US 8,569,291 B2Granted

Bicyclic dihydroimidazolone CGRP receptor antagonists

AssigneeMerck Sharp & Dohme Corp.

InventorCraig A. Stump

Life of this patent

Estimating the term…

Abstract

Compounds of formula (I): wherein variables B, G1, G2, G3, G4, Ea, Eb, Ec, A1, A2, A3, A4, R6 and RPG and Y are as described herein, which are antagonists of CGRP receptors and which are useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved.

Claims9

Dependent claims

A compound of formula ID:

wherein:
B is a heterocycle selected from the group consisting of:
wherein T, U, V, and W are each independently a carbon atom or a nitrogen atom, wherein no more than two of T, U, V and W are nitrogen atoms;
wherein X is selected from:
(1) —O—,
(2) —S(O)q—,
(3) —Si(ORa)—C1-4alkyl-, where alkyl is unsubstituted or substituted with 1-5 halo,
(4) —Si(C1-4alkyl)2, where each alkyl is independently unsubstituted or substituted with 1-5 halo-,
(5) —N(R8)—,
(6) —(C═O)—,
(7) —C(R8)(Ra)—,
(8) —C(N(Rb)—SO2Rd)(Ra)—,
(9) —C(N(Rb)(C═O)Ra)(Ra)—,
(10) —C(N(Rb)(C═O)ORa)(Ra)—,
(11) —CR10R11—,
(12) —N(R11)—, and
(13) —CR3R4—;
B is unsubstituted or substituted with 1-7 substituents each independently selected from R1, R2, R3, R4, R10, and R11, wherein R1, R2, and R3 are independently selected from:
(1) —C1-6alkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —O—C1-6 alkyl,
(d) —C3-6 cycloalkyl,
(e) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, oxazolyl, thiazolyl, thienyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy, trifluoromethyl and —OCF3,
(f) —CO2R19
(g) —NR20R21,
(h) —SO2R22,
(i) —CONR20aR21a,
(j) trifluoromethyl,
(k) —OCO2R19,
(l) —(NR20a)CO2R19,
(m) —O(CO)NR20aR21a,
(n) —(NR19)(CO)NR20aR21a, and
(o) —O—C3-6cycloalkyl,
(2) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —O—C1-6alkyl,
(d) trifluoromethyl,
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy and trifluoromethyl,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, tetrazolyl, azepanyl, benzimidazolyl, benzopyranyl, benzofuryl, benzothiazolyl, benzoxazolyl, chromanyl, furyl, imidazolinyl, indolinyl, indolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, isoindolinyl, tetrahydroisoquinolinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, pyrazolidinyl, pyrazolyl, pyrrolyl, quinazolinyl, tetrahydrofuryl, thiazolinyl, purinyl, naphthyridinyl, quinoxalinyl, 1,3-dioxolanyl, oxadiazolyl, piperidinyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(b) halo,
(c) hydroxy,
(d) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(e) —C3-6cycloalkyl,
(f) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, or morpholinyl,
which is unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy and trifluoromethyl,
(g) —CO2R19,
(h) —(CO)R19,
(i) —NR20R21,
(j) —CONR20R21,
(k) oxo, and
(l) —S(O)qR22,
(4) halo,
(5) oxo,
(6) hydroxy,
(7) —O—C1-6alkyl which is unsubstituted or substituted with 1-5 halo,
(8) —CN,
(9) —CO2R19,
(10) —NR20R21,
(11) —SO2R22,
(12) —CONR20aR21a,
(13) —OCO2R19,
(14) —(NR20a)CO2R19,
(15) —O(CO)NR20aR21a,
(16) —(NR19)(CO)NR20aR21a,
(17) —(CO)—(CO)NR20aR21a,
(18) —(CO)—(CO)OR19,
(19) —SO2NR20aR21a, and
(20) hydrogen;
or R3 and R4 and the carbon atom to which they are attached join to form a ring selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, dioxolanyl, dioxanyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiapyranyl, oxetanyl, thietanyl and tetrahydrothienyl, wherein the sulfur is optionally oxidized to the sulfone or sulfoxide, which ring is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6allcyl, which is unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —ORa,
(iii) —C3-6cycloalkyl,
(iv) —CO2Ra,
(v) —NRbRc,
(vi) —S(O)qRd,
(vii) —C(═O)NRbRc, and
(viii) phenyl,
(b) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperdinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, wherein the phenyl or heterocycle is optionally fused to the ring, and which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —ORa,
(iv) —CO2Ra,
(v) —O(C═O)Ra,
(vi) —CN,
(vii) —NRbRc,
(viii) oxo,
(ix) —C(═O)NRbRc,
(x) —N(Rb)C(═O)Ra,
(xi) —N(Rb)CO2Ra,
(xii) —O(C═O)NRbRc, and
(xiii) —S(O)qRd,
(c) —ORa,
(d) halo,
(a) —CO2Ra,
(b) —C(═O)NRbRc,
(c) —S(O)qRd,
(d) —CN,
(e) —NRbRc,
(f) —N(Rb)C(═O)Ra,
(g) —N(Rb)SO2Rd,
(h) —O—CO2Rd,
(i) —O—(C═O)—NRbRc,
(j) —NRb—(C═O)—NRbRc,
(k) —C(═O)Ra, and
(l) oxo;
R4 is independently selected from:
(1) hydrogen,
(2) —C(═O)Ra,
(3) —CO2Ra,
(4) —S(═O)Rd,
(5) —SO2Rd,
(6) —C(═O)NRbRc,
