1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione | 1217897-98-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
• 英文别名: 1-acetyl-2-(2-chlorouhenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione；1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)pyrazolo[4,3-c]pyridine-3,6-dione
• CAS: 1217897-98-7
• 化学式: C₂₁H₁₇ClN₄O₃
• 分子量: 408.844
• InChiKey: ZTLRXINOMBWBNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  73.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(2-氯苯基)-4-甲基-5-(吡啶-2-基甲基)-1H-吡唑并[4,3-c]吡啶-3,6(2H,5H)-二酮 、 乙酸酐 在 sodium acetate 作用下， 反应 1.0h， 以82%的产率得到1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
  参考文献：
  名称：

  First in Class, Potent, and Orally Bioavailable NADPH Oxidase Isoform 4 (Nox4) Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis

  摘要：

  We describe the design, synthesis, and optimization of first-in-class series of inhibitors of NADPH oxidase isoform 4 (Nox4), an enzyme implicated in several pathologies, in particular idiopathic pulmonary fibrosis, a life-threatening and orphan disease. Initially, several moderately potent pyrazolopyridine dione derivatives were found during a high-throughput screening campaign. SA R investigation around the pyrazolopyridine dione core led to the discovery of several double-digit nanomolar inhibitors in cell free assays of reactive oxygen species (ROS) production, showing high potency on Nox4 and Nox1. The compounds have little affinity for Nox2 isoform and are selective for Nox4/1 isoforms. The specificity of these compounds was confirmed in an extensive in vitro pharmacological profile, as well as in a counterscreening assay for potential ROS scavenging. Concomitant benefits are good oral bioavailability and high plasma concentrations in vivo, allowing further clinical trials for the potential treatment of fibrotic diseases, cancers, and cardiovascular and metabolic diseases.

  DOI：

  10.1021/jm100773e
• 作为试剂：
  描述：

  2-(2-氯苯基)-4-甲基-5-(吡啶-2-基甲基)-1H-吡唑并[4,3-c]吡啶-3,6(2H,5H)-二酮 、 sodium acetate 、 乙酸酐 在 乙酸乙酯 、 水 、 Sodium sulfate-III 、 1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione 作用下， 反应 1.0h， 以to afford 0.228 g of the desired compound 1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione as a white solid (82% yield)的产率得到1-acetyl-2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione
  参考文献：
  名称：

  Pyrazolo pyridine derivatives as NADPH oxidase inhibitors

  摘要：

  本发明涉及式（I）的吡唑吡啶衍生物、其制药组合物以及它们用于治疗和/或预防与尼克酰胺腺嘌呤二核苷酸磷酸酰化酶（NADPH氧化酶）有关的疾病或症状的用途。

  公开号：

  US08940760B2

文献信息

• PYRAZOLO PYRIDINE DERIVATIVES AS NADPH OXIDASE INHIBITORS
  申请人：Page Patrick

  公开号：US20110172266A1

  公开（公告）日：2011-07-14

  The present invention is related to pyrazolo pyridine derivatives of Formula (I), pharmaceutical composition thereof and to their use for the treatment and/or prophylaxis of disorders or conditions related to Nicotinamide adenine dinucleotide phosphate oxidase (NADPH Oxidase).

  本发明涉及式（I）的吡唑吡啶衍生物，其药物组成物，以及它们用于治疗和/或预防与尼克酰胺腺嘌呤二核苷酸磷酸酰化酶（NADPH氧化酶）相关的疾病或病症的用途。
• METHODS OF PRESERVING AND PROTECTING PANCREATIC BETA CELLS AND TREATING OR PREVENTING DIABETES BY INHIBITING NOX-1
  申请人：EASTERN VIRGINIA MEDICAL SCHOOL

  公开号：US20160010061A1

  公开（公告）日：2016-01-14

  Methods of preserving and/or protecting pancreatic beta cells by inhibiting NOX-1. In a further aspect, NOX-1 inhibitors are administered to a subject in order to preserve and/or protect beta cells in the prevention or treatment of diabetes. NOX-1 inhibitors are also disclosed; The method can be used to preserve beta cell/islet survival in vitro, or in vivo in cells exposed to stressful stimuli including but not limited to inflammation, inflammatory cytokines, high glucose, or elevated free fatty acids.
• US8481562B2
  申请人：——

  公开号：US8481562B2

  公开（公告）日：2013-07-09
• US8940760B2
  申请人：——

  公开号：US8940760B2

  公开（公告）日：2015-01-27
• US9688960B2
  申请人：——

  公开号：US9688960B2

  公开（公告）日：2017-06-27