5-甲基-2-吡啶-3-基-2H-吡唑-3-羧酸乙酯 | 1026601-25-1

• 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-甲基-2-吡啶-3-基-2H-吡唑-3-羧酸乙酯
• 英文名称: ethyl 3-methyl-1-(pyridin-3-yl)-1H-pyrazole-5-carboxylate
• 英文别名: Ethyl 5-methyl-2-pyridin-3-ylpyrazole-3-carboxylate
• CAS: 1026601-25-1
• 化学式: C₁₂H₁₃N₃O₂
• 分子量: 231.254
• InChiKey: UGQCIGFNPXITRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-甲基-2-吡啶-3-基-2H-吡唑-3-羧酸乙酯 在 platinum(IV) oxide 氢气 、 三甲基铝 、 溶剂黄146 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 正己烷 、 二氯甲烷 、 丙酮 为溶剂， 20.0~40.0 ℃ 、137.9 kPa 条件下， 反应 33.75h， 生成 5-Methyl-2-piperidin-3-yl-2H-pyrazole-3-carboxylic acid (2'-tert-butylsulfamoyl-biphenyl-4-yl)-amide
  参考文献：
  名称：

  Structure-Based Design of Novel Guanidine/Benzamidine Mimics:  Potent and Orally Bioavailable Factor Xa Inhibitors as Novel Anticoagulants

  摘要：

  As part of an ongoing effort to prepare orally active factor Xa inhibitors using structure-based drug design techniques and molecular recognition principles, a systematic study has been performed on the pharmacokinetic profile resulting from replacing the benzamidine in the P1 position with less basic benzamidine mimics or neutral residues. It is demonstrated that lowering the pK(a) of the P1 ligand resulted in compounds (3-benzylamine, 15a; 1-aminoisoquinoline, 24a; 3-aminobenzisoxazole, 23a; 3-phenylcarboxamide, 22b; and 4-methoxyphenyl, 22a) with improved pharmacokinetic features mainly as a result of decreased clearance, increased volume of distribution, and enhanced oral absorption. This work resulted in a series of potent and orally bioavailable factor Xa inhibitors that ultimately led to the discovery of SQ311, 24a. SQ311, which utilizes a 1-aminoisoquinoline as the P1 ligand, inhibits factor Xa with a K-i of 0.33 nM and demonstrates both good in vivo antithrombotic efficacy and oral bioavailability.

  DOI：

  10.1021/jm020578e
• 作为产物：
  描述：

  3-肼基吡啶 、 2-(甲氧基亚胺)-4-氧代-戊酸乙酯 以 乙醇 为溶剂， 反应 5.0h， 生成 5-甲基-2-吡啶-3-基-2H-吡唑-3-羧酸乙酯
  参考文献：
  名称：

  Structure-Based Design of Novel Guanidine/Benzamidine Mimics:  Potent and Orally Bioavailable Factor Xa Inhibitors as Novel Anticoagulants

  摘要：

  As part of an ongoing effort to prepare orally active factor Xa inhibitors using structure-based drug design techniques and molecular recognition principles, a systematic study has been performed on the pharmacokinetic profile resulting from replacing the benzamidine in the P1 position with less basic benzamidine mimics or neutral residues. It is demonstrated that lowering the pK(a) of the P1 ligand resulted in compounds (3-benzylamine, 15a; 1-aminoisoquinoline, 24a; 3-aminobenzisoxazole, 23a; 3-phenylcarboxamide, 22b; and 4-methoxyphenyl, 22a) with improved pharmacokinetic features mainly as a result of decreased clearance, increased volume of distribution, and enhanced oral absorption. This work resulted in a series of potent and orally bioavailable factor Xa inhibitors that ultimately led to the discovery of SQ311, 24a. SQ311, which utilizes a 1-aminoisoquinoline as the P1 ligand, inhibits factor Xa with a K-i of 0.33 nM and demonstrates both good in vivo antithrombotic efficacy and oral bioavailability.

  DOI：

  10.1021/jm020578e

文献信息

• [EN] KCNT1 INHIBITORS AND METHODS OF USE<br/>[FR] INHIBITEURS DE KCNT1 ET PROCÉDÉS D'UTILISATION
  申请人：PRAXIS PREC MEDICINES INC

  公开号：WO2020227101A1

  公开（公告）日：2020-11-12

  The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.

  本发明部分涉及用于预防和/或治疗神经系统疾病或紊乱、与过度神经元兴奋性有关的疾病或病况，以及基因（例如KCNT1）中的功能增强突变的化合物和组合物。本文还提供了治疗神经系统疾病或紊乱、与过度神经元兴奋性有关的疾病或病况，以及基因如KCNT1中的功能增强突变的方法。
• Calpain modulators and therapeutic uses thereof
  申请人：Blade Therapeutics, Inc.

  公开号：US10934261B2

  公开（公告）日：2021-03-02

  Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.

  本文公开了小分子钙蛋白酶调节剂组合物、药物组合物及其用途和制备方法。
• [EN] CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF<br/>[FR] MODULATEURS DE CALPAIN ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：BLADE THERAPEUTICS INC

  公开号：WO2018064119A8

  公开（公告）日：2019-04-25
• CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF
  申请人：BLADE THERAPEUTICS, INC.

  公开号：US20200123114A1

  公开（公告）日：2020-04-23

  Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.
• KCNT1 INHIBITORS AND METHODS OF USE
  申请人：Praxis Precision Medicines, Inc.

  公开号：US20220259193A1

  公开（公告）日：2022-08-18

  The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.