US 8,148,390 B2Granted

Monocyclic anilide spirolactam CGRP receptor antagonists

AssigneeMerck Sharp & Dohme Corp.

InventorsCraig A. Stump, Ian M. Bell, Harold G. Selnick

Life of this patent

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Abstract

The present invention is directed to compounds of Formula I: (where variables A1, A2, B, J, K, m, n, R4, R5a, R5b and R5c are as defined herein) useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. 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.

Claims19

Dependent claims

A compound of the formula I:

wherein:
B is a heterocycle selected from the group consisting of:
wherein X1, X2, X3 and X4 are each carbon, and one of X1, X2, X3 and X4 present on B is spirally substituted to form a ring or ring system selected from:
indanyl, azaindanyl, 1,2,3,4-tetrahydronaphthalenyl, 5,6,7,8-tetrahydroquinolinyl, 5,6,7,8-tetrahydroisoquinolinyl, 2,3-dihydro-1-benzofuranyl, chromanyl, 3,4-dihydro-1H-isochromenyl, 2,3-dihydro-1-benzothiophenyl, thiochromanyl, 3,4-dihydro-1H-isothiochromenyl, 6,7,8,9-tetrahydro-5H-benzo[7]annulenyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 2,3,4,5-tetrahydro-1H-1-benzazepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 2,3,4,5-tetrahydro-1H-2-benzazepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1H-3-benzazepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, cycloheptyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, thiepanyl, oxepanyl and azepanyl,
which ring or ring system is unsubstituted or substituted with one or more substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-3 substituents where the substituents are independently selected from:
halo, hydroxy, —OC1-6alkyl, —C3-6cycloalkyl, —CO2R9, —NR10R11, —SO2R12, —CONR10aR11a, phenyl and heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, and morpholinyl,
(b) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, piperidinyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
halo, hydroxy, —CN, —C3-6cycloalkyl, —C1-6alkyl (which is unsubstituted or substituted with 1-6 fluoro), and —OC1-6alkyl (which is unsubstituted or substituted with 1-6 fluoro, halo, or hydroxyl),
(c) —SO2R12,
(d) hydroxy,
(e) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(f) —COR12,
(g) —NR10R11,
(h) halo,
(i) —CN,
(j) —CONR10aR11a,
(k) oxo, and
(l) —C3-6cycloalkyl,
and wherein the remaining members of the group X1, X2, X3 and X4 present on B are each independently unsubstituted or substituted with one or two substituents selected from R1 and R2, where:
R1 and R2 are each 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—C1-6alkyl,
(d) —C3-6cycloalkyl,
(e) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, 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:
—C1-6alkyl, —OC1-6alkyl, halo, hydroxy, trifluoromethyl, —CN, and —OCF3,
(f) —CO2R9, and
(g) —CONR10aR11a;
(2) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
halo, hydroxy, —OC1-6alkyl, trifluoromethyl and phenyl,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyrrolidinyl, thiazolyl, oxazolyl, piperidinyl 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) —OC1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(e) —C3-6cycloalkyl,
(f) phenyl which is unsubstituted or substituted with 1-5 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxyl and trifluoromethyl,
(g) —CO2R9,
(h) —NR10R11;
(i) —CONR10aR11a, and
(j) —SO2R12;
(4) halo,
(5) hydroxy,
(6) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(7) —CN,
(8) —CO2R9,
(9) —NR10R11;
(10) —SO2R12, and
(11) —CONR10aR11a;
or, wherein X1, X2, X3 and X4 are each carbon, and one of X1, X2, X3 and X4 present on B is —(C═O)—,
wherein another one of the members of the group X1, X2, X3 and X4 present on B is optionally spirally substituted to form a ring or ring system selected from:
