CGRP antagonists

1. A compound according to Formula I

or a pharmaceutically acceptable salt thereof,

wherein:

V is (R 1 )(R 2 )NCOCH(R 4 )NH where the carbon bearing R 4 has an absolute configuration of either R or S;

R 4 is C 1-6 alkyl substituted in the ω-position with amino, formylamino, C 1-6 alkylamino, C 1-6 dialkylamino, C 1-6 alkoxycarbonylamino, C 1-6 alkanoylamino, or benzyloxycarbonylamino;

R 1 and R 2 together with the nitrogen to which they are attached form X,

wherein X is azetidinyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, pyrazolinyl, pyrazolidinyl, azepinyl, diazepinyl, piperazinyl, piperidinyl, morpholino or thiomorpholino;

 wherein X is optionally substituted with Y, wherein Y is dioxolanyl, C 1-9 alkyl, C 2-9 alkenyl, C 2-9 alkynyl, C 1-4 alkylamino, C 1-4 dialkylamino, C 1-4 alkoxy, C 3-7 cycloalkyl, phenyl, azetidinyl, furanyl, thienyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, pyrrolidinonyl, imidazolyl, imidazolinyl, imidazolidinyl, imidazolidinonyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, azepinyl, diazepinyl, pyridyl, pyrimidinyl, dihydrobenzimidazolonyl, piperazinyl, piperidinyl, morpholino, benzothiazolyl, benzisothiazolyl or thiomorpholino;

 and wherein X and Y are optionally interrupted with Z, wherein Z is NHC(O)O, NHC(O)NH, NC(O)NH 2 , NH, C 1-3 alkylene, C 1-3 alkylene, C 1-3 alkenylene-NHC(O)O—C 1-3 alkylene; and optionally and independently substituted with 1 or 2 of the same or different substituents selected from the group consisting of C 1-4 alkyl, amino, C 1-3 alkylamino, [(C 1-3 alkyl) 2 amino]C 1-6 alkyl, (C 1-3 alkyl) 0-2 ureido, phenyl and benzyl;

 X and Y optionally and independently contain 1 or 2 carbonyls wherein the carbon atom of said carbonyl is a member of the heterocycles comprising X and Y;

Q is Q′ or Q″;

wherein

Q′ is (S y ) s R 3 ; and

Q″ is NH(S y ) s R 3 , NHC(O)(S y ) s R3, NHC(O)O(S y ) s R 3 , NHC(O)NH(S y ) s R 3 , O(S y ) s R 3 , (S y ) s NHR 3 , (S y ) s NHC(O)R 3 , (S y ) s NHC(O)OR 3 , (S y ) s NHC(O)NHR 3 or (S y ) s OR 3 ; wherein S y is C 1-3 alkylene or C 1-3 alkylidene and s is 0 or 1;

U is CH 2 , O, or NH, provided that if Q is Q″, then U is CH 2 ;

R 3 is indazolyl, benzotriazolyl, benzooxazolinonyl;

and wherein R 3 is optionally substituted with 1 to 3 of the same or different substituents selected from the group consisting of benzyl, phenyl, phenoxy, (C 1-4 )phenylalkoxy, (C 1-3 )benzoylalkyl, cyano, amino, nitro, halo, C 1-6 alkyl, (C 1-3 )haloalkyl, (C 1-3 )haloalkoxy, (C 1-3 )alkylamine, (C 1-3 )dialkylamine, OR 3′ , C(O)R 3′ , C(O)OR 3′ , OC(O)R 3′ , N(R 3′ ) 2 , C(O)N(R 3′ ) 2 , N(R 3′ )C(O)(R 3′ ) 2 , N(R 3′ )C(O)N(R 3′ ) 2 , N(R 3′ )C(O)OR 3′ , OC(O)N(R 3′ ) 2 , N(R 3′ )SO 2 R 3′ , SO 2 N(R 3′ ) 2 and SO 2 R 3′ ;

R 3′ is H or C 1-6 alkyl, provided that if R 3a is C(O)R 3′ , CHC(O)OR 3′ , CH(CH 3 )C(O)OR 3′ or C(O)OR 3′ , then said C(O)R 3′ , CHC(O)OR 3′ , CH(CH 3 )C(O)OR 3′ or C(O)OR 3′ are unsubstituted;

D is O;

A is CH;

m and n are independently 1;

E is N, CH or C;

p is 1;

G, J and E together form A x where

A x is a fused heterocycle having two fused rings with 5 to 7 members in each of said rings, said heterocycle containing one to four of the same or different heteroatoms selected from the group consisting of O, N and S and optionally containing 1 or 2 carbonyls wherein the carbon atom of said carbonyl is a member of said fused heterocycle;

wherein A x is optionally substituted with C 1-4 alkyl, C 1-4 alkoxy, C 1-4 haloalkyl, cyano, C 3-7 cycloalkyl, phenyl, halophenyl, halo, furanyl, pyrrolyl, pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, pyridyl, pyrimidinyl, piperidinyl, piperazinyl or morpholine.

2. A compound of claim 1 where the carbon bearing R 4 is of the (S) configuration.

3. A compound of claim 1 where X is piperazinyl or piperidinyl and Y is pyridinyl or piperidinyl.

4. A compound of claim 1 where R 4 is C 1-6 alkyl substituted in the ω-position with amino, C 1-6 alkylamino, C 1-6 dialkylamino, C 1-6 alkoxycarbonylamino, or C 1-6 alkanoylamino.

5. A compound of claim 1 where R 4 is aminobutyl or (t-butoxycarbonylamino)butyl.

6. A compound of claim 1 where Q is (S y ) n R 3 .

7. A compound of claim 1 where Q is (indazolyl)methyl, (benzotriazolyl)methyl, or (benzoxazolinonyl)methyl optionally substituted with 1 to 3 of the same or different substituents selected from the group consisting of halo, cyano, or C 1-2 alkyl, or C 1-2 halolkyl.

8. A compound of claim 1 where U is NH.

9. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

10. A method of treating migraine in a patient in need thereof comprising the administration of an antimigraine effective amount of a compound of claim 1 .