5-methyl-3-pyridin-4-yl-6-phenylisoxazolo[4,5c]pyridin-4(5H)-one | 479077-04-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-methyl-3-pyridin-4-yl-6-phenylisoxazolo[4,5c]pyridin-4(5H)-one
• 英文别名: 5-methyl-6-phenyl-3-(pyridin-4-yl)isoxazolo[4,5-c]pyridin-4(5H)-one；5-methyl-6-phenyl-3-pyridin-4-yl-[1,2]oxazolo[4,5-c]pyridin-4-one
• CAS: 479077-04-8
• 化学式: C₁₈H₁₃N₃O₂
• 分子量: 303.32
• InChiKey: BGCDFCJIPDVNPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  59.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 生成 5-methyl-3-pyridin-4-yl-6-phenylisoxazolo[4,5c]pyridin-4(5H)-one
  参考文献：
  名称：

  Isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists

  摘要：

  This Letter describes the synthesis and evaluation of mGluR7 antagonists in the isoxazolopyridone series. In the course of modi. cation in this class, novel solid support synthesis of the isoxazolopyridone scaffold was developed. Subsequent chemical modi. cation led to the identification of several potent derivatives with improved physicochemical properties compared to a hit compound 1. Among these, 2 showed good oral bioavailability and brain penetrability, suggesting that 2 may be useful for in vivo study to elucidate the role of mGluR7. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.070

文献信息

• Novel isoxazolopyridone derivatives and their use
  申请人：——

  公开号：US20040176407A1

  公开（公告）日：2004-09-09

  The invention relates to isoxazolopyridone derivatives of a formula (I-a): 1 wherein R 1a represents an optionally-substituted heteroaryl or phenyl group, R 2a represents an optionally-substituted phenyl or heteroaryl group, and R 3a represents a methyl group, provided that, (1) when R 1a is an unsubstituted phenyl group, then R 2a must not be a para-substituted phenyl group of which the substituent is any of a methoxy group, a chloro group, a methyl group, a trifluoromethyl group, a fluoro group, a bromomethyl group or a dimethylaminomethyl group, and R 2a must not be an unsubstituted heteroaryl group, and (2) when R 1a is a 4-tolyl group or a 4-fluorophenyl group, then R 2a must not be an unsubstituted phenyl group, a 4-methoxyphenyl group or a 4-fluorophenyl group, or their pharmaceutically-acceptable salts. The isoxazolopyridone derivatives or their pharmaceutically-acceptable salts of the invention have a metabotropic glutamic acid receptor-antagonistic effect, and are useful for remedy of, for example, anxiety disorders, psychosomatic disorders, obsessive-compulsive neurosis, bipolar disorders, melancholia, eating disorders, schizophrenia, multi-infarct dementia, Alzheimer disease, epilepsy, Parkinson disease, Huntington's chorea, pain or retrograde neurosis.

  本发明涉及一种式（I-a）的异噁唑吡啶酮衍生物：其中，R1代表可选取代的杂环芳基或苯基，R2代表可选取代的苯基或杂环芳基，R3代表甲基，但是当（1）R1a为未取代的苯基时，R2a不能是对位上的取代苯基，其取代基为甲氧基、氯基、甲基、三氟甲基、氟基、溴甲基或二甲氨基甲基中的任何一种，且R2a不能是未取代的杂环芳基，当（2）R1a为4-甲基苯基或4-氟苯基时，R2a不能是未取代的苯基、4-甲氧基苯基或4-氟苯基，或其药学上可接受的盐。本发明的异噁唑吡啶酮衍生物或其药学上可接受的盐具有代谢型谷氨酸受体拮抗作用，可用于治疗例如焦虑症、心身疾病、强迫症、双相障碍、忧郁症、进食障碍、精神分裂症、多发性梗塞性痴呆、阿尔茨海默病、癫痫、帕金森病、亨廷顿舞蹈症、疼痛或逆行神经病的疗法。
• NOVEL ISOXAZOLOPYRIDONE DERIVATIVES AND USE THEREOF
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1408042A1

  公开（公告）日：2004-04-14

  The invention relates to isoxazolopyridone derivatives of a formula (I-a): wherein R1a represents an optionally-substituted heteroaryl or phenyl group, R2a represents an optionally-substituted phenyl or heteroaryl group, and R3a represents a methyl group, provided that, (1) when R1a is an unsubstituted phenyl group, then R2a must not be a para-substituted phenyl group of which the substituent is any of a methoxy group, a chloro group, a methyl group, a trif luoromethyl group, a fluoro group, a bromomethyl group or a dimethylaminomethyl group, and R2a must not be an unsubstituted heteroaryl group, and (2) when R1a is a 4-tolyl group or a 4-fluorophenyl group, then R2a must not be an unsubstituted phenyl group, a 4-methoxyphenyl group or a 4-fluorophenyl group, or their pharmaceutically-acceptable salts. The isoxazolopyridone derivatives or their pharmaceutically-acceptable salts of the invention have a metabotropic glutamic acid receptor-antagonistic effect, and are useful for remedy of, for example, anxiety disorders, psychosomatic disorders, obsessive-compulsive neurosis, bipolar disorders, melancholia, eating disorders, schizophrenia, multi-infarct dementia, Alzheimer disease, epilepsy, Parkinson disease, Huntington's chorea, pain or retrograde neurosis.

  本发明涉及式（I-a）的异噁唑并吡啶酮衍生物： 其中 R1a 代表任选取代的杂芳基或苯基，R2a 代表任选取代的苯基或杂芳基，R3a 代表甲基，条件是：(1) 当 R1a 是未取代的苯基时，则 R2a 不得是对位取代的苯基，其取代基为甲氧基、氯基、甲基、三氟甲基、氟基、溴甲基或甲基中的任何一个、(2) 当 R1a 是 4-甲苯基或 4-氟苯基时，则 R2a 不得是未取代的苯基、4-甲氧基苯基或 4-氟苯基或它们的药学上可接受的盐。 本发明的异噁唑吡啶酮衍生物或它们的药学上可接受的盐具有代谢型谷氨酸受体拮抗作用，可用于治疗焦虑症、心身疾病、强迫性神经症、双相情感障碍、忧郁症、饮食失调、精神分裂症、多梗塞性痴呆、阿尔茨海默病、癫痫、帕金森病、亨廷顿舞蹈症、疼痛或逆行性神经症等。
• US7053219B2
  申请人：——

  公开号：US7053219B2

  公开（公告）日：2006-05-30
• Isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists
  作者：Masayuki Nakamura、Hideki Kurihara、Gentaroh Suzuki、Morihiro Mitsuya、Mitsuru Ohkubo、Hisashi Ohta

  DOI：10.1016/j.bmcl.2009.11.070

  日期：2010.1

  This Letter describes the synthesis and evaluation of mGluR7 antagonists in the isoxazolopyridone series. In the course of modi. cation in this class, novel solid support synthesis of the isoxazolopyridone scaffold was developed. Subsequent chemical modi. cation led to the identification of several potent derivatives with improved physicochemical properties compared to a hit compound 1. Among these, 2 showed good oral bioavailability and brain penetrability, suggesting that 2 may be useful for in vivo study to elucidate the role of mGluR7. (C) 2009 Elsevier Ltd. All rights reserved.