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, indanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, azaindanyl, 1,2,3,4-tetrahydronaphthalenyl, 5,6,7,8-tetrahydroquinolinyl, 5,6,7,8-tetrahydroisoquinolinyl, 2,3-dihydro-1-benzofuranyl, chromanyl, 3,4-dihydro-1H-isochromenyl, 2,3-dihydro-1-benzothiophenyl, thiochromanyl, 3,4-dihydro-1H-isothiochromenyl, 6,7,8,9-tetrahydro-5H-benzo[7]annulenyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 2,3,4,5-tetrahydro-1H-1-benzazepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 2,3,4,5-tetrahydro-1H-2-benzazepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1H-3-benzazepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, thiepanyl, oxepanyl and azepanyl,
which ring or ring system is unsubstituted or substituted with one or more substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-3 substituents where the substituents are independently selected from:
halo, hydroxy, —OC1-6alkyl, —C3-6cycloalkyl, —CO2R9, —NR10R11, —SO2R12, —CONR10aR11a phenyl and heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, and morpholinyl,
(b) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, piperidinyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
halo, hydroxy, —CN, —C3-6cycloalkyl, —C1-6alkyl (which is unsubstituted or substituted with 1-6 fluoro), and —OC1-6alkyl (which is unsubstituted or substituted with 1-6 fluoro, halo, or hydroxyl),
(c) —SO2R12,
(d) hydroxy,
(e) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(f) —COR12,
(g) —NR10R11,
(h) halo,
(i) —CN,
(j) —CONR10aR11a,
(k) oxo, and
(l) —C3-6cycloalkyl,
and wherein the remaining members of the group X1, X2, X3 and X4 present on B are each independently unsubstituted or substituted with one or more substituents selected from R1 and R2 as defined,
A1 and A2 are each independently selected from:
(1) a bond, and
(2) —CR13R14—,
wherein one of A1 and A2 is optionally absent;
G1, G2, and G3 are each independently selected from:
(1) —C(R5)═,
(2) —N═, and
(3) —(N+—O−)═,
wherein at least two of G1, G2 and G3 are —C(R5)═;
J is independently selected from:
(1) ═C(R6a)—,
(2) —CR13R14—,
(3) —N(R15)—, and
(4) —C(═O)—;
Y is independently selected from:
(1) ═C(R6b)—,
(2) —CR13R14—,
(3) —C(═O)—,
(4) —SO2—,
(5) ═N—, and
(6) —N(R6b)—;
R4 is selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —C3-6cycloalkyl,
(c) —CF3, and
(d) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(3) —C3-6cycloalkyl,
(4) benzyl, and
(5) phenyl;
R5 is selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —OC1-6alkyl,
(d) —C3-6cycloalkyl,
(e) phenyl,
(f) —CONR10aR11a,
(g) —CO2R9, and
(h) —NR10R11,
(3) —C3-6cycloalkyl,
(4) phenyl, which is unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) —C1-4-alkyl, which is unsubstituted or substituted with 1-3 fluoro,
(b) halo,
(c) hydroxy, and
(d) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(5) halo,
(6) hydroxy,
(7) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(8) —CN,
(9) —CO2R9,
(10) —NR10R11,
(11) —SO2R12,
(12) —CONR10aR11a,
(13) —OCO2R9, and
(14) —(NR10a)CO2R9;
R6a and R6b are each independently selected from:
(1) hydrogen;
(2) —C1-4alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —O—C1-6alkyl,
(c) —C3-6cycloalkyl, and
(d) phenyl or heterocycle, wherein heterocycle is selected from:
imidazolyl, oxazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thiazolyl, thienyl, triazolyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy, trifluoromethyl and —OCF3,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyrrolidinyl, azetidinyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, tetrahydrofuryl, piperidinyl, and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) —C1-4alkyl which is unsubstituted or substituted with 1-5 fluoro,
(b) halo,
(c) hydroxy,
(d) —O—C1-4alkyl which is unsubstituted or substituted with 1-5 fluoro,
(e) —C3-6cycloalkyl, and
(f) phenyl,
(4) halo,
(5) hydroxy,
(6) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(7) —CN,
(8) —CO2R9,
(9) —NR10R11, and
(10) —CONR10aR11a;
