Tert-butyl 3-(3-carbamoyl-5-ethyl-4-nitropyrazol-1-yl)azetidine-1-carboxylate | 334828-08-9

• 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: Tert-butyl 3-(3-carbamoyl-5-ethyl-4-nitropyrazol-1-yl)azetidine-1-carboxylate
• CAS: 334828-08-9
• 化学式: C₁₄H₂₁N₅O₅
• 分子量: 339.351
• InChiKey: PCZZXKZPFCDOBR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  136
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Tert-butyl 3-(3-carbamoyl-5-ethyl-4-nitropyrazol-1-yl)azetidine-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 双(三甲基硅烷基)氨基钾 、 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 溶剂黄146 、 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 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 20.0~130.0 ℃ 、344.75 kPa 条件下， 反应 72.5h， 生成 5-[2-n-butoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridin-3-yl]-3-ethyl-2-(1-methylazetidin-3-yl)-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

文献信息

• Pharmaceutically Active Compounds
  申请人：Bunnage Mark Edward

  公开号：US20100035891A1

  公开（公告）日：2010-02-11

  Compounds of the formula (I): wherein R 1 , R 2 , R 4 and R 13 are as defined or a pharmaceutically or veterinarily acceptable salt or polymorph thereof, or a pharmaceutically or veterinarily acceptable solvate or pro-drug thereof: are potent and selective inhibitors of type 5 cyclic guanosine 3′,5′-monophosphate phosphodiesterase (cGMP PDE5) and have utility in the treatment of, inter alia, male erectile dysfunction (MED) and female sexual dysfunction (FSD).

  化合物的式子（I）：其中R1、R2、R4和R13如定义所述，或其药学或兽医学可接受的盐或多晶体，或其药学或兽医学可接受的溶剂或前药：是5型环磷酸鸟苷3'，5'-单磷酸磷酸二酯酶（cGMP PDE5）的强效和选择性抑制剂，并在治疗男性勃起功能障碍（MED）和女性性功能障碍（FSD）等方面具有用途。
• US7176311B2
  申请人：——

  公开号：US7176311B2

  公开（公告）日：2007-02-13
• 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.