Claims
- 1. A compound according to formula (I),
- 2. A compound according to claim 1, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, wherein:
G is a bond; Ar is an aryl or heteroaryl substituted with one to three R1; R1 is selected from alkyl, substituted alkyl, halogen, cyano, nitro, OR10, NR10R11, C(═O)R10, CO2R10 , C(═O)NR10R11, NR10C(═O)R11, NR10C(═O)OR11, SR10, S(O)oR10a, NR10SO2R10a, NHCH(alkyl)CO2R10, SO2NR10R11, cycloalkyl, heterocyclo, aryl, and heteroaryl; R10 and R11 (i) are selected independently of each other from hydrogen, alkyl, substituted alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclo; or (ii) R10 is taken together with R11 to form a heteroaryl or heterocyclo; R10a is alkyl, substituted alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclo; and o is 1 or 2.
- 3. (Canceled)
- 4. A compound according to claim 1, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, in which:
R16 is selected from cycloalkyl, heterocyclo, aryl or heteroaryl optionally substituted with one to three R18; R18 is selected from C1-6alkyl, substituted C1-6alkyl, halogen, cyano, nitro, OR20, NR20R21, C(═O)R20, CO2R20, C(═O)NR20R21, C(═O)NR20SO2R20a, NR20C(═O)R21, NR20C(═O)OR21, SR20, S(O)uR20a, NR20SO2R20a, NHCH(alkyl)CO2R20, SO2NR20R21, C3-7cycloalkyl, phenyl, four to seven membered heterocyclo, or five or six membered heteroaryl, said C3-7cycloalkyl, phenyl, four to seven membered heterocyclo, or five or six membered heteroaryl groups in turn being optionally substituted with one to two R22; R20 and R21 are selected from hydrogen, alkyl, alkenyl, C3-7cycloalkyl, phenyl, benzyl, phenylethyl, napthyl, a four to seven membered heterocylo, or a five to six membered heteroaryl, or when attached to the same nitrogen atom may join to form a heterocyclo or heteroaryl; wherein each of R20 and R21 in turn is optionally substituted with one to two R22; R20a is selected from hydrogen, alkyl, alkenyl, CO2H, CO2(alkyl), C3-7cycloalkyl, phenyl, benzyl, phenylethyl, napthyl, a four to seven membered heterocyclo, or a five to six membered heteroaryl; wherein each R20a in turn is optionally substituted with one to two R22; and R22 is selected from the group consisting of (C1-4)alkyl, (C2-4)alkenyl, hydroxy, cyano, CF3, O(C1-4alkyl), OCF3, C(═O)H, C(═O)(C1-4alkyl), CO2H, CO2(C1-4alkyl), NHCO2(C1-4alkyl), —S(C1-4alkyl), —NH2, NH(C1-4alkyl), N(C1-4alkyl)2, N(CH3)3+, SO2(C1-4alkyl), C(═O)(C1-4alkylene)NH2, C(═O)(C1-4alkylene)NH(alkyl), and C(═O)(C1-4alkylene)N(C1-4alkyl)2.
- 5. A compound according to claim 4, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, in which:
R1a and R1b are independently selected from halogen, C1-4alkyl, hydroxy, alkoxy, haloalkyl, haloalkoxy, cyano, nitro, —CO2H, —C(═O)H, —CO2alkyl, —C(═O)alkyl, —C(═O)NH(CH2)1-4CO2H, —C(═O)NH(CH2)1-4CO2(alkyl), and S(O)2alkyl; or from phenyl, benzyl, phenyloxy, benzyloxy and heteroaryl in turn optionally substituted with halogen, C1-4alkyl, hydroxy, alkoxy, haloalkyl, haloalkoxy, cyano, nitro, —CO2H, —C(═O)H, —CO2alkyl, and/or —C(═O)alkyl; or alternatively, two R1b groups join together with each other or one R1b joins together with R1a to form a fused benzo ring; R4a and R4c are selected from halogen, alkyl, cyano, haloalkyl, haloalkoxy, nitro, aryloxy, and arylthio; n is 0, 1, or 2; and y is 0, 1 or2.
- 6. A compound according to claim 1, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, having the formula:
- 7. A compound according to claim 6, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, in which R1a is halogen or cyano, and R4a and R4c are independently selected from halogen, alkyl, cyano, trifluoromethyl, and nitro.
