| 主权项 |
1. A compound of structural formula I:or a pharmaceutically acceptable salt thereof, wherein:
T is CR3; U is CR1; V is CR2; W is CR4; X is selected from:
(1) —CH2—,(2) —CHF—,(3) —CF2—,(4) —S—,(5) —O—,(6) —O—CH2—,(7) —O—CH2CH2—,(8) —NH—,(9) —C(O)—,(10) —NHC(O)—,(11) —C(O)NH—,(12) —NHSO2—,(13) —SO2NH—, and(14) —CO2—, wherein each CH2 is unsubstituted or substituted with 1 or 2 substituents selected from: hydroxy, halogen, NH2, C1-6alkyl, CO2H, CO2C1-6alkyl, COC1-6alkyl, phenyl and —CH2phenyl, and wherein each NH is unsubstituted or substituted with 1 substituent selected from: C1-6alkyl, CO2H, CO2C1-6alkyl, COC1-6alkyl, phenyl and —CH2phenyl; Y is selected from: wherein Y is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents selected from Rb; Z is selected from:
(1) NR5,(2) —S—, and(3) —O—; each R1 and R2 is independently selected from:
(1) hydrogen,(2) halogen,(3) CN,(4) CF3,(5) —C1-6alkyl,(6) —C2-6alkenyl,(7) —C2-6alkynyl,(8) —(CH2)pC3-10cycloalkyl,(9) —(CH2)pC3-7cycloalkyl-aryl,(10) —(CH2)pC3-7cycloalkyl-heteroaryl,(11) —(CH2)pC4-10cycloalkenyl,(12) —(CH2)pC4-7cycloalkenyl-aryl,(13) —(CH2)pC4-7cycloalkenyl-heteroaryl,(14) —(CH2)pC2-10cycloheteroalkyl,(15) —(CH2)pC2-10cycloheteroalkenyl,(16) —(CH2)paryl,(17) —(CH2)paryl-C1-8alkyl,(18) —(CH2)paryl-C2-8alkenyl,(19) —(CH2)paryl-C2-8alkynyl-C1-8alkyl,(20) —(CH2)paryl-C2-8alkynyl-C3-7cycloalkyl,(21) —(CH2)paryl-C2-8alkynyl-C3-7cycloalkenyl,(22) —(CH2)paryl-C2-8alkynyl-C2-10cycloheteroalkyl,(23) —(CH2)paryl-C2-8alkynyl-C2-10cycloheteroalkenyl,(24) —(CH2)paryl-C2-8alkynyl-aryl,(25) —(CH2)paryl-C2-8alkynyl-heteroaryl,(26) —(CH2)paryl-C3-7cycloalkyl,(27) —(CH2)paryl-C2-10cycloheteroalkyl,(28) —(CH2)paryl-C2-10cycloheteroalkenyl,(29) —(CH2)paryl-aryl,(30) —(CH2)paryl-heteroaryl,(31) —(CH2)pheteroaryl,(32) —(CH2)pheteroaryl-C3-7cycloalkyl,(33) —(CH2)pheteroaryl-C2-10cycloheteroalkyl,(34) —(CH2)pheteroaryl-C2-10cycloheteroalkenyl,(35) —(CH2)pheteroaryl-aryl,(36) —(CH2)pheteroaryl-heteroaryl,(37) —C2-6alkenyl-alkyl,(38) —C2-6alkenyl-aryl,(39) —C2-6alkenyl-heteroaryl,(40) —C2-6alkenyl-C3-7cycloalkyl,(41) —C2-6alkenyl-C3-7cycloalkenyl,(42) —C2-6alkenyl-C2-7cycloheteroalkyl,(43) —C2-6alkenyl-C2-7cycloheteroalkenyl,(44) —C2-6 alkynyl-(CH2)1-3—O-aryl,(45) —C2-6alkynyl-alkyl,(46) —C2-6alkynyl-aryl,(47) —C2-6alkynyl-heteroaryl,(48) —C2-6alkynyl-C3-7cycloalkyl,(49) —C2-6alkynyl-C3-7cycloalkenyl,(50) —C2-6alkynyl-C2-7cycloheteroalkyl,(51) —C2-6alkynyl-C2-7cycloheteroalkenyl, and(52) —C(O)NH—(CH2)0-3phenyl, wherein