective amount of at Polyethylene Glycol 6000 O42O least one additional active ingredient. Titanium dioxide O600 Talc O514 2. The pharmaceutical composition according to claim 1, Iron oxidered O.O26 wherein the additional active ingredient is selected from the group consisting of melanocortin agonists, prostaglandin E1 Total Film coated tablet 133.OOO agonists, elevators of cyclic guanosine 3',5'-monophosphate (cGMP), 5-HT-1A agonists, dopamine agonists, dopamine D4 antagonists, 5-HT-2A/C antagonists, selective androgen Example 9 receptor modulators (SARMs), selective estrogen receptor modulators (SERMs), estrogens, androgens and C.-adrener Composition gic receptor antagonist. 3. The pharmaceutical composition according to claim 2, 0144) comprising a therapeutically effective amount offilibanserin and a therapeutically effective amount of one or more mel anocortin agonist, optionally in combination with a pharma Constituents mg tablet ceutically acceptable excipient. 4. The pharmaceutical composition according to claim 3, Core wherein the melanocortin agonist is selected from the group Flibanserin (free base) 1OOOOO consisting of PT-141, MCL-0129, PG-917, and Ro-27-3225, Dibasic Calciumphosphate, anhydrous 69.750 or a pharmaceutically acceptable acid addition salt thereof, a Microcrystalline cellulose 69.750 HPMC (e.g. Methocel E5) 2.750 hydrate and/or a solvate thereof, an optical isomer thereof, or Carboxymethylcellulose sodium S.OOO a mixture of the enantiomers or a racemate thereof. Colloidal silicon dioxide 1.2SO 5. The pharmaceutical composition according to claim 2, Magnesium Stearate 1...SOO comprising a therapeutically effective amount offilibanserin Coating and a therapeutically effective amount of one or more pros HPMC (e.g. Methocel E5) 2400 taglandin E1 agonists, optionally in combination with a phar Polyethylene Glycol 6000 O.7OO maceutically acceptable excipient. Titanium dioxide 1.043 6. The pharmaceutical composition according to claim 5. Talc 0.857 wherein the prostaglandin E1 agonist, is selected from the Total Film coated tablet group consisting of ornoprostil, limaprost, alprostadil, geme prost, liprostin, NMI-775, prostaglandin E (PGE-1), papav erine, dioxyline, ethaverine, phentolamine, praZosin, minoxi dil, nitroglycerin, alpha blockers, nitric oxide donors, and Example 10 peptides, or a pharmaceutically acceptable acid addition salt Composition thereof, a hydrate and/or a solvate thereof, an optical isomer thereof, or a mixture of the enantiomers or a racemate thereof. (0145 7. The pharmaceutical composition according to claim 2, comprising a therapeutically effective amount offilibanserin and a therapeutically effective amount of one or more eleva tors of c(GMP, optionally in combination with a pharmaceu Constituents mg tablet tically acceptable excipient. Core 8. The pharmaceutical composition according to claim 7. wherein the elevator of c(GMP is selected from the group Flibanserin (free base) 2O.OOO Lactose monohydrate 13O.OOO consisting of Vardenafil, sildenafil, tadalafil. NCX-911, Sch Microcrystalline cellulose 43.1OO 444877, FR-229934, 4-bromo-5-(pyridylmethylamino)-6- Hydroxypropyl Cellulose (e.g. Klucel LF) 1.900 3-(4-chlorophenyl)-propoxy-3(2H)pyridaZinone, 1-4-(1, 3-benzodioxol-5-ylmethyl)amiono-6-chloro-2- US 2011/O 105519 A1 May 5, 2011 16