(7) —C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl,
(d) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6 alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —ORa,
(iv) —NRbRc,
(v) —C(═O)Ra,
(vi) —CO2Ra, and
(vii) oxo;
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —CF3,
(m) —O—CO2Rd,
(n) —O—(C═O)—NRbRc,
(o) —NRb—(C═O)—NRbRc, and
(p) —C(═O)Ra;
(8) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —ORa, and
(d) C1-6alkyl, which is unsubstituted or substituted with 1-6 halo;
R6 is selected from:
(1) hydrogen;
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) halo,
(b) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(c) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 fluoro, and
(d) phenyl or heterocycle, wherein heterocycle is selected from:
azepinyl, azepanyl, azetidinyl, benzimidazolyl, benzisoxazolyl, benzofuranyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, benzopyrazolyl, benzotriazolyl, dibenzofuranyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, furanyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, morpholinyl, naphthyridinyl, oxazolyl, oxadiazolyl, 2-oxoazepinyl, 4-oxonaphthyridinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxopyridyl, 2-oxoquinolinyl, piperidyl, piperazinyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridazinyl, pyridinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydrofuranyl, tetrahydrofuryl, tetrahydroimidazopyridinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, thienyl, isoxazolyl, tetrahydrothienyl, tetrahydropyranyl, oxetanyl, tetrahydrothiapyranyl, thietanyl, and triazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy, trifluoromethyl, —CN, and —OCF3,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
azepinyl, azepanyl, azetidinyl, benzimidazolyl, benzisoxazolyl, benzofuranyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, benzopyrazolyl, benzotriazolyl, dibenzofuranyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, furanyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, morpholinyl, naphthyridinyl, oxazolyl, oxadiazolyl, 2-oxoazepinyl, 4-oxonaphthyridinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxopyridyl, 2-oxoquinolinyl, piperidyl, piperazinyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridazinyl, pyridinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydrofuranyl, tetrahydrofuryl, tetrahydroimidazopyridinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, thienyl, isoxazolyl, tetrahydrothienyl, tetrahydropyranyl, oxetanyl, tetrahydrothiapyranyl, thietanyl, and triazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 fluoro,
(d) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —CN,
(iii) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo, and
(iv) —ORa,
(a) —CO2Ra,
(f) —C(═O)NRbRc,
(a) —S(O)qRd,
(b) —CN,
(c) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —O—CO2Rd,
(m) —O—(C═O)—NRbRc,
(n) —NRb—(C═O)—NRbRc,
(o) —C(═O)Ra, and
(p) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(4) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(5) —CN,
(6) —CO2R19,
(7) —NR20R21, and
(8) —CONR20aR21a
(9) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —ORa, and
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents where the substituents are each independently selected from:
(i) —ORa,
(ii) halo,
(iii) —CN, and
(iv) —C1-6allcyl, which is unsubstituted or substituted with 1-5 halo,
R8 is selected from:
(1) hydrogen,
(2) —C(═O)Ra,
(3) —CO2Ra,
(4) —S(═O)Rd,
(5) —SO2Rd,
(6) —C(═O)NRbRc,
(7) —C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl,
(d) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6allcyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —ORa,
(iv) —NRbRc,
(v) —C(═O)Ra,
(vi) —CO2Ra,
(vii) oxo, and
(viii) —CN,
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —CF3,
(m) —O—CO2Rd,
(n) —O—(C═O)—NRbRc,
(o) —NRb—(C═O)—NRbRc, and
(p) —C(═O)Ra,
(8) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —ORa, and
(d) C1-6alkyl, which is unsubstituted or substituted with 1-6 halo;
or R4 and R8 and the atoms to which they are attached join to form a 4-, 5-, 6- or 7-membered alkyl- or heteroalkyl-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 unsubstituted or substituted with 1-4 substituents each independently selected from:
(a) halo,
(b) phenyl, which is unsubstituted or substituted with 1-3 substituents each independently selected from:
halo, ORa, CN, and —C(═O)ORa,
(c) —ORa, and
