5-amino-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazole-4-carboxamide | 264141-20-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-amino-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazole-4-carboxamide
• 英文别名: 5-amino-3-(methylthio)-1-(2,4,6-trichlorophenyl)pyrazole-4-carboxamide；5-amino-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)pyrazole-4-carboxamide
• CAS: 264141-20-0
• 化学式: C₁₁H₉Cl₃N₄OS
• 分子量: 351.644
• InChiKey: CCLACDJATYIELW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-amino-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazole-4-carboxamide 在 乙酰胺 作用下， 以4.343 g (58%)的产率得到6-Methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine-4-ol
  参考文献：
  名称：

  Pyrazolopyrimidines as CRF antagonists

  摘要：

  以下为该化合物的中文翻译及其药用酸盐： 该化合物的化学式为：其中A为NR1R2、CR1R2R11、或C(═CR1R12)R2、NHCR1R2R11、OCR1R2R11、SCR1R2R11、NHNR1R2、CR2R11NHR1、CR2R11OR1、CR2R11SR1或C(O)R2；其中其余变量定义如下，用于治疗炎症性疾病。

  公开号：

  US06218397B1
• 作为产物：
  描述：

  2-氰基-3,3-双(甲基硫代)丙烯酰胺 、 2,4,6-三氯苯肼 、 水 以 甲醇 为溶剂， 反应 2.5h， 以to give 14.323 g (81.5% yield) of the title compound as a white solid的产率得到5-amino-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  Pyrazolopyrimidines as CRF antagonists

  摘要：

  化合物的公式：及其药学上可接受的酸盐，其中A为NR1R2、CR1R2R11或C(═CR1R12)R2、NHCR1R2R11、OCR1R2R11、SCR1R2R11、NHNR1R2、CR2R11NHR1、CR2R11OR1、CR2R11SR1或C(O)R2；其中其余变量在下文中定义，用于治疗炎症性疾病。

  公开号：

  US06218397B1

文献信息

• 6-Substituted pyrazolo[3,4-d] pyrimidin-4-ones useful as cyclin dependent kinase inhibitors
  申请人：——

  公开号：US20020013328A1

  公开（公告）日：2002-01-31

  The present invention relates to the synthesis of a novel class of pyrazolo[3,4-d]pyrimidin-4-ones of formula (I), alternatively represented by the tautomer (II): 1 that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cyclin dependent kinase 1-8 and their regulatory subunits know as cyclins A-H, K, N, and T. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

  本发明涉及合成一类新型吡唑并［3,4-d］嘧啶-4-酮的化合物，其化学式为（I），或者以互变异构体（II）表示： 1 这些化合物是强效的cyclin依赖激酶抑制剂，与被称为cyclin依赖激酶1-8的催化亚基及其调节亚基cyclin A-H、K、N和T有关。 本发明还提供了一种新的治疗癌症或其他增殖性疾病的方法，通过给予这些化合物之一或其药用可接受的盐形式的治疗有效剂量。另外，可以通过给予本发明化合物之一与一个或多个其他已知的抗癌或抗增殖剂的治疗有效组合来治疗癌症或其他增殖性疾病。
• 6-substituted pyrazolo [3,4-d] pyrimidin-4-ones useful as cyclin dependent kinase inhibitors
  申请人：DuPont Pharmaceuticals Company

  公开号：US06531477B1

  公开（公告）日：2003-03-11

  The present invention relates to the synthesis of a novel class of pyrazolo[3,4-d]pyrimidin-4-ones of formula (I), alternatively represented by the tautomer (II): that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cyclin dependent kinase 1-8 and their regulatory subunits know as cyclins A-H, K, N, and T. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

  本发明涉及合成一种新型吡唑并［3,4-d］嘧啶-4-酮类化合物，其化学式为（I），或其互变异构体（II），这些化合物是强效的细胞周期蛋白依赖性激酶抑制剂，与催化亚基细胞周期蛋白依赖性激酶1-8及其调节亚基细胞周期蛋白A-H，K，N和T有关。本发明还提供了一种治疗癌症或其他增生性疾病的新方法，通过给予这些化合物或其药学上可接受的盐形式的治疗有效剂量。或者，可以通过给予本发明化合物之一和一种或多种其他已知的抗癌或抗增生剂的治疗有效组合来治疗癌症或其他增生性疾病。
• 6-substituted pyrazolo[3,4-d]pyrimidin-4-ones useful as cyclin dependent kinase inhibitors
  申请人：DuPont Pharmaceuticals Company

  公开号：US06559152B2

  公开（公告）日：2003-05-06

  The present invention relates to the synthesis of a novel class of pyrazolo[3,4-d]pyrimidin-4-ones of formula (I), alternatively represented by the tautomer (II): that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cyclin dependent kinase 1-8 and their regulatory subunits know as cyclins A-H, K, N, and T. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

  本发明涉及一种新型嘧唑并[3,4-d]嘧啶-4-酮类化合物，其化学式为(I)，或可用互变异构体(II)表示，该化合物是强效的细胞周期蛋白依赖性激酶抑制剂，与催化亚基细胞周期蛋白依赖性激酶1-8以及其调控亚基，即A-H，K，N和T有关。本发明还提供了一种治疗癌症或其他增殖性疾病的新方法，即通过给患者注射这些化合物或其药学上可接受的盐形式的治疗有效剂量。另外，也可以通过给患者注射本发明化合物和一种或多种其他已知的抗癌或抗增殖剂的治疗有效组合来治疗癌症或其他增殖性疾病。
• Synthesis and Biological Evaluation of 1-Aryl-4,5-dihydro-1<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidin-4-one Inhibitors of Cyclin-Dependent Kinases
  作者：Jay A. Markwalder、Marc R. Arnone、Pamela A. Benfield、Michael Boisclair、Catherine R. Burton、Chong-Hwan Chang、Sarah S. Cox、Philip M. Czerniak、Charity L. Dean、Deborah Doleniak、Robert Grafstrom、Barbara A. Harrison、Robert F. Kaltenbach、David A. Nugiel、Karen A. Rossi、Susan R. Sherk、Lisa M. Sisk、Pieter Stouten、George L. Trainor、Peter Worland、Steven P. Seitz

  DOI：10.1021/jm020455u

  日期：2004.11.1

  Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.
• PYRAZOLOPYRIMIDINES AS CRF ANTAGONISTS
  申请人：PFIZER INC.

  公开号：EP0674642B1

  公开（公告）日：2000-08-23