quinozolinyl-4-piperidine-carboxylic acid, monosodium wherein salt, (+)-cis-5,6a, 7.9,9.9a-hexahydro-2-[4-(trifluoromethyl) R" represents hydrogen, halogen or Coalkyl; phenylmethyl-5-methyl-cyclopent-4.5imidazo[2.1-bpurin R" represents hydrogen, C-alkyl, Calkenyl, C2-alky nyl, haloC-alkyl, Cascycloalkyl, Cascycloalkyl-C- 4(3H)one, furazlocillin, cis-2-hexyl-5-methyl-3,4,5,6a,7,8,9, 3alkyl, arylCalkyl or heteroarylalkyl, 9a-octahydrocyclopent4.5-imidazo[2.1-bpurin-4-one, R represents an optionally substituted monocyclic aro 3-acetyl-1-(2-chlorobenzyl)-2 propylindole-6-carboxylate, matic ring selected from benzene, thiophene, furan and 3-acetyl-1-(2-chlorobenzyl)-2-propylindole-6-carboxylate, pyridine or an optionally Substituted bicyclic ring 4-bromo-5-(3-pyridylmethylamino)-6-(3-(4-chlorophenyl) propoxy)-3-(2H)pyridazinone, 1-methyl-5(5-morpholi noacetyl-2-n-propoxyphenyl)-3-n-propyl-1,6-dihydro-7H pyrazolo(4.3-d)pyrimidin-7-one, 1-4-(1,3-benzodioxol-5- ylmethyl)amino]-6-chloro-2-quinazolinyl-4- piperidinecarboxylic acid, monosodium salt, GF-196960, E-8010, E-4010, Bay-38-3045, Bay-38-9456, FR226807, Sch-51866, 5-(2-ethoxy-5-morpholinoacetylphenyl)-1-me attached to the rest of the molecule via one of the ben thyl-3-n-propyl-1,6-dihydro-7H-pyrazolo 4,3-dipyrimidin Zene ring carbon atoms and wherein the fused ring A is 7-one, 3-ethyl-5-5-(4-ethylpiperazin-1-ylsulfonyl)-2-n-pro a 5- or 6 membered ring which may be saturated or poxyphenyl-2-(pyridin-2-yl)methyl-2,6-dihydro-7H partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected pyrazolo 4.3-dpyrimidin-7-one, 3-ethyl-5-5-(4-ethyl from oxygen, Sulphur and nitrogen; and piperazin-1-ylsulfonyl)-2-(2-methoxyethoxy)pyridin-3-yl R represents hydrogen or C-alkyl, or R' and R together 2-(pyridin-2-yl)methyl-2,6-dihydro-7H-pyrazolo 4.3-dpy represent a 3- or 4-membered alkyl or alkenyl chain, or rimidin-7-one, (+)-3-ethyl-5-5-(4-ethylpieperazin-1-ylsul a pharmaceutically acceptable acid addition salt thereof, fonyl)-2-(2-methoxy-1(R)-methylethoxy)pyridin-3-yl)-2- a hydrate and/or a solvate thereof, an optical isomer methyl-2,6-dihydro-7H-pyrazolo 4,3-dipyrimidin-7-one, thereof, or a mixture of the enantiomers or a racemate 5-2-ethoxy-5-(4-ethyl piperazin-1-ylsulfonyl)pyridin-3-yl)- thereof. 3-ethyl-2-2-methoxyethyl-2,6-dihydro-7H-pyrazolo 4,3- 10. The pharmaceutical composition according to claim 7. dpyrimidin-7-one, 5-2-iso-butoxy-5-(4-ethylpiperazin-1- wherein the elevator of c(GMP is selected from the com ylsulfonyl)pyridin-3-yl)-3-ethyl-2-(1-methylpiperidin-4- pounds of formula 2c.2 yl)-2,6-dihydro-7H-pyrazolo 4,3-dipyrimidin-7-one, 5-2- ethoxy-5-(4-ethylpiperazin-1-ylsulfonyl)pyridin-3-yl)-3-

ethyl-2-phenyl-2,6-dihydro-7H-pyrazolo 4,3-dipyrimidin 7-one, 5-(5-Acetyl-2-propoxy-3-pyridinyl)-3-ethyl-2-(1- isopropyl-3-azetidinyl)-2,6-dihydro-7H-pyrazolo 4,3-d pyrimidin-7-one, 5-(5-Acetyl-2-butoxy-3-pyridinyl)-3- ethyl-2-(1-ethyl-3-azetidinyl)-2,6-dihydro-7H-pyrazolo4. 3-dipyrimidin-7-one, 4-(4-chlorobenzyl)amino-6,7,8- trimethoxyquinazoline, 7,8-dihydro-8-oxo-6-2- propoxyphenyl)-1H-imidazo4.5-gquinazoline, 1-3-1-(4- fluorophenyl)methyl-7,8-dihydro-8-oxo-1H-imidazo[4,5- gquinazolin-6-yl-4-propoxyphenylcarboxamide, 2-2- ethoxy-5-(4-ethyl-piperazine-1-sulfonyl)-phenyl-5-methyl wherein 7-propyl-3H-imidazo[5.1-f-1,2,4-triazin-4-one, and 1-6- R" represents hydrogen, halogen or Cigalkyl: ethoxy-5-3-ethyl-6,7-dihydro-2-(2-methoxyethyl)-7-oxo R" represents hydrogen, C-alkyl, haloC-alkyl, Cascy 2H-pyrazolo 