Piperidinone carboxamide spirohydantoin CGRP receptor antagonists

摘要

The present invention is directed to piperidinone carboxamide spirohydantoin derivatives which are antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as migraine. 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.

主权项

1. A compound of Formula I:or a pharmaceutically acceptable salt thereof, wherein:
R1 is selected from the group consisting of: C1-4alkyl, cyclopropylmethyl, cyclobutylmethyl and [1-(trifluoromethyl)cyclopropyl]methyl, each of which is optionally substituted with one to four substituents as allowed by valence independently selected from the group consisting of: F and hydroxy; R2 is hydrogen or methyl; when R2 is hydrogen then
R3 is selected from hydrogen, F or Cl;R4 is selected from hydrogen, F or Cl;R5 is hydrogen;R6 is selected from hydrogen or F; andR7 is selected from hydrogen, F or Cl;except that at least two of R3, R4, R6 and R7 must be F or Cl unless R3 is F in which case R4, R6 and R7 may all be hydrogen; and if R4 is Cl then R7 cannot be Cl; when R2 is methyl then
R3 is selected from hydrogen, methyl, F, Cl, or Br;R4 is selected from hydrogen, methyl, F or Cl;R5 is selected from hydrogen or F;R6 is selected from hydrogen or F; andR7 is selected from hydrogen, methyl, F or Cl;except that if R5 is F then at least three of R3, R4, R6 and R7 must be F; and if R4 is methyl or Cl then R7 cannot be methyl or Cl; and R8 is selected from the group consisting of: hydrogen, C1-4alkyl, cyclopropylmethyl, and cyclobutylmethyl, each of which is optionally substituted with one to three fluoro substituents as allowed by valence.