乙炔基衍生物;ETHYNYL DERIVATIVES

摘要

本发明系关于式I之化合物其中Y 为N或C-R 1' ；G 为含有0、1、2或3个杂原子之5员或6员芳族或杂芳族环，其系选自由苯基、具有不同N-位置之吡啶基、咪唑基、吡嗪基、嘧啶基、苯硫基、噻唑基、吡唑基或噻二唑基组成之群，该等基团视情况经1、2或3个选自由卤素、低碳烷基、低碳烷氧基、经卤素取代之低碳烷氧基或NRR'组成之群的取代基取代；R及R'彼此独立地为氢或低碳烷基，或可连同其所连接之N原子形成可含有额外的氧、NH或N-低碳烷基之五员或六员饱和杂环基；R 1 为氢、卤素或经卤素取代之低碳烷基；R 1' 为氢、卤素或经卤素取代之低碳烷基；R 2 为氢、低碳烷基、低碳烷氧烷基、环烷基或杂环烷基；或R 2 可连同基团G中最近的碳原子形成基团其中A为-CH2-、-CH2CH2或-C(CH3)2-，R 3 为苯基或吡啶基，其中该吡啶基中之N原子可在不同位置；或关于医药学上可接受之盐或酸加成盐，关于外消旋混合物，或关于其相对应的对映异构体及/或光学异构体及/或其立体异构体。;已出人意料地发现，该等通式I之化合物为代谢型麸胺酸受体4(mGluR4)之正向异位调节剂(PAM)，其适用于治疗帕金森氏病(Parkinson's disease)、焦虑症、呕吐、强迫症、自闭症、神经保护、癌症、抑郁症及2型糖尿病。 The present invention relates to compounds of formula I wherein Y is N or C-R 1’; G is a 5 or 6-membered aromatic or heteroaromatic ring containing 0, 1, 2 or 3 heteroatoms, selected from the group consisting of phenyl, pyridinyl with different N-positions, imidazolyl, pyrazinyl, pyrimidinyl, thiophenyl, thiazolyl, pyrazolyl or thiadiazolyl, which are optionally substituted by l, 2 or 3 substituents, selected from the group consisting of halogen, lower alkyl, lower alkoxy, lower alkoxy substituted by halogen or NRR’; R and R’; R 1 is hydrogen, halogen or lower alkyl substituted by halogen; R 1’; R 2 is hydrogen, lower alkyl, lower alkoxyalkyl, cycloalkyl or heterocycloalkyl; or R 2 may form together with the closest carbon atom in group G a group for A being -CH2-, -CH2CH2, or -C(CH3)2-, R 3 is phenyl or pyridinyl, wherein the N atom in the pyridinyl group may be in different positions; or to a pharmaceutically acceptable salt or acid addition salt, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. ;It has been surprisingly been found that the compounds of general formula I are positive allosteric modulators (PAMs) of metabotropic glutamate receptor 4 (mGluR4), useful for the treatment of Parkinson’s disease, anxiety, emesis, obsessive compulsive disorder, autism, neuroprotection, cancer, depression and diabetes type 2.