CGRP receptor antagonists

A compound of Formula I:

• wherein:
• Z is selected from:
• A is C(R2)2;
• B is (C(R2)2)n;
• D is selected from R1, OR1, N(R1)2, NR1C(O)R1, C(O)R1, S(O)mR1, C(O)OR1, C(O)N(R1)2, C(O)NR10R11, C(NR1)N(R1)2, and C(NR1)R1;
• R1 is independently selected from:
• 1) H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-6 cycloalkyl, and heterocycle, unsubstituted or substituted with one or more substituents each independently selected from:
• a) C1-6 alkyl,
• b) C3-6 cycloalkyl,
• c) aryl, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• e) heterocycle, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• f) (F)pC1-3 alkyl,
• g) halogen,
• h) OR4,
• i) O(CH2)s OR4,
• j) CO2R4,
• k) (CO)NR10R11,
• l) O(CO)NR10R11,
• m) N(R4)(CO)NR10R11,
• n) N(R10)(CO)R11,
• o) N(R10)(CO)OR11,
• p) SO2NR10R11,
• q) N(R10) SO2R11,
• r) S(O)mR10,
• s) CN,
• t) NR10R11,
• u) N(R10)(CO)NR4R11, and,
• v) O(CO)R4, and
• 2) aryl or heteroaryl, unsubstituted or substituted with one or more substituents each independently selected from:
• a) C1-6 alkyl,
• b) C3-6 cycloalkyl,
• c) aryl, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• e) heterocycle, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• f) (F)pC1-3 alkyl,
• g) halogen,
• h) OR4,
• i) O(CH2)sOR4,
• j) CO2R4,
• k) (CO)NR10R11,
• l) O(CO)NR10R11,
• m) N(R4)(CO)NR10R11,
• n) N(R10)(CO)R11,
• o) N(R10)(CO)OR11,
• p) SO2NR10R11,
• q) N(R10) SO2R11,
• r) S(O)mR10,
• s) CN,
• t) NR10R11,
• u) N(R10)(CO)NR4R11, and
• v) O(CO)R4;
• R1 can be optionally joined to R2 to form a 4-8 membered ring;
• R2 is independently selected from:
• 1) H, C0-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-6 cycloalkyl and heterocycle, unsubstituted or substituted with one or more substituents each independently selected from:
• a) C1-6 alkyl,
• b) C3-6 cycloalkyl,
• c) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R4,
• d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• e) heterocycle, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• f) (F)pC1-3 alkyl,
• g) halogen,
• h) OR4,
• i) O(CH2)sOR4,
• j) CO2R4,
• k) (CO)NR10R11,
• l) O(CO)NR10R11,
• m) N(R4)(CO)NR10R11,
• n) N(R10)(CO)R11,
• o) N(R10)(CO)OR11,
• p) SO2NR10R11,
• q) N(R10) SO2R11,
• r) S(O)mR10,
• s) CN,
• t) NR10R11,
• u) N(R10)(CO)NR4R11, and,
• v) O(CO)R4, and
• 2) aryl or heteroaryl, unsubstituted or substituted with one or more substituents each independently selected from:
• a) C1-6 alkyl,
• b) C3-6 cycloalkyl,
• c) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R4,
• d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• e) heterocycle, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• f) (F)pC1-3 alkyl,
• g) halogen,
• h) OR4,
• i) O(CH2)sOR4,
• j) CO2R4,
• k) (CO)NR10R11,
• l) O(CO)NR10R11,
• m) N(R4)(CO)NR10R11,
• n) N(R10)(CO)R11,
• o) N(R10)(CO)OR11,
• p) SO2NR10R11,
• q) N(R10)SO2R11,
• r) S(O)mR10,
• s) CN,
• t) NR10R11,
• u) N(R10)(CO)NR4R11, and
• v) O(CO)R4,
• where any two independent R2 on the same or adjacent atoms optionally join to form a ring selected from cyclobutyl, cyclopentenyl, cyclopentyl, cyclohexenyl, cyclohexyl, phenyl, naphthyl, thienyl, thiazolyl, thiazolinyl, oxazolyl, oxazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrimidyl, pyrazinyl, pyrrolyl, pyrrolinyl, morpholinyl, thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide, azetidinyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydropyridyl, furanyl, dihydrofuranyl, dihydropyranyl and piperazinyl;