- 8. A compound according to claim 1, having the formula (Ie),
- 9. A compound according to claim 8, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, in which:
R1a is halogen, cyano, nitro, trifluoromethyl, OCF3, aryl or heteroaryl; R1b is halogen, C1-4alkyl, cyano, nitro, —CO2H, —C(═O)H, —CO2alkyl, or —C(═O)alkyl; R2 is hydrogen, C1-6alkyl, or C1-6alkyl substituted with CO2H or CO2(C1-4alkyl); R9 is selected from hydrogen, C1-10alkyl, substituted C1-10alkyl, C2-10alkenyl, substituted C2-10alkenyl, C3-6cycloalkyl, phenyl, pyridyl, pyridazinyl, pyrimidinyl, —(CH2)sphenyl, —(CH2)stetrazolyl, —CH2)spyridyl, —(CH2)sthienyl, —(CH2)scarbazolyl, —(CH2)sindolyl, —CH2)sfuryl, —(CH2)squinolyl, —(CH2)sC3-6cycloalkyl, —(CH2)sthiazolyl, —(CH2)spyrrolyl, —(CH2)simidazolyl, —(CH2)sisoxazolyl, —(CH2)sbenzofuryl, —(CH2)spyrazolyl, —C(═O)H, —C(═O)(alkyl), —C(═O)C1-10alkyl, —C(═O)phenyl, —C(═O)piperidyl, —C(═O)morpholinyl, —C(═O)C3-6cycloalkyl, —C(═O)pyrrolidinyl, —C(═O)quinolyl, —C(═O)imidazolyl, —C(═O)pyrazolyl, —C(═O)thiazolyl, —C(═O)quinoxalinyl, —C(═O)pyridyl, —C(═O)-1,2,5,6-tetrahydropyridyl, —C(═O)benzothiazolyl, —C(═O)benzotriazolyl, —C(═O)benzodioxanyl, —C(═O)benzooxadiazolyl, —C(═O)1,2,3,4-tetrahydroquinolyl, —C(═O)thienopyrazolyl, —C(═O)(CH2)stetrazolyl, —C(═O)(CH2)spyridyl, —C(═O)(CH2)sphenyl, —C(═O)(CH2)spyrrolidinyl, —C(═O)(CH2)spiperidyl, —C(═O)CH═CH(phenyl), —C(═O)CH═CH(pyridyl), —C(═O)CH2O(alkyl), —C(═O)CH2S(alkyl), —C(═O)CH2S(pyridyl), —C(═O)CH2SO2(alkyl), —C(═O)CH2SO2(phenyl), —C(═O)CH2NH(phenyl), —C(═O)CH2NH(benzyl), —C(═O)CH2NH(thiazolyl), —C(═O)CH2NHC(═O)pyridyl, —C(═O)CH2NHC(═O)phenyl, —(CH2)tSO2(alkyl), —(CH2)tSO2(phenyl), —(CH2)tSO2(thienyl), —(CH2)tSO2(imidazolyl), —(CH2)tSO2(furyl), (CH2)tSO2(pyrrolyl), SO2NH(phenyl), —C(═S)NH2, —C(═S)NH(alkyl), —C(═S)NH(phenyl), —CH2)C(═O)pyrrolidinyl, —(CH2)C(═O)piperidyl, —CH2)C(═O)piperazinyl, —CO2(alkyl), —CO2(phenyl), —CO2(benzyl), NHCO2(alkyl), —(CH2)tC(═O)NH(phenyl), —(CH2)tC(═O)NH(piperidyl), —(CH2)tC(═O)NH(thienyl), —(CH2)tC(═O)NH(thiazolyl), —(CH2)tC(═O)NH(cyclopentyl), —(CH2)tC(═O)NH(cyclopentenyl), —(CH2)tC(═O)NH(benzyl), —(CH2)tC(═O)NH(pyrrolidinyl), —CH2)tC(═O)NH(piperazinyl), —(CH2)tC(═O)NH2, —(CH2)tC(═O)NH(alkyl), —(CH2)tC(═O)N(alkyl)2, —CH2)tC(═O)N(C1-4alkyl)(phenyl), —(CH2)tC(═O)N(C1-4alkyl)(thienyl), —CH2)tC(═O)N(C1-4alkyl)(thiazolyl), —(CH2)tC(═O)N(C1-4alkyl)(benzyl), —(CH2)tC(═O)N(C1-4alkyl)CO2(alkyl), wherein each R9 is optionally substituted with one to two R18; R18 is selected from —(CH2)qhalogen, —(CH2)qnitro, —(CH2)qcyano, —(CH2)qhaloalkyl, —(CH2)qhaloalkoxy, —(CH2)qSR24, C3-7cycloalkyl, —SO2R24, —OR24, —(CH2)qCO2, —(CH2)qNR24R25, —(CH2)qNHCO2R24, —C(═O)NH—SO2R24, —C(═O)(CH2)qNR24R25, —O(CH2)rNR24R25, —C(═O)R24, —(CH2)qR24 and —C1-4alkyl or —C2-4alkenyl optionally substituted with CO2R24; R24 is selected from hydrogen, alkyl, phenyl, benzyl, C3-7cycloalkyl, five or six membered heteroaryl, and four to seven membered heterocyclo, in turn optionally substituted with one to two C1-4alkyl, halogen, hydroxy, trifluoromethyl, trifluoromethoxy, —CO2H, CO2C1-4alkyl, C1-4alkoxy, —S(C1-4alkyl), amino, and/or amino C1-4alkyl, provided that when R24 is attached to a sulfonyl group as in —SO2R24, then R24 is not hydrogen; R25 is selected from hydrogen and alkyl; and n is 0, 1, or 2; p is 1 or 2; q is 0, 1, 2, 3,or4; r is 1, 2, 3, or 4; s is 0,1, 2, 3, or 4; and t is 1,2, 3, or4.
