| 主权项 |
1. A compound of structural formula I: or a pharmaceutically acceptable salt thereof; wherein “a” is a single bond or a double bond, provided that if “a” is a double bond, then R6 is absent and Y is selected from the group consisting of: C—Rg, —C—OC1-6alkyl, CF, and N; T is selected from the group consisting of:
(1) CH,(2) N, and(3) N-oxide; U is selected from the group consisting of:
(1) CR1,(2) N, and(3) N-oxide; V is selected from the group consisting of:
(1) CR2,(2) N, and(3) N-oxide; W is selected from the group consisting of:
(1) CH,(2) N, and(3) N-oxide, provided that no more than two of T, U, V and W are selected from N and N-oxide, further provided that if both T and W are N or N-oxide, then R3 is absent, and further provided that both U and V are not N or N-oxide; Y is selected from the group consisting of:
(1) oxygen,(2) sulfur,(3) —CRgRg,(4) C═O,(5) —C(Rg)OC1-6alkyl,(6) —CF2, and(7) —NRc; A is selected from the group consisting of:
(1) aryl,(2) heteroaryl,(3) C3-6cycloalkyl, and(4) C2-5cycloheteroalkyl, wherein A is unsubstituted or substituted with one to five substituents selected from Ra; B is selected from the group consisting of:
(1) hydrogen,(2) aryl,(3) aryl-O—,(4) aryl-C1-10alkyl-,(5) aryl-C1-10alkyl-O—,(6) C3-6cycloalkyl,(7) C3-6cycloalkyl-C1-10alkyl-,(8) C3-6cycloalkyl-C1-10alkyl-O—,(9) C3-6cycloalkenyl,(10) C3-6cycloalkenyl-C1-10alkyl-,(11) C3-6cycloalkenyl-C1-10alkyl-O—,(12) C2-5cycloheteroalkyl,(13) C3-6cycloheteroalkyl-C1-10alkyl-,(14) C3-6cycloheteroalkyl-C1-10alkyl-O—,(15) heteroaryl,(16) heteroaryl-O—,(17) heteroaryl-C1-10 alkyl-, and(18) heteroaryl-C1-10 alkyl-O—, wherein B is unsubstituted or substituted with one to five substituents selected from Rb; R1 and R2 are each independently selected from:
(1) a bond,(2) hydrogen,(3) halogen,(4) —ORk,(5) —CN,(6) —C1-6alkyl,(7) —C3-6cycloalkyl,(8) —C3-6cycloalkyl-C1-3alkyl-,(9) —C2-6cycloheteroalkyl, and(10) —C2-6cycloheteroalkyl-C1-3alkyl-, wherein each alkyl, cycloalkyl and cycloheteroalkyl is unsubstituted or substituted with one to three substituents selected from RL, and wherein one of R1 and R2 is substituted with a substituent selected from R7, or R1 and R2 together with the atom(s) to which they are attached form a C3-6cycloalkyl ring or a C2-5cycloheteroalkyl ring containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—Rg, wherein each R1 and R2 is unsubstituted or substituted with one to three substituents selected from RL, and wherein one of R1 and R2 is substituted with a substituent selected from R7; R3 is selected from the group consisting of:
(1) hydrogen,(2) halogen,(3) —ORe,(4) —CN,(5) —C1-6alkyl,(6) —C3-6cycloalkyl, and(7) —C3-6cycloalkyl-C1-33alkyl-, wherein each alkyl and cycloalkyl is unsubstituted or substituted with one to three substituents selected from Ri; R4 is selected from the group consisting of:
(1) hydrogen,(2) halogen,(3) ORe,(4) C1-6alkyl,(5) C1-6alkyl-O—,(6) C3-6cycloalkyl,(7) C3-6cycloalkyl-O—,(8) C3-6cycloalkyl-C1-10alkyl-,(9) C3-6cycloalkyl-C1-10alkyl-O—,(10) C2-5cycloheteroalkyl,(11) C2-5cycloheteroalkyl-O—,(12) C2-5cycloheteroalkyl-C1-10alkyl-,(13) C2-5cycloheteroalkyl-C1-10alkyl-O—,(14) aryl,(15) aryl-O—,(16) aryl-C1-10alkyl-,(17) heteroaryl,(18) heteroaryl-O—, and(19) heteroaryl-C1-10alkyl-, wherein each alkyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to three substituents selected from Rj, provided that when R4 is selected from the group consisting of:
