(2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-3-yl)(4-chlorophenyl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-3-yl)(4-chlorophenyl)methanone
• 英文别名: 2-Amino-3-(4-chlorobenzoyl)-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene；(2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-3-yl)-(4-chlorophenyl)methanone
• 化学式: C₁₆H₁₆ClNOS
• 分子量: 305.828
• InChiKey: YMKSODDTUCIDIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  71.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2'-溴-4-氯苯乙酮 在 吗啉 、 sulfur 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 生成 (2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-3-yl)(4-chlorophenyl)methanone
  参考文献：
  名称：

  Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1-adenosine receptor

  摘要：

  New derivatives of PD 81,723, an allosteric enhancer of agonist binding to the A(1)-adenosine receptor, have been synthesized and evaluated in an intact cell assay. Compounds 3a, 3o and 3p appeared to be more potent than PD 81.723 and at a concentration of 0.1 mu M caused significant reductions of cAMP content of CHO cells expressing the human A(1)-adenosine receptor. Compounds 4e and 4o appeared to be allosteric enhancers at a low concentration and antagonists at a higher concentration, whereas compounds 3c, 3g, 3s and ill appeared to be weak antagonists that are also allosteric enhancers at the: higher concentration of 10 mu M. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00379-6

文献信息

• 2-Amino-3-aroyl-4,5-alkylthiophenes:  Agonist Allosteric Enhancers at Human A₁ Adenosine Receptors
  作者：C. Elisabet Tranberg、Andrea Zickgraf、Brian N. Giunta、Henning Luetjens、Heidi Figler、Lauren J. Murphree、Ruediger Falke、Holger Fleischer、Joel Linden、Peter J. Scammells、Ray. A. Olsson

  DOI：10.1021/jm010081p

  日期：2002.1.1

  2-Amino-3-benzoylthiophenes are allosteric enhancers (AE) of agonist activity at the A(1) adenosine receptor. The present report describes syntheses and assays of the AE activity at the human A(1)AR (hA(1)AR) of a panel of compounds consisting of nine 2-amino-3-aroylthiophenes (3a-i), eight 2-amino-3-benzoyl-4,5-dimethylthiophenes (12a-h), three 3-aroyl-2-carboxy-4,5-dimethylthiophenes (15a-c), 10 2-amino-3-benzoyl-5,6-dihydro-4H-cyclopenta[b]thiophenes (17a-j), 14 2-amino-3-benzoyl-4,5,6,7-tetrahydrobenzo[b]thiophenes (18a-n), and 15 2-amino-3-benzoyl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophenes (19a-o). An in vitro assay employing the A(1)AR agonist [I-125]ABA and membranes from CHO-K1 cells stably expressing the hA(1)AR measured, as an index of AE activity, the ability of a candidate AE to stabilize the agonist-A(1)AR-G protein ternary complex. Compounds 3a-i had little or no AE activity, and compounds 12a-h had only modest activity, evidence that AE activity depended absolutely on the presence of at least a methyl group at C-4 and C-5. Compounds 17a-c lacked AE activity, suggesting the 2-amino group is essential. Polymethylene bridges linked thiophene C-4 and C-5 of compounds 17a-j, 18a-n, and 19a-o. AE activity increased with the size of the -(CH2)(n)- bridge, n = 3 < n = 4 < n = 5. The 3-carbethoxy substituents of 17a, 18a, and 19a did not support AE activity, but a 3-aroyl group did. Bulky (or hydrophobic) substituents at the meta and para positions of the 3-benzoyl group and also 3-naphthoyl groups greatly enhanced activity. Thus, the hA(1)AR contains an allosteric binding site able to accommodate 3-aroyl substituents that are bulky and/or hydrophobic but not necessarily planar. A second region in the allosteric binding site interacts constructively with alkyl substituents at thiophene C-4 and/or C-5.
• THIOPHENS AND THEIR USE AS ANTI-TUMOR AGENTS
  申请人：Compass Pharmaceuticals LLC

  公开号：EP1802634A2

  公开（公告）日：2007-07-04
• Thiophens and Their Use as Anti-Tumor Agents
  申请人：Ward John

  公开号：US20090143411A1

  公开（公告）日：2009-06-04

  The present invention provides novel compounds and pharmaceutical compositions thereof, as well as methods for using the compounds and pharmaceutical compositions for treating tumors. Examples of specific tumor types that the compounds may be used to treat include, but are not limited to sarcomas, melanomas, neuroblastomas, carcinomas (including but not limited to lung, renal cell, ovarian, liver, bladder, and pancreatic carcinomas), and mesotheliomas.
• [EN] COMPOSITIONS AND THEIR USE AS ANTI-TUMOR AGENTS<br/>[FR] COMPOSITIONS ET LEUR UTILISATION EN TANT QU'AGENTS ANTITUMORAUX
  申请人：COMPASS PHARMACEUTICALS LLC

  公开号：WO2006044826A2

  公开（公告）日：2006-04-27

  [EN] The present invention provides novel compounds and pharmaceutical compositions thereof, as well as methods for using the compounds and pharmaceutical compositions for treating tumors. Examples of specific tumor types that the compounds may be used to treat include, but are not limited to sarcomas, melanomas, neuroblastomas, carcinomas (including but not limited to lung, renal cell, ovarian, liver, bladder, and pancreatic carcinomas), and mesotheliomas.
  [FR] L'invention concerne de nouveaux composés et des compositions pharmaceutiques comportant ces nouveaux composés, ainsi que des méthodes pour utiliser les composés et les compositions pharmaceutiques de l'invention pour traiter des tumeurs. Des exemples de types de tumeur spécifiques pouvant être traités par l'utilisation des composés de l'invention comprennent, de manière non exhaustive: les sarcomes, les mélanomes, les neuroblastomes, les carcinomes (comprenant, de manière non exhaustive, les carcinomes de poumons, des cellules rénales, des ovaires, du foie, de la vessie et du pancréas), et des mésothéliomes.
• Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1-adenosine receptor
  作者：Pier Giovanni Baraldi、Abdel Naser Zaid、Ilaria Lampronti、Francesca Fruttarolo、Maria Giovanna Pavani、Mojgan Aghazadhe Tabrizi、John C Shryock、Edward Leung、Romeo Romagnoli

  DOI：10.1016/s0960-894x(00)00379-6

  日期：2000.9

  New derivatives of PD 81,723, an allosteric enhancer of agonist binding to the A(1)-adenosine receptor, have been synthesized and evaluated in an intact cell assay. Compounds 3a, 3o and 3p appeared to be more potent than PD 81.723 and at a concentration of 0.1 mu M caused significant reductions of cAMP content of CHO cells expressing the human A(1)-adenosine receptor. Compounds 4e and 4o appeared to be allosteric enhancers at a low concentration and antagonists at a higher concentration, whereas compounds 3c, 3g, 3s and ill appeared to be weak antagonists that are also allosteric enhancers at the: higher concentration of 10 mu M. (C) 2000 Elsevier Science Ltd. All rights reserved.