• R10 and R11 are each independently selected from:
• H, C1-6 alkyl, (F)pC1-6 alkyl, C3-6 cycloalkyl, aryl, heteroaryl, and benzyl, unsubstituted or substituted with halogen, hydroxy or C1-C6 alkoxy, where R10 and R11 optionally join to form a ring selected from:
• azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, which is ring is unsubstituted or substituted with 1-5 substituents each independently selected from R4;
• R4 is independently selected from:
• H, C1-6 alkyl, (F)pC1-6 alkyl, C3-6 cycloalkyl, aryl, heteroaryl and benzyl, unsubstituted or substituted with halogen, hydroxy or C1-C6 alkoxy;
• W is O, NR4 or C(R4)2;
• X is C or S;
• Y is O, (R4)2, NCN, NSO2CH3 or NCONH2, or Y is O2 when X is S;
• R6 is independently selected from H and:
• a) C1-6 alkyl,
• b) C3-6 cycloalkyl,
• c) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R4,
• d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• e) heterocycle, unsubstituted or substituted with 1-5 substituents each independently selected from R4,
• f) (F)pC1-3 alkyl,
• g) halogen,
• h) OR4,
• i) O(CH2)sOR4,
• j) CO2R4,
• k) (CO)NR10R11,
• l) O(CO)NR10R11,
• m) N(R4)(CO)NR10R11,
• n) N(R10)(CO)R11,
• o) N(R10)(CO)OR11,
• p) SO2NR10R11,
• q) N(R10) SO2R11,
• r) S(O)mR10,
• s) CN,
• t) NR10R11,
• u) N(R10)(CO)NR4R11, and
• v) O(CO)R4;
• J is a bond, C(R6)2, O or NR6;
• V is selected from a bond, C(R6)2, O, S(O)m, NR6, C(R6)2—C(R6)2, C(R6)═C(R6), C(R6)2—N(R6), C(R6)═N, N(R6)—C(R6)2, N═C(R6), and N(R6)—N(R6);
• G-L is selected from:
• N, N—C(R6)2, C═C(R6), C═N, C(R6), C(R6)—C(R6)2, C(R6)—C(R6)2—C(R6)2, C═C(R6)—C(R6)2, C(R6)—C(R6)═C(R6), C(R6)—C(R6)2—N(R6), C═C(R6)—N(R6), C(R6)—C(R6)═N, C(R6)—N(R6)—C(R6)2, C═N—C(R6)2, C(R6)—N═C(R6), C(R6)—N(R6)—N(R6), C═N—N(R6), N—C(R6)2—C(R6)2, N—C(R6)═C(R6), N—C( R6)2—N(R6), N—C(R6)═N, N—N(R6)—C(R6)2 and N—N═C(R6);
• Q is selected from:
• (1) ═C(R7a)—,
• (2) —C(R7a)2—,
• (3) —C(═O)—,
• (4) —S(O)m—,
• (5) ═N—, and
• (6) —N(R7a)—;
• T is selected from:
• (1) ═C(R7b)—,
• (2) —C(R7b)2—,
• (3) —C(═O)—,
• (4) —S(O)m—,
• (5) ═N—, and
• (6) —N(R7b)—;
• R3 is independently selected from H, substituted or unsubstituted C1-C3 alkyl, F, CN and CO2R4;
• R7a and R7b are each independently selected from R2, where R7a and R7b and the atom or atoms to which they are attached optionally join to form a ring selected from C3-6 cycloalkyl, aryl, heterocycle, and heteroaryl, which ring is unsubstituted or substituted with 1-10 substituents each independently selected from R6;
• “heteroaryl” is a 5- to 7-membered monocyclic- or 9- to 10-membered fused bicyclic heterocyclic ring system which contains an aromatic ring, any ring of which may be saturated partially saturated, or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O and S, and wherein the N and S heteroatoms may optionally be oxidized, and the N may optionally be quaternized, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring;
• “heterocyclic” is a 5- to 7-membered monocyclic- or 8- to 11-membered bicyclic heterocyclic ring system which is either saturated or unsaturatated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O and S, and wherein the N and S heteroatoms may optionally be oxidized, and the N heteroatom may be optionally be quaternized, and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring;
• p is 0 to 2q+1, for a substituent with q carbons;
• m is 0,1 or 2;
• n is 1;
• s is 1,2 or 3;
• or a pharmaceutically acceptable salt or individual diastereomers thereof.