3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1,7-dimethylthieno[3,2-d]pyrimidine-2,4-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 3-[2,6-difluoro-4-(2-phenylethynyl)phenyl]-1,7-dimethylthieno[3,2-d]pyrimidine-2,4-dione
• 英文别名: 3-[2,6-Difluoro-4-(2-phenylethynyl)phenyl]-1,7-dimethylthieno[3,2-d]pyrimidine-2,4-dione
• 化学式: C₂₂H₁₄F₂N₂O₂S
• 分子量: 408.428
• InChiKey: KUNWSKGTYFFAGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  68.9
• 氢给体数：
  0
• 氢受体数：
  5

文献信息

• [EN] ETHYNYL DERIVATIVES<br/>[FR] DÉRIVÉS D'ÉTHYNYLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015044075A1

  公开（公告）日：2015-04-02

  The present invention relates to compounds of formula I wherein Y is N or C-R1'; 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 1, 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' are independently from each other hydrogen or lower alkyl, or may form together with the N atom to which they are attached a five or six membered saturated heterocyclic group which may contain an additional oxygen, NH, or N-lower alkyl group; R1 is hydrogen, halogen or lower alkyl substituted by halogen; R1' is hydrogen, halogen or lower alkyl substituted by halogen; R2 is hydrogen, lower alkyl, lower alkoxyalkyl, cycloalkyl or heterocycloalkyl; or R2 may form together with the closest carbon atom in group G a group (IA) for A being -CH2-, -CH2CH2, or -C(CH3)2-, R3 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.

  本发明涉及符号I的化合物，其中Y为N或C-R1'；G为含有0、1、2或3个杂原子的5或6元芳香或杂芳环，所选自苯基、带有不同N-位置的吡啶基、咪唑基、吡啶嗪基、嘧啶基、噻吩基、噻唑基、吡唑基或噻二唑基，这些基可以选择性地被1、2或3个卤素、低烷基、低烷氧基、被卤素或NRR'取代；R和R'彼此独立地为氢或低烷基，或者可以与它们连接的N原子一起形成一个含有额外氧、NH或N-低烷基的五元或六元饱和杂环基；R1为氢、卤素或被卤素取代的低烷基；R1'为氢、卤素或被卤素取代的低烷基；R2为氢、低烷基、低烷氧基烷基、环烷基或杂环烷基；或者R2可以与基团G中最近的碳原子一起形成一个(A为-CH2-、- 或-C(CH3)2-)的基团(IA)；R3为苯基或吡啶基，其中吡啶基中的N原子可能在不同位置；或者为药学上可接受的盐或酸加合盐，或为外消旋混合物，或为其对应的对映体和/或光学异构体和/或立体异构体。令人惊讶的是发现，一般式I化合物是代谢型谷氨酸受体4(mGluR4)的阳性变构调节剂(PAMs)，对帕金森病、焦虑、呕吐、强迫症、自闭症、神经保护、癌症、抑郁症和2型糖尿病的治疗有用。
• ETHYNYL DERIVATIVES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20160207890A1

  公开（公告）日：2016-07-21

  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.

  令人惊讶地发现，一般式I的化合物是代谢型谷氨酸受体4（mGluR4）的阳性变构调节剂（PAMs），可用于治疗帕金森病、焦虑、呕吐、强迫症、自闭症、神经保护、癌症、抑郁症和2型糖尿病。
• US9676732B2
  申请人：——

  公开号：US9676732B2

  公开（公告）日：2017-06-13