or where R6a and R6b and the atom(s) to which they are attached are joined 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 unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl which is unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) hydroxy,
(iii) —O—C1-6alkyl,
(iv) —C3-6cycloalkyl,
(v) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, or morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
—C1-6 alkyl, —O—C1-6alkyl, halo, hydroxy, trifluoromethyl and —OCF3,
(vi) —CO2R9,
(vii) —NR10R11,
(viii) —SO2R12,
(ix) —CONR10aR11a, and
(x) —(NR10a)CO2R9,
(b) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, piperidinyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents are each independently selected from:
—C1-6alkyl which is unsubstituted or substituted with 1-6 fluoro, halo, hydroxy, —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro and —C3-6cycloalkyl,
(c) halo,
(d) —SO2R12,
(e) hydroxy,
(f) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(g) —CN,
(h) —COR12,
(i) —NR10R11,
(j) —CONR10aR11a,
(k) —CO2R9,
(l) —(NR10a)CO2R9,
(m) —O(CO)NR10aR11a,
(n) —(NR9)(CO)NR10aR11a, and
(o) oxo;
R7 is selected from:
(1) hydrogen;
(2) —C1-4alkyl, which is unsubstituted or substituted with 1-5 substituents where the substituents are each independently selected from:
(a) halo,
(b) —OC1-6alkyl,
(c) —C3-6cycloalkyl,
(d) phenyl or heterocycle, wherein heterocycle is selected from:
imidazolyl, oxazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thiazolyl, thienyl, triazolyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
—CN, —C1-6alkyl, —OC1-6alkyl, halo, hydroxy, trifluoromethyl and —OCF3,
(e) —COR12,
(f) —NR10R11,
(g) —CONR10aR11a,
(h) —CO2R9,
(i) —(NR10a)CO2R9,
(j) —O(CO)NR10aR11a,
(k) —(NR9)(CO)NR10aR11a,
(l) —CN, and
(m) hydroxy,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyrrolidinyl, azetidinyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, tetrahydrofuryl, piperidinyl, and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) —C1-4alkyl which is unsubstituted or substituted with 1-5 fluoro,
(b) halo,
(c) hydroxy,
(d) —OC1-6alkyl which is unsubstituted or substituted with 1-5 fluoro,
(e) —C3-6cycloalkyl, and
(f) phenyl, and
(g) —CN,
(4) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
halo, hydroxy, —OC1-6alkyl, trifluoromethyl and phenyl;
R9 is independently selected from:
(1) hydrogen,
(2) —C1-6 alkyl, which is unsubstituted or substituted with 1-6 substituents, substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —C3-6cycloalkyl, 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;
R10 and R11 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, and
(e) phenyl,
(3) —C4-6cycloalkyl,
(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) benzyl, 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, and
(d) trifluoromethyl,
(6) —COR9, and
(7) —SO2R12;
R10a and R11a 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,
(3) —C5-6cycloalkyl, 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,
(5) benzyl, 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, and
(d) trifluoromethyl,
or where R10a and R11a 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) —COR9, and
(8) —SO2R12;
R12 is selected from:
(1) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(2) —C3-6cycloalkyl,
(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;
R13 and R14 are each independently selected from:
(1) hydrogen,
(2) C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C3-6cycloalkyl,
(b) —OC1-6alkyl,
(c) halo,
(d) hydroxy, and
(e) phenyl,
(3) hydroxy, and
(4) halo;
R15 is selected from:
(1) hydrogen,
(2) —C1-6alkyl which is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected from:
(a) halo,
(b) hydroxy,
(c) —O—C1-6alkyl,
(d) —C3-6cycloalkyl,
(e) phenyl, and
(f) —NR10R11;
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, or thienyl, which is unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy, and
(e) trifluoromethyl;
m is 1;
and
n is 1;
or a pharmaceutically acceptable salt thereof and individual enantiomers and diastereomers thereof.

