Claims for Patent: 8,754,096

Summary for Patent: 8,754,096

Title:	Piperidinone carboxamide azaindane CGRP receptor antagonists
Abstract:	The present invention is directed to piperidinone carboxamide azaindane 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.
Inventor(s):	Ian M. Bell, Mark E. Fraley, Steven N. Gallicchio, Anthony Ginnetti, Helen J. Mitchell, Daniel V. Paone, Donnette D. Staas, Heather E. Stevenson, Cheng Wang, C. Blair Zartman
Assignee:	Merck Sharp and Dohme LLC
Application Number:	US13/293,166
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,754,096
Patent Claims:	1. A compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein: X is selected from —C(R8)═ or —N═, wherein R8 is hydrogen, F or CN; 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 or more substituents as allowed by valence independently selected from the group consisting of: F and hydroxy; R2 is selected from hydrogen and 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; and R7 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; and R7 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. 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is —N═. 3. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is —CH═. 4. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is —C(CN)═. 5. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R1 is C1-4alkyl, optionally substituted with 1 to 3 F or hydroxy, or both. 6. The compound of claim 5, or a pharmaceutically acceptable salt thereof, wherein R1 is selected from: isopropyl, 2,2,2-trifluoroethyl, 2,2-difluoroethyl, 2-methylpropyl, 3,3,3-trifluoropropyl and 3,3,3-trifluoro-2-hydroxypropyl. 7. The compound of claim 6, or a pharmaceutically acceptable salt thereof, wherein R1 is 2,2,2-trifluoroethyl. 8. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is hydrogen. 9. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein at least two of R3, R4, R6 and R7 are F or Cl, except that if R4 is Cl then R7 cannot be Cl. 10. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R3 if F and R4, R6 and R7 are hydrogen. 11. The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R2 is methyl. 12. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein R5 is F and at least three of R3, R4, R6 and R7 are F. 13. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein R5 is hydrogen and if R4 is methyl or Cl then R7 cannot be methyl or Cl. 14. The compound of claim 11, or a pharmaceutically acceptable salt thereof, wherein R3 is selected from hydrogen, methyl, F or Cl; R4 is selected from hydrogen, methyl, F or Cl; R5 is hydrogen; R6 is selected from hydrogen or F; and R7 is selected from hydrogen, methyl, F or Cl; except that if R4 is methyl or Cl then R7 cannot be methyl or Cl. 15. A pharmaceutical composition which comprises an inert carrier and the compound of claim 1, or a pharmaceutically acceptable salt thereof. 16. A method of treating headache in a mammalian patient in need of such treatment, which comprises administering to the patient a therapeutically effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof. 17. The method of claim 16, wherein the headache is migraine headache. 18. The compound or a pharmaceutically acceptable salt thereof. 19. A pharmaceutical composition which comprises an inert carrier and the compound of claim 18, or a pharmaceutically acceptable salt thereof. 20. A method of treating migraine in a mammalian patient in need of such treatment, which comprises administering to the patient a therapeutically effective amount of the compound of claim 18, or a pharmaceutically acceptable salt thereof. 21. The compound or a pharmaceutically acceptable salt thereof. 22. A pharmaceutical composition which comprises an inert carrier and the compound of claim 21, or a pharmaceutically acceptable salt thereof. 23. A method of treating migraine in a mammalian patient in need of such treatment, which comprises administering to the patient a therapeutically effective amount of the compound of claim 21, or a pharmaceutically acceptable salt thereof. 24. The compound or a pharmaceutically acceptable salt thereof. 25. A pharmaceutical composition which comprises an inert carrier and the compound of claim 24, or a pharmaceutically acceptable salt thereof. 26. A method of treating migraine in a mammalian patient in need of such treatment, which comprises administering to the patient a therapeutically effective amount of the compound of claim 24, or a pharmaceutically acceptable salt thereof. 27. The compound or a pharmaceutically acceptable salt thereof. 28. A pharmaceutical composition which comprises an inert carrier and the compound of claim 27, or a pharmaceutically acceptable salt thereof. 29. A method of treating migraine in a mammalian patient in need of such treatment, which comprises administering to the patient a therapeutically effective amount of the compound of claim 27, or a pharmaceutically acceptable salt thereof. 30. A compound selected from the following group R2 Ar H 2-fluorophenyl Me 2-chlorophenyl Me 3-methylphenyl H 2,3-difluorophenyl H 2,3,5-trifluorophenyl H 2-chloro-6-fluorophenyl H 2,6-dichlorophenyl H 2,3-dichlorophenyl H 2,3,6-trifluorophenyl Me 2,3,5,6-tetrafluorophenyl Me 3-fluoro-2-methylphenyl or a pharmaceutically acceptable salt of any of the foregoing compounds. 31. A pharmaceutical composition which comprises an inert carrier and a compound of claim 30, or a pharmaceutically acceptable salt thereof. 32. A method of treating migraine in a mammalian patient in need of such treatment, which comprises administering to the patient a therapeutically effective amount of a compound of claim 30, or a pharmaceutically acceptable salt thereof. 33. A compound selected from the following group: R1 Ar cyclobutylmethyl 2,3-difluorophenyl 2-methylpropyl 2-fluorophenyl cyclobutylmethyl 2-fluorophenyl isopropyl 2-fluorophenyl (2S)-3,3,3-trifluoro-2-hydroxypropyl 2,3-difluorophenyl or a pharmaceutically acceptable salt of any of the foregoing compounds. 34. A pharmaceutical composition which comprises an inert carrier and the compound of claim 33, or a pharmaceutically acceptable salt thereof. 35. A method of treating migraine in a mammalian patient in need of such treatment, which comprises administering to the patient a therapeutically effective amount of a compound of claim 33, or a pharmaceutically acceptable salt thereof.