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(12) United States Patent (10) Patent No.: US 7,897,616 B2 Zoller Et Al

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(12) United States Patent (10) Patent No.: US 7,897,616 B2 Zoller Et Al US0078.97616B2 (12) United States Patent (10) Patent No.: US 7,897,616 B2 Zoller et al. (45) Date of Patent: Mar. 1, 2011 (54) IMIDAZOPYRIDIN-2-ONE DERIVATIVES AS (56) References Cited INHIBITORS OF LIPASES AND U.S. PATENT DOCUMENTS PHOSPHOLPASES 4,144,341 A 3, 1979 Clark et al. (75) Inventors: Gerhard Zoller, Frankfurt am Main FOREIGN PATENT DOCUMENTS (DE); Stefan Petry, Frankfurt am Main WO WO O2/3O886 4/2002 (DE); Markus Follmann, Wülfrath WO WO 2005, O73199 8, 2005 (DE); Gunter Muller, Frankfurt am WO WO 2006/022954 3, 2006 Main (DE); Norbert Tennagels, WO WO 2006/097808 9, 2006 Frankfurt am Main (DE) WO WO 2006,131231 12/2006 OTHER PUBLICATIONS (73) Assignee: Sanofi-Aventis, Paris (FR) Hcaplus 1979: 145541 abstract, “Synthesis and analgesic activity of (*) Notice: Subject to any disclaimer, the term of this 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridines”. Clark patent is extended or adjusted under 35 et al., 1978.* U.S.C. 154(b) by 234 days. * cited by examiner Primary Examiner Zinna N Davis (21) Appl. No.: 12/235,053 (74) Attorney, Agent, or Firm Scully, Scott, Murphy & (22) Filed: Sep. 22, 2008 Presser, P.C. (57) ABSTRACT (65) Prior Publication Data The present invention relates to imidazopyridin-2-one deriva tives of the formula I with the definitions specified in the US 2009/0076068 A1 Mar. 19, 2009 description, to their pharmaceutically usable salts and to their Related U.S. Application Data use as medicaments. (63) Continuation of application No. PCT/EP2007/ 002637, filed on Mar. 26, 2007. (I) 4 ,6 (30) Foreign Application Priority Data X 3 Mar. 28, 2006 (DE) ....................... 10 2006 O14685 O 6X CO Yx2 N (51) Int. Cl. 7 R2 CO7D 47L/04 (2006.01) WNN A6 IK 3/437 (2006.01) V (52) U.S. Cl. ....................................... 514/303:546/118 R1 (58) Field of Classification Search ................. 546/118: 514/303 See application file for complete search history. 9 Claims, No Drawings US 7,897,616 B2 1. 2 MIDAZOPYRIDIN-2-ONE DERVATIVES AS be mono- or polysubstituted preferably by halogen, (C- INHIBITORS OF LIPASES AND C)-alkyl, (C-C)-alkyloxy, hydroxyl, (C-C)-alkylmer PHOSPHOLIPASES capto, amino, (C-C)-alkylamino, di-(C-C)-alky lamino, mono-(C-C)-alkylaminocarbonyl, di-(C-Cs)- This application is a Continuation of International Appli 5 alkylaminocarbonyl, (C-C)-alkyloxycarbonyl, (C-C)- cation No. PCT/EP2007/002637, filed Mar. 26, 2007, which alkylcarbonyl, cyano, nitro, trifluoromethyl, is incorporated herein by reference in its entirety. trifluoromethyloxy, pentafluorosulfanyl, (C-C)-alkylsul fonyl, aminosulfonyl: FIELD OF THE INVENTION R1" is (C-C)-alkyl, (C-C)-cycloalkyl, (C-C)-alkyle 10 nearyl, (C-C)-alkyleneheteroaryl, (C-C)-alkylene The present invention relates to imidazopyridin-2-one (C-C)-cycloalkyl, bicycle, where aryl, heteroaryl, derivatives of the formula I, to their pharmaceutically usable cycloalkyl or bicycle may be mono- or polysubstituted salts and to their use as medicaments. preferably by halogen, (C-C)-alkyl, (C-C)-alkyloxy, hydroxyl, (C-C)-alkylmercapto, amino, (C-C)-alky