353 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/530,898Filed 7 Mar 2008 · us provisional application
Priority: 12 Mar 2007
Published: US 2010/0152216 A117 Jun 2010
Granted: 3 Apr 2012
Term ends: Not estimatedThe source records don’t support an estimate.

Classification27 codes

C07D 471/20
In which the condensed system contains three hetero rings: spiro-condensed systems
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 5/00
Drugs for disorders of the endocrine system

Family

Application60/906,399Us provisional application · filed 12 Mar 2007
US 2010/0152216 A1Pre-grant publication · published 17 Jun 2010
US 8,148,390 B2This patent

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

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Abstract

A compound of the formula I:

wherein:
B is a heterocycle selected from the group consisting of:
wherein X1, X2, X3 and X4 are each carbon, and one of X1, X2, X3 and X4 present on B is spirally substituted to form a ring or ring system selected from:
indanyl, azaindanyl, 1,2,3,4-tetrahydronaphthalenyl, 5,6,7,8-tetrahydroquinolinyl, 5,6,7,8-tetrahydroisoquinolinyl, 2,3-dihydro-1-benzofuranyl, chromanyl, 3,4-dihydro-1H-isochromenyl, 2,3-dihydro-1-benzothiophenyl, thiochromanyl, 3,4-dihydro-1H-isothiochromenyl, 6,7,8,9-tetrahydro-5H-benzo[7]annulenyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 2,3,4,5-tetrahydro-1H-1-benzazepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 2,3,4,5-tetrahydro-1H-2-benzazepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1H-3-benzazepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, cycloheptyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, thiepanyl, oxepanyl and azepanyl,
which ring or ring system is unsubstituted or substituted with one or more substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-3 substituents where the substituents are independently selected from:
halo, hydroxy, —OC1-6alkyl, —C3-6cycloalkyl, —CO2R9, —NR10R11, —SO2R12, —CONR10aR11a, phenyl and heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, and morpholinyl,
(b) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, piperidinyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
halo, hydroxy, —CN, —C3-6cycloalkyl, —C1-6alkyl (which is unsubstituted or substituted with 1-6 fluoro), and —OC1-6alkyl (which is unsubstituted or substituted with 1-6 fluoro, halo, or hydroxyl),
(c) —SO2R12,
(d) hydroxy,
(e) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(f) —COR12,
(g) —NR10R11,
(h) halo,
(i) —CN,
(j) —CONR10aR11a,
(k) oxo, and
(l) —C3-6cycloalkyl,
and wherein the remaining members of the group X1, X2, X3 and X4 present on B are each independently unsubstituted or substituted with one or two substituents selected from R1 and R2, where:
R1 and R2 are each 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—C1-6alkyl,
(d) —C3-6cycloalkyl,
(e) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, 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:
—C1-6alkyl, —OC1-6alkyl, halo, hydroxy, trifluoromethyl, —CN, and —OCF3,
(f) —CO2R9, and
(g) —CONR10aR11a;
(2) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
halo, hydroxy, —OC1-6alkyl, trifluoromethyl and phenyl,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyrrolidinyl, thiazolyl, oxazolyl, piperidinyl 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) —OC1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(e) —C3-6cycloalkyl,
(f) phenyl which is unsubstituted or substituted with 1-5 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxyl and trifluoromethyl,
(g) —CO2R9,
(h) —NR10R11;
(i) —CONR10aR11a, and
(j) —SO2R12;
(4) halo,
(5) hydroxy,
(6) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(7) —CN,
(8) —CO2R9,
(9) —NR10R11;
(10) —SO2R12, and
(11) —CONR10aR11a;
or, wherein X1, X2, X3 and X4 are each carbon, and one of X1, X2, X3 and X4 present on B is —(C═O)—,
wherein another one of the members of the group X1, X2, X3 and X4 present on B is optionally spirally substituted to form a ring or ring system selected from:
cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, indanyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, azaindanyl, 1,2,3,4-tetrahydronaphthalenyl, 5,6,7,8-tetrahydroquinolinyl, 5,6,7,8-tetrahydroisoquinolinyl, 2,3-dihydro-1-benzofuranyl, chromanyl, 3,4-dihydro-1H-isochromenyl, 2,3-dihydro-1-benzothiophenyl, thiochromanyl, 3,4-dihydro-1H-isothiochromenyl, 6,7,8,9-tetrahydro-5H-benzo[7]annulenyl, 2,3,4,5-tetrahydro-1-benzoxepinyl, 2,3,4,5-tetrahydro-1H-1-benzazepinyl, 2,3,4,5-tetrahydro-1-benzothiepinyl, 1,3,4,5-tetrahydro-2-benzoxepinyl, 2,3,4,5-tetrahydro-1H-2-benzazepinyl, 1,3,4,5-tetrahydro-2-benzothiepinyl, 1,2,4,5-tetrahydro-3-benzoxepinyl, 2,3,4,5-tetrahydro-1H-3-benzazepinyl, 1,2,4,5-tetrahydro-3-benzothiepinyl, morpholinyl, tetrahydropyranyl, tetrahydrofuranyl, thiepanyl, oxepanyl and azepanyl,
