3-(hydroxymethyl)-4-methylpyrazolo<1,5-a>pyridine | 127717-26-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: 3-(hydroxymethyl)-4-methylpyrazolo<1,5-a>pyridine
• 英文别名: (4-methylpyrazolo[1,5-a]pyridin-3-yl)methanol
• CAS: 127717-26-4
• 化学式: C₉H₁₀N₂O
• 分子量: 162.191
• InChiKey: ANUUXFLENGFODE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  37.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(hydroxymethyl)-4-methylpyrazolo<1,5-a>pyridine 在 manganese(IV) oxide 、 碳酸氢钠 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 96.5h， 生成 N,2-dimethyl-N'-((4-methylpyrazolo[1,5-a]pyridin-3-yl)methylene)-5-nitrobenzenesulfonohydrazide
  参考文献：
  名称：

  Discovery of pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors

  摘要：

  We have made a novel series of pyrazolo[1,5-a]pyridines as PI3 kinase inhibitors, and demonstrated their selectivity for the p110 alpha isoform over the other Class Ia PI3 kinases. We investigated the SAR around the pyrazolo[1,5-a] pyridine ring system, and found compound 5x to be a particularly potent example (p110 alpha IC50 0.9 nM). This compound inhibits cell proliferation and phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity, and showed in vivo activity in an HCT-116 human xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.029
• 作为产物：
  描述：

  1-amino-3-methylpyridin-1-ium iodide 在 二异丁基氢化铝 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-(hydroxymethyl)-4-methylpyrazolo<1,5-a>pyridine
  参考文献：
  名称：

  Benzimidazolone as potent chymase inhibitor: Modulation of reactive metabolite formation in the hydrophobic (P1) region

  摘要：

  A new class of chymase inhibitor featuring a benzimidazolone core with an acid side chain and a P-1 hydrophobic moiety is described. Incubation of the lead compound with GSH resulted in the formation of a GSH conjugate on the benzothiophene P-1 moiety. Replacement of the benzothiophene with different heterocyclic systems such as indoles and benzoisothiazole is feasible. Among the P-1 replacements, benzoisothiazole prevents the formation of GSH conjugate and an in silico analysis of oxidative potentials agreed with the experimental outcome. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.126

文献信息

• Miki, Yasuyoshi; Nakamura, Noriko; Hachiken, Hiroko, Journal of Heterocyclic Chemistry, 1989, vol. 26, p. 1739 - 1745
  作者：Miki, Yasuyoshi、Nakamura, Noriko、Hachiken, Hiroko、Takemura, Shoji

  DOI：——

  日期：——
• MIKI, YASUYOSHI;NAKAMURA, NORIKO;HACHIKEN, HIROKO;TAKEMURA, SHOJI, J. HETEROCYCL. CHEM., 26,(1989) N, C. 1739-1745
  作者：MIKI, YASUYOSHI、NAKAMURA, NORIKO、HACHIKEN, HIROKO、TAKEMURA, SHOJI

  DOI：——

  日期：——
• [EN] INHIBITORS OF CYSTEINE PROTEASES AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE CYSTÉINE PROTÉASES ET LEURS MÉTHODES D'UTILISATION
  申请人：[en]PARDES BIOSCIENCES, INC.

  公开号：WO2023044171A1

  公开（公告）日：2023-03-23

  The disclosure provides compounds with nitrile warheads and their use in treating medical diseases or disorders, such as viral infections. Pharmaceutical compositions and methods of making various compounds with nitrile warheads are provided. The compounds are contemplated to inhibit proteases, such as the 3C, CL- or 3CL-like protease.
• Benzimidazolone as potent chymase inhibitor: Modulation of reactive metabolite formation in the hydrophobic (P1) region
  作者：Ho Yin Lo、Peter A. Nemoto、Jin Mi Kim、Ming-Hong Hao、Kevin C. Qian、Neil A. Farrow、Daniel R. Albaugh、Danielle M. Fowler、Richard D. Schneiderman、E. Michael August、Leslie Martin、Melissa Hill-Drzewi、Steven S. Pullen、Hidenori Takahashi、Stéphane De Lombaert

  DOI：10.1016/j.bmcl.2011.05.126

  日期：2011.8

  A new class of chymase inhibitor featuring a benzimidazolone core with an acid side chain and a P-1 hydrophobic moiety is described. Incubation of the lead compound with GSH resulted in the formation of a GSH conjugate on the benzothiophene P-1 moiety. Replacement of the benzothiophene with different heterocyclic systems such as indoles and benzoisothiazole is feasible. Among the P-1 replacements, benzoisothiazole prevents the formation of GSH conjugate and an in silico analysis of oxidative potentials agreed with the experimental outcome. (C) 2011 Elsevier Ltd. All rights reserved.
• Discovery of pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors
  作者：Jackie D. Kendall、Patrick D. O’Connor、Andrew J. Marshall、Raphaël Frédérick、Elaine S. Marshall、Claire L. Lill、Woo-Jeong Lee、Sharada Kolekar、Mindy Chao、Alisha Malik、Shuqiao Yu、Claire Chaussade、Christina Buchanan、Gordon W. Rewcastle、Bruce C. Baguley、Jack U. Flanagan、Stephen M.F. Jamieson、William A. Denny、Peter R. Shepherd

  DOI：10.1016/j.bmc.2011.11.029

  日期：2012.1

  We have made a novel series of pyrazolo[1,5-a]pyridines as PI3 kinase inhibitors, and demonstrated their selectivity for the p110 alpha isoform over the other Class Ia PI3 kinases. We investigated the SAR around the pyrazolo[1,5-a] pyridine ring system, and found compound 5x to be a particularly potent example (p110 alpha IC50 0.9 nM). This compound inhibits cell proliferation and phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity, and showed in vivo activity in an HCT-116 human xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.