- 10. A compound according to claim 1, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, wherein R9 is selected from:
- 11. (Canceled)
- 12. A compound according to claim 1, having the formula,
- 13. A compound according to claim 1, having the formula,
- 14. A compound according to claim 1, having the formula,
- 15. A compound having the formula,
- 16. A compound according to claim 15, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, wherein R4a, and R4c are chloro.
- 17. A compound according to claim 15, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, wherein R1a is cyano or halogen.
- 18. A compound according to claim 15, having the formula,
- 19. A compound according to claim 18, or a pharmaceutically-acceptable salt, hydrate, prodrug, or enantiomer thereof, in which:
R2 is selected from hydrogen, C1-6alkyl, and C1-6alkyl substituted with amino, NH(C1-4alkyl), N(alkyl)2, C(═O)H, C(═O)C1-4alkyl, CO2H, CO2(C1-4alkyl), SO2C1-4alkyl, SO3H, and/or PO(OH)2; R4a and R4c are selected from halogen, C1-4alkyl, cyano, halo C1-4alkyl, and haloC1-4alkoxy; R9 is A1-Q-A2-R16; R16 is selected from (a) hydrogen and C1-6alkyl or C2-6alkenyl optionally substituted with one to two of OH, O(C1-4alkyl), —CO2H, —CO2(C1-4alkyl), NH2, —NH(C1-4alkyl), and/or N(C1-4alkyl)2, or from (b) furanyl, indolyl, carbazolyl, pyrazolyl, pyrrolyl, thienyl, pyridyl, pyrimidinyl, benzofuranyl, isoxazolyl, imidazolyl, triazolyl, tetrazolyl, phenyl, piperidyl, pyrrolidinyl, pyridazinyl, C3-7cycloalkyl, piperazinyl, thiazolyl, morpholinyl, 1,2,5,6-tetrahydropyridyl, quinoxalinyl, benzothiazolyl, benzotriazolyl, benzodioxanyl, benzooxadiazolyl, thienopyrazolyl, tetrahydroquinolinyl, and quinolinyl, wherein each of said cyclic R16 groups in turn is optionally substituted with up to three R18; R17 is hydrogen or alkyl; and R18 is selected from hydrogen, (C1-6)alkyl, (C2-6)alkenyl, CO2H, CO2(C1-6alkyl), C(═O)H, C(═O)(C1-6alkyl), halogen, cyano, hydroxy, (C1-4)alkoxy, (C1-4)haloalkyl, (C1-4)haloalkoxy, NH2, NH(C1-4alkyl), N(C1-4alkyl)2, N(C1-4alkyl)3+, —C(═O)(CH2)NH2, —NHCO2(C1-4alkyl), SO2(C1-4alkyl), phenyl, C3-7cycloalkyl, five to six membered heteroaryl, and four to seven membered heterocyclo, wherein each group R18 in turn is optionally substituted with one to two of (C1-4) alkyl, (C2-4) alkenyl, CO2H, CO2(C1-4alkyl), C(═O)H, C(═O)(C1-4alkyl), halogen, cyano, hydroxy, (C1-4)alkoxy, trifluoromethyl, trifluoromethoxy, NH2, NH(C1-4alkyl), N(C1-4alkyl)2, N(C1-4alkyl)3+, —C(═O)(CH2)NH2, —NHCO2(C1-4alkyl), and/or SO2(C1-4alkyl).
- 20. A compound according to claim 19, having the formula,
- 21. A compound according to claim 19, having the formula,
- 22. A pharmaceutical composition comprising at least one compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.
- 23. A pharmaceutical composition comprising at least one compound according to claim 15 and a pharmaceutically acceptable carrier or diluent.
- 24. (Canceled)
- 25. (Canceled)
- 26. (Canceled)
- 27. (Canceled)
- 28. (Canceled)
- 29. (Canceled)
- 30. A compound according to claim 8, or a pharmaceutically-acceptable salt, hydrate, salt, hydrate, prodrug, or enantiomer thereof, wherein R9 is selected from:
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No. 60/326,361, filed Oct. 1, 2001, U.S. Provisional Application No. 60/354,113, filed Feb. 4, 2002, and U.S. Provisional Application No. 60/400,259, filed Aug. 1, 2002, each of which is incorporated herein by reference.
Provisional Applications (3)
|
Number |
Date |
Country |
|
60326361 |
Oct 2001 |
US |
|
60354113 |
Feb 2002 |
US |
|
60400259 |
Aug 2002 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
10262182 |
Oct 2002 |
US |
Child |
10852576 |
May 2004 |
US |