which ring or ring system is unsubstituted or substituted with one or more substituents each independently selected from:
(a) —C1-6alkyl, which is unsubstituted or substituted with 1-3 substituents where the substituents are independently selected from:
halo, hydroxy, —OC1-6alkyl, —C3-6cycloalkyl, —CO2R9, —NR10R11, —SO2R12, —CONR10aR11a phenyl and heterocycle, wherein said heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, and morpholinyl,
(b) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, piperidinyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
halo, hydroxy, —CN, —C3-6cycloalkyl, —C1-6alkyl (which is unsubstituted or substituted with 1-6 fluoro), and —OC1-6alkyl (which is unsubstituted or substituted with 1-6 fluoro, halo, or hydroxyl),
(c) —SO2R12,
(d) hydroxy,
(e) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(f) —COR12,
(g) —NR10R11,
(h) halo,
(i) —CN,
(j) —CONR10aR11a,
(k) oxo, and
(l) —C3-6cycloalkyl,
and wherein the remaining members of the group X1, X2, X3 and X4 present on B are each independently unsubstituted or substituted with one or more substituents selected from R1 and R2 as defined,
A1 and A2 are each independently selected from:
(1) a bond, and
(2) —CR13R14—,
wherein one of A1 and A2 is optionally absent;
G1, G2, and G3 are each independently selected from:
(1) —C(R5)═,
(2) —N═, and
(3) —(N+—O−)═,
wherein at least two of G1, G2 and G3 are —C(R5)═;
J is independently selected from:
(1) ═C(R6a)—,
(2) —CR13R14—,
(3) —N(R15)—, and
(4) —C(═O)—;
Y is independently selected from:
(1) ═C(R6b)—,
(2) —CR13R14—,
(3) —C(═O)—,
(4) —SO2—,
(5) ═N—, and
(6) —N(R6b)—;
R4 is selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —C3-6cycloalkyl,
(c) —CF3, and
(d) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(3) —C3-6cycloalkyl,
(4) benzyl, and
(5) phenyl;
R5 is selected from:
(1) hydrogen,
(2) —C1-6alkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —OC1-6alkyl,
(d) —C3-6cycloalkyl,
(e) phenyl,
(f) —CONR10aR11a,
(g) —CO2R9, and
(h) —NR10R11,
(3) —C3-6cycloalkyl,
(4) phenyl, which is unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) —C1-4-alkyl, which is unsubstituted or substituted with 1-3 fluoro,
(b) halo,
(c) hydroxy, and
(d) —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(5) halo,
(6) hydroxy,
(7) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(8) —CN,
(9) —CO2R9,
(10) —NR10R11,
(11) —SO2R12,
(12) —CONR10aR11a,
(13) —OCO2R9, and
(14) —(NR10a)CO2R9;
R6a and R6b are each independently selected from:
(1) hydrogen;
(2) —C1-4alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) halo,
(b) —O—C1-6alkyl,
(c) —C3-6cycloalkyl, and
(d) phenyl or heterocycle, wherein heterocycle is selected from:
imidazolyl, oxazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thiazolyl, thienyl, triazolyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
—C1-6alkyl, —O—C1-6alkyl, halo, hydroxy, trifluoromethyl and —OCF3,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyrrolidinyl, azetidinyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, tetrahydrofuryl, piperidinyl, and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) —C1-4alkyl which is unsubstituted or substituted with 1-5 fluoro,
(b) halo,
(c) hydroxy,
(d) —O—C1-4alkyl which is unsubstituted or substituted with 1-5 fluoro,
(e) —C3-6cycloalkyl, and
(f) phenyl,
(4) halo,
(5) hydroxy,
(6) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(7) —CN,
(8) —CO2R9,
(9) —NR10R11, and
(10) —CONR10aR11a;
or where R6a and R6b and the atom(s) to which they are attached are joined 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 unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C1-6alkyl which is unsubstituted or substituted with 1-3 substituents each independently selected from:
(i) halo,
(ii) hydroxy,
(iii) —O—C1-6alkyl,
(iv) —C3-6cycloalkyl,
(v) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thienyl, or morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-5 substituents each independently selected from:
—C1-6 alkyl, —O—C1-6alkyl, halo, hydroxy, trifluoromethyl and —OCF3,
(vi) —CO2R9,
(vii) —NR10R11,
(viii) —SO2R12,
(ix) —CONR10aR11a, and
