| 主权项 |
1. A compound of formula I: wherein: B is selected from the group consisting of C3-10cycloalkyl, phenyl, naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, azepanyl, azepinyl, azetidinyl, benzimidazolyl, benzisoxazolyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, benzopyrazolyl, benzotriazolyl, chromanyl, cinnolinyl, dibenzofuryl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, isoxazolyl, isoxazolinyl, isoxazolidinyl, morpholinyl, naphthyridinyl, oxazolyl, oxazolinyl, oxazolidinyl, oxazepanyl, oxadiazolyl, 2-oxoazepinyl, 4-oxonaphthyridinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxopyridinyl, 2-oxoquinolinyl, 2-oxobenzimidazolinyl, phthalazinyl, piperidinyl, piperazinyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiopyranyl, tetrahydroimidazopyridinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiazepinyl, thiazolyl, thiazolinyl, thiazolidinyl, thienyl, thienofuryl, thienothienyl, triazolinyl and triazolyl, wherein B is optionally substituted with 1-7 substituents each independently selected from the group consisting of:
(1) -C1-6alkyl, which is optionally substituted with 1-7 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —C3-6cycloalkyl,(d) phenyl or heterocycle, wherein the heterocycle is selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl and morpholinyl, and wherein said phenyl or heterocycle is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(i) —C1-6alkyl,(ii) —O—C1-6alkyl,(iii) halo,(iv) hydroxy,(v) trifluoromethyl, and(vi) —OCF3,(e) —CO2Ra,(f) —NRbRc,(g) —SO2Rd,(h) —CONRbRc,(i) trifluoromethyl,(j) —OCO2Ra,(k) —(NRb)CO2Ra,(l) —O(CO)NRbRc, and(m) —(NRa)(CO)NRbRc,(2) —C3-6cycloalkyl, which is optionally substituted with 1-7 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) trifluoromethyl and(d) phenyl, which is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(i) —C1-6alkyl,(ii) —O—C1-6alkyl,(iii) halo,(iv) hydroxy and(v) trifluoromethyl,(3) phenyl or heterocycle, wherein the heterocycle is selected from pyridinyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, tetrazolyl, azepanyl, benzimidazolyl, benzopyranyl, benzofuryl, benzothiazolyl, benzoxazolyl, chromanyl, furyl, imidazolidinyl, imidazolinyl, indazolyl, indolinyl, indolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, isoindolinyl, tetrahydroisoquinolinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, pyrazolidinyl, pyrazolyl, pyrrolyl, quinazolinyl, tetrahydrofuryl, thiazolinyl, purinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, 1,3-dioxolanyl, oxadiazolyl, piperidinyl and morpholinyl, and wherein the phenyl or heterocycle is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(a) —C1-6alkyl which is optionally substituted with 1-6 fluoro,(b) halo,(c) —ORa,(d) —C3-6cycloalkyl,(e) phenyl or heterocycle, wherein the heterocycle is selected from pyridinyl, pyrimidinyl, pyrazinyl, thienyl and morpholinyl,
and wherein the phenyl or heterocycle is optionally substituted with 1-5 substituents each independently selected from the group consisting of:(i) —C1-6alkyl,(ii) —O—C1-6alkyl,(iii) halo,(iv) hydroxy and(v) trifluoromethyl,(f) —CO2Ra,(g) —NRbRc,(h) —CONRbRc,(i) —SO2Rd, and(j) oxo,(4) halo,(5) oxo,(6) —ORa,(7) —CN,(8) —CO2Ra,(9) —NRbRc,(10) —SO2Rd,(11) —CONRbRc,(12) —OCO2Ra,(13) —(NRb)CO2Ra,(14) —(NRb)(CO)NRbRc,(15) —SO2NRbRc,(16) —S(O)vRd;or wherein two of the substituents on B and the atom(s) to which they are attached are joined to form a ring selected from azetidinyl, azepanyl, azepinyl, cyclopropyl, cyclobutyl, cyclopentenyl, cyclopentyl, cyclohexenyl, cyclohexyl, phenyl, naphthyl, thienyl, thiazolyl, thiazolinyl, oxazolyl, oxazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, thiadiazolyl, oxadiazolyl, isoxazolyl, pyrazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, pyrrolyl, pyrrolinyl, morpholinyl, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridinyl, furanyl, dihydrofuranyl, dihydropyranyl, dihydrothienyl, tetrahydrothienyl, dihydrothiopyranyl, tetrahydrothiopyranyl, pyrrolidinyl, piperidinyl, and