5-氨基-3-(4-吡啶基)-异噁唑 | 19790-96-6

• 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
• 中文名称: 5-氨基-3-(4-吡啶基)-异噁唑
• 中文别名: 3-(吡啶-4-基)异恶唑-5-胺
• 英文名称: 3-(pyridin-4-yl)isoxazol-5-amine
• 英文别名: 5-Amino-3-<4-pyridyl>-isoxazol；3-(Pyridin-4-yl)-1,2-oxazol-5-amine；3-pyridin-4-yl-1,2-oxazol-5-amine
• CAS: 19790-96-6
• 化学式: C₈H₇N₃O
• mdl: MFCD07787187
• 分子量: 161.163
• InChiKey: BXJIHGSHLZBSFO-UHFFFAOYSA-N

物化性质

• 密度：
  1.276

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  64.9
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  5-氨基-3-(4-吡啶基)-异噁唑 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.75h， 生成 (S)-2-amino-3-phenyl-N-(3-(pyridin-4-yl)isoxazol-5-yl)propanamide
  参考文献：
  名称：

  Aminopyrazole–Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies

  摘要：

  Herein, we report the lead optimization of amrinone-phenylalanine based GPR142 agonists. Structure-activity relationship studies led to the discovery of aminopyrazole-phenylalanine carboxylic acid 22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to be suitable for in vivo proof-of-concept studies. Compound 23 displayed good efficacy in a mouse oral glucose tolerance test (OGTT). Compound 22 showed GPR142 dependent stimulation of insulin secretion in isolated mouse islets and demonstrated a statistically significant glucose lowering effect in a mouse model bearing transplanted human islets.

  DOI：

  10.1021/ml4000854
• 作为产物：
  描述：

  异烟酸乙酯 在 盐酸羟胺 、 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 mineral oil 为溶剂， 生成 5-氨基-3-(4-吡啶基)-异噁唑
  参考文献：
  名称：

  Identification of diphenylalkylisoxazol-5-amine scaffold as novel activator of cardiac myosin

  摘要：

  To identify novel potent cardiac myosin activator, a series of diphenylalkylisoxazol-5-amine compounds 4-7 have been synthesized and evaluated for cardiac myosin ATPase activation. Among the 37 compounds, 4a (CMA at 10 µM = 81.6%), 4w (CMA at 10 µM = 71.2%) and 6b (CMA at 10 µM = 67.4%) showed potent cardiac myosin activation at a single concentration of 10 µM. These results suggested that the introduction of the amino-isoxazole ring as a bioisostere for urea group is acceptable for the cardiac myosin activation. Additional structure-activity relationship (SAR) studies were conducted. Para substitution (-Cl, -OCH₃, -SO₂N(CH₃)₂) to the phenyl rings or replacement of a phenyl ring with a heterocycle (pyridine, piperidine and tetrahydropyran) appeared to attenuate cardiac myosin activation at 10 µM. Additional hydrogen bonding acceptor next to the amino group of the isoxazoles did not enhance the activity. The potent isoxazole compounds showed selectivity for cardiac myosin activation over skeletal and smooth muscle myosin, and therefore these potent and selective isoxazole compounds could be considered as a new series of cardiac myosin ATPase activators for the treatment of systolic heart failure.

  DOI：

  10.1016/j.bmc.2020.115742

文献信息

• [EN] COMPOUNDS<br/>[FR] COMPOSÉS
  申请人：CTXT PTY LTD

  公开号：WO2020002587A1

  公开（公告）日：2020-01-02

  A compound of formula (I), or a pharmaceutically acceptable salt thereof.

  式（I）的化合物，或其药用可接受的盐。
• Compositions useful as inhibitors of rock and other protein kinases
  申请人：Green Jeremy

  公开号：US20060019956A1

  公开（公告）日：2006-01-26

  The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

  本发明涉及作为蛋白激酶抑制剂有用的化合物。本发明还提供了包含所述化合物的药学上可接受的组合物，并且提供了使用这些组合物治疗各种疾病、状况或障碍的方法。
• Novel therapeutic compounds
  申请人：Breinlinger Eric C.

  公开号：US20090069288A1

  公开（公告）日：2009-03-12

  Disclosed herein are novel compounds of Formula (I), wherein the variables are defined as herein. The compounds of Formula (I) are useful as kinase inhibitors and as such would be useful in treating certain conditions and diseases, especially inflammatory conditions and diseases as well as proliferative disorders such as cancer.

  本文公开了公式（I）的新化合物，其中变量如本文所定义。公式（I）的化合物可用作激酶抑制剂，因此可用于治疗某些疾病和病症，特别是炎症性疾病和疾病以及增生性疾病，如癌症。
• PHENYLANALINE AMIDE DERIVATIVES USEFUL FOR TREATING INSULIN-RELATED DISEASES AND CONDITIONS
  申请人：Du Xiaohui

  公开号：US20120115811A1

  公开（公告）日：2012-05-10

  Provided herein are compounds of formula I: wherein A, B, X, R 1 , R 2 and subscript n are as defined in the following disclosure. Compositions comprising the compounds are also provided, as well as methods for their use, for example, in treatment of type 2 diabetes and type 2 diabetes-related conditions.

  本文所提供的是I式化合物：其中A、B、X、R1、R2和下标n如下所述。本文还提供了包含该化合物的组合物，以及使用它们的方法，例如用于治疗2型糖尿病和2型糖尿病相关疾病的方法。
• SUBSTITUTED PICOLINAMIDE KINASE INHIBITORS
  申请人：Portola Pharmaceuticals, Inc.

  公开号：US20140113931A1

  公开（公告）日：2014-04-24

  Provided are picolinamide compounds for inhibiting of Syk kinase, intermediates used in making such compounds, methods for their preparation, pharmaceutical compositions thereof, methods for inhibiting Syk kinase activity, and methods for treating conditions mediated at least in part by Syk kinase activity.

  提供了用于抑制Syk激酶的吡啶甲酰胺化合物，制备这种化合物所使用的中间体，制备这种化合物的方法，制备药物组成物的方法，抑制Syk激酶活性的方法以及治疗至少部分通过Syk激酶活性介导的疾病的方法。