4-[(3-cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenylsulfonyl chloride | 182251-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[(3-cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenylsulfonyl chloride
• 英文别名: 4-[4-(3-Cyclopentylpropyl)-5-Tetrazolon-1-Yl]-Benzenesulfonyl Chloride；4-[4-(3-cyclopentylpropyl)-5-oxotetrazol-1-yl]benzenesulfonyl chloride
• CAS: 182251-92-9
• 化学式: C₁₅H₁₉ClN₄O₃S
• 分子量: 370.86
• InChiKey: BRPHETJUYPPIBS-UHFFFAOYSA-N

物化性质

• 沸点：
  474.3±47.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  90.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[(3-cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenylsulfonyl chloride 在 dimethyl sulfide borane 、 硫酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 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
• 作为产物：
  描述：

  3-环戊基丙酸 在 sodium azide 、 甲基叔丁基醚 、 dimethyl sulfide borane 、 三乙胺 作用下， 以 正辛烷 、 二甲基亚砜 为溶剂， 反应 48.0h， 生成 4-[(3-cyclopentylpropyl)-5-oxo-4,5-dihydrotetrazol-1-yl]phenylsulfonyl chloride
  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。
• [EN] COMBINATION THERAPY FOR THE TREATMENT OF DIABETES AND OBESITY<br/>[FR] TRAITEMENT COMBINE DU DIABETE ET DE L'OBESITE
  申请人：MERCK & CO., INC.

  公开号：WO1997016189A1

  公开（公告）日：1997-05-09

  (EN) The combination of the $g(b)3 adrenergic receptor agonist Compound A and a compound which modifies feeding behavior (e.g., the OB protein) is useful in the treatment of obesity and diabetes, either as compounds, pharmaceutically acceptable salts, pharmaceutical compoisition ingredients. Methods of treating obesity and diabetes are also described.(FR) L'invention porte sur la combinaison d'un composé A agoniste du récepteur adrénergique $g(b)3 et d'un composé modifiant le comportement alimentaire (par exemple la protéine OB) qui s'avèrent utiles contre l'obésité et le diabète. En utilisant soit la composition elle-même, soit ses sels pharmacocompatibles, soit des préparations pharmaceutiques dont ils sont les principes actifs. L'invention porte également sur les procédés de traitement associés.

  将$g(b)3肾上腺素受体激动剂Compound A与改变饮食行为的化合物（例如OB蛋白质）结合使用，可用于治疗肥胖症和糖尿病，无论是作为化合物、药学上可接受的盐、药物组成成分。还描述了治疗肥胖和糖尿病的方法。
• Cyclic amine phenyl beta-3 adrenergic receptor agonists
  申请人：——

  公开号：US20020028835A1

  公开（公告）日：2002-03-07

  This invention provides compounds of Formula I having the structure 1 wherein, R 1 , R 2 , R 3 , R 4 , R 5 , T, T 1 , T 2 , and X are as defined hereinbefore, or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, glaucoma, ocular hypertension and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.

  本发明提供了具有结构1的化合物，其中R1、R2、R3、R4、R5、T、T1、T2和X如前所定义，或其药学上可接受的盐，其在治疗或抑制与胰岛素抵抗或高血糖有关的代谢紊乱（通常与肥胖或葡萄糖不耐症有关）、动脉粥样硬化、胃肠道疾病、神经遗传性炎症、青光眼、眼压增高和频繁排尿方面非常有用；尤其适用于治疗或抑制2型糖尿病。
• Novel (4-Piperidin-1-yl)-phenyl Sulfonamides as Potent and Selective Human β3 Agonists
  作者：Baihua Hu、John Ellingboe、Stella Han、Elwood Largis、Kitae Lim、Michael Malamas、Ruth Mulvey、Chuansheng Niu、Alexander Oliphant、Jeffrey Pelletier、Thiruvikraman Singanallore、Fuk-Wah Sum、Jeff Tillett、Victoria Wong

  DOI：10.1016/s0968-0896(01)00114-6

  日期：2001.8

  A series of novel (4-piperidin-1-yl)-phenyl sulfonamides was prepared and evaluated for their biological activity on the human beta (3)-adrenergic receptor (AR). Replacement of the 3,4-dihydroxyl group of the catechol moiety with 4-hydroxyl-3-methyl sulfonamide on the left-hand side of the compounds resulted in a number of potent full agonists at the beta (3) receptor. Modification of the right-hand side of the compounds by incorporation of a free carboxylic acid resulted in a few potent human beta (3) agonists with low affinities for beta (1)- and beta (2)-ARs. N-Alkyl substitution on the 4-piperidin-1-yl-phenylamine further increased the beta (3) potency while maintaining the selectivity. For example, sulfonamide 48 is a potent full beta (3) agonist (EC50 = 0.004 muM, IA = 1.0) with > 500-fold selectivity over beta (1)- and beta (2)-ARs. (C) 2001 Elsevier Science Ltd. All rights reserved.
• L-770,644: A potent and selective human β3 adrenergic receptor agonist with improved oral bioavailability
  作者：Thomas L. Shih、Mari R. Candelore、Margaret A. Cascieri、Shuet-Hing L. Chiu、Lawrence F. Colwell、Liping Deng、William P. Feeney、Michael J. Forrest、Gary J. Hom、D.Euan MacIntyre、Randall R. Miller、Ralph A. Stearns、Catherine D. Strader、Laurie Tota、Matthew J. Wyvratt、Michael H. Fisher、Ann E. Weber

  DOI：10.1016/s0960-894x(99)00182-1

  日期：1999.5

  L-770,644 (9c) is a potent and selective agonist of the human pg adrenergic receptor (EC50 = 13 nM). It shows good oral bioavailability in both dogs and rats (%F = 27), and is a full agonist for glycerolemia in the rhesus monkey (ED50 = 0.21 mg/kg). Based on its desirable in vitro and in vivo properties, L-770,644 was chosen for further preclinical evaluation. (C) 1999 Elsevier Science Ltd. All rights reserved.