6-溴-1a,2,3,7b-四氢-1-噁-环丙[a]萘 | 75693-20-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 中文名称: 6-溴-1a,2,3,7b-四氢-1-噁-环丙[a]萘
• 英文名称: (+/-)-cis-6-bromo-1a,2,3,7b-tetrahydronaphtho[1,2-b]oxirene
• 英文别名: 6-Bromo-1a,2,3,7b-tetrahydro-1-oxa-cyclopropa[a]naphthalene；6-bromo-1a,2,3,7b-tetrahydronaphtho[1,2-b]oxirene
• CAS: 75693-20-8
• 化学式: C₁₀H₉BrO
• 分子量: 225.085
• InChiKey: SYSQBWSXGVPPCP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-溴-1a,2,3,7b-四氢-1-噁-环丙[a]萘 在 sodium azide 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 1.5h， 以92%的产率得到trans-1-azido-7-bromo-1,2,3,4-tetrahydro-2-naphthol
  参考文献：
  名称：

  5,6,6a，8,9,11a-六氢萘[1'，2'：4,5]咪唑[2,1-b]噻唑和5,6,6a，9,10,11a的合成及免疫活性-六氢萘[2'，1'：4,5]咪唑并[2,1-b]噻唑。

  摘要：

  一系列5,6,6a，8,9,11a-六氢萘[1'，2'：4,5]咪唑[2，qb]噻唑（17和20）和5,6,6a，9,10，已合成了11a-六氢萘[2'，1'：4,5]咪唑并[2,1-b]噻唑，其中顺式和/或反式-1,2-二氨基-1,2,3,4-四氢萘为关键中间体并随后评估其免疫活性（对抗体形成和迟发型超敏反应的影响）。在测试的化合物中，反式-5,6,6a，8,9,11a-六氢萘[1'，2'：4,5]咪唑[2,1-b]噻唑（反式17a）和（+/-） -5,6,6a beta，8,9,11a alpha-hexahydro-8 beta-hydroxy-9 beta-methyl-8 alpha-phenylnaphth [1'，2'：4,5]咪唑[2，1-b]噻唑（20a）在小鼠中显示出最大的免疫活性，其程度与左旋咪唑相当，并且在急性毒理学研究中发现其毒性明显低于左旋咪唑。通过X射线晶体学确定18a和20a的结构。

  DOI：

  10.1021/jm00186a015
• 作为产物：
  描述：

  trans-2,7-dibromo-1,2,3,4-tetrahydro-1-naphthol 在 potassium tert-butylate 作用下， 以 苯 为溶剂， 反应 2.0h， 生成 6-溴-1a,2,3,7b-四氢-1-噁-环丙[a]萘
  参考文献：
  名称：

  Chini, Marco; Crotti, Paolo; Minutolo, Filippo, Gazzetta Chimica Italiana, 1994, vol. 124