4-amino-5,5-dimethyl-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one | 1228787-03-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 4-amino-5,5-dimethyl-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one
• 英文别名: 4-amino-5,5-dimethyl-2-[3-[(2,3,6-trifluorophenyl)methyl]indazol-1-yl]-7H-pyrrolo[2,3-d]pyrimidin-6-one
• CAS: 1228787-03-8
• 化学式: C₂₂H₁₇F₃N₆O
• 分子量: 438.412
• InChiKey: NXIBFDKAAHJUKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(2-bromo-5-chlorophenyl)-2-(2,3,6-trifluorophenyl)ethan-1-one 在 copper(l) iodide 、 10 wt% Pd(OH)2 on carbon 、 三氟化硼乙醚 、 氢气 作用下， 以 N-甲基吡咯烷酮 、 甲醇 为溶剂， 反应 4.51h， 生成 4-amino-5,5-dimethyl-2-[3-(2,3,6-trifluorobenzyl)-1H-indazol-1-yl]-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one
  参考文献：
  名称：

  Soluble guanylate cyclase stimulators for the treatment of hypertension: Discovery of MK-2947

  摘要：

  The NO-sGC-cGMP signaling pathway plays an important role in the cardiovascular system. Loss of nitric oxide tone or impaired signaling has been associated with cardiovascular diseases, such as hypertension, pulmonary hypertension and heart failure. Direct activation of sGC enzyme independent of NO represents a novel approach for modulating NO signaling with tremendous therapeutic potential. Herein, we describe the design of a structurally novel class of heme-dependent sGC stimulators containing the 3,3-dimethylpyrrolidin-2-one moiety which resulted in the identification of the potent, selective stimulator 30 (MK-2947) for the treatment of hypertension.

  DOI：

  10.1016/j.bmcl.2020.127574

文献信息

• SOLUBLE GUANYLATE CYCLASE ACTIVATORS
  申请人：Brockunier Linda L.

  公开号：US20110218202A1

  公开（公告）日：2011-09-08

  Compounds of Formula I are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of the Formula I, to their use for the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of the Formula I.

  公式I的化合物能够调节体内环状鸟苷酸单磷酸（“cGMP”）的产生，一般适用于治疗和预防与cGMP平衡紊乱相关的疾病。此外，本发明还涉及制备公式I化合物的过程，以及它们用于治疗和预防上述疾病和制备药物的用途，以及包含公式I化合物的制药制剂。
• The use of sGC stimulators, sGC activators, alone and combinations with PDE5 inhibitors for the treatment of systemic sclerosis (SSc)
  申请人：BIP Patents

  公开号：EP2594270A2

  公开（公告）日：2013-05-22

  The use of sGC stimulators, sGC activators alone, or in combination with PDE5 inhibitors for the prevention and treatment of fibrotic diseases, such as systemic sclerosis, scleroderma, and the concomitant fibrosis of internal organs.

  将 sGC 刺激剂、sGC 激活剂单独使用或与 PDE5 抑制剂联合使用，用于预防和治疗纤维化疾病，如系统性硬化症、硬皮病以及伴随而来的内脏器官纤维化。
• 4-amino-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one or 4-amino-5,8-dihydropyrido[2,3-d]pyrimidin-7(6H)-one derivatives as activators of the soluble guanylat cyclase for the treatment of cardiovascular diseases
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2373317B1

  公开（公告）日：2016-12-14
• US8741910B2
  申请人：——

  公开号：US8741910B2

  公开（公告）日：2014-06-03
• Soluble guanylate cyclase stimulators for the treatment of hypertension: Discovery of MK-2947
  作者：Linda Brockunier、John Stelmach、Jian Guo、Tracy Spencer、Keith Rosauer、Alka Bansal、Sheng-Jian Cai、Nancy Chen、John Cummings、Li Huang、Timothy Johnson、Sonia Levesque、Lin Luo、Kevin Maloney、Joseph Metzger、Christopher Mortko、Karen Ortega、Lee-Yuh Pai、Antonio Pereira、Gino Salituro、Jackie Shang、Cherrie Shepherd、Shiyao Sherrie Xu、Qifeng Yang、Jisong Cui、Sophie Roy、Emma Parmee、Subharekha Raghavan

  DOI：10.1016/j.bmcl.2020.127574

  日期：2020.11

  The NO-sGC-cGMP signaling pathway plays an important role in the cardiovascular system. Loss of nitric oxide tone or impaired signaling has been associated with cardiovascular diseases, such as hypertension, pulmonary hypertension and heart failure. Direct activation of sGC enzyme independent of NO represents a novel approach for modulating NO signaling with tremendous therapeutic potential. Herein, we describe the design of a structurally novel class of heme-dependent sGC stimulators containing the 3,3-dimethylpyrrolidin-2-one moiety which resulted in the identification of the potent, selective stimulator 30 (MK-2947) for the treatment of hypertension.