(d) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo;
R10 is selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —CN,
(d) phenyl, and
(e) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo;
R11 is selected from the group consisting of:
phenyl, naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, azepinyl, azepanyl, azetidinyl, benzimidazolyl, benzisoxazolyl, benzofuranyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, benzopyrazolyl, benzotriazolyl, chromanyl, cinnolinyl, dibenzofuranyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, furanyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, morpholinyl, naphthyridinyl, oxazolyl, oxadiazolyl, 2-oxoazepinyl, 4-oxonaphthyridinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxopyridyl, 2-oxoquinolinyl, piperidyl, piperazinyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridazinyl, pyridinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydrofuranyl, tetrahydrofuryl, tetrahydroimidazopyridinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, thienyl, triazolyl, isoxazolyl, tetrahydrothienyl, tetrahydropyranyl, oxetanyl, tetrahydrothiapyranyl, and thietanyl, where R11 is unsubstituted or substituted with 1-5 substituents each independently selected from R12, R13, R14, R15a and R15b;
R12, R13, R14, R15a and R15b are each independently selected from:
(1) —C1-6allcyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl,
(d) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperdinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo, and
(iii) —ORa,
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —CF3,
(m) —O—CO2Rd,
(n) —O—(C═O)—NRbRc,
(o) —NRb—(C═O)—NRbRc, and
(p) —C(═O)Ra,
(2) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —ORa, and
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents where the substituents are each independently selected from:
(i) —ORa,
(ii) halo,
(iii) —CN, and
(iv) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(3) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperdinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(d) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo, and
(iii) —ORa,
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —O—CO2Rd,
(m) —O—(C═O)—NRbRc,
(n) —NRb—(C═O)—NRbRc,
(o) —C(═O)Ra, and
(p) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(4) halo,
(5) oxo,
(6) —ORa,
(7) —CN,
(8) —CO2Ra,
(9) —C(═O)Ra,
(10) —NRbRc,
(11) —S(O),:iRd,
(12) —C(═O)NRbRc,
(13) —O—CO2Rd,
(14) —N(Rb)CO2Rd,
(15) —O—(C═O)—NRbRc,
(16) —NRb—(C═O)—NRbRc,
(17) —SO2NRbRc,
(18) —N(Rb)SO2Rd,
or R15a and R15b and the atom(s) to which they are attached join to form a ring selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thietanyl and tetrahydrothienyl, wherein the sulfur is optionally oxidized to the sulfone or sulfoxide, which ring is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6allcyl, which is unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —ORa,
(iii) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(iv) —CO2Ra,
(v) —NRbRc,
(vi) —S(O)qRd,
(vii) —C(═O)NRbRc, and
(viii) phenyl,
(b) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6allcyl, which is unsubstituted or substituted with 1-5 halo, and
(iii) —ORa,
(c) —ORa,
(d) halo,
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —O—CO2Rd,
(m) —O—(C═O)—NRbRc,
(n) —NRb—(C═O)—NRbRc, and
(o) —C(═O)Ra;
R19 is selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-6 substituents, each independently selected from:
(a) halo,
(b) hydroxy,
(c) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo, and
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) —C1-4alkyl,
(ii) —OC1-6alkyl,
(iii) halo,
(iv) trifluoromethyl, and
(v) —OCF3,
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 substituents, substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo, and
(e) phenyl,
(4) phenyl or heterocycle, wherein heterocycle is selected from:
pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, thienyl, pyrrolidinyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, tetrazolyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, imidazolinyl, indolinyl, indolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, isoindolinyl, tetrahydroisoquinolinyl, tetrahydrofuryl, quinoxalinyl, piperidinyl, piperazinyl, and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo
(c) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo
(d) —C3-6cycloalkyl,
(e) oxo,
(f) —CN,
(g) hydroxy, and
(h) phenyl;