BACKGROUND OF THE INVENTION 15 lamino, di-(C-C)-alkylamino, mono-(C-C)-alkylami nocarbonyl, di-(C-Cs)-alkylaminocarbonyl, (C-C)- In addition to the imidazopyridin-2-one derivatives alkyloxycarbonyl, (C-C)-alkylcarbonyl, cyano, nitro, described in the present application, structurally similar com trifluoromethyl, trifluoromethyloxy, (C-C)-alkylsulfo pounds with pharmacological action have already been nyl, aminosulfonyl: described in the prior art. For instance, U.S. Pat. No. 4,144, R2 is hydrogen; 341 describes imidazopyridin-2-one derivatives for the treat R3 is the same or different and is hydrogen, (C-C)-alkyl, ment of fever and pain. WO02/30886 describes angiogenesis benzyl: inhibitors which have animidazopyridin-2-one base structure R4, R5 are the same or different and are each hydrogen, among other compounds. (C-C)-alkyl, aryl, (C-C)-cycloalkyl, (C-C)-alkyle Compounds with inhibitory action on endothelial lipase 25 nearyl, (C-C)-alkylene-(C-C)-cycloalkyl; are described in the prior art, for example in WO2004/ R6 is hydrogen, (C-C)-alkyl, (C-C)-alkylenearyl, (C- 094394, WO2004/094393 or WO2004/093872. Cl)-alkylene-heterocycle, (C-C)-alkylene-(C-C)-cy It is an object of the present invention to provide alternative cloalkyl, bicycle, where aryl, heterocycle, cycloalkyl or compounds which bring about inhibition of endothelial bicycle may be mono- or polysubstituted preferably by lipase. 30 halogen, (C-C)-alkyl, (C-C)-alkyloxy, hydroxy, (C- C)-alkylmercapto, amino, (C-C)-alkylamino, di-(C- SUMMARY OF THE INVENTION C)-alkylamino, mono-(C-C)-alkylaminocarbonyl, di (C-C)-alkylaminocarbonyl, (C-C)-alkoxycarbonyl, The invention provides imidazopyridin-2-one derivatives (C-C)-alkylcarbonyl, trifluoromethyl, trifluoromethy of the formula I 35 loxy, cyano, (C-C)-alkylsulfonyl, aminosulfonyl: O (I) -(C=O) NR1'R2: 4 R6 O X 3\ -(C=O) O R1": x1 N 2 40 O with the proviso that, when R1 is (C-C)-alkyl, R6 is not 6.Nx NX (C-C)-alkylenearyl, (C-C)-alkylene-heterocycle, (C- 7 V R2 Cl)-alkylene-(C-C)-cycloalkyl or bicycle; / WNN the tautomeric forms of the compounds and their physiologi V 45 R1 cally compatible salts. DETAILED DESCRIPTION OF THE INVENTION where: Preference is given to compounds of the formula I in which X is the same or different and is —C(—R)—or—N—, where 50 at least one X and at most two X are —N—; W is —(C=O)-. W is —(C=O)— —(S—O)— —(SO)—: Preference is equally given to compounds of the formula I R is the same or different and is hydrogen, halogen, (C-C)- in which alkyl, (C-C)-haloalkyl, (C-C)-alkyloxy-(C-C)-alky X is the same or different and is —C(—R)—or—N , where one X is —N—. lene, aryl, heterocycle, hydroxyl, (C-C)-alkyloxy, (C- 55 Cs)-haloalkyloxy, aryloxy, cyano, nitro, -S(O) (C- Preference is also given to compounds of the formula I in C)-alkyl, where p=0, 1 or 2, aminosulfonyl, which pentafluorosulfanyl, amino, (C-C)-alkylamino, di-(C- X is the same or different and is —C(—R)—or—N , where C)-alkylamino, (C-C)-alkylcarbonyl, COOR3, one X is —N—; CO NR4R5, O CO. NR4R5, O CO (C-C)- 60 W is —(C=O)–: alkylene-CO-O (C-C)-alkyl, O CO (C-C)- R is the same or different and is hydrogen, halogen, (C-C)- alkylene-CO-OH, O CO (C-C)-alkylene-CO— alkyl, hydroxyl, phenoxy, trifluoromethyl, COOR3, pen