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US 2006/0135511 A1Published application
Benzodiazepine cgrp receptor antagonists
AssigneeMerck & Co., Inc.
InventorChristopher Burgey
Life of this patent
Estimating the term…
Abstract
The present invention is directed to compounds of Formula I: I (where variables R1?, R/ 2?, R3?, R 4?, R6?, R7?, G, J, Q, T, U, V, W, X and Y 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.
Claims57
A compounds of formula I:
- wherein:
- R is 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 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 where the substituents are independently selected from R4,
- e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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 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 where the substituents are independently selected from R4,
- e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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
- R2 is independently selected from H and:
- 1) C1-6 alkyl,
- 2) C3-6 cycloalkyl,
- 3) aryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R4,
- 4) heteroaryl, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R4,
- 5) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R4,
- 6) (F)pC1-3 alkyl,
- 7) halogen,
- 8) OR4.
- 9) O(CH2)sOR4,
- 10) CO2R4,
- 11) (CO)NR10R11,
- 12) O(CO)NR10R11,
- 13) N(R4)(CO)NR10R11,
- 14) N(R10)(CO)R11,
- 15) N(R10)(CO)OR11,
- 16) SO2NR10R11,
- 17) N(R10)SO2R11,
- 18) S(O)mR10,
- 19) CN,
- 20) NR10R11,
- 21) N(R10)(CO)NR4R 1, and
- 22) O(CO)R4;
- R7 is 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 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 where the substituents are independently selected from R4,
- e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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,
- v) O(CO)R4;
- and
- 2) aryl or heteroaryl, unsubstituted or substituted with one or more substituents 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 where the substituents are independently selected from R4,
- e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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)NR4R 1, and
- v) O(CO)R4;
- R4 is 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;
- R5 is independently selected from H, substituted or unsubstituted C1-C6 alkyl, C3-6 cycloalkyl, aryl, heteroaryl, OR4, N(R4)2, CO2R4 and (F)pC1-6 alkyl;
- 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;
- R3 is independently selected from H, substituted or unsubstituted C1-C3 alkyl, CN and CO2R4;
- 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 where the substituents are independently selected from R4,
- e) heterocycle, unsubstituted or substituted with 1-5 substituents where the substituents are 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)NR4R 1, and
- v) O(CO)R4;
- R10 and R11 are 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 may be joined together to form a ring selected from:
- azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl, which is unsubstituted or substituted with 1-5 substituents where the substituents are independently selected from R4;
- G-J is selected from:
- N, N—C(R5)2C═C(R5), C═N;
- C(R5), C(R5)—C(R5)2C(R5)—C(R5)2—C(R5)2, C═C(R5)—C(R5)2, C(R5)—C(R5)═C(R5), C(R5)—C(R5)2—N(R5), C═C(R5), C(R5)═N, C(R5)—N(R5)—C(R5)2, C═N—C(R5)2, C(R5)—N═C(R5), C(R5)—N(R5)—N(R5), C═N—N(R5), N—C(R5)2, —C(R5)2, N—C(R5)═C(R5), N—C(R5)2.—N(R5), N—C(R5)═N, N—N(R5)—C(R5)2 and N—N═C(R5);
- Q, T, U and V are each independently a carbon atom or a nitrogen atom wherein at least one but no more than three of Q, T, U and V are nitrogen atoms, and wherein when any of Q, T, U, or V is a carbon atom it is unsubstituted or substituted where the substituents are independently selected from R6;
- p is 0 to 2q+1, for a substituent with q carbons;
- m is 0, 1 or 2;
- n is 0 or 1;
- s is 1, 2 or 3;
- and pharmaceutically acceptable salts and individual diastereomers thereof.
160 more elements
A compound selected from:
- and pharmaceutically acceptable salts and individual diastereomers thereof.
Dependencies are inferred from the claim text.