4-[4-(3-环戊基丙基)-5-羰基-4,5-二氢-1H-四唑-1-基]-N-[4-[2-[2(R)-羟基-2-(3-吡啶基)乙胺基]乙基]苯基]苯磺酰胺 | 173901-95-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-[4-(3-环戊基丙基)-5-羰基-4,5-二氢-1H-四唑-1-基]-N-[4-[2-[2(R)-羟基-2-(3-吡啶基)乙胺基]乙基]苯基]苯磺酰胺
• 英文名称: L 770644
• 英文别名: (R)-N-[4-[2-[[2-hydroxy-2-(pyridin-3-yl)ethyl]amino]ethyl]phenyl]-4-[4-(3-cyclopentylpropyl)-5-tetrazolon-1-yl]benzenesulfonamide；Benzenesulfonamide, 4-(4-(3-cyclopentylpropyl)-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)-N-(4-(2-(((2R)-2-hydroxy-2-(3-pyridinyl)ethyl)amino)ethyl)phenyl)-；4-[4-(3-cyclopentylpropyl)-5-oxotetrazol-1-yl]-N-[4-[2-[[(2R)-2-hydroxy-2-pyridin-3-ylethyl]amino]ethyl]phenyl]benzenesulfonamide
• CAS: 173901-95-6
• 化学式: C₃₀H₃₇N₇O₄S
• 分子量: 591.734
• InChiKey: GCRTUWDFTYDUFB-LJAQVGFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  42
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  148
• 氢给体数：
  3
• 氢受体数：
  9

制备方法与用途

L-770644是B3肾上腺素能受体的激动剂。

反应信息

• 作为产物：
  描述：

  4-(氯磺酰)异氰酸苯酯 在 dimethyl sulfide borane 、 硫酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 正辛烷 、 水 、 乙酸乙酯 为溶剂， 反应 48.0h， 生成 4-[4-(3-环戊基丙基)-5-羰基-4,5-二氢-1H-四唑-1-基]-N-[4-[2-[2(R)-羟基-2-(3-吡啶基)乙胺基]乙基]苯基]苯磺酰胺
  参考文献：
  名称：

  Practical chemoenzymatic synthesis of a 3-pyridylethanolamino β3 adrenergic receptor agonist

  摘要：

  A chemoenzymatic synthesis of beta(3) agonist 1 suitable for large scale preparation is described. The key chiral 3-pyridylethanolamine intermediate (R)-7 was prepared via an improved Neber rearrangement and a yeast-mediated asymmetric reduction. The tetrazolone fragment of the molecule was constructed via a dipolar cycloaddition between 1-(cyclopentyl)-3-propylazide and p-chlorosulfonyl phenylisocyanate. Sulfonamide coupling of these two intermediates under Shotten-Baumann conditions, followed by a borane reduction of the amide afforded 1 in 20-32% overall yield from 3-acetylpyridine, (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)01353-2

文献信息

• Substituted sulfonamides as selective .beta..sub.3 agonists for the
  申请人：Merck & Co., Inc.

  公开号：US05561142A1

  公开（公告）日：1996-10-01

  Substituted sulfonamides are selective .beta..sub.3 adrenergic receptor agonists with very little .beta..sub.1 and .beta..sub.2 adrenergic receptor activity and as such the compounds are capable of increasing lipolysis and energy expenditure in cells. The compounds thus have potent activity in the treatment of Type II diabetes and obesity. The compounds can also be used to lower triglyceride levels and cholesterol levels or raise high density lipoprotein levels or to decrease gut motility. In addition, the compounds can be used to reduced neurogenic inflammation or as antidepressant agents. The compounds are prepared by coupling an aminoalkylphenyl-sulfonamide with an appropriately substituted epoxide. Compositions and methods for the use of the compounds in the treatment of diabetes and obesity and for lowering triglyceride levels and cholesterol levels or raising high density lipoprotein levels or for increasing gut motility are also disclosed.