piperazinyl, which ring is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(a) —C1-6alkyl, which is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(i) halo,(ii) —ORa,(iii) —C3-6cycloalkyl, which is optionally substituted with 1-5 substituents each independently selected from the group consisting of:(I) —C1-6alkyl,(II) —O—C1-6alkyl,(III) halo and(IV) hydroxy,(iv) phenyl or heterocycle, wherein the heterocycle is selected from pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl and morpholinyl, which phenyl or heterocycle is optionally substituted with 1-5 substituents each independently selected from the group consisting of:(I) —C1-6alkyl,(II) —O—C1-6alkyl,(III) halo,(IV) hydroxy,(V) trifluoromethyl and(VI) —OCF3,(v) —CO2Ra,(vi) —NRbRc, and(vii) —SO2Rd,(b) —C3-6cycloalkyl, which is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(i) halo,(ii) hydroxy,(iii) —O—C1-6alkyl,(iv) trifluoromethyl and(v) phenyl,(c) phenyl or heterocycle, wherein the heterocycle is selected from pyridinyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, piperidinyl and morpholinyl, which phenyl or heterocycle is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(i) halo,(ii) hydroxy,(iii) —C3-6cycloalkyl,(iv) —O—C1-6alkyl which is optionally substituted with 1-6 fluoro, and(v) —C1-6alkyl which is optionally substituted with 1-6 fluoro,(d) halo,(e) —SO2Rd,(f) —ORa,(g) oxo,(h) —CN,(i) —CORa,(j) —NRbRc,(k) —CONRbRc,(l) —CO2Ra; A1 is selected from:
(1) a bond,(2) —CReRf—,(3) —CH2CReRf—,(4) —CReRfCH2—,(5) —(C═O)—,(6) —N(Rb)—,(7) —O—,(8) —S(O)v—,(9) —C(Rg)═C(Rh)—, or(10) —C≡C—; A2 is selected from:
(1) —CReRf—,(2) —N(Rb)—,(3) —O—,(4) —S(O )v—,(5) —C(Rg)═C(Rh)—,(6) —C≡C—, or(7) a bond, wherein A2 cannot be a bond unless A3 is —C(Rg)═C(Rh)— or —C≡C—; A3 is selected from:
(1) —CReRf—,(2) —N(Rb)—,(3) —O—,(4) —S(O)v—,(5) —C(Rg)═C(Rh)— or(6) —C≡C—; A5 and A7 are each independently selected from the group consisting of:
(1) —O—,(2) —S(O)v—,(3) —CReRf—,(4) —N(Rb)—,(5) —(C═O)—, and(6) a bond, A6 and A8 are each independently selected from the group consisting of:
(1) —O—,(2) —S(O)v—,(3) —CReRf—,(4) —N(Rb)—, and(5) —(C═O)—, G1 is selected from:
(1) —C(R2a)═,(2) —N═, or(3) —(N+—O−)═; G2 is selected from:
(1) —C(R2b)═,(2) —N═, or(3) —(N+O−)═; G3 is selected from:
(1) —C(R2c)═,(2) —N═, or(3) —(N+O−)═; R2a, R2b and R2c are each independently selected from the group consisting of:
(1) hydrogen,(2) —C1-6alkyl, which is optionally substituted with 1-6 halo,(3) halo,(4) —ORa, and(5) —CN; J is selected from:
(1) ═C(R3a)—,(2) —CR4R5—,(3) —C(═O)—, or(4) —N(Rb)—; Y is selected from:
(1) ═C(R3b)—,(2) —-CR4R5—,(3) —C(═O)—,(4) ═N—, or(5) —N(Rb)—; R3a and R3b are each independently selected from the group consisting of:
(1) hydrogen,(2) —C1-4alkyl, which is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —C3-6cycloalkyl,(d) phenyl or heterocycle, wherein said heterocycle is selected from: imidazolyl, oxazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thiazolyl, thienyl, triazolyl, isoxazolyl and morpholinyl, which phenyl or heterocycle is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(i) halo,(ii) —ORa,(iii) —CN and(iv) C1-6alkyl, which is optionally substituted with 1-6 halo,(3) phenyl or heterocycle, wherein heterocycle is selected from: imidazolyl, oxazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, tetrahydrofuryl, piperidinyl, piperazinyl, pyrrolidinyl, azetidinyl, thiazolyl, thienyl, triazolyl, isoxazolyl and morpholinyl, which phenyl or heterocycle is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —C3-6cycloalkyl,(d) —C1-4alkyl which is optionally substituted with 1-6 halo, and(e) phenyl, which is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(i) halo,(ii) —C1-6alkyl, which is optionally substituted with 1-6 