R20 and R21 are each independently selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —OCF3,
(d) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo, and
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(ii) —OC1- 6alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —CN,
(iv) halo, and
(v) trifluoromethyl,
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(4) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(b) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3, and
(g) —CN,
(5) —COR19, and
(6) —SO2R22;
R20a and R21a are each independently selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(b) halo,
(c) hydroxy,
(d) —OCF3,
(e) —C3-6cycloalkyl, and
(f) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(ii) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —CN
(iv) halo, and
(v) trifluoromethyl,
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-5 halo,
(4) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(b) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3, and
(g) —CN,
or where R20a and R21a join to form a ring selected from azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, piperazinyl and morpholinyl, which ring is unsubstituted or substituted with 1-5 substituents each independently selected from:
(1) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(2) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(3) halo,
(4) hydroxy,
(5) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-4alkyl, which is unsubstituted or substituted with 1-3 halo,
(b) —O—C1-4alkyl, which is unsubstituted or substituted with 1-3 halo, and
(c) halo,
(6) benzyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-4alkyl, which is unsubstituted or substituted with 1-3 halo,
(b) —OC1-4alkyl, which is unsubstituted or substituted with 1-3 halo, and
(c) halo,
(7) —COR19, and
(8) —SO2R22;
R22 is selected from:
(1) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(2) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-5 halo,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(b) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3,
(g) —CN, and
(h) benzyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(ii) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) halo, and
(iv) trifluoromethyl;
Ra is independently selected from:
(1) hydrogen,
(2) C1-6alkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(a) halo,
(b) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(c) hydroxyl,
(d) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(e) —CN, and
(f) 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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(iii) —CN,
(iv) nitro,
(v) hydroxyl, and
(vi) —C1-6allcyl, which is unsubstituted or 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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(d) nitro,
(e) hydroxyl, and
(f) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo, and
(4) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo;
Rb and Rc are independently selected from:
(1) hydrogen,
(2) C1-6allcyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —ORa,
(iii) —C1-6alkyl, which is unsubstituted or 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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) halo,
(b)—ORa,
(c)—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(d)—C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(e)—CN, and
(f)—CO2Ra,
(4) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo;
or Rb and Rc and the nitrogen 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 unsubstituted or substituted with 1-4 substituents each independently selected from:
(i) halo,
(ii) —ORa, and
(iii) —C1-6allcyl, which is unsubstituted or substituted with 1-6 halo, and
(iv) phenyl;
Rd is independently selected from:
(1) C1-6allcyl, which is unsubstituted or substituted with 1-4 substituents each independently selected from:
(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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —ORa,
(iii) —C1-6allcyl, which is unsubstituted or 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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) halo,
(b)—ORa,
(c)—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(d)—C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(e) —CN, and
(f) —CO2Ra, and
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo;
q is 0, 1, or 2;
or a pharmaceutically acceptable salt thereof and individual enantiomers and diastereomers thereof.

