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(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) CORRECTED VERSION (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 2 July 2009 (02.07.2009) WO 2009/082437 A9 (51) International Patent Classification: KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, C07D 207/08 (2006.01) A61K 31/402 (2006.01) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, C07D 207/09 (2006.01) A61P 5/26 (2006.01) NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, C07D 498/04 (2006.01) SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (21) International Application Number: PCT/US2008/013657 (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (22) International Filing Date: G M M N S D S L s z τ z U G Z M 12 December 2008 (12.12.2008) z w Eurasian (A M B γ KG> M D RU> τ (25) Filing Language: English TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (26) Publication Language: English M C M T N L N O P L P T R O S E S I s T R OAPI (30) Priority Data: B F ' B J ' C F ' C G ' C I' C M ' G A ' G N ' 0 G W ' M L ' M R ' 61/008,731 2 1 December 2007 (21 .12.2007) US N E ' S N ' T D ' T G ) - (71) Applicant (for all designated States except US): LIG- Declarations under Rule 4.17: AND PHARMACEUTICALS INCORPORATED [US/ — as to applicant's entitlement to apply for and be granted US]; 11085 N. Torrey Pines Road, Suite 300, La Jolla, a patent (Rule 4.1 7(U)) CA 92037 (US). , ,. , . , . — as to the applicant s entitlement to claim the priority oj (72) Inventor; and the earlier application (Rule 4.1 7(Hi)) (75) Inventor/Applicant (for US only): ZHI, Lin [US/US]; 3988 Via Cangrejo, San Diego, CA 92130 (US). Publish ed: — with international search report (Art. 21(3)) (74) Agents: SEIDMAN, Stephanie, L. et al; Bell Boyd & / Lloyd LLP, 3580 Carmel Mountain Road, Suite 200, San (88) Date of publication of the international search report: Diego, CA 92 130 (US). 3 September 2009 (81) Designated States (unless otherwise indicated, for every (48) Date of publication of this corrected version: kind of national protection available): AE, AG, AL, AM, 12 August 2010 AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, , τ , . CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, (15) oπ nation about Com* i on: EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, See NotlCe o f 12 AugUSt 201 ° HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, (54) Title: SELECTIVE ANDROGEN RECEPTOR MODULATORS (SARMS) AND USES THEREOF Formula I Formula II Formula III (57) Abstract: Provided herein are compounds of formulae I to II that bind to androgen receptors and/or modulate activity of an drogen receptors; and to methods for making and using such compounds. Also provided are compositions including such com pounds and methods for making and using such compositions. SELECTIVE ANDROGEN RECEPTOR MODULATORS (SARMs) AND USES THEREOF Related Applications Benefit of priority is claimed to U.S. Provisional Patent Application Serial No. 61/008,731, to Lin Zhi, filed on December 21, 2007, entitled "SELECTIVE ANDROGEN RECEPTOR MODULATORS (SARMs) AND USES THEREOF." Where permitted, the subject matter of the-above mentioned application is incorporated by reference in its entirety. Field Provided herein are selective androgen receptor modulator (SARM) compounds that bind to androgen receptors and/or modulate activity of androgen receptors, and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions. Also provided are methods for the treatment of androgen receptor mediated diseases. Background Certain intracellular receptors (IRs) have been shown to regulate transcription of certain genes (e.g., see R. M. Evans, Science 240: 889 (1988)). Certain of such IRs are steroid receptors, such as androgen receptors, estrogen receptors, mineralo- corticoid receptors, and progesterone receptors. Gene regulation by such receptors typically involves binding of an IR by a ligand. In certain instances, a ligand binds to an IR, forming a receptor/ligand complex. Such a receptor/ligand complex can then translocate to the nucleus of a cell, where it binds to the DNA of one or more gene regulatory regions. Once bound to the DNA of a particular gene regulatory region, a receptor/ligand complex can modulate the production of the protein encoded by that particular gene. In certain instances, an androgen receptor/ligand complex regulates expression of certain proteins. In certain instances, an androgen receptor/ligand complex can interact directly with the DNA of a particular gene regulatory region or with other transcription factors. In certain instances, such interactions result in modulation