  磺胺代替物是选择性的β3肾上腺素受体激动剂，几乎没有β1和β2肾上腺素受体活性，因此这些化合物能够增加细胞内的脂肪分解和能量消耗。因此，这些化合物在治疗2型糖尿病和肥胖症方面具有强效活性。这些化合物还可以用于降低甘油三酯水平和胆固醇水平，或提高高密度脂蛋白水平，或降低肠道蠕动。此外，这些化合物可以用于减少神经源性炎症或作为抗抑郁剂。这些化合物是通过将氨基烷基苯磺胺与适当取代的环氧化合物偶联而制备的。还公开了这些化合物在治疗糖尿病和肥胖症，降低甘油三酯水平和胆固醇水平，提高高密度脂蛋白水平或增加肠道蠕动的组合物和方法。
• Propanolamine derivatives
  申请人：Fujisawa Pharmaceutical Co. Ltd.

  公开号：US20020120148A1

  公开（公告）日：2002-08-29

  This invention relates to new propanolamine derivatives or salts thereof represented by the following formula [I]: 1 Wherein each symbol is as defined in the specification or salts thereof which have gut selective sympathomimetic, anti-ulcerous, anti-pancreatitis, lipolytic, anti-urinary incontinence and anti-pollakiuria activities, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method for the prevention and/or treatment diseases indicated in the specification to a human being or an animal.

  这项发明涉及新的丙醇胺衍生物或其盐，其化学式如下所示：1其中每个符号如规范中定义，或具有选择性肠道交感神经兴奋作用、抗溃疡、抗胰腺炎、脂解作用、抗尿失禁和抗尿频活性的盐，以及其制备方法、包含相同的药物组合物以及用于预防和/或治疗规范中指示的疾病的方法，适用于人类或动物。
• Use of beta 3 adrenergic receptor agonists in the treatment of dysuria
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP1382333A2

  公开（公告）日：2004-01-21

  The application relates to the use of a β3 adrenergic receptor agonist selected from the group consisting of formulas (IV),(V),(VI),(VII) and (VIII) for the manufacture of a medicament for the prophylactic and/or the therapeutic treatment of dysuria. In the above formulae, the various groups, substituents and variables have the meanings given in the description.

  本申请涉及选自式(IV)、(V)、(VI)、(VII)和(VIII)组成的组中的β3 肾上腺素能受体激动剂的用途。 用于制造预防和/或治疗排尿困难的药物。在上式中，各基团、取代基和变量具有说明中给出的含义。
• Verwendung eines beta-3-Adrenozeptor-Agonisten zur Behandlung von Nieren- und Blasenbeschwerden
  申请人：Boehringer Ingelheim Pharma GmbH & Co.KG

  公开号：EP1769792A1

  公开（公告）日：2007-04-04

  Diese Erfindung betrifft die Verwendung von beta-3-Adrenozeptor-Agonisten zur Vorbeugung und Behandlung von Nierenschäden und / oder funktionalen Blasenbeschwerden, insbesondere von Blasenbeschwerden neurogenen Ursprungs in Folge von Rückenmarksschädigungen.

  本发明涉及使用β-3肾上腺素受体激动剂预防和治疗肾损伤和/或功能性膀胱问题，特别是脊髓损伤导致的神经源性膀胱问题。
• Use of a beta-3 agonist for the treatment of disorders of the prostate and of the lower urogenital tract
  申请人：Michel Christian Martin

  公开号：US20060084700A1

  公开（公告）日：2006-04-20

  This invention describes the use of beta-3-adrenoceptor agonists for the treatment of disorders associated with the prostate. These include disorders like those occurring in a prostatitis, where attributable to inflammatory processes or chronic irritation, or disorders like those associated with benign changes of the prostate. The invention is particularly suitable for the treatment of benign prostatic hyperplasia (BPH).

  本发明描述了使用β-3肾上腺素受体激动剂治疗与前列腺有关的疾病。这些疾病包括由炎症过程或慢性刺激引起的前列腺炎等疾病，或与前列腺良性病变有关的疾病。本发明尤其适用于治疗良性前列腺增生症（BPH）。