2-(4-pyrazolo[1,5-b]pyridazin-3-ylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide | 1146395-50-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-pyrazolo[1,5-b]pyridazin-3-ylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide
• 英文别名: 2-(4-pyrazolo[1,5-b]pyridazin-3-ylphenyl)-N-[(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl]acetamide
• CAS: 1146395-50-7
• 化学式: C₂₃H₂₀F₃N₅O₂
• 分子量: 455.439
• InChiKey: DUFFIOALCYNCEY-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (R)-1-(5-(2,2,2-三氟乙氧基)吡啶-2-基)乙胺 、 (4-pyrazolo[1,5-b]pyridazin-3-ylphenyl)acetic acid 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 2-(4-pyrazolo[1,5-b]pyridazin-3-ylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide
  参考文献：
  名称：

  短效T型钙通道拮抗剂可显着改变啮齿动物的睡眠结构。

  摘要：

  已经使用体外和体内试验鉴定并评估了新型的短效T型钙通道拮抗剂苯基乙酰胺。苯基乙酰胺的4位杂环取代提供了有效的和选择性的拮抗剂，这些拮抗剂在临床前物种中表现出所需的短血浆半衰期。领先的化合物TTA-A8以具有出色的体内功效的化合物出现，这是由其在EEG遥测模型中对大鼠睡眠结构的显着调节，良好的药代动力学特性以及出色的临床前安全性所表明的。TTA-A8最近进入了人类临床试验，并且与我们的预测一致，以20 mg口服剂量进行的初步研究（n = 12）提供的最高C max为1.82 +/- 0.274μM，表观终末半衰期为3.0 +/- 1.1小时

  DOI：

  10.1021/ml100170e

文献信息

• [EN] HETEROCYCLE PHENYL AMIDE T-TYPE CALCIUM CHANNEL ANTAGONISTS<br/>[FR] ANTAGONISTES DE CANAUX CALCIQUES DE TYPE T À BASE DE PHÉNYLE AMIDE HÉTÉROCYCLIQUE
  申请人：MERCK & CO INC

  公开号：WO2009054984A1

  公开（公告）日：2009-04-30

  The present invention is directed to heterocycle phenyl amide compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.

  本发明涉及杂环苯酰胺化合物，这些化合物是T型钙通道的拮抗剂，可用于治疗或预防涉及T型钙通道的疾病和疾病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及T型钙通道的疾病中使用这些化合物和组合物。
• HETEROCYCLE PHENYL AMIDE T-TYPE CALCIUM CHANNEL ANTAGONISTS
  申请人：Barrow James C.

  公开号：US20100261724A1

  公开（公告）日：2010-10-14

  The present invention is directed to heterocycle phenyl amide compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.

  本发明涉及杂环苯酰胺化合物，其为T型钙通道的拮抗剂，可用于治疗或预防涉及T型钙通道的疾病和疾病。本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及T型钙通道的疾病中的使用。
• Heterocycle phenyl amide T-type calcium channel antagonists
  申请人：Barrow James C.

  公开号：US08637513B2

  公开（公告）日：2014-01-28

  The present invention is directed to heterocycle phenyl amide compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.

  本发明涉及杂环苯酰胺化合物，其为T型钙通道的拮抗剂，可用于治疗或预防涉及T型钙通道的疾病和疾病。本发明还涉及包含这些化合物的制药组合物及其在预防或治疗涉及T型钙通道的疾病中的使用。
• US8637513B2
  申请人：——

  公开号：US8637513B2

  公开（公告）日：2014-01-28
• Short-Acting T-Type Calcium Channel Antagonists Significantly Modify Sleep Architecture in Rodents
  作者：Zhi-Qiang Yang、Kelly-Ann S. Schlegel、Youheng Shu、Thomas S. Reger、Rowena Cube、Christa Mattern、Paul J. Coleman、Jim Small、George D. Hartman、Jeanine Ballard、Cuyue Tang、Yuhsin Kuo、Thomayant Prueksaritanont、Cindy E. Nuss、Scott Doran、Steve V. Fox、Susan L. Garson、Yuxing Li、Richard L. Kraus、Victor N. Uebele、Adekemi B. Taylor、Wei Zeng、Wei Fang、Cynthia Chavez-Eng、Matthew D. Troyer、Julie Ann Luk、Tine Laethem、William O. Cook、John J. Renger、James C. Barrow

  DOI：10.1021/ml100170e

  日期：2010.12.9

  A novel phenyl acetamide series of short-acting T-type calcium channel antagonists has been identified and evaluated using in vitro and in vivo assays. Heterocycle substitutions of the 4-position of the phenyl acetamides afforded potent and selective antagonists that exhibited desired short plasma half-lives across preclinical species. Lead compound TTA-A8 emerged as a compound with excellent in vivo

  已经使用体外和体内试验鉴定并评估了新型的短效T型钙通道拮抗剂苯基乙酰胺。苯基乙酰胺的4位杂环取代提供了有效的和选择性的拮抗剂，这些拮抗剂在临床前物种中表现出所需的短血浆半衰期。领先的化合物TTA-A8以具有出色的体内功效的化合物出现，这是由其在EEG遥测模型中对大鼠睡眠结构的显着调节，良好的药代动力学特性以及出色的临床前安全性所表明的。TTA-A8最近进入了人类临床试验，并且与我们的预测一致，以20 mg口服剂量进行的初步研究（n = 12）提供的最高C max为1.82 +/- 0.274μM，表观终末半衰期为3.0 +/- 1.1小时