(2-amino-5,6-dihydro-4H-cyclopenta[b]thiophen-3-yl)-naphthalen-2-yl-methanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (2-amino-5,6-dihydro-4H-cyclopenta[b]thiophen-3-yl)-naphthalen-2-yl-methanone
• 英文别名: (2-amino-5,6-dihydro-4H-cyclopenta[b]thiophen-3-yl)-naphthalen-2-ylmethanone
• 化学式: C₁₈H₁₅NOS
• 分子量: 293.389
• InChiKey: AKVOCTBVCGJYJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 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-萘甲酸乙酯 在 吗啉 、 sodium hydride 、 sulfur 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 25.0h， 生成 (2-amino-5,6-dihydro-4H-cyclopenta[b]thiophen-3-yl)-naphthalen-2-yl-methanone
  参考文献：
  名称：

  新型2-氨基-3-萘甲噻吩作为A1腺苷受体的变构增强剂的合成及其生物学效应。

  摘要：

  当前的研究描述了一系列新型的2-氨基-3-萘噻吩并在噻吩的4-位和5-位以及萘环上有可变的修饰。以多种方式测量了变构增强子的活性：（1）在表达克隆的人A（C）的中国仓鼠卵巢（CHO）细胞中，在A（1）-腺苷激动剂（CPA）存在的情况下评估对福司柯林刺激的cAMP积累的影响。 1）-腺苷受体（hA（1）AR）; （2）这些化合物取代[（3）H] DPCPX，[（3）H] ZM 241385和[（3）H] MRE 3008F20与表达hA（ 1），hA（2A）和hA（3）腺苷受体；（3）对[（3）H] CCPA与表达hA（1）AR的CHO细胞膜结合的影响，含有天然腺苷A（1）受体的大鼠大脑和人类皮质膜制剂；（4）[（3）H] CCPA从CHO-hA1膜解离的动力学。药理分析比较了各种活性与参考化合物PD 81,723（化合物1）的活性。在CHO：hA（1）分析中，几种化合物似乎比PD 81,7

  DOI：

  10.1021/jm0210212

文献信息

• Allosteric adenosine receptor modulators
  申请人：——

  公开号：US20010047008A1

  公开（公告）日：2001-11-29

  The present invention relates to compounds of formulas (IA) and (IB): 1 the preparation thereof, pharmaceutical formulations thereof, and their use in medicine as allosteric adenosine receptor modulators for uses including protection against hypoxia and ischemia induced injury and treatment of adenosine-sensitive cardiac arrhythmias.

  本发明涉及以下化合物的公式（IA）和（IB）：其制备、药物配方以及在医学中作为变构腺苷受体调节剂的用途，包括保护免受缺氧和缺血引起的损伤以及治疗对腺苷敏感的心律失常。
• 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.
• EP1401441A4
  申请人：——

  公开号：EP1401441A4

  公开（公告）日：2006-09-06
• ALLOSTERIC ADENOSINE RECEPTOR MODULATORS
  申请人：King Pharmaceuticals Research and Development Inc.

  公开号：EP1401441A2

  公开（公告）日：2004-03-31
• US6727258B2
  申请人：——

  公开号：US6727258B2

  公开（公告）日：2004-04-27