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US 8,796,260 B2Granted
Imidazobenzazepine CGRP receptor antagonists
AssigneeMerck Sharp & Dohme Corp.
InventorsHoward G. Selnick, Ian M. Bell
Life of this patent
Estimating the term…
Abstract
Compounds of Formula I: I (where variables R1A, R1B, R2, R3, R4, A, and Z are as defined herein) useful as antagonists of CGRP receptors, and useful in the treatment or prevention of diseases in which CGRP receptors are involved, such as headache, and in particular 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 receptors are involved.
Claims12
A compound of formula (II):
- wherein:
- A is NR5 or C(R5)2;
- Z is selected from:
- and when A is NR5, Z is additionally selected from:
- R1A and R1B are independently selected from:
- 1) H, C1-C6 alkyl, C3-6 cycloalkyl and heterocycle, wherein said alkyl, cycloalkyl and heterocycle is optionally 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 R5,
- d) heteroaryl, unsubstituted or substituted with 1-5 substituents each independently selected from R5,
- e) heterocycle, unsubstituted or substituted with 1-5 substituents each independently selected from R5,
- f) (F)pC1-3 alkyl,
- g) halogen,
- h) OR5,
- i) O(CH2)sOR5,
- j) CO2R5,
- k) CN,
- l) NR10R11, and
- m) O(CO)R5;
- and
- 2) aryl or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more substituents independently selected from:
- a) C1-6 alkyl,
- b) C3-6 cycloalkyl,
- c) (F)pC1-3 alkyl,
- d) halogen,
- e) OR5,
- f) CO2R5,
- g) (CO)NR10R11,
- h) SO2NR10R11,
- i) N(R10) SO2R11,
- j) S(O)mR5,
- k) CN,
- l) NR10R11, and
- m) O(CO)R4;
- R4 is hydrogen, halo, C1-6alkyl, or C2-6 alkenyl;
- R5 is selected from:
- H, C1-6 alkyl, C3-6 cycloalkyl, aryl, heteroaryl and benzyl, wherein said alkyl, cycloalkyl, aryl or heteroaryl moiety is optionally substituted with halogen, hydroxy or C1-C6 alkoxy;
- R10 and R11 are independently selected from:
- H, C1-6 alkyl, C3-6 cycloalkyl, aryl, heteroaryl and benzyl, wherein said alkyl, cycloalkyl, aryl or heteroaryl moiety is optionally substituted with halogen, hydroxy or C1-C6 alkoxy, provided that when R10 and R11 are bonded to the same nitrogen atom, then R10 and R11 and the nitrogen to which they are both attached form a ring selected from:
- azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl, which ring is unsubstituted or substituted with 1-5 substituents each independently selected from R5;
- p is 0 to 2q+1, for a substituent with q carbons
- m is 0 to 2;
- s is 1 to 3
- or a pharmaceutically acceptable salt thereof, or individual stereoisomer thereof.
41 more elements
Dependencies are inferred from the claim text.