(x) —(NR10a)CO2R9,
(b) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyridazinyl, pyrrolidinyl, azetidinyl, piperidinyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents are each independently selected from:
—C1-6alkyl which is unsubstituted or substituted with 1-6 fluoro, halo, hydroxy, —O—C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro and —C3-6cycloalkyl,
(c) halo,
(d) —SO2R12,
(e) hydroxy,
(f) —O—C1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(g) —CN,
(h) —COR12,
(i) —NR10R11,
(j) —CONR10aR11a,
(k) —CO2R9,
(l) —(NR10a)CO2R9,
(m) —O(CO)NR10aR11a,
(n) —(NR9)(CO)NR10aR11a, and
(o) oxo;
R7 is selected from:
(1) hydrogen;
(2) —C1-4alkyl, which is unsubstituted or substituted with 1-5 substituents where the substituents are each independently selected from:
(a) halo,
(b) —OC1-6alkyl,
(c) —C3-6cycloalkyl,
(d) phenyl or heterocycle, wherein heterocycle is selected from:
imidazolyl, oxazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, piperidinyl, piperazinyl, pyrrolidinyl, thiazolyl, thienyl, triazolyl and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
—CN, —C1-6alkyl, —OC1-6alkyl, halo, hydroxy, trifluoromethyl and —OCF3,
(e) —COR12,
(f) —NR10R11,
(g) —CONR10aR11a,
(h) —CO2R9,
(i) —(NR10a)CO2R9,
(j) —O(CO)NR10aR11a,
(k) —(NR9)(CO)NR10aR11a,
(l) —CN, and
(m) hydroxy,
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, thienyl, pyrrolidinyl, azetidinyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, tetrahydrofuryl, piperidinyl, and morpholinyl, which phenyl or heterocycle is unsubstituted or substituted with 1-3 substituents each independently selected from:
(a) —C1-4alkyl which is unsubstituted or substituted with 1-5 fluoro,
(b) halo,
(c) hydroxy,
(d) —OC1-6alkyl which is unsubstituted or substituted with 1-5 fluoro,
(e) —C3-6cycloalkyl, and
(f) phenyl, and
(g) —CN,
(4) —C3-6cycloalkyl, which is unsubstituted or substituted with 1-7 substituents each independently selected from:
halo, hydroxy, —OC1-6alkyl, trifluoromethyl and phenyl;
R9 is independently selected from:
(1) hydrogen,
(2) —C1-6 alkyl, which is unsubstituted or substituted with 1-6 substituents, substituents each independently selected from:
(a) halo,
(b) hydroxy,
(c) —OC1-6alkyl, which is unsubstituted or substituted with 1-5 halo,
(d) —C3-6cycloalkyl, 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;
R10 and R11 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, and
(e) phenyl,
(3) —C4-6cycloalkyl,
(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) benzyl, 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, and
(d) trifluoromethyl,
(6) —COR9, and
(7) —SO2R12;
R10a and R11a 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,
(3) —C5-6cycloalkyl, 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,
(5) benzyl, 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, and
(d) trifluoromethyl,
or where R10a and R11a 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) —COR9, and
(8) —SO2R12;
R12 is selected from:
(1) —C1-6alkyl, which is unsubstituted or substituted with 1-6 fluoro,
(2) —C3-6cycloalkyl,
(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;
R13 and R14 are each independently selected from:
(1) hydrogen,
(2) C1-6alkyl, which is unsubstituted or substituted with 1-5 substituents each independently selected from:
(a) —C3-6cycloalkyl,
(b) —OC1-6alkyl,
(c) halo,
(d) hydroxy, and
(e) phenyl,
(3) hydroxy, and
(4) halo;
R15 is selected from:
(1) hydrogen,
(2) —C1-6alkyl which is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected from:
(a) halo,
(b) hydroxy,
(c) —O—C1-6alkyl,
(d) —C3-6cycloalkyl,
(e) phenyl, and
(f) —NR10R11;
(3) phenyl or heterocycle, wherein heterocycle is selected from:
pyridyl, pyrimidinyl, pyrazinyl, or thienyl, which is unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from:
(a) —C1-6alkyl,
(b) —O—C1-6alkyl,
(c) halo,
(d) hydroxy, and
(e) trifluoromethyl;
m is 1;
and
n is 1;
or a pharmaceutically acceptable salt thereof and individual enantiomers and diastereomers thereof.

353 more elements

Facts

Application

12/530,898Filed 7 Mar 2008 · us provisional application

Priority

12 Mar 2007

Published

US 2010/0152216 A117 Jun 2010

Granted

3 Apr 2012

Term ends

Not estimatedThe source records don’t support an estimate.

Classification27 codes

C07D 471/20
In which the condensed system contains three hetero rings: spiro-condensed systems
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
A61P 5/00
Drugs for disorders of the endocrine system