NR4R5; tafluorosulfanyl, amino, (C-C)-alkylamino, di-(C-C)- R1, R1" are the same or different and are each (C-C)-alkyl, alkylamino, (C-C)-alkylsulfonyl, aminosulfonyl, (C-C)-cycloalkyl, (C-C)-alkylenearyl, (C-C)-alky 65 phenyl, (C-C)-heterocycle, (C-C)-alkylcarbonyl, leneheteroaryl, (C-C)-alkylene-(C-C)-cycloalkyl, CO NR4R5, O CO. NR4R5, O CO (C-C)- bicycle, where aryl, heteroaryl, cycloalkyl or bicycle may alkylene-CO O (C-C)-alkyl, O—CO (C-C)- US 7,897,616 B2 3 4 alkylene-CO NR4R5 or unsubstituted or mono- or poly alkoxycarbonyl, (C-C)-alkylcarbonyl, cyano, trifluo F-substituted (C-C)-alkyloxy; romethyl, trifluoromethyloxy; R1, R1" are the same or different and are each (C-C)-alkyl, R1" is (C-Co)-alkyl, —CH2-phenyl, (C-C)-alkylenehet (C-C)-alkylenearyl, (C-C)-alkylene-heterocycle, (C- eroaryl or bicycle of the formula Ic Cl)-alkylene-(C-C)-cycloalkyl, (C-C)-bicycle, 5 Ic where aryl, heterocycle, cycloalkyl or bicycle may be mono- or poly Substituted preferably by halogen, (C-C)- alkyl, (C-C)-alkyloxy, hydroxyl, amino, (C-C)-alky lamino, (C-C)-alkyloxycarbonyl, (C-C)-alkylcarbo Yg nyl, cyano, trifluoromethyl, trifluoromethyloxy; R1" is (C-C)-alkyl, (C-C)-alkylenearyl, (C-C)-alky 10 ( lene-heterocycle, (C-C)-alkylene-(C-C)-cycloalkyl, (C-C)-bicycle, where aryl, heterocycle, cycloalkyl or bicycle may be mono- or polysubstituted preferably by where q1 or 2, halogen, (C-C)-alkyl, (C-C)-alkyloxy, hydroxyl, where phenyl, heteroaryl or bicycle of the formula Ic may amino, (C-C)-alkylamino, (C-C)-alkyloxycarbonyl, 15 be mono- to disubstituted preferably by halogen, (C- (C-C)-alkylcarbonyl, cyano, trifluoromethyl, trifluorom C)-alkyl, (C-C)-alkyloxy, hydroxyl, amino, (C-C)- ethyloxy; alkoxycarbonyl, (C-C)-alkylcarbonyl, cyano, trifluo R2 is hydrogen; romethyl, trifluoromethyloxy; R3 is hydrogen, (C-C)-alkyl, benzyl, R2 is hydrogen; R4, R5 are the same or different and are each hydrogen, R3 is hydrogen, (C-C)-alkyl, (C-C)-alkyl, (C-C)-cycloalkyl, phenyl, (C-C)-alky R6 is hydrogen, (C-C)-alkyl, (C-C)-alkylene-phenyl, lenephenyl, (C-C)-alkylene-(C-C)-cycloalkyl: (C-C)-alkylene-heteroaryl, where phenyl or heteroaryl R6 is hydrogen, (C-C)-alkyl, (C-C)-alkylene-phenyl, may be mono- or polysubstituted by halogen, (C-C)- (C-C)-alkylene-heterocycle, (C-C)-alkylene-(C- alkyl, (C-C)-alkyloxy, hydroxyl, (C-C)-alkoxycarbo C)-cycloalkyl, where phenyl, heterocycle, cycloalkyl 25 nyl, (C-C)-alkylcarbonyl, trifluoromethyl; may be mono- or poly Substituted preferably by halogen, O (C-C)-alkyl, (C-C)-alkyloxy, hydroxyl, (C-C)- -(C=O) NR1'R2 alkoxycarbonyl, (C-C)-alkylcarbonyl, cyano, trifluo O romethyl, trifluoromethyloxy, (C-C)-alkylsulfonyl: -(C=O) O R1": O 30 the tautomeric forms of the compounds and their physiologi O cally compatible salts. (C=O) O R1": Very particular preference is given to the compounds of the formula I in which the tautomeric forms of the compounds and their physiologi cally compatible salts. 35 X is the same or different and is —C(—R)—or—N , where Preference is also given to the compounds of the formula I one X is —N—; in which W is —(C=O)–: X in positions 5 and 6 are identical or different and are each R is the same or different and is hydrogen, halogen, hydroxyl, =C(—R)—, and in position 7 or 4 is =N-.
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