each CH2 is unsubstituted or substituted with 1 or 2 substituents selected from: halogen, CF3, —OH, —NH2, —C1-6alkyl, —OC1-6alkyl, —NHC1-6alkyl, and —N(C1-6alkyl)2, and wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, phenyl, aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from Ra, provided that at least one of and only one of R1 and R2 is selected from the group consisting of: hydrogen, halogen, —CN, —CF3, —C1-6alkyl, —C2-6alkenyl and —C2-6alkynyl; R3 and R4 are each independently selected from:
(1) hydrogen,(2) halogen,(3) —C1-6alkyl,(4) —C2-6alkenyl,(5) —C2-6alkynyl,(6) —C3-10cycloalkyl,(7) —C3-10cycloalkenyl,(8) aryl,(9) heteroaryl,(10) —CN,(11) —CF3,(12) —OH,(13) —OC1-6alkyl,(14) —NH2,(15) —NHC1-6alkyl,(16) —N(C1-6alkyl)2,(17) —SC1-6alkyl,(18) —SOC1-6alkyl,(19) —SO2C1-6alkyl,(20) —NHSO2C1-6alkyl,(21) —NHC(O)C1-6alkyl,(22) —SO2NHC1-6alkyl, and(23) —C(O)NHC1-6alkyl; R5 is selected from:
(1) hydrogen,(2) —C1-6alkyl,(3) —C1-6alkenyl,(4) —(CH2)uOH,(5) —CH2CO2H, and(6) —CH2CO2C1-6alkyl; each Ra is independently selected from the group consisting of:
(1) —(CH2)m-halogen,(2) oxo,(3) —(CH2)mOH,(4) —(CH2)mN(Rj)2,(5) —(CH2)mNO2,(6) —(CH2)mCN,(7) —C1-6alkyl,(8) —(CH2)mCF3,(9) —(CH2)mOCF3,(10) —O—(CH2)m—OC1-6 alkyl,(11) —(CH2)mN(Rj)C(O)Rf,(12) —(CH2)mN(Rj)CO2Rf,(13) —(CH2)mC(═N—OH)N(Rj)2,(14) —(CH2)mOC1-6alkyl,(15) —(CH2)mO—(CH2)m—C3-7cycloalkyl,(16) —(CH2)mO—(CH2)m—C2-7cycloheteroalkyl,(17) —(CH2)mO—(CH2)m-aryl,(18) —(CH2)mO—(CH2)m-heteroaryl,(19) —(CH2)mSC1-6alkyl,(20) —(CH2)mS(O)C1-6alkyl,(21) —(CH2)mSO2C1-6alkyl,(22) —(CH2)mSO2(CH2)m—C3-7cycloalkyl,(23) —(CH2)mSO2(CH2)m—C2-7cycloheteroalkyl,(24) —(CH2)mSO2(CH2)m-aryl,(25) —(CH2)mSO2(CH2)m-heteroaryl,(26) —(CH2)mSO2NH2,(27) —(CH2)mSO2NHC1-6alkyl,(28) —(CH2)mSO2NHC3-7cycloalkyl,(29) —(CH2)mSO2NHC2-7cycloheteroalkyl,(30) —(CH2)mSO2NH-aryl,(31) —(CH2)mSO2NH-heteroaryl,(32) —(CH2)mNHSO2—C1-6alkyl,(33) —(CH2)mNHSO2—C3-7cycloalkyl,(34) —(CH2)mNHSO2—C2-7cycloheteroalkyl,(35) —(CH2)mNHSO2-aryl,(36) —(CH2)mNHSO2NH-heteroaryl,(37) —(CH2)mN(Rj)—C1-6alkyl,(38) —(CH2)mN(Rj)—C3-7cycloalkyl,(39) —(CH2)mN(Rj)—C2-7cycloheteroalkyl,(40) —(CH2)mN(Rj)—C2-7cycloheteroalkenyl,(41) —(CH2)mN(Rj)-aryl,(42) —(CH2)mN(Rj)-heteroaryl,(43) —(CH2)mC(O)Rf,(44) —(CH2)mC(O)N(Rj)2,(45) —(CH2)mN(Rj)C(O)N(Rj)2,(46) —(CH2)mCO2H,(47) —(CH2)mOCOH,(48) —(CH2)mCO2Rf,(49) —(CH2)mOCORf,(50) —(CH2)mC3-7cycloalkyl,(51) —(CH2)mC3-7cycloalkenyl,(52) —(CH2)mC2-6cycloheteroalkyl,(53) —(CH2)mC2-6cycloheteroalkenyl,(54) —(CH2)maryl, and(55) —(CH2)mheteroaryl, wherein