4,3-dipyrimidin-5-yl)-3-pyridylsulfonyl-4- cloalkyl, C-scycloalkyC-alkyl, arylC-alkyl or het ethylpiperazine, or a pharmaceutically acceptable acid eroarylC-alkyl, and addition salt thereof, a hydrate and/or a solvate thereof, an R represents an optionally substituted monocyclic aro optical isomer thereof, or a mixture of the enantiomers or a matic ring selected from benzene, thiophene, furan and racemate thereof. pyridine or an optionally Substituted bicyclic ring 9. The pharmaceutical composition according to claim 7. wherein the elevator of cQMP is selected from the com pounds of formula 2c.1

2c.1 attached to the rest of the molecule via one of the benene ring carbonatoms and wherein the fused ring A is a 5- or 6-membered ring which may be saturated or partially or fully unsaturated and comprises carbon atoms and optionally one or two heteroatoms selected from oxy gen, Sulphur and nitrogen, or a pharmaceutically accept able acid addition salt thereof, a hydrate and/or a solvate thereof, an optical isomer thereof, or a mixture of the enantiomers or a racemate thereof. US 2011/O 105519 A1 May 5, 2011

11. The pharmaceutical composition according to claim 2, Amperozide, AT 1015, Balaperidone, BIMG 80, Deramci comprising a therapeutically effective amount offilibanserin clane, EGIS 8465, EGIS 9933, Fananserin, FG 5803, FG and a therapeutically effective amount of one or more 5-HT 5893, FG-5938, FG-5974, GMC 1169, GMC 283, GMC306, 1A agonists, optionally in combination with a pharmaceuti GMC 6139, ICI-169369, Irindalone, IT 657, JL-13, Lubaz cally acceptable excipient. odone, LY 215840, LY-367265, NRA-0045, Org-38457, 12. The pharmaceutical composition according to claim PNU-96415E, QF 0510B, QF 1003B, QF 1004B, RO 11, wherein the 5-HT-1A agonist is selected from the group 600946, Ro-60-0759, RP 71602, RS-102221, S 16924, S consisting of Urapidil, Buspirone, Aripiprazole, Ziprasidone, 213571, S35031, S-17828, S-21357-1, SB 200646A, SB Naftopidil, Tandospirone, Nemonapride, Gepirone, Repino 206553, SB 221284, SB 228357, SB 242084, SB 243213, tan, Sumanirole, Xaliproden hydrochloride, Bifeprunox, SDZ SER 082, TY 12283, TY-11223 and ZD-3638, or a AP-521, SUN-N4057, Sarizotan, MKC-242, OPC-14523, pharmaceutically acceptable acid addition salt thereof, a Eptapirone maleate, SLV-308, BTS-79018, R-137696, hydrate and/or a solvate thereof, an optical isomer thereof, or F-13640, SSR-181507, SLV-314, SLV-319, 7-OH-DPAT, a mixture of the enantiomers or a racemate thereof. VN-2222, PD-158771, RS-30199, WAY-100012, A-74283, 17. The pharmaceutical composition according to claim 2, Enilospirone, Org-13011, B-8805-033, AP-159, AZ-16596, comprising a therapeutically effective amount offilibanserin Anpirtoline, EbalZotan, Binospirone, MDL-72832, and a therapeutically effective amount of one or more dopam RU-24969, Bay-r-1531, Ipsapirone, BIMG 80, BMS ine D4 antagonists, optionally in combination with a pharma 181100, BMS-181101, BMS-181970, BMY-7378, ceutically acceptable excipient. BW-1205U90, B-20991, HAT-90B, Nerisopam, LY-175644, 18. The pharmaceutical composition according to claim LY-178210, LY-228729, LY-274600, LY-274601, 17, wherein the dopamine D4 antagonist is selected from the LY-293284, LY-301317, LY-315535, E-4414, E-6265 citrate, group consisting of olanzapine, Ziprasidone, MDL-814608A, Lesopitron, RGH-1756, RGH-1757, 1192U90, HP-236, NRA-0562, S-18126, SPI-376, YM-50001, 1192U90, ALX FG-5938, LEK-8804, LB-50016, RWJ-25730, EMD-56551, D4, Balaperidone, BIMG 