5-methyl-3-(4-pyridinyl)-4-isoxazolecarboxylic acid | 90771-23-6

• 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-(4-pyridinyl)-4-isoxazolecarboxylic acid
• 英文别名: 5-methyl-3-pyridin-4-yl-isoxazole-4-carboxylic acid；5-methyl-3-pyridin-4-yl-4-isoxazole-carboxylic acid；5-Methyl-4-carboxy-3-pyridyl-(4)-isoxazol；5-methyl-3-pyridin-4-yl-1,2-oxazole-4-carboxylic acid
• CAS: 90771-23-6
• 化学式: C₁₀H₈N₂O₃
• mdl: MFCD06589776
• 分子量: 204.185
• InChiKey: WHOBCXXYJKABST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  盐酸甲胺 、 5-methyl-3-(4-pyridinyl)-4-isoxazolecarboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 5.0h， 以66%的产率得到N-5-dimethyl-3-phenyl-4-isoxazolecarboxamide
  参考文献：
  名称：

  EP1408042

  摘要：

  公开号：
• 作为产物：
  描述：

  N-hydroxyisonicotinimidoyl chloride 生成 5-methyl-3-(4-pyridinyl)-4-isoxazolecarboxylic acid
  参考文献：
  名称：

  1113. 6-氨基青霉烯酸的衍生物。第七部分。其他3,5-二取代的异恶唑-4-羧酸衍生物

  摘要：

  DOI：

  10.1039/jr9630005845

文献信息

• Synthesis, Identification, and Structure–Activity Relationship Analysis of GATA4 and NKX2-5 Protein–Protein Interaction Modulators
  作者：Mikael Jumppanen、Sini M. Kinnunen、Mika J. Välimäki、Virpi Talman、Samuli Auno、Tanja Bruun、Gustav Boije af Gennäs、Henri Xhaard、Ingo B. Aumüller、Heikki Ruskoaho、Jari Yli-Kauhaluoma

  DOI：10.1021/acs.jmedchem.9b01086

  日期：2019.9.12

  cytotoxicity. The structure-activity relationship (SAR) analysis revealed that the aromatic isoxazole substituent in the southern part regulates the inhibition of GATA4-NKX2-5 transcriptional synergy. Moreover, inhibition of GATA4 transcriptional activity correlated with the reduced cell viability. In summary, comprehensive SAR analysis accompanied by data analysis successfully identified potent and selective

  转录因子GATA4和NKX2-5直接相互作用并协同激活几种心脏基因和牵张诱导的心肌肥大。以前，我们将苯基异恶唑羧酰胺1确定为命中化合物，该化合物可抑制GATA4-NKX2-5转录协同作用。在此，通过合成和表征220个衍生物和与结构相关的化合物，探索了1分子结构周围的化学空间。除了协同转录激活，还评估了所选化合物对GATA4和NKX2-5转录活性的影响以及潜在的细胞毒性。结构-活性关系（SAR）分析表明，南部的芳族异恶唑取代基可调节对GATA4-NKX2-5转录协同的抑制作用。而且，对GATA4转录活性的抑制与细胞活力的降低有关。总之，综合的SAR分析和数据分析成功地确定了GATA4-NKX2-5转录协同作用的有效和选择性抑制剂，并揭示了对其重要的结构特征。
• Isoxazole pyrazoloindane derivatives as cognition enhancing GABA-A alpha 5 subtype ligands
  申请人：——

  公开号：US20040006226A1

  公开（公告）日：2004-01-08

  The present invention provides compounds of formula I: 1 in which: one of X and Y is a nitrogen atom substituted by a group R 6 ′ and the other is a carbon atom substituted by an isoxazole group substituted on its carbon atoms by groups R 3 and R 4 ; one of R 6 and R 6 ′ is hydrogen; either all of W 1 , W 2 , W 3 and W 4 are carbon or one of W 1 , W 2 , W 3 and W 4 is nitrogen and the rest are carbon; and R 1 and R 2 are, independently, a small group, heteroaromatic ring or a 4-7 membered cyclic amine ring; processes for making them; pharmaceutical composition containing them; their use in therapy, particularly for enhancing cognition in conditions such as Alzheimer's Disease; and methods of treatment using them.

  本发明提供了化合物的公式I：其中：X和Y中的一个是由基团R6′取代的氮原子，另一个是由异唑啉基团取代的碳原子，其碳原子上取代有基团R3和R4；R6和R6′中的一个是氢；W1、W2、W3和W4中的所有或其中一个是氮，其余为碳；R1和R2分别是小基团、杂环芳香环或4-7成员环胺基；制备它们的方法；含有它们的药物组合物；它们在治疗中的应用，特别是在增强认知方面，如阿尔茨海默病等情况；以及使用它们的治疗方法。
• 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。
• 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.