公开(公告)号：US20160207890A1

公开(公告)日：2016-07-21

申请号：US15081573

申请日：2016-03-25

申请人： Hoffmann-La Roche Inc.

发明人： Barbara BIEMANS ,  Wolfgang GUBA ,  Georg JAESCHKE ,  Antonio RICCI ,  Daniel RUEHER ,  Eric VIEIRA

IPC分类号： C07D239/96 ,  C07D473/04 ,  C07D487/06 ,  C07D475/04 ,  C07D405/14 ,  C07D513/04 ,  C07D401/10 ,  C07D401/04 ,  C07D405/04 ,  C07D487/04 ,  C07D495/04

CPC分类号： C07D239/96 ,  C07D239/91 ,  C07D401/04 ,  C07D401/10 ,  C07D405/04 ,  C07D405/14 ,  C07D471/04 ,  C07D473/04 ,  C07D475/02 ,  C07D475/04 ,  C07D487/04 ,  C07D487/06 ,  C07D495/04 ,  C07D513/04

摘要： 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.

摘要翻译： 已经令人惊奇地发现，通式I的化合物是代谢型谷氨酸受体4（mGluR4）的正变构调节剂（PAM），其可用于治疗帕金森病，焦虑症，呕吐，强迫症，孤独症，神经保护，癌症 ，抑郁症和糖尿病2型。

公开(公告)号：US20200291033A1

公开(公告)日：2020-09-17

申请号：US16790290

申请日：2020-02-13

申请人： Hoffmann-La Roche Inc.

发明人： Georg JAESCHKE ,  Fionn O'HARA ,  Eric VIEIRA

IPC分类号： C07D487/04

摘要： The present invention relates to compounds of formula I wherein L is a bond, a triple bond, —C(O)NH— or —NHC(O)—; R1 is phenyl or a five or six-membered heteroaryl group, optionally substituted by lower alkyl, lower alkyl substituted by halogen or lower alkoxy substituted by halogen; R2 is fluoro; R3 is fluoro or chloro; R4 is hydrogen, lower alkyl, halogen, lower alkyl substituted by hydroxy, S(O)2CH3, or is a five or six-membered heteroaryl group or a heterocycloalkyl group, which are optionally substituted by lower alkyl, hydroxy or ═O; R5 and R6 are both methyl and the dotted line is a bond, or R5 and R6 are both methyl and the dotted line is nothing, or one of R5 and R6 is hydrogen and the other is methyl, and the dotted line is nothing; or to a pharmaceutically acceptable salt or acid addition salt, to all possible tautomeric forms, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. The compounds may be used for the treatment of Parkinson's disease, anxiety, emesis, obsessive compulsive disorder, autism, neuroprotection, cancer, depression and diabetes type 2.

公开(公告)号：US20180127429A1

公开(公告)日：2018-05-10

申请号：US15867097

申请日：2018-01-10

申请人： Hoffmann-La Roche Inc.

发明人： Georg JAESCHKE ,  Fionn O'HARA ,  Jean-Marc PLANCHER ,  Antonio RICCI ,  Daniel RUEHER ,  Eric VIEIRA

IPC分类号： C07D487/04 ,  A61P25/00 ,  A61P3/08 ,  A61P25/22 ,  A61P25/24 ,  A61P35/00 ,  A61P25/16

CPC分类号： C07D487/04 ,  A61P3/08 ,  A61P25/00 ,  A61P25/16 ,  A61P25/22 ,  A61P25/24 ,  A61P35/00 ,  C07B2200/07 ,  C07B2200/09

摘要： The present invention relates to compounds of formula I wherein R1 is hydrogen, F or Cl; L is a bond or lower alkylene; R2 is —(CH2)nO-lower alkyl, lower alkyl substituted by halogen, —(CH2)nC(O)O-lower alkyl, phenyl substituted by lower alkyl or halogen, or is a 5 or 6-membered heteroaryl group, selected from pyridinyl, pyrimidinyl, pyridazinyl, thiazolyl, imidazolyl, pyrazolyl or triazolyl, which are optionally substituted by lower alkyl, halogen, lower alkoxy, ═O, benzyloxy, cycloalkyloxy, hydroxy, cyano, lower alkyl substituted by halogen, or by —(CH2)nO-lower alkyl; n is 1, 2 or 3; R3 is hydrogen, lower alkyl or —(CH2)nO-lower alkyl; R4 is phenyl, pyridinyl or pyrimidinyl, optionally substituted by F; Y is CF or CCl; 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 stereoisomers thereof. The compounds may be used for the treatment of Parkinson's disease, anxiety, emesis, obsessive compulsive disorder, autism, neuroprotection, cancer, depression and diabetes type 2.