80, CI-1030, CP-293019, Fan EMD-67478, EMD-77697, Roxindole, Vilazodone, BP-554, anserin, JL-13, L-741742, L-745870, L-751852, L-772620, CGP-50281, CGS-12066B, CGS-18102, SDZ-MAR-327, L-800892, LU-35138, LUR-2366, NEO-376, NGB-4420, CL-870801, CP-110330, CP-146662, CP-291952, FCE NGD-941, NRA-0045, NRA-0074, NRA-0154, NRA-0160, 23892, FG-5865, FG-5893, OSU-191, Sunepitron, NRA-0161, NRA-0215, NRA-0219, NRA-0544, U-67413B, U-86170, U-86192A, U-92016A, U-93385, PD-089232, PD-108306, PD-165167, PD-167063, Eptapirone, Mazapertine succinate, SL-870765, SL-880338, PD-168306, PD-172760, PD-172760, PD-172938, SR-59026, Bromerguride, Alnespirone, S-14506, S-14671, PD-35680, PD-82011, PNU-106161, PNU-106675, S-15535, S-15931, S-16924, S-213571, S-215521, Elopipra QF-1003B, QF-1004B, Ro-62-4599, S-16924, S-17828, Sch Zole, Eltoprazine, Flesinoxan, Umespirone, SUN-8399, 71450, Sonepiprazole, U-101958, U-103073E, U-96415E S-23751, PM-1000, LY 41, Adatanserin, WY-48723, and YM-43611, or a pharmaceutically acceptable acid addi Zalospirone and MDL-73975, or a pharmaceutically accept tion salt thereof, a hydrate and/or a solvate thereof, an optical able acid addition salt thereof, a hydrate and/or a solvate isomer thereof, or a mixture of the enantiomers or a racemate thereof, an optical isomer thereof, or a mixture of the enanti thereof. omers or a racemate thereof. 19. The pharmaceutical composition according to claim 2, 13. The pharmaceutical composition according to claim 2, comprising a therapeutically effective amount offilibanserin comprising a therapeutically effective amount offilibanserin and a therapeutically effective amount of one or more selec and a therapeutically effective amount of one or more dopam tive androgen receptor modulators (SARM), optionally in ine agonists, optionally in combination with a pharmaceuti combination with a pharmaceutically acceptable excipient. cally acceptable excipient. 20. The pharmaceutical composition according to claim 14. The pharmaceutical composition according to claim 19, wherein the selective androgen receptor modulator 13, wherein the dopamine agonist is selected from the group (SARM) is selected from the group consisting of LGD2226, consisting of ABT-724, CP-226269, bromocriptin, caber LGD1331, bicalutamide, , hydroxyfluta golin, alpha-dihydroergocryptin, lisuride, pergolide, prami mide, spironolactone, 4-(trifluoromethyl)-2(1H)pyrrolidone pexol, roXindol, ropinirol, Sopirinol, talipexol, bupropion and 3.2-gquinolinone, 1,2-dihydropyridono.5,6-glquinoline terguride, or a pharmaceutically acceptable acid addition salt and piperidino.3.2-gquinolinone, or a pharmaceutically thereof, a hydrate and/or a solvate thereof, an optical isomer acceptable acid addition salt thereof, a hydrate and/or a sol thereof, or a mixture of the enantiomers or a racemate thereof. vate thereof, an optical isomer thereof, or a mixture of the 15. The pharmaceutical composition according to claim 2, enantiomers or a racemate thereof. comprising a therapeutically effective amount offilibanserin 21. The pharmaceutical composition according to claim 2, and a therapeutically effective amount of one or more comprising a therapeutically effective amount offilibanserin 5-HT2A/2C antagonists, optionally in combination with a and a therapeutically effective amount of one or more estro pharmaceutically acceptable excipient. gens, optionally in combination with a pharmaceutically 16. The pharmaceutical composition according to claim acceptable excipient. 