524 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/119,534Filed 10 Sep 2009 · us provisional application
Priority: 18 Sep 2008
Published: US 2011/0224230 A115 Sep 2011
Granted: 29 Oct 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07D 417/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms,…
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/04
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00

Family

Application61/192,469Us provisional application · filed 18 Sep 2008
US 2011/0224230 A1Pre-grant publication · published 15 Sep 2011
US 8,569,291 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of formula ID:

wherein:
B is a heterocycle selected from the group consisting of:
wherein T, U, V, and W are each independently a carbon atom or a nitrogen atom, wherein no more than two of T, U, V and W are nitrogen atoms;
wherein X is selected from:
(1) —O—,
(2) —S(O)q—,
(3) —Si(ORa)—C1-4alkyl-, where alkyl is unsubstituted or substituted with 1-5 halo,
(4) —Si(C1-4alkyl)2, where each alkyl is independently unsubstituted or substituted with 1-5 halo-,
(5) —N(R8)—,
(6) —(C═O)—,
(7) —C(R8)(Ra)—,
(8) —C(N(Rb)—SO2Rd)(Ra)—,
(9) —C(N(Rb)(C═O)Ra)(Ra)—,
(10) —C(N(Rb)(C═O)ORa)(Ra)—,
(11) —CR10R11—,
(12) —N(R11)—, and
(13) —CR3R4—;
B is unsubstituted or substituted with 1-7 substituents each independently selected from R1, R2, R3, R4, R10, and R11, wherein R1, R2, and R3 are independently selected from:
(1) —C1-6alkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —O—C1-6 alkyl,
(d) —C3-6 cycloalkyl,
(e) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, oxazolyl, thiazolyl, thienyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy, trifluoromethyl and —OCF3,
(f) —CO2R19
(g) —NR20R21,
(h) —SO2R22,
(i) —CONR20aR21a,
(j) trifluoromethyl,
(k) —OCO2R19,
(l) —(NR20a)CO2R19,
(m) —O(CO)NR20aR21a,
(n) —(NR19)(CO)NR20aR21a, and
(o) —O—C3-6cycloalkyl,
(2) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —O—C1-6alkyl,
(d) trifluoromethyl,
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy and trifluoromethyl,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, imidazolyl, triazolyl, tetrazolyl, azepanyl, benzimidazolyl, benzopyranyl, benzofuryl, benzothiazolyl, benzoxazolyl, chromanyl, furyl, imidazolinyl, indolinyl, indolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, isoindolinyl, tetrahydroisoquinolinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, pyrazolidinyl, pyrazolyl, pyrrolyl, quinazolinyl, tetrahydrofuryl, thiazolinyl, purinyl, naphthyridinyl, quinoxalinyl, 1,3-dioxolanyl, oxadiazolyl, piperidinyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydrothiopyranyl, and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(b) halo,
(c) hydroxy,
(d) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(e) —C3-6cycloalkyl,
(f) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, or morpholinyl,
which is unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy and trifluoromethyl,
(g) —CO2R19,
(h) —(CO)R19,
(i) —NR20R21,
(j) —CONR20R21,
(k) oxo, and
(l) —S(O)qR22,
(4) halo,
(5) oxo,
(6) hydroxy,
(7) —O—C1-6alkyl which is unsubstituted or substituted with 1-5 halo,
(8) —CN,
(9) —CO2R19,
(10) —NR20R21,
(11) —SO2R22,
(12) —CONR20aR21a,
(13) —OCO2R19,
(14) —(NR20a)CO2R19,
(15) —O(CO)NR20aR21a,
(16) —(NR19)(CO)NR20aR21a,
(17) —(CO)—(CO)NR20aR21a,
(18) —(CO)—(CO)OR19,
(19) —SO2NR20aR21a, and
(20) hydrogen;
or R3 and R4 and the carbon atom to which they are attached join to form a ring selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, dioxolanyl, dioxanyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiapyranyl, oxetanyl, thietanyl and tetrahydrothienyl, wherein the sulfur is optionally oxidized to the sulfone or sulfoxide, which ring is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6allcyl, which is unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —ORa,
(iii) —C3-6cycloalkyl,
(iv) —CO2Ra,
(v) —NRbRc,
(vi) —S(O)qRd,
(vii) —C(═O)NRbRc, and
(viii) phenyl,
(b) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperdinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, wherein the phenyl or heterocycle is optionally fused to the ring, and which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —ORa,
(iv) —CO2Ra,
(v) —O(C═O)Ra,
(vi) —CN,
(vii) —NRbRc,
(viii) oxo,
(ix) —C(═O)NRbRc,
(x) —N(Rb)C(═O)Ra,
(xi) —N(Rb)CO2Ra,
(xii) —O(C═O)NRbRc, and
(xiii) —S(O)qRd,
(c) —ORa,
(d) halo,
(a) —CO2Ra,
(b) —C(═O)NRbRc,
(c) —S(O)qRd,
(d) —CN,
(e) —NRbRc,
(f) —N(Rb)C(═O)Ra,
(g) —N(Rb)SO2Rd,
(h) —O—CO2Rd,
(i) —O—(C═O)—NRbRc,
(j) —NRb—(C═O)—NRbRc,
(k) —C(═O)Ra, and
(l) oxo;
R4 is independently selected from:
(1) hydrogen,
(2) —C(═O)Ra,
(3) —CO2Ra,
(4) —S(═O)Rd,
(5) —SO2Rd,
(6) —C(═O)NRbRc,
(7) —C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl,
(d) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6 alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —ORa,
