N-substituted nonaryl-heterocyclic NMDA/NR2B antagonists

摘要

Disclosed are compounds of the formula (I), or pharmaceutically acceptable salts thereof, wherein NonAr is a nonaromatic 5-7 membered ring containing 1 or 2 nitrogen ring atoms or an aza bicyclo octane ring; HetAr is a 5 or 6 membered heteroaromatic ring containing 1-3 nitrogen ring atoms, or isoxazolyl, thiazolyl, thiadiazolyl, quinolinyl, quinazolinyl, purinyl, pteridinyl, benzimidazolyl, pyrrolopyrimidinyl, or imidazopyridinyl; HetAr is optionally substituted with 1 or 2 substituents, each substituent independently is C1-4alkyl, C1-4alkoxy, C2-4alkynyl, trifluoromethyl, hydroxy, hydroxyC1-4alkyl, fluoro, chloro, bromo, iodo, cyano, methylsulfanyl, cyclopropylethynyl-, phenylethynyl-, heteroarylethynyl-, -N(C0-4alkyl)(C0-4alkyl), nitro, (C1-2alkyl)(C1-2alkyl)NCH2-, (C1-2alkyl)HNCH2-, Si(CH3)3-C-, or NH2C(O)-; A is -C-0-4alkyl-; B is aryl(CH2)0-3-O-C(O)-, heteroaryl(CH2)----1-3--O-C(O)-, indanyl(CH2)---0-3--O-C(O)-, aryl(CH2)1-3-C(O)-, aryl-cyclopropyl-C(O)-, heteroaryl-cyclopropyl-C(O)-, heteroaryl(CH2)1-3,-C(O)-, heteroaryl(CH2)1-3, aryl(CH2)1-3-NH-C(O)-, aryl(CH2)1-3-NH-C(NCN)-, aryl(CH2)1-3-SO2-, heteroaryl(CH2)1-3-SO2-, wherein any of the aryl or heteroaryl is optionally substituted by 1-5 substituants, each substituent independently is C1-4alkyl, C3-6cycloalkyl, C1-4alkoxy, trifluoromethyl, bromo, fluoro or chloro; and X is H, OH, F, C1-4alkyl C1-4alkoxy, NH2, or X taken with an adjacent bond is =O. Further disclosed is the use of compounds of the formula (I) in the preparation of a medicament for the treatment of pain, migraine, depression, schizophrenia, Parkinson's disease, or stroke.