2-甲基-2-丙基3'-氨基-1',4'-二氢-5'H-螺[环丙烷-1,6'-吡咯并[3,4-c]吡唑]-5'-羧酸酯 | 946497-95-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡唑类
• 中文名称: 2-甲基-2-丙基3'-氨基-1',4'-二氢-5'H-螺[环丙烷-1,6'-吡咯并[3,4-c]吡唑]-5'-羧酸酯
• 英文名称: tert-butyl 3'-amino-1'H-spiro[cyclopropane-1,6'-pyrrolo[3,4-c]pyrazole]-5'(4'H)-carboxylate
• 英文别名: Tert-butyl 3'-amino-1'H-spiro[cyclopropane-1,6'-pyrrolo[3,4-C]pyrazole]-5'(4'H)-carboxylate；tert-butyl 3-aminospiro[1,4-dihydropyrrolo[3,4-c]pyrazole-6,1'-cyclopropane]-5-carboxylate
• CAS: 946497-95-6
• 化学式: C₁₂H₁₈N₄O₂
• 分子量: 250.301
• InChiKey: GEEYXEHYZYEWAT-UHFFFAOYSA-N

物化性质

• 沸点：
  462.5±45.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  84.2
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-甲基-2-丙基3'-氨基-1',4'-二氢-5'H-螺[环丙烷-1,6'-吡咯并[3,4-c]吡唑]-5'-羧酸酯 在 盐酸 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 20.0h， 以96%的产率得到4',5'-dihydro-1'H-spiro[cyclopropane-1,6'-pyrrolo[3,4-c]pyrazol]-3'-amine dihydrochloride
  参考文献：
  名称：

  2,4-Diamino-8-quinazoline carboxamides as novel, potent inhibitors of the NAD hydrolyzing enzyme CD38: Exploration of the 2-position structure-activity relationships

  摘要：

  Starting from 4-amino-8-quinoline carboxamide lead 1a and scaffold hopping to the chemically more tractable quinazoline, a systematic exploration of the 2-substituents of the quinazoline ring, utilizing structure activity relationships and conformational constraint, resulted in the identification of 39 novel CD38 inhibitors. Eight of these analogs were 10-100-fold more potent human CD38 inhibitors, including the single digit nanomolar inhibitor 1am. Several of these molecules also exhibited improved therapeutic indices relative to hERG activity. A representative analog 1r exhibited suitable pharmacokinetic parameters for in vivo animal studies, including moderate clearance and good oral bioavailability. These inhibitor compounds will aid in the exploration of the enzymatic functions of CD38, as well as furthering the study of the therapeutic implications of NAD enhancement in metabolic disease models. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.03.021
• 作为产物：
  描述：

  1-[(2-氰基乙基)氨基]环丙烷羧酸 在 potassium tert-butylate 、 四甲基氢氧化铵 、 溶剂黄146 、 肼 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙腈 为溶剂， 生成 2-甲基-2-丙基3'-氨基-1',4'-二氢-5'H-螺[环丙烷-1,6'-吡咯并[3,4-c]吡唑]-5'-羧酸酯
  参考文献：
  名称：

  [EN] INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
  [FR] INHIBITEURS DE LA KINASE CYCLINE-DÉPENDANTE 7 (CDK7)

  摘要：

  公开号：

  WO2016105528A3

文献信息

• INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US20210115051A1

  公开（公告）日：2021-04-22

  The present invention provides novel compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., cyclin-dependent kinase 7 (CDK7)), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.
• 2,4-Diamino-8-quinazoline carboxamides as novel, potent inhibitors of the NAD hydrolyzing enzyme CD38: Exploration of the 2-position structure-activity relationships
  作者：David N. Deaton、Curt D. Haffner、Brad R. Henke、Michael R. Jeune、Barry G. Shearer、Eugene L. Stewart、J. Darren Stuart、John C. Ulrich

  DOI：10.1016/j.bmc.2018.03.021

  日期：2018.5

  Starting from 4-amino-8-quinoline carboxamide lead 1a and scaffold hopping to the chemically more tractable quinazoline, a systematic exploration of the 2-substituents of the quinazoline ring, utilizing structure activity relationships and conformational constraint, resulted in the identification of 39 novel CD38 inhibitors. Eight of these analogs were 10-100-fold more potent human CD38 inhibitors, including the single digit nanomolar inhibitor 1am. Several of these molecules also exhibited improved therapeutic indices relative to hERG activity. A representative analog 1r exhibited suitable pharmacokinetic parameters for in vivo animal studies, including moderate clearance and good oral bioavailability. These inhibitor compounds will aid in the exploration of the enzymatic functions of CD38, as well as furthering the study of the therapeutic implications of NAD enhancement in metabolic disease models. (C) 2018 Elsevier Ltd. All rights reserved.
• [EN] INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)<br/>[FR] INHIBITEURS DE LA KINASE CYCLINE-DÉPENDANTE 7 (CDK7)
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2016105528A3

  公开（公告）日：2016-08-18