(iv) —NRbRc,
(v) —C(═O)Ra,
(vi) —CO2Ra, and
(vii) oxo;
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —CF3,
(m) —O—CO2Rd,
(n) —O—(C═O)—NRbRc,
(o) —NRb—(C═O)—NRbRc, and
(p) —C(═O)Ra;
(8) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —ORa, and
(d) C1-6alkyl, which is unsubstituted or substituted with 1-6 halo;
R6 is selected from:
(1) hydrogen;
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) halo,
(b) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(c) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 fluoro, and
(d) phenyl or heterocycle, wherein heterocycle is selected from:
azepinyl, azepanyl, azetidinyl, benzimidazolyl, benzisoxazolyl, benzofuranyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, benzopyrazolyl, benzotriazolyl, dibenzofuranyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, furanyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, morpholinyl, naphthyridinyl, oxazolyl, oxadiazolyl, 2-oxoazepinyl, 4-oxonaphthyridinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxopyridyl, 2-oxoquinolinyl, piperidyl, piperazinyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridazinyl, pyridinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydrofuranyl, tetrahydrofuryl, tetrahydroimidazopyridinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, thienyl, isoxazolyl, tetrahydrothienyl, tetrahydropyranyl, oxetanyl, tetrahydrothiapyranyl, thietanyl, and triazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy, trifluoromethyl, —CN, and —OCF3,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
azepinyl, azepanyl, azetidinyl, benzimidazolyl, benzisoxazolyl, benzofuranyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, benzopyrazolyl, benzotriazolyl, dibenzofuranyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, furanyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, morpholinyl, naphthyridinyl, oxazolyl, oxadiazolyl, 2-oxoazepinyl, 4-oxonaphthyridinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxopyridyl, 2-oxoquinolinyl, piperidyl, piperazinyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridazinyl, pyridinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydrofuranyl, tetrahydrofuryl, tetrahydroimidazopyridinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, thienyl, isoxazolyl, tetrahydrothienyl, tetrahydropyranyl, oxetanyl, tetrahydrothiapyranyl, thietanyl, and triazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 fluoro,
(d) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —CN,
(iii) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo, and
(iv) —ORa,
(a) —CO2Ra,
(f) —C(═O)NRbRc,
(a) —S(O)qRd,
(b) —CN,
(c) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —O—CO2Rd,
(m) —O—(C═O)—NRbRc,
(n) —NRb—(C═O)—NRbRc,
(o) —C(═O)Ra, and
(p) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(4) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(5) —CN,
(6) —CO2R19,
(7) —NR20R21, and
(8) —CONR20aR21a
(9) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —ORa, and
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents where the substituents are each independently selected from:
(i) —ORa,
(ii) halo,
(iii) —CN, and
(iv) —C1-6allcyl, which is unsubstituted or substituted with 1-5 halo,
R8 is selected from:
(1) hydrogen,
(2) —C(═O)Ra,
(3) —CO2Ra,
(4) —S(═O)Rd,
(5) —SO2Rd,
(6) —C(═O)NRbRc,
(7) —C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl,
(d) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6allcyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —ORa,
(iv) —NRbRc,
(v) —C(═O)Ra,
(vi) —CO2Ra,
(vii) oxo, and
(viii) —CN,
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —CF3,
(m) —O—CO2Rd,
(n) —O—(C═O)—NRbRc,
(o) —NRb—(C═O)—NRbRc, and
(p) —C(═O)Ra,
(8) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —ORa, and
(d) C1-6alkyl, which is unsubstituted or substituted with 1-6 halo;
or R4 and R8 and the atoms to which they are attached join to form a 4-, 5-, 6- or 7-membered alkyl- or heteroalkyl-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 unsubstituted or substituted with 1-4 substituents each independently selected from:
(a) halo,
(b) phenyl, which is unsubstituted or substituted with 1-3 substituents each independently selected from:
halo, ORa, CN, and —C(═O)ORa,
(c) —ORa, and
(d) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo;
R10 is selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —CN,
(d) phenyl, and
(e) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo;
R11 is selected from the group consisting of:
phenyl, naphthyl, tetrahydronaphthyl, indanyl, biphenyl, phenanthryl, anthryl, azepinyl, azepanyl, azetidinyl, benzimidazolyl, benzisoxazolyl, benzofuranyl, benzofurazanyl, benzopyranyl, benzothiopyranyl, benzofuryl, benzothiazolyl, benzothienyl, benzoxazolyl, benzopyrazolyl, benzotriazolyl, chromanyl, cinnolinyl, dibenzofuranyl, dihydrobenzofuryl, dihydrobenzothienyl, dihydrobenzothiopyranyl, dihydrobenzothiopyranyl sulfone, furyl, furanyl, imidazolidinyl, imidazolinyl, imidazolyl, indolinyl, indolyl, isochromanyl, isoindolinyl, isoquinolinyl, isothiazolidinyl, isothiazolyl, morpholinyl, naphthyridinyl, oxazolyl, oxadiazolyl, 2-oxoazepinyl, 4-oxonaphthyridinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxopyridyl, 2-oxoquinolinyl, piperidyl, piperazinyl, pyrazinyl, pyrazolidinyl, pyrazolyl, pyridazinyl, pyridinyl, pyridyl, pyrimidinyl, pyrimidyl, pyrrolidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrahydrofuranyl, tetrahydrofuryl, tetrahydroimidazopyridinyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, thiazolyl, thiazolinyl, thienofuryl, thienothienyl, thienyl, triazolyl, isoxazolyl, tetrahydrothienyl, tetrahydropyranyl, oxetanyl, tetrahydrothiapyranyl, and thietanyl, where R11 is unsubstituted or substituted with 1-5 substituents each independently selected from R12, R13, R14, R15a and R15b;
R12, R13, R14, R15a and R15b are each independently selected from:
(1) —C1-6allcyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl,
(d) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperdinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo, and
(iii) —ORa,
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —CF3,
(m) —O—CO2Rd,
(n) —O—(C═O)—NRbRc,
(o) —NRb—(C═O)—NRbRc, and
(p) —C(═O)Ra,
(2) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —ORa, and
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents where the substituents are each independently selected from:
(i) —ORa,
(ii) halo,
(iii) —CN, and
(iv) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(3) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperdinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —ORa,
(c) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(d) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo, and
(iii) —ORa,
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —O—CO2Rd,
(m) —O—(C═O)—NRbRc,
(n) —NRb—(C═O)—NRbRc,
(o) —C(═O)Ra, and
(p) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(4) halo,
(5) oxo,
(6) —ORa,
(7) —CN,
(8) —CO2Ra,
(9) —C(═O)Ra,
(10) —NRbRc,
(11) —S(O),:iRd,
(12) —C(═O)NRbRc,
(13) —O—CO2Rd,
(14) —N(Rb)CO2Rd,
(15) —O—(C═O)—NRbRc,
(16) —NRb—(C═O)—NRbRc,
(17) —SO2NRbRc,
(18) —N(Rb)SO2Rd,
or R15a and R15b and the atom(s) to which they are attached join to form a ring selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thietanyl and tetrahydrothienyl, wherein the sulfur is optionally oxidized to the sulfone or sulfoxide, which ring is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6allcyl, which is unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —ORa,
(iii) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(iv) —CO2Ra,
(v) —NRbRc,
(vi) —S(O)qRd,
(vii) —C(═O)NRbRc, and
(viii) phenyl,
(b) phenyl or heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, morpholinyl, thiazolyl and oxazolyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) halo,
(ii) —C1-6allcyl, which is unsubstituted or substituted with 1-5 halo, and
(iii) —ORa,
(c) —ORa,
(d) halo,
(e) —CO2Ra,
(f) —C(═O)NRbRc,
(g) —S(O)qRd,
(h) —CN,
(i) —NRbRc,
(j) —N(Rb)C(═O)Ra,
(k) —N(Rb)SO2Rd,
(l) —O—CO2Rd,
(m) —O—(C═O)—NRbRc,
(n) —NRb—(C═O)—NRbRc, and
(o) —C(═O)Ra;
R19 is selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-6 substituents, each independently selected from:
(a) halo,
(b) hydroxy,
(c) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo, and
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) —C1-4alkyl,
(ii) —OC1-6alkyl,
(iii) halo,
(iv) trifluoromethyl, and
(v) —OCF3,
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 substituents, substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo, and
(e) phenyl,
(4) phenyl or heterocycle, wherein heterocycle is selected from:
pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, thienyl, pyrrolidinyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, tetrazolyl, benzimidazolyl, benzothiazolyl, benzoxazolyl, imidazolinyl, indolinyl, indolyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, isoindolinyl, tetrahydroisoquinolinyl, tetrahydrofuryl, quinoxalinyl, piperidinyl, piperazinyl, and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo
(c) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo
(d) —C3-6cycloalkyl,
(e) oxo,
(f) —CN,
(g) hydroxy, and
(h) phenyl;
R20 and R21 are each independently selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —OCF3,
(d) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo, and
(e) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(ii) —OC1- 6alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —CN,
(iv) halo, and
(v) trifluoromethyl,
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(4) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(b) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3, and