of transcriptional activation. Androgen therapy has been used to treat a variety of male disorders such as reproductive disorders and primary or secondary male hypogonadism. A number of natural or synthetic AR agonists have been investigated for the treatment of musculoskeletal disorders, such as bone disease, hematopoietic disorders, neuromuscular disease, rheumatological disease, wasting disease, and for hormone replacement therapy (HRT), such as female androgen deficiency. In addition, AR antagonists, such as flutamide and bicalutamide, are used to treat prostate cancer. The effectiveness of known modulators of steroid receptors is often tempered by their undesired side-effect profile, particularly during long-term administration. For example, potential side effects of androgen therapy for women include acne, weight gain, excess facial and body hair, permanent lowering of the voice, and adverse lipid changes. In men, adverse effects can include disordered sleep and breathing, polycythemia, and repression of high density lipoprotein. Thus there is a need for compounds that do not exhibit the adverse side-effects. It is among the objects herein to provide such compounds that modulate the activity of androgen receptor. Summary Compounds for use in compositions and methods for modulating the activity of androgen receptor are provided. The compounds provided herein are non-steroidal Selective Androgen Receptor Modulators or SARMs. In particular, non-steroidal SARMs display therapeutic benefit but generally do not display adverse androgenic effects, such as prostate enlargement, acne, hirsutism, virilization and masculinization. The compounds selectively modulate (agonize or antagonize) the function of the AR, such as in a tissue-selective manner, to produce the effects of androgens without or with reduced negative or undesired androgenic properties. Among the compounds provided herein are agonists of androgen receptor. Among the compounds provided herein are antagonists of androgen receptor. Among the compounds provided herein are androgen receptor partial agonists. Among the compounds provided herein are tissue specific selective androgen receptor modulators. They can be used for oral testosterone replacement therapy. Compounds provided herein display agonist activity with EC 0 values generally less than 1 micromolar. Compounds provided herein display antagonist activity with IC50 values generally less than 2 micromolar. SARMs provided herein generally target anabolic tissue, such as connective tissue, including bone and muscle, and can be used to increase the mass of a connective tissue in a subject and to reverse connective tissue loss in a subject. Among the disorders that can be treated are muscle wasting, cachexia, frailty and osteoporosis and other muscle and bone disorders, including those enumerated below. Compounds provided herein have a structure of Formula I or Formula II or Formula III: Formula I Formula // Formula III where R1 is halogen pseudohalogen, optionally substituted lower alkyl, optionally substituted haloalkyl or NO2, particularly lower haloalkyl or halogen, and in particular is CF , F, or Cl; R2 is hydrogen, halogen, pseudohalogen, optionally substituted lower alkyl or optionally substituted lower haloalkyl, particularly hydrogen or methyl; R3 is hydrogen, halogen, pseudohalogen, optionally substituted lower alkyl or optionally substituted lower haloalkyl, particularly hydrogen or lower alkyl, and in particular hydrogen or methyl; R4 is halogen or lower haloalkyl, particularly CF or halogen, 5 and in particular Cl or CF3; and R is lower alkyl or lower haloalkyl, particularly Ci to C4 alkyl or Ci to C4 haloalkyl, and in particular methyl, ethyl or CF3. Also provided are pharmaceutically acceptable salts, esters and prodrugs of compounds of Formula I or Formula II or Formula III. In some embodiments, the compounds provided herein exhibit tissue selective androgen receptor agonist activity. In some embodiments, the compounds provided herein exhibit tissue selective androgen receptor antagonist activity. In some embodiments, the compounds provided herein are androgen receptor selective binding compounds. Compounds provided herein are effective for treating one or more androgen receptor mediated diseases or conditions. Such conditions and diseases include those caused by androgen deficiency and/or those that can be ameliorated by androgen administration. In certain embodiments, compounds provided herein are effective for treating one or more diseases or conditions responsive to an androgen receptor agonist. In certain embodiments, compounds provided herein are effective in