(1) ORe,(2) C1-6alkyl-O—,(3) C3-6cycloalkyl-O—,(4) C3-6cycloalkyl-C1-10alkyl-O—,(5) C2-5cycloheteroalkyl-O—,(6) C2-5cycloheteroalkyl-C1-10alkyl-O—,(7) aryl-O—, and(8) heteroaryl-O—, then Y is selected from the group consisting of:
(1) —CRgRg,(2) C═O,(3) —C(Rg)OC1-6alkyl, and(4) —CF2; R5 is selected from the group consisting of:
(1) hydrogen,(2) —C1-6alkyl, and(3) —C3-6cycloalkyl, wherein each alkyl and cycloalkyl is unsubstituted or substituted with one to three substituents selected from Rj; R6 is selected from the group consisting of:
(1) hydrogen,(2) —C1-6alkyl, and(3) —C3-6cycloalkyl, wherein each alkyl and cycloalkyl is unsubstituted or substituted with one to three substituents selected from Rj; R7 is selected from the group consisting of:
(1) —CO2R8,(2) —C1-6alkyl-CO2R8,(3) —C1-6alkyl-CONHSO2Rm,(4) —C1-6alkyl-SO2NHCORm,(5) —C1-6alkyl-tetrazolyl, and(6) a cycloheteroalkyl selected from the group consisting of: R8 is selected from the group consisting of:
(1) hydrogen,(2) —C1-6alkyl,(3) —C3-6cycloalkyl, and(4) aryl-C1-6alkyl, wherein each alkyl, cycloalkyl and aryl is unsubstituted or substituted with one to three substituents selected from Rj; Ra is selected from the group consisting of:
(1) —C1-6alkyl,(2) halogen,(3) —ORe,(4) —NRcS(O)nRe,(5) —S(O)nRe,(6) —S(O)nNRcRd,(7) —NRcRd,(8) —C(O)Re,(9) —OC(O)Re,(10) —CO2Re,(11) —CN,(12) —C(O)NRcRd,(13) —NRcC(O)Re,(14) —NRcC(O)ORe,(15) —NRcC(O)NRcRd,(16) —CF3,(17) —OCF3,(18) —OCHF2,(19) aryl,(20) heteroaryl,(21) —C3-6cycloalkyl,(22) —C3-6cycloalkenyl, and(23) —C2-5cycloheteroalkyl, wherein each alkyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with —C1-6alkyl, halogen, —O—C1-6alkyl and —CF3; Rb is independently selected from the group consisting of:
(1) —C1-10alkyl,(2) —C2-10alkenyl,(3) —CF3,(4) halogen,(5) —CN,(6) —OH,(7) —OC1-10alkyl,(8) —OC2-10alkenyl,(9) —O(CH2)pOC1-10alkyl,(10) —O(CH2)pC3-6cycloalkyl,(11) —O(CH2)pC3-6 cycloalkyl-C1-10alkyl-,(12) —O(CH2)pC2-5cycloheteroalkyl,(13) —O(CH2)pC2-5cycloheteroalkyl-C1-10alkyl-,(14) —O-aryl,(15) —O-heteroaryl,(16) —O-aryl-C1-10alkyl-,(17) —O-heteroaryl-C1-10alkyl-,(18) —O(CH2)pNRcS(O)mRe,(19) —O(CH2)pS(O)mRe,(20) —O(CH2)pS(O)mNRcRd,(21) —O(CH2)pNRcRd,(22) —C(O)Re,(23) —OC(O)Re,(24) —CO2Re,(25) —C(O)NRcRd,(26) —NRcC(O)Re,(27) —NRcC(O)ORe,(28) —NRcC(O)NRcRd,(29) —O(CH2)pO—C3-6cycloalkyl,(30) —O(CH2)pO—C2-5cycloheteroalkyl,(31) —OCF3,(32) —OCHF2,(33) —(CH2)pC3-6cycloalkyl,(34) —(CH2)pC2-5cycloheteroalkyl,(35) aryl,(36) heteroaryl,(37) aryl-C1-10alkyl-, and(38) heteroaryl-C1-10alkyl-, wherein each CH, CH2, alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with —C1-6alkyl, halogen, —O—C1-6alkyl and —CF3; Rc and Rd are each independently selected from the group consisting of:
(1) hydrogen,(2) C1-10alkyl,(3) C2-10alkenyl,(4) C3-6cycloalkyl,(5) C3-6cycloalkyl-C1-10alkyl-,(6) C2-5cycloheteroalkyl,(7) C2-5cycloheteroalkyl-C1-10alkyl-,(8) aryl,(9) heteroaryl,(10) aryl-C1-10alkyl-, and(11) heteroaryl-C1-10alkyl-, wherein each alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to three substituents independently selected from Rf, or Rc and Rd together with the atom(s) to which they are attached form a C2-5 cycloheteroalkyl ring containing 0-2 additional heteroatoms independently selected from oxygen, sulfur and N—Rg, wherein each Rc and Rd is unsubstituted or substituted with one to three substituents independently selected from Rf; each Re is independently selected from the group consisting of:
(1) hydrogen,(2) —C1-10alkyl,(3) —C2-10 alkenyl,(4) —C3-6cycloalkyl,(5) —C3-6cycloalkyl-C1-10alkyl-,(6) —C2-5cycloheteroalkyl,(7) —C2-5cycloheteroalkyl-C1-10alkyl-,(8) aryl,(9) aryl-C1-10alkyl-,(10) heteroaryl, and(11) heteroaryl-C1-10alkyl-, wherein each alkyl, alkenyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with one to three substituents selected from Rh; each Rf is selected from the group consisting of:
(1) halogen,(2) C1-10alkyl,(3) —OH,(4) —O—C1-4alkyl,(5) —S(O)m—C1-4alkyl,(6) —CN,(7) —CF3,(8) —OCHF2, and(9) —OCF3, wherein each alkyl is unsubstituted or substituted with one to three substituents independently selected from: —OH, halogen, C1-6alkyl, cyano and S(O)2C1-6alkyl; each Rg is selected from the group consisting of:
(1) hydrogen,(2) —C(O)Re, and(3) —C1-10alkyl, wherein each alkyl is unsubstituted or substituted with one to five halogens; each Rh is selected from the group consisting of:
(1) halogen,(2) C1-10alkyl,(3) —OH,(4) —O—C1-4alkyl,(5) —S(O)m—C1-4alkyl,(6) —CN,(7) —CF3,(8) —OCHF2, and(9) —OCF3, wherein each alkyl is unsubstituted or substituted with one to three substituents independently selected from: —OH, halogen, C1-6alkyl, cyano and S(O)2C1-6alkyl; Ri is independently selected from the group consisting of:
(1) —C1-6alkyl,(2) —ORe,(3) —NRcS(O)mRe,(4) halogen,(5) —S(O)mRe,(6) —S(O)mNRcRd,(7) —NRcRd,(8) —C(O)Re,(9) —OC(O)Re,(10) —CO2Re,(11) —CN,(12) —C(O)NRcRd,(13) —NRcC(O)Re,(14) —NRcC(O)ORe,(15) —NRcC(O)NRcRd,(16) —CF3,(17) —OCF3,(18) —OCHF2,(19) —C3-6cycloalkyl, and(20) —C2-5cycloheteroalkyl; Rj is independently selected from the group consisting of:
(1) —C1-6alkyl,(2) —ORe,(3) —NRcS(O)mRe,(4) halogen,(5) —S(O)mRe,(6) —S(O)mNRcRd,(7) —NRcRd,(8) —C(O)Re,(9) —OC(O)Re,(10) —CO2Re,(11) —CN,(12) —C(O)NRcRd,(13) —NRcC(O)Re,(14) —NRcC(O)ORe,(15) —NRcC(O)NRcRd,(16) —CF3,(17) —OCF3,(18) —OCHF2,(19) —C3-6cycloalkyl, and(20) —C2-5cycloheteroalkyl; each Rk is independently selected from the group consisting of:
(1) hydrogen,(2) —C1-6alkyl,(3) —C1-6alkyl-SO2C1-6alkyl,(4) —CF3, and(5) —CHF2, wherein each alkyl is unsubstituted or substituted with one to three substituents independently selected from: —OH, —OC1-6alkyl, halogen, cyano, and —S(O)2C1-6alkyl; each RL is independently selected from the group consisting of:
(1) —CO2C1-6alkyl,(2) —C1-10alkyl,(3) —C2-10 alkenyl,(4) —C2-10alkynyl,(5) —C3-6cycloalkyl,(6) —C2-6cycloheteroalkyl,(7) aryl, and(8) heteroaryl, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with 1-4 substituents selected from C1-6alkyl, halogen, and —OC1-6alkyl; each Rm is independently selected from the group consisting of:
(1) —C1-10alkyl,(2) —C2-10 alkenyl,(3) —C3-6 cycloalkyl,(4) —C3 cycloalkyl-C1-10alkyl-,(5) —C2-5cycloheteroalkyl,(6) —C2-5cycloheteroalkyl-C1-10alkyl-,(7) aryl,(8) heteroaryl,(9) aryl-C1-10alkyl-, and(10) heteroaryl-C1-10alkyl-; each n is independently selected from: 0, 1 or 2; each m is independently selected from: 0, 1 or 2; and each p is independently selected from: 0, 1, 2, 3, 4, 5 or 6. |