halo, and(iii) —ORa,(4) halo,(5) —ORa,(6) —CN,(7) —CO2Ra,(8) —NRbRc, and(9) —C(═O)NRbRc;or R3a and R3b and the carbon atom(s) to which they are attached join to form a ring selected from cyclopentenyl, cyclohexenyl, phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, furanyl, dihydrofuranyl, dihydropyranyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, thienyl, dihydrothienyl and dihydrothiopyranyl, which ring is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(a) —C1-6alkyl, which is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(i) halo,(ii) —ORa,(iii) —C3-6cycloalkyl,(iv) phenyl or heterocycle, wherein heterocycle is selected from pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl and morpholinyl, which phenyl or heterocycle is optionally substituted with 1-5 substituents each independently selected from the group consisting of:(I) —ORa,(II) halo,(III) —CN, and(IV) —C1-6alkyl which is optionally substituted with 1-6 halo,(v) —CO2Ra,(vi) —NRbRc,(vii) —S(O)vRd,(viii) —C(═O)NRbRc,(ix) —N(Rb)CO2R1, and(x) —N(Rb)SO2Rd,(b) phenyl or heterocycle, wherein said heterocycle is selected from pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, azetidinyl, piperazinyl, pyrrolidinyl, thienyl and morpholinyl, which phenyl or heterocycle is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(i) halo,(ii) —ORa,(iii) —CN, and(iv) —C1-6alkyl which is optionally substituted with 1-6 halo,(c) halo,(d) —S(O)vRd,(e) —ORa,(f) —CN,(g) —C(═O)Ra,(h) —NRbRc,(i) —C(═O)NRbRc,(j) —CO2Ra,(k) —(NRb)CO2Ra,(l) —O—(C═O)—NRbRc,(m) —(NRb)—(C═O)—NRbRc,(n) oxido,(o) oxo, and(p) —(NRb)SO2Rd; R4 and R5 are each independently selected from the group consisting of:
(1) hydrogen,(2) halo,(3) —ORa,(4) —C1-6alkyl, which is optionally substituted with 1-4 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —CN,(d) phenyl or heterocycle, wherein said heterocycle is selected from pyridyl, pyrimidinyl, thienyl, pyridazinyl, piperidinyl, azetidinyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and pyrazinyl, which phenyl or heterocycle is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(i) —ORa,(ii) halo,(iii) —CN and(iv) —C1-6alkyl which is optionally substituted with 1-6 halo,(5) phenyl or heterocycle wherein heterocycle is selected from pyridyl, pyrimidinyl, thienyl, pyridazinyl, piperidinyl, azetidinyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and pyrazinyl, which phenyl or heterocycle is optionally substituted with 1-5 substituents each independently selected from the group consisting of:
(a) halo,(b) —CN,(c) —ORa,(d) nitro and(e) —C1-6alkyl which is optionally substituted with 1-6 halo;or R4 and R5 and the atom to which they are attached join to form a 4-, 5-, or 6-membered ring optionally containing a heteroatom selected from N, O, and S, wherein the sulfur is optionally oxidized to the sulfone or sulfoxide, which ring is optionally substituted with 1-4 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —C1-6alkyl, which is optionally substituted with 1-6 halo, and(d) phenyl; Ra is selected from:
(1) hydrogen,(2) C1-6alkyl, which is optionally substituted with 1-7 substituents each independently selected from the group consisting of:
(a) halo,(b) —O—C1-6alkyl, which is optionally substituted with 1-6 halo,(c) hydroxyl,(d) —CN, and(e) phenyl or heterocycle wherein said heterocycle is selected from pyridyl, pyrimidinyl, thienyl, pyridazinyl, piperidinyl, azetidinyl, furanyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and pyrazinyl, which phenyl or heterocycle is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(i) halo,(ii) —O—C1-6alkyl, which is optionally substituted with 1-6 halo,(iii) —CN,(iv) nitro,(v) hydroxyl, and(vi) —C1-6alkyl, which is optionally substituted with 1-6 halo,(3) phenyl or heterocycle wherein said heterocycle is selected from pyridyl, pyrimidinyl, thienyl, pyridazinyl, piperidinyl, azetidinyl, furanyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and pyrazinyl, which phenyl or heterocycle is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(a) halo,(b) —CN,(c) —O—C1-6alkyl, which is optionally substituted with 1-6 halo,(d) nitro,(e) hydroxyl, and(f) —C1-6alkyl, which is optionally substituted with 1-6 halo, and(4) —C3-6cycloalkyl, which is optionally substituted with 1-6 halo; Rb and Rc are each independently selected from:
(1) hydrogen,(2) C1-6alkyl, which is optionally substituted with 1-7 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —CN,(d) —CO2Ra,(e) phenyl or heterocycle, wherein said heterocycle is selected from pyridyl, pyrimidinyl, thienyl, pyridazinyl, piperidinyl, azetidinyl, furanyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and pyrazinyl, which phenyl or heterocycle is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(i) halo,(ii) —ORa,(iii) —C1-6alkyl, which is optionally substituted with 1-6 halo, and(iv) nitro,(3) phenyl or heterocycle, wherein said heterocycle is selected from pyridyl, pyrimidinyl, thienyl, pyridazinyl, piperidinyl, azetidinyl, furanyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and pyrazinyl, which phenyl or heterocycle is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —C1-6alkyl, which is optionally substituted with 1-6 halo,(d) —C3-6cycloalkyl, which is optionally substituted with 1-6 halo,(e) —CN, and(f) —CO2Ra,(4) —C3-6cycloalkyl, which is optionally substituted with 1-6 halo;or Rb and Rc and the nitrogen atom to which they are attached join to form a 4-, 5-, or 6-membered ring optionally containing an additional heteroatom selected from N, O, and S, wherein the sulfur is optionally oxidized to the sulfone or sulfoxide, which ring is optionally substituted with 1-4 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa, and(c) —C1-6alkyl, which is optionally substituted with 1-6 halo, and(d) phenyl; Rd is selected from:
(1) C1-6alkyl, which is optionally substituted with 1-4 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —CO2Ra,(d) —CN, and(e) phenyl or heterocycle, wherein said heterocycle is selected from pyridyl, pyrimidinyl, thienyl, pyridazinyl, piperidinyl, azetidinyl, furanyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and pyrazinyl, which phenyl or heterocycle is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(i) halo,(ii) —ORa,(iii) —C1-6alkyl, which is optionally substituted with 1-6 halo, and(iv) nitro,(2) phenyl or heterocycle, wherein said heterocycle is selected from pyridyl, pyrimidinyl, thienyl, pyridazinyl, piperidinyl, azetidinyl, furanyl, piperazinyl, pyrrolidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl and pyrazinyl, which phenyl or heterocycle is optionally substituted with 1-3 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —C1-6alkyl, which is optionally substituted with 1-6 halo,(d) —C3-6cycloalkyl, which is optionally substituted with 1-6 halo(e) —CN, and—CO2Ra, and(3) —C3-6cycloalkyl, which is optionally substituted with 1-6 halo; Re and Rf are each independently selected from the group consisting of:
(1) hydrogen,(2) —C1-4alkyl, which is optionally substituted with 1-6 halo,(3) —ORa,(4) —CN,(5) halo,(6) phenyl, and(7) benzyl;or where Re and Rf and the carbon atom(s) to which they are attached join to form a 3-, 4-, 5-, or 6-membered ring optionally containing a heteroatom selected from N, O, and S, wherein the sulfur is optionally oxidized to the sulfone or sulfoxide, which ring is optionally substituted with 1-4 substituents each independently selected from the group consisting of:
(a) halo,(b) —ORa,(c) —C1-6alkyl, which is optionally substituted with 1-6 halo, and(d) phenyl; Rg and Rh are each independently selected from the group consisting of:
(1) hydrogen,(2) —C1-4alkyl, which is optionally substituted with 1-6 halo,(3) —ORa,(4) halo,(5) phenyl, and(6) benzyl; v is 0, 1, or 2; and pharmaceutically acceptable salts thereof. |
