(2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-3-yl)(phenyl)methanone | 50508-70-8

• 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)(phenyl)methanone
• 英文别名: (2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-3-yl)-phenylmethanone
• CAS: 50508-70-8
• 化学式: C₁₆H₁₇NOS
• 分子量: 271.383
• InChiKey: LSYRTPSVHOYMRI-UHFFFAOYSA-N

物化性质

• 沸点：
  508.8±50.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  19
• 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

• 作为反应物：
  描述：

  (2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-3-yl)(phenyl)methanone 在 对甲苯磺酸 、 sodium nitrite 、 potassium iodide 作用下， 以 水 、 乙腈 为溶剂， 反应 0.5h， 生成 (5,6,7,8-tetrahydro-2-iodo-4H-cyclohepta[b]thiophen-3-yl)(phenyl)methanone
  参考文献：
  名称：

  设计和微波辅助合成新型2-苯基/ 2-苯基乙炔基-3-芳酰基噻吩作为有效的抗增殖剂† ‡

  摘要：

  在本研究中，已设计并通过微波辅助方法合成了2-苯基/ 2-苯基乙炔基-3-芳酰基噻吩。评价所有合成的化合物对各种人类癌细胞系的体外抗增殖活性。发现化合物12j和14h是针对所有测试癌细胞系的最有希望的化合物，尤其是针对A-375（分别为IC 50 = 1.07±0.1和0.81±0.1μM）和MIA PaCa-2（IC 50 = 5.35）分别为±0.6和3.00±1.0μM）癌细胞系，与标准紫杉醇相当。此外，最有效的化合物12j和通过钙黄绿素AM和克隆形成测定证实了14h，并且发现其诱导了G 2 / M期的细胞周期停滞，表明细胞暴露于选定的衍生物会产生有丝分裂失败。在计算机模拟中，ADME研究赋予口服药物类似有效化合物的特征。

  DOI：

  10.1039/c6md00256k
• 作为产物：
  描述：

  苯甲酰乙腈 、 环庚酮 在 吗啉 、 sulfur 作用下， 以 乙醇 为溶剂， 反应 12.25h， 生成 (2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-3-yl)(phenyl)methanone
  参考文献：
  名称：

  基于结合口袋的新型选择性BRD4-BD1抑制剂的设计，合成和生物学评估。

  摘要：

  含溴结构域的蛋白质4（BRD4）由两个串联的溴结构域（BD1和BD2）组成，是纤维化和癌症中的关键表观遗传调控因子，据报道BD1和BD2在翻译后修饰中具有独特的作用。但是，针对这两个域的选择性抑制剂很少。本文中，本研究使用计算机辅助药物设计（CADD）方法设计并合成了一系列新型选择性BRD4-BD1抑制剂，重点在于探索BD1和BD2结合口袋的差异，并发现His437是实现这一目标的关键途径BRD4-BD1选择性。我们的结果表明，化合物3u是一种有效的选择性BRD4-BD1抑制剂，BD1的IC50值为0.56μM，而BD2的IC50值为> 100μM。该化合物对几种人类癌症和成纤维细胞系具有广泛的抗增殖活性，这可能与其降低c-Myc和胶原I的表达能力有关。此外，它还可以诱导A375细胞凋亡。相反，选择性BD2抑制剂RVX-208没有显示任何这些活性。我们的发现突出表明BRD4-BD1的功能可

  DOI：

  10.1016/j.bmc.2019.03.037

文献信息

• 2-amino-3-aroyl-4,5 alkylthiophenes: agonist allosteric enhancers at human A1 adenosine receptors
  申请人：——

  公开号：US20030078248A1

  公开（公告）日：2003-04-24

  The present invention relates to a compound of formula (I): 1 wherein: R 3 is selected from the group consisting of 1-napthyl, 2-napthyl and cycloalkylphenyl; and R 4 and R 5 taken together form a ring having from 5 to 10 carbon atoms. Additionally, the invention provides a therapeutic method for preventing or treating a pathological condition or symptom in a mammal subject, such as a human, wherein increased angiogenesis is desired, comprising administering to a mammal in need of such therapy an effective amount of the aforementioned thiophene selective adenosine A 1 allosteric enhancer.

  本发明涉及以下式（I）的化合物：其中：R3选择自1-萘基、2-萘基和环烷基苯基所组成的群；以及R4和R5一起形成含有5到10个碳原子的环。此外，本发明提供了一种治疗方法，用于预防或治疗哺乳动物主体（如人类）中的病理状况或症状，其中需要增加血管生成，包括向需要此类治疗的哺乳动物中施用上述噻吩选择性腺苷A1受体变构增强剂的有效量。
• 2-Amino-3-aroyl-4,5 alkylthiophenes: agonist allosteric enhancers at human A1 adenosine receptors
  申请人：——

  公开号：US20040180948A1

  公开（公告）日：2004-09-16

  The present invention relates to a compound of formula (I): 1 wherein: R 3 is selected from the group consisting of 1-napthyl, 2-napthyl and cycloalkylphenyl; and R 4 and R 5 taken together form a ring having from 5 to 10 carbon atoms. Additionally, the invention provides a therapeutic method for preventing or treating a pathological condition or symptom in a mammal subject, such as a human, wherein increased angiogenesis is desired, comprising administering to a mammal in need of such therapy an effective amount of the aforementioned thiophene selective adenosine A 1 allosteric enhancer.

  本发明涉及一种式（I）的化合物：1其中：R3选自1-萘基，2-萘基和环烷基苯基的群组；以及R4和R5一起形成一个具有5至10个碳原子的环。此外，本发明提供了一种治疗方法，用于预防或治疗哺乳动物受体中的病理状况或症状，例如人类，其中需要增加血管生成，包括向需要此种治疗的哺乳动物中注射上述噻吩选择性腺苷A1异构增强剂的有效剂量。
• 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.
• 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.
• US6713638B2
  申请人：——

  公开号：US6713638B2

  公开（公告）日：2004-03-30