15, wherein the 5-HT2A/2C antagonists is selected from the 22. The pharmaceutical composition according to claim group consisting of Aripiprazole, Fluoxetine, Nefazodone, 21, wherein the estrogen is selected from the group consisting Pizotifen, Risperidone, Sarpogrelate, Ziprasidone, Ago of estradiol (i.e. 1,3,5-estratriene-3,17(3-diol, or “ 17 B-estra melatine, Asenapine, Eplivanserin, Iloperidone, ketanserin, diol) 17C-estradiol, ethinylestradiol (i.e., 17O-ethinylestra ritanserin, M 100907, Netamiftide, Ocaperidone, S-20098, diol), ethinylestradiol 3-acetate, ethinylestradiol 3-benzoate, Abaperidone, ACP-103, EMD 281014, EMR 62218, LU-31 estriol, estriol Succinate, polyestrol phosphate, estrone, 130, SL 650472, EGIS-10037, LEK-8829, Nantenine, estrone acetate, estrone sulfate, piperazine estrone Sulfate, QF-2004B, R-107500, S 35120, S-14297, Amesergide, quinestrol, and mestranol, or a pharmaceutically acceptable US 2011/O 105519 A1 May 5, 2011

acid addition salt thereof, a hydrate and/or a solvate thereof, 164.384), fulvestrant, raloxifene, trans-2,3-dihydroralox an optical isomer thereof, or a mixture of the enantiomers or ifene, 4' halo-raloxifene, 2-(alkyl raloxifene, 2-cycloalkyl ral a racemate thereof. oxifene, 2-naphthyl raloxifene, 6-methoxy-2-(4-methox 23. The pharmaceutical composition according to claim 2, yphenyl)-3-(4-nitrobenzoyl)-benzobthiophene, arzoxifene, comprising a therapeutically effective amount offilibanserin 2-(4-methoxyphenyl)-3-(4-(2-(1-piperidinyl)ethoxy)-phe and a therapeutically effective amount of one or more andro noxybenzobthiophene-6-ol); LY 1 17018 (6-hydroxy-2-(4- gens, optionally in combination with a pharmaceutically hydroxyphenyl)benzobthien-3-yl)(4-(2-(1-pyrrolidinyl) acceptable excipient. ethoxy)phenyl)methanone), baZedoxifen, idoxifene (1-2-4- 24. The pharmaceutical composition according to claim (1E)-1-(4-Iodophenyl)-2-phenyl-1-butenylphenoxyethyl 23, wherein the androgen is selected from the group consist pyrrolidine), droloxifene (3-(1E)-1-4-2-(Dimethylamino) ing of including androsterone, androsterone acetate, andros ethoxyphenyl-2-phenyl-1-butenylphenol), tamoxifen terone propionate, androsterone benzoate, androstenediol. ((Z)-2-[4-(1,2-Diphenyl-1-butenyl)phenoxy-N,N-dimeth androstenediol-3-acetate, androstenediol-17-acetate, andros ylethanamine), toremifene (2-4-(17)-4-Chloro-1,2-diphe tenediol-3,17-diacetate, androstenediol-17-benzoate, nyl-1-butenyl)phenoxy-N,N-dimethylethanamine), clomi androstenediol-3-acetate-17-benzoate, androstenedione, eth phene (2-4-(2-Chloro-1,2-diphenylethenyl)phenoxy-N,N- ylestrenol, Oxandrolone, nandrolone phenpropionate, nan diethylethanamine), meproxifene ((4-(1-(4-(2- drolone decanoate, nandrolone furylpropionate, nandrolone (dimethylamino)ethoxy)phenyl)-2-(4-(1-methylethyl) cyclohexanepropionate, nandrolone benzoate, nandrolone phenyl)-1-butenyl)-phenol), trioxifene, Zindoxifene, cyclohexanecarboxylate, stanozolol, dromostanolone, dro lasofoxifene, nafoxidine, 3-4-1-(4-fluorophenyl)-2-phe mostanolone propionate, testosterone, dehydroepiandroster nyl-but-1-enylphenylacrylic acid, 3-4-(1,2-diphenyl-but one (“), Sodium dehydroepiandrosterone Sulfate, 1-enyl)-phenyl-acrylic acid, cis-6-phenyl-5-(4-(2-pyrroli and 4-dihydrotestosterone (“stanolone' and 5C-dihydrotest