4-Amino-5-ethyl-1-[2-(4-morpholinyl)ethyl]-1H-pyrazole-3-carboxamide | 459833-45-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-Amino-5-ethyl-1-[2-(4-morpholinyl)ethyl]-1H-pyrazole-3-carboxamide
• 英文别名: 4-Amino-5-ethyl-1-(2-morpholin-4-ylethyl)pyrazole-3-carboxamide
• CAS: 459833-45-5
• 化学式: C₁₂H₂₁N₅O₂
• 分子量: 267.331
• InChiKey: ZOHYMUBHVQVRNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  99.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-Amino-5-ethyl-1-[2-(4-morpholinyl)ethyl]-1H-pyrazole-3-carboxamide 在 双(三甲基硅烷基)氨基钾 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 44.0h， 生成 5-[2-cyclopropylmethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-3-ethyl-[2-(morpholin-4-yl)ethyl]-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
  参考文献：
  名称：

  The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics

  摘要：

  This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published. 2,3 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.022
• 作为产物：
  描述：

  5-ethyl-1-[2-(4-morpholinyl)ethyl]-4-nitro-1H-pyrazole-3-carboxamide 在 palladium 10% on activated carbon 、 氢气 作用下， 生成 4-Amino-5-ethyl-1-[2-(4-morpholinyl)ethyl]-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics

  摘要：

  This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published. 2,3 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.10.022

文献信息

• Pharmaceutically active compounds
  申请人：——

  公开号：US20030064990A1

  公开（公告）日：2003-04-03

  Compound of general formula I: 1 wherein R 1 , R 2 , R 3 , R 4 , X, Y and R 5 have the meanings given herein which are useful in the curative and prophylactic treatment of a medical condition for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.

  通式I：1中R1、R2、R3、R4、X、Y和R5的含义如下，对于需要抑制环状鸟苷酸3′,5′-单磷酸酯酶（例如cGMP PDE5）的医疗状况的治疗和预防是有用的。
• US6770645B2
  申请人：——

  公开号：US6770645B2

  公开（公告）日：2004-08-03
• The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics
  作者：David J. Rawson、Stephen Ballard、Christopher Barber、Laura Barker、Kevin Beaumont、Mark Bunnage、Susan Cole、Martin Corless、Stephen Denton、David Ellis、Marion Floc’h、Laura Foster、James Gosset、Frances Holmwood、Charlotte Lane、David Leahy、John Mathias、Graham Maw、William Million、Cedric Poinsard、Jenny Price、Rachel Russel、Stephen Street、Lesa Watson

  DOI：10.1016/j.bmc.2011.10.022

  日期：2012.1

  This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published. 2,3 (C) 2011 Elsevier Ltd. All rights reserved.