(g) —CN,
(5) —COR19, and
(6) —SO2R22;
R20a and R21a are each independently selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-6 substituents each independently selected from:
(a) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(b) halo,
(c) hydroxy,
(d) —OCF3,
(e) —C3-6cycloalkyl, and
(f) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(ii) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) —CN
(iv) halo, and
(v) trifluoromethyl,
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-5 halo,
(4) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(b) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3, and
(g) —CN,
or where R20a and R21a join to form a ring selected from azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, piperazinyl and morpholinyl, which ring is unsubstituted or substituted with 1-5 substituents each independently selected from:
(1) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(2) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(3) halo,
(4) hydroxy,
(5) phenyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-4alkyl, which is unsubstituted or substituted with 1-3 halo,
(b) —O—C1-4alkyl, which is unsubstituted or substituted with 1-3 halo, and
(c) halo,
(6) benzyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-4alkyl, which is unsubstituted or substituted with 1-3 halo,
(b) —OC1-4alkyl, which is unsubstituted or substituted with 1-3 halo, and
(c) halo,
(7) —COR19, and
(8) —SO2R22;
R22 is selected from:
(1) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(2) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-5 halo,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(b) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(c) halo,
(d) hydroxy,
(e) trifluoromethyl,
(f) —OCF3,
(g) —CN, and
(h) benzyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(i) —C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(ii) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(iii) halo, and
(iv) trifluoromethyl;
Ra is independently selected from:
(1) hydrogen,
(2) C1-6alkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(a) halo,
(b) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(c) hydroxyl,
(d) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(e) —CN, and
(f) 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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(iii) —CN,
(iv) nitro,
(v) hydroxyl, and
(vi) —C1-6allcyl, which is unsubstituted or 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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) halo,
(b) —CN,
(c) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(d) nitro,
(e) hydroxyl, and
(f) —C1-6alkyl, which is unsubstituted or substituted with 1-6 halo, and
(4) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo;
Rb and Rc are independently selected from:
(1) hydrogen,
(2) C1-6allcyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —ORa,
(iii) —C1-6alkyl, which is unsubstituted or 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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) halo,
(b)—ORa,
(c)—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(d)—C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(e)—CN, and
(f)—CO2Ra,
(4) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo;
or Rb and Rc and the nitrogen 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 unsubstituted or substituted with 1-4 substituents each independently selected from:
(i) halo,
(ii) —ORa, and
(iii) —C1-6allcyl, which is unsubstituted or substituted with 1-6 halo, and
(iv) phenyl;
Rd is independently selected from:
(1) C1-6allcyl, which is unsubstituted or substituted with 1-4 substituents each independently selected from:
(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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) —ORa,
(iii) —C1-6allcyl, which is unsubstituted or 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 unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) halo,
(b)—ORa,
(c)—C1-6alkyl, which is unsubstituted or substituted with 1-6 halo,
(d)—C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo,
(e) —CN, and
(f) —CO2Ra, and
(3) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-6 halo;
q is 0, 1, or 2;
or a pharmaceutically acceptable salt thereof and individual enantiomers and diastereomers thereof.

524 more elements

Facts

Application

13/119,534Filed 10 Sep 2009 · us provisional application

Priority

18 Sep 2008

Published

US 2011/0224230 A115 Sep 2011

Granted

29 Oct 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification12 codes

C07D 417/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms,…
A61P 25/00
Drugs for disorders of the nervous system
A61P 25/04
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00