each CH2 is unsubstituted or substituted with 1 or 2 substituents selected from: oxo, —OH, —(CH2)1-3OH, —CN, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, oxo, —C1-6alkyl, —C1-6alkyl substituted with 1-5 OH, —OC1-6alkyl, halogen, —CH2F, —CHF2, —CF3, —CO2H, —CO2C1-6alkyl, —C3-7cycloalkyl, phenyl, CH2phenyl, heteroaryl and CH2heteroaryl, and wherein alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: oxo, —OH, —(CH2)1-5OH, —(CH2)1-5CN, —CN, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C1-6alkyl, —C1-6alkyl substituted with 1-5 OH, —OC1-6alkyl, halogen, —CH2F, —CHF2, —CF3, —(CH2)1-5CF3 optionally substituted with 1, 2 or 3 —OH—CO2H, —CO2C1-6alkyl, —SO2C1-6alkyl, —C3-7cycloalkyl, phenyl, CH2phenyl, heteroaryl and CH2heteroaryl; each Rb is independently selected from:
(1) hydrogen,(2) —C1-6alkyl,(3) —C1-6alkenyl,(4) —(CH2)n—C3-10cycloalkyl,(5) —(CH2)n—C3-10cycloalkenyl,(6) —(CH2)n—C2-10cycloheteroalkyl,(7) —(CH2)n—C2-10cycloheteroalkenyl,(8) —(CH2)n-aryl,(9) —(CH2)n-heteroaryl,(10) oxo,(11) —(CH2)n—CF3,(12) —(CH2)n—CN,(13) —(CH2)t-halogen,(14) —(CH2)s-OH,(15) —(CH2)n—NO2,(16) —(CH2)n—NH2,(17) —(CH2)n—NH(C1-6alkyl),(18) —(CH2)n—N(C1-6alkyl)2,(19) —(CH2)n—NHCO2H,(20) —(CH2)n-OC1-6alkyl,(21) —(CH2)n-OC1-6alkenyl,(22) —(CH2)n—COC1-6alkyl,(23) —(CH2)n—CO2H,(24) —(CH2)n—OCOH,(25) —(CH2)n—CO2Ri,(26) —(CH2)n—OC(O)Ri,(27) —(CH2)q-C(O)N(Re)2,(28) —(CH2)q-CO2N(Re)2,(29) —(CH2)n—C(O)(CH2)nN(Rg)2,(30) —(CH2)n—OC(O)(CH2)nN(Rg)2,(31) —(CH2)n-N(Re)C(O)C1-6alkyl,(32) —(CH2)n—N(Re)SO2Ri,(33) —(CH2)n—SO2C1-6alkyl,(34) —(CH2)n—SO2N(Re)Rg,(35) —(CH2)n—SO2N(Re)C(O)Ri,(36) —(CH2)n—SO2N(Re)CO2Ri,(37) —(CH2)n—SO2N(Re)CON(Rg)2,(38) —(CH2)n—C(O)N(Re)SO2Ri,(39) —(CH2)n—N(Re)C(O)N(Rg)2,(40)=N(OH), and(41)=N(OC1-6alkyl), wherein each CH2 is unsubstituted or substituted with 1 or 2 substituents selected from: —C1-6alkyl, —OH, halogen and —NH2 wherein each NH is unsubstituted or substituted with 1 substituent selected from Rc, and wherein each alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from Rc, or wherein two Rb substituents and the carbon to which they are attached may form a 3 to 6 membered cycloalkyl ring, a 3-6 membered cycloalkenyl ring, a 3-6 membered cycloheteroalkyl ring or a 3-6 membered cycloheteroalkenyl ring, wherein the ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from Rc; each Rc is independently selected from:
(1) halogen,(2) oxo,(3) —(CH2)rOH,(4) —(CH2)rN(Re)2,(5) —(CH2)rCN,(6) —C1-6alkyl,(7) —CF3,(8) —C1-6alkyl-OH,(9) —OCH2OC1-6alkyl,(10) —(CH2)rOC1-6alkyl,(11) —OCH2aryl,(12) —(CH2)rSC1-6alkyl,(13) —(CH2)rC(O)Rf,(14) —(CH2)rC(O)N(Re)2,(15) —(CH2)rCO2H,(16) —(CH2)rCO2Rf,(17) —(CH2)rC3-7cycloalkyl,(18) —(CH2)rC2-6cycloheteroalkyl,(19) —(CH2)raryl, and(20) —(CH2)rheteroaryl, wherein each CH2 is unsubstituted or substituted with 1 or 2 substituents selected from: oxo, —OH, —CN, —N(Rh)2, —C1-6alkyl, —OC1-6alkyl, halogen, —CH2F, —CHF2, —CF3, —CO2H, —CO2C1-6alkyl, —C3-7cycloalkyl and heteroaryl, and wherein alkyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: oxo, —OH, —CN, —N(Rh)2, —C1-6alkyl, —OC1-6alkyl, halogen, —CH2F, —CHF2, —CF3, —CO2H, —CO2C1-6alkyl, —C3-7cycloalkyl and heteroaryl; each Re, Rg and Rh is independently selected from:
(1) hydrogen,(2) —C1-6alkyl, and(3) —O—C1-6alkyl, wherein alkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: —OH, oxo, halogen, C1-6alkyl, —OC1-6alkyl, —NH2, —NH(C1-6alkyl), and —N(C1-6alkyl)2; each Rj is independently selected from:
(1) hydrogen,(2) C1-6alkyl,(3) C3-6cycloalkyl,(4) —C(O)Ri,(5) —CO2Ri, and(6) —SO2Ri, wherein alkyl and cycloalkyl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: —OH, oxo, halogen, C1-6alkyl, —OC1-6alkyl, —NH2, —NH(C1-6alkyl), and —N(C1-6alkyl)2; each Rf and Ri is independently selected from:
(1) C1-6alkyl,(2) —(CH2)rC4-7cycloalkyl,(3) —(CH2)rC4-7cycloalkenyl,(4) —(CH2)rC3-7cycloheteroalkyl,(5) —(CH2)rC3-7cycloheteroalkenyl,(6) —(CH2)raryl, and(7) —(CH2)rheteroaryl, wherein alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, cycloheteroalkenyl, aryl and heteroaryl are unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from: oxo, —OH, —CN, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2, —C1-6alkyl, —OC1-6alkyl, halogen, —CH2F, —CHF2, —CF3, —CO2H, —CO2C1-6alkyl, —C3-7cycloalkyl, and heteroaryl; n is 0, 1, 2, 3 or 4; m is 0, 1, 2, 3 or 4; p is 0, 1, 2, or 3; q is 0, 1, 2, 3 or 4; r is 0, 1 or 2; s is 0, 1, 2, 3 or 4; t is 0, 1, 2, 3 or 4, and u is 0, 1, 2, 3 or 4. |