din-1-yl-ethoxy)phenyl)-5,6,7,8-tetrahydronaphthalene-2- osterone; the testosterone and 4-dihydrotestosterone esters ol, cis-6-(4-fluorophenyl)-5-[4-(2-piperidin-1-yl-ethoxy)- formed from the hydroxyl group present at the C-17 position phenyl-5,6,7,8-tetrahydronaphthalene-2-ol. cis-1-6'- and the enanthate, propionate, cypionate, phenylacetate, pyrrolidinoethoxy-3-pyridyl-2-phenyl-6-hydroxy-1,2,3,4- acetate, isobutyrate, buciclate, heptanoate, decanoate, penta tetrahydro-naphthalene, cis-6-(4'-hydroxyphenyl)-5-[4-(2- decanoate, undecanoate, pelargonate, tridecanoate, palmi piperidin-1-yl-ethoxy)-phenyl-5,6,7,8- tate, caprate, isocaprate, C.-methylcaprate, B-methylcaprate, tetrahydronaphthalen-2-ol. 6-(4-hydroxyphenyl)-5-[4-(2- laurate, C.-methylpelargonate, B-methylpelargonate, Bf3 piperidin-1-yl-ethoxy)-benzyl-naphthalen-2-ol. 1-(4'- dimethylpelargonate, B-(p-methylcyclohexyl)propionate, pyrrolidinoethoxyphenyl)-2-(4"-fluorophenyl)-6-hydroxy 3-(p-ethylcyclohexyl)-propionate, 3-(cycloheptyl)propi 1,2,3,4-tetrahydroisoquinoline, 1-(4'- onate, C.-methyl-cyclohexyl-propionate, B-methyl-3-cyclo pyrrolidinoethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4 hexyl-propionate, cyclododecyl-carboxylate, adamantine-1- tetrahydroisoquinoline, or a pharmaceutically acceptable carboxylate, adamant-1-yl-acetate, methyl-O-cyclohexyl acid addition salt thereof, a hydrate and/or a solvate thereof, propionate, and C-(bicyclo-2.2.2-oct-1-yl)-propionate, 3-n- an optical isomer thereof, or a mixture of the enantiomers or hexylcyclobutanecarboxylate, 3-n-butylcyclopentanecar a racemate thereof. boxylate, 4-n-butylcyclohexanecarboxylate, 4-n-pentylcy 29. A method for the treatment of disorders selected from clohexanecarboxylate and n-hexylcyclohexanecarboxylate; the group consisting of Hypoactive Sexual Desire Disorder, methyl testosterone, testolactone, oxymetholone, fluoxyme loss of sexual desire, lack of sexual desire, decreased sexual sterone, or a pharmaceutically acceptable acid addition salt desire, inhibited sexual desire, loss of libido, libido distur thereof, a hydrate and/or a solvate thereof, an optical isomer bance, and frigidity, comprising administering a therapeuti thereof, or a mixture of the enantiomers or a racemate thereof. cally effective amount of flibanserin, or a pharmaceutically 25. The pharmaceutical composition according to claim 2, acceptable acid addition salt thereof and/or a hydrate and/or a comprising a therapeutically effective amount offilibanserin solvate thereof, in combination with a therapeutically effec and a therapeutically effective amount of one or more C-adr tive amount of an additional active ingredient, or a pharma energic receptor antagonists, optionally in combination with ceutically acceptable acid addition salt thereof, a hydrate a pharmaceutically acceptable excipient. and/or a Solvate thereof, an optical isomer thereof, or a mix 26. The pharmaceutical composition according to claim ture of the enantiomers or a racemate thereof, separately or 25, wherein the C-adrenergic receptor antagonist is selected together within one pharmaceutical composition. from the group consisting of phentolamine mesylate, HMP 30. A method for the treatment of premenstrual disorders, 12, REC-15/2615 and MPV 1248 (atipamezole), or a phar comprising administering a therapeutically effective amount maceutically acceptable acid addition salt thereof, a hydrate offilibanserin, or a pharmaceutically acceptable