2-乙氧基-5-[(4-乙基-1-哌嗪基)磺酰基]烟酸 | 247582-73-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2-乙氧基-5-[(4-乙基-1-哌嗪基)磺酰基]烟酸
• 中文别名: 3-吡啶羧酸,2-乙氧基-5-[(4-乙基-1-哌嗪基)磺酰]-
• 英文名称: 2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)nicotinic acid
• 英文别名: 2-Ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)pyridine-3-carboxylic Acid；2-ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)-3-carboxylic acid；pyridine-2-ethoxy-5-(4-ethylpiperazin-1-ylsulphonyl)-3-carboxylic acid；2-Ethoxy-5-(4-ethylpiperazin-4-ium-1-yl)sulfonylpyridine-3-carboxylate
• CAS: 247582-73-6
• 化学式: C₁₄H₂₁N₃O₅S
• 分子量: 343.404
• InChiKey: PCRIWLRXFJTJPJ-UHFFFAOYSA-N

物化性质

• 沸点：
  519.1±60.0 °C(Predicted)
• 密度：
  1.322±0.06 g/cm3(Predicted)
• 溶解度：
  >51.5 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-乙氧基-5-[(4-乙基-1-哌嗪基)磺酰基]烟酸 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 乙醇 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 5-[2-乙氧基-5-(4-乙基哌嗪-1-基磺酰基)吡啶-3-基]-3-乙基-2-(2-甲氧基乙基)-2,6-二氢-7H-吡唑并[4,3-D]嘧啶-7-酮
  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：

  3-溴-2-氯吡啶-5-磺酰氯 在 四(三苯基膦)钯 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 100.0 ℃ 、1.38 MPa 条件下， 反应 39.0h， 生成 2-乙氧基-5-[(4-乙基-1-哌嗪基)磺酰基]烟酸
  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

• Pyrazolopyrimidinone CGMP PDE5 inhibitors for the treatment of sexual dysfunction
  申请人：Pfizer Inc.

  公开号：US06407114B1

  公开（公告）日：2002-06-18

  There is provided compounds of formula IA and of formula IB, wherein R1, R2, R3, R4 and A have meanings given in the description, 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.

  提供了式IA和式IB的化合物， 其中R1、R2、R3、R4和A的含义如描述中所示，在治疗和预防需要抑制环状鸟苷3′,5′-单磷酸酯酶（例如cGMP PDE5）的医疗状况中非常有用。
• The Process Development of a Scaleable Route to the PDE5 Inhibitor UK-357,903
  作者：David J. Dale、John Draper、Peter J. Dunn、Michael L. Hughes、Farhat Hussain、Philip C. Levett、Gordon B. Ward、Albert S. Wood

  DOI：10.1021/op0200468

  日期：2002.11.1

  the 2-ethoxyphenyl moiety of sildenafil, necessitating the development of new chemistry. Particular items of note are (i) the new six-step route to the advanced 2-ethoxy-5-(4-ethylpiperazinylsulfonyl)nicotinic acid intermediate and the subsequent telescoping to a two-pot process, (ii) the telescoping of the two steps from N-[3-carbamoyl-5-ethyl-1-(2-pyridylmethyl)-1H-pyrazol-4-yl]-2-ethoxy-5-(4-et

  概述了开发候选药物 UK-357,903 的可扩展途径的案例历史。尽管与西地那非（伟哥）的结构部分相似，但在 UK-357,903 中引入中心吡啶部分对商业过程产生了重大影响。特别是，UK-357,903 的三重活化 2-烷氧基吡啶基部分比西地那非的 2-乙氧基苯基部分更容易受到亲核攻击，因此需要开发新的化学方法。特别值得注意的项目是 (i) 新的六步法制备先进的 2-乙氧基-5-(4-乙基哌嗪基磺酰基)烟酸中间体以及随后的两锅法，
• Pyrazolopyrimidine derivatives
  申请人：Pfizer Limited

  公开号：EP1241170A3

  公开（公告）日：2003-03-12

  The present invention provides a compound of formula (I): where Q is a group of formula:These compounds inhibit cyclic guanosine 3',5'-monophosphate phosphodiesterases (cGMP PDEs). More notably, the compounds are potent and selective inhibitors of the type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterases and have utility therefore in a variety of therapeutic areas. In particular, the present compounds are of value for the curative or prophylactic treatment of mammalian sexual disorders.

  本发明提供了一个式（I）的化合物：其中Q是一个式的基团：这些化合物抑制环鸟苷3',5'-磷酸二酯酶（cGMP PDEs）。更重要的是，这些化合物是强效且选择性地抑制类型5环鸟苷3',5'-磷酸二酯酶，并因此在多种治疗领域中具有用途。特别是，目前的化合物对于治疗哺乳动物性功能障碍具有价值。
• Novel process for the preparation of pyrazolopyrimidinones
  申请人：——

  公开号：US20020013465A1

  公开（公告）日：2002-01-31

  There is provided a process for the production a compound of general formula I: 1 wherein A, R 1 , R 2 , R 3 and R 4 have meanings given in the description, which process comprises the dehydrogenation of a compound of general formula II, 2

  提供了一种生产一般式I的化合物的过程：其中A、R1、R2、R3和R4具有描述中给出的含义，该过程包括对一般式II的化合物进行脱氢。
• Crystalline therapeutic agent
  申请人：——

  公开号：US20020040140A1

  公开（公告）日：2002-04-04

  A polymorph of 1-{6-ethoxy-5-[3-ethyl-6,7-dihydro-2-(2-methoxyethyl)-7-oxo-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-pyridylsulfonyl}-4-ethylpiperazine.

  1-{6-乙氧基-5-[3-乙基-6,7-二氢-2-(2-甲氧基乙基)-7-氧代-2H-吡唑并[4,3-d]嘧啶-5-基]-3-吡啶磺酰基}-4-乙基哌嗪的多晶形态。