Amino-heterocycles as VR-1 antagonists for treating pain

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

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C514S255050, C514S269000, C514S275000, C514S337000, C544S238000, C544S298000, C544S333000, C544S405000, C546S256000, C546S268100

Reexamination Certificate

active

07442701

ABSTRACT:
The present invention provides a compound of formula (I): wherein V represents NR5, O, S, SO or S(O)2; W and X each independently represent CH or N; Y represents N, CH or C—Ar2, with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C—Ar2, with the proviso that when Y is N or CH then Z is C—Ar2, and with the further proviso that when Y is C—Ar2then Z is CH; Ar1represents a fused 9 or 10 membered heterobicyclic ring system containing one, two, three or four heteroatoms selected from nitrogen, oxygen and sulfur, wherein at least one of the rings in said ring system is aromatic; Ar2represents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; R1represents halogen, hydroxy, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, haloC1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, hydroxyC1-6alkoxy, C3-7cycloalkyl, C3-7cycloalkoxy, C3-5cycloalkylC1-4alkyl, cyano, nitro, SR6, SOR6, SO2R6, COR6, NR3COR6, CONR3R4, NR3SO2R6, SO2NR3R4, —(CH2)mcarboxy, esterified —(CH2)mcarboxy or —(CH2)mNR3R4; R2represents hydrogen, halogen, hydroxy, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy, haloC1-6alkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; R3and R4are each independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl or fluoroC1-6alkyl; or R3and R4and the nitrogen atom to which they are attached together form a heteroaliphatic ring of 4 to 7 ring atoms, optionally substituted by one or two groups selected from hydroxy or C1-4alkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O)2, or NR5; R5represents hydrogen, C1-4alkyl, hydroxyC1-4alkyl or C1-4alkoxyC1-4alkyl; R6represents hydrogen, C1-6alkyl, fluoroC1-6alkyl, C3-7cycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; m is either zero or an integer from 1 to 4; n is either zero or an integer from 1 to 3; or a pharmaceutically acceptable salt, N-oxide or a prodrug thereof; a pharmaceutical composition comprising it; its use in methods of treatment; use of it for the manufacture of a medicament for treating VR-1 related conditions such as those in which pain and/or inflammation predominate; and methods of treatment using it.

REFERENCES:
patent: WO 98/41508 (1998-09-01), None
patent: WO 02/08221 (2002-01-01), None
patent: WO 03/068749 (2003-08-01), None
patent: WO 03/080578 (2003-10-01), None
Bold et al, Journal of Medicinal Chemistry, 2000, vol. 43, No. 16, p. 3200.

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