acid addition and/or a Solvate thereof, an optical isomer thereof, or a mix salt thereof and/or a hydrate and/or a solvate thereof, in com ture of the enantiomers or a racemate thereof. bination with a therapeutically effective amount of an addi 27. The pharmaceutical composition according to claim 2, tional active ingredient, or a pharmaceutically acceptable comprising a therapeutically effective amount offilibanserin acid addition salt thereof, a hydrate and/or a solvate thereof, and a therapeutically effective amount of one or more selec an optical isomer thereof, or a mixture of the enantiomers or tive estrogen receptor modulators (SERM), optionally in a racemate thereof, separately or together within one phar combination with a pharmaceutically acceptable excipient. maceutical composition. 28. The pharmaceutical composition according to claim 31. A method for the treatment of sexual aversion disorder 27, wherein the selective estrogen receptor modulator in females, comprising administering a therapeutically effec (SERM) is selected from the group consisting of tibolone, tive amount of flibanserin, or a pharmaceutically acceptable diethylstilbestrol, moxestrol, N-butyl-3,17-dihydroxy-N- acid addition salt thereof and/or a hydrate and/or a solvate methyl-estra-1,3,5(10)-triene-7-undecanamide (ICI thereof, in combination with a therapeutically effective US 2011/O 105519 A1 May 5, 2011

amount of an additional active ingredient, or a pharmaceuti addition salt thereof and/or a hydrate and/or a solvate thereof, cally acceptable acid addition salt thereof, a hydrate and/or a in combination with a therapeutically effective amount of an solvate thereof, an optical isomer thereof, or a mixture of the additional active ingredient, or a pharmaceutically acceptable enantiomers or a racemate thereof, separately or together acid addition salt thereof, a hydrate and/or a solvate thereof, an optical isomer thereof, or a mixture of the enantiomers or within one pharmaceutical composition. a racemate thereof, separately or together within one phar 32. A method for the treatment of sexual arousal disorder in maceutical composition. females, comprising administeringatherapeutically effective 34. A method for the treatment of sexual pain disorders in amount offilibanserin, or a pharmaceutically acceptable acid females, comprising administering atherapeutically effective addition salt thereof and/or a hydrate and/or a solvate thereof, amount offilibanserin, or a pharmaceutically acceptable acid in combination with a therapeutically effective amount of an addition salt thereof and/or a hydrate and/or a solvate thereof, additional active ingredient, or a pharmaceutically acceptable in combination with a therapeutically effective amount of and acid addition salt thereof, a hydrate and/or a solvate thereof, additional active ingredient, or a pharmaceutically acceptable an optical isomer thereof, or a mixture of the enantiomers or acid addition salt thereof, a hydrate and/or a solvate thereof, a racemate thereof, separately or together within one phar an optical isomer thereof, or a mixture of the enantiomers or maceutical composition. a racemate thereof, separately or together within one phar 33. A method for the treatment of orgasmic disorder in maceutical composition. females, comprising administeringatherapeutically effective amount offilibanserin, or a pharmaceutically acceptable acid c c c c c