| 主权项 |
1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:wherein:
R1 is selected from the group consisting of
(a) hydrogen,(b) halogen,(c) CN,(d) C1-6 alkyl optionally substituted with one or more groups independently selected from the group consisting of ORa, C3-6cycloalkyl, and halogen,(e) C2-6 alkenyl optionally substituted with OC1-6alkyl,(f) C2-6 alkynyl,(g) C3-6 cycloalkyl,(h) OH,(i) —O—C1-6 alkyl optionally substituted with one or more groups independently selected from
(i) aryl,(ii) 5- or 6-membered heteroaryl optionally substituted with one or more groups independently selected from C1-6 alkyl,(iii) 4- to 8-membered heterocyclyl optionally substituted with one or more groups independently selected from oxo, halogen, C1-6 alkyl,(iv) —CO2Ra,(v) —CONRbRc,(vi) —NRbRc, and(vii) —ORa,(j) -A-X, wherein A is a bond or O, X is selected from the group consisting of
(i) 4- to 8-membered heterocyclyl optionally substituted with one or more groups independently selected from halogen, C1-6 alkyl, —C1-6 haloalkyl, —C1-6 hydroxyalkyl, CORa, CO2Ra,(ii) C3-6 cycloalkyl optionally substituted with one or more groups independently selected from C1-6 alkyl, —ORa, —CO2Ra, —NRbRc,(iii) heteroaryl optionally substituted with a benzyl which is optionally substituted with ORa,(k) O—CH2C≡C-pyrimidinyl,(l) —S(O)n—C1-6 alkyl,(m) —CORa,(n) —CO2Ra,(o) —CONRbRc,(p) —NRbRc, R2 is selected from the group consisting of
(a) H,(b) halogen,(c) C1-6 alkyl,(d) O—C1-6 alkyl,(e) C1-6 haloalkyl and(f) O—C1-6 haloalkyl; or R1 and R2 on adjacent carbon atoms together represent (CH2)3-4; R3 is H, halogen, ORa, or C1-4alkyl, R4 is selected from the group consisting of
(a) H,(b) halogen,(c) C1-6 alkyl optionally substituted with one or more groups independently selected from
(i) halogen,(ii) ORa,(iii) OC(O)Ra,(iv) NRbRc,(v) NHC(O)Ra, and(vi) NHC(O)NHRb,(d) C2-6 alkenyl,(e) C2-6 alkynyl,(f) C3-6 cycloalkyl(g) ORa,(h) NO2,(i) NRbRc,(j) NHC(O)Ra,(k) NHC(O)NHRb,(l) NHC(O)NHC(O)NRbRc, R5 is selected from the group consisting of
(a) H,(b) halogen,(c) C1-8alkyl, C2-6alkenyl, C2-6 alkynyl, each of which is optionally substituted with one or more groups independently selected from Ry,(d) C3-12 carbocycle, or a carbon-linked 3- to 12-membered heterocyclyl each optionally substituted with one or more groups independently selected from Rz,(e) heteroaryl optionally substituted with C1-3 alkyl (optionally substituted with one or more OH or CN or heterocycle);(f) —C(O)Ra,(g) —C(O)2Ra, and(h) —C(O)NRbRc, R5(i) is selected from the group consisting of H and C1-3alkyl; Ra is selected from the group consisting of
(a) H,(b) C1-6 alkyl optionally substituted with one or more groups independently selected from
(i) halogen,(ii) CN,(iii) OH,(iv) OC1-4alkyl,(v) heterocyclyl optionally substituted with oxo,(vi) C(O)C1-6alkyl optionally substituted with OH,(vii) CO2H,(viii) CO2C1-6alkyl,(ix) CONRb(i)Rc(i),(x) SO2C1-6alkyl,(xi) —NRb(i)Rc(i),(xii) NRb(i)C(O)NRb(i)Rc(i);(xiii) phenyl, and(xiv) heteroaryl optionally substituted with OH,(c) C2-6alkenyl,(d) C3-6 cycloalkyl optionally substituted with one or more groups independently selected from
(i) OH,(ii) CO2H,(iii) CO2C1-6alkyl,(iv) CONRb(i)Rc(i)(e) phenyl optionally substituted with one or more groups independently selected from
(i) C2-6alkynyl,(ii) CN,(iii) halogen,(iv) OH,(vi) OC(O)C1-6alkyl,(vii) CO2H,(viii) CO2C1-6alkyl,(f) heteroaryl optionally substituted with one or more groups independently selected from C1-6alkyl, C1-6haloalkyl, (CH2)0-2CO2H, OH, halogen, phenyl optionally substituted with CO2H, and(g) heterocyclyl optionally substituted with oxo, Rb and Rc are independently selected from the group consisting of
(a) H,(b) C1-6 alkyl optionally substituted with one or more groups independently selected from
(i) ORa,(ii) halogen,(iii) heterocyclyl optionally substituted with oxo, OH, C1-6 alkyl (optionally substituted with OH),(iv) C3-6 cycloalkyl optionally substituted with one or two groups selected from C1-4alkyl, CH2OH, CONRb(i)Rc(i), and CO2Ra,(v) heteroaryl optionally substituted with C1-6alkyl optionally substituted with OH, CO2H or heteroaryl optionally substituted with a heteroaryl,(vi) SO2NRb(i)Rc(i),(vii) SO2C1-4alkyl,(viii) CONRb(i)Rc(i),(ix) NRb(i)Rc(i),(x) CO2Ra,(xi) aryl optionally substituted with one or more groups selected from halogen, ORa, C1-6alkyl (optionally substituted with halogen, heterocycle (optionally substituted with oxo), or ORa), SO2NH2, and heteroaryl optionally substituted with CH2OH(xii) SO3H,(xiii) NRb(i)CONRb(i)Rc(i),(xiv) CN, and(xv) NHC(O)Ra,(c) C3-6 alkenyl optionally substituted with F;(d) C3-6 cycloalkyl (optionally fused to a benzene ring) optionally substituted with one or more groups independently selected from
(i) C1-4alkyl,(ii) ORa,(iii) CH2OH,(iv) CO2Ra, and(v) CONRb(i)Rc(i),(e) aryl optionally substituted with one or two groups independently selected from
(i) C1-6alkyl (optionally substituted with ORa),(ii) CN,(iii) ORa,(iv) halogen, and(v) OCOC1-4alkyl;(f) heteroaryl optionally substituted with one or more groups independently selected from
(i) ORa,(ii) CO2Ra and(iii) C1-6 alkyl optionally substituted with OH,(g) heterocyclyl optionally substituted with one or more groups indepdently selected from
(i) oxo,(ii) OH and(iii)C1-6 alkyl, or Rb, Rc and the nitrogen atom to which they are attached together form a 5-, 6- or 7-membered heterocycle having 0 or 1 additional heteroatom selected from O, P(O)(C1-6alkyl), S(O)n and N—Rx, and optionally substituted with one or more groups independently selected from
(a) oxo,(b) thioxo,(c) C1-6 alkyl optionally substituted with one or more groups independently selected from
(i) ORa,(ii) CO2Ra,(iii) OP(O)(C1-6alkyl)2,(iv) aryl, and(v) halogen,(d) ORa,(e) C(O)Ra,(f) C(O)2Ra,(g) CONRb(i)Rc(i),(h) P(O)(OH)2,(i) SO2Ra, and(j) CN, or Rb, Rc and the nitrogen atom to which they are attached together form wherein W is CH or N; H Rb(i) and Rc(i) are independently selected from the group consisting of
(a) H and(b) C1-6 alkyl optionallly substituted with OH, CO2H or CO2C1-6alkyl; or Rb(i), Rc(i) and the nitrogen atom to which they are attached together form a 5- or 6-membered heterocycle having 0 or 1 additional heteroatom selected from O, S and N—Rx, and optionally substituted with one or more groups independently selected from oxo, Ru is selected from the group consisting of
(a) C1-6 alkyl optionally substituted with one to three groups selected from halogen, OH, SO2Ra, CONRbRc, NRbRc, phenyl, heterocyclyl and heteroaryl,(b) C3-8 cycloalkyl optionally substituted with OH, CO2Ra, —CONH2,(c) heterocycle optionally substituted with oxo,(d) aryl optionally substituted with C2-6alkynyl, CN, halogen, ORa,(e) heteroaryl optionally substituted with OH, Rx is selected from the group consisting of
(a) H,(b) C1-6 alkyl optionally substituted with heterocycle,(c) phenyl optionally substituted with OH or OC1-4alkyl,(d) —C(O)—C1-6 alkyl,(e) —C(O)2—C1-6 alkyl,(f) —C(O)NH2, —C(O)NH—C1-6 alkyl, —C(O)N(C1-6 alkyl)2,(g) —C(O)2NHC(O)NH2, —C(O)2NHC(O)NH—C1-6 alkyl, —C(O)2NHC(O)N(C1-6 alkyl)2,(h) —SO2—C1-6 alkyl (optionally substituted with halogen), —SO2-heteroaryl (optionally substituted with alkyl),(i) —S(O)2NH2, —S(O)2NH—C1-6 alkyl, —S(O)2N(C1-6 alkyl)2,(j) —SO2NHC(O)2—C1-6 alkyl, Ry is selected from the group consisting of
(a) aryl optionally substituted with one or more groups independently selected from
(i) halogen,(ii) C1-6alkyl optionally substituted with OH or CO2Ra,(iii) C2-6alkenyl optionally substituted with CO2Ra,(iv) phenyl optionally substituted with CO2Ra,(v) CORa,(vi) CO2Ra,(vii) CONRbRc,(viii) ORa,(ix) S(O)nRa,(x) SO2NRbRc,(xi) SO2NHC(O)Ra,(xii) NO2, and(xiii) NHC(O)Ra,(b) heteroaryl optionally substituted with one or more groups independently selected from
(i) halogen,(ii) C1-6 alkyl optionally substituted with CO2Ra,(iii) C3-6 cycloalkyl,(iv) aryl optionally substituted with CO2Ra,(v) CONRbRc,(vi) ORa,(vii) SO2Ra, and(viii) CO2Ra,(c) C3-8 cycloalkyl optionally substituted with one or more groups independently selected from
(i) C1-6 alkyl,(ii) CO2Ra, and(iii) NRbRc,(d) C6-8cycloalkenyl (optionally substituted with CO2Ra),(e) halogen,(f) CN,(g) —C(O)Ra,(h) —C(O)2Ra,(i) C(O)CO2Ra,(j) —C(O)NRbRc,(k) —C(O)NHC(O)NRbRc,(l) —ORa,(m) —OC(O)Ra,(n) —NRbRc,(o) —NHC(O)Ru,(p) —NHC(O)NRbRc,(q) —NHC(O)NHC(O)NH2,(r) —NHSOmRa (s) —NHSO2NRbRc,(t) SOnRa,(u) —SO2NRbRc,(v) —SO2NHC(O)Ra,(w) —SO2NHC(O)2Ra,(x) SO3H,(y) —P(O)(ORa)2, and(z) CONHOH;(aa) heterocyclyl optionally substituted with one or more groups independently selected from oxo, thioxo, C1-6alkyl, and CO2Ra; Rz is selected from the group consisting of
(a) a group selected from Ry,(b) C1-6 alkyl optionally substituted with one or more groups independently selected from halogen, NRbRc, ORa, CN, phenyl (optionally substituted with C1-6alkanoic acid), CONRbRc, and —CO2Ra,(c) oxo, and(d) ═NORa, m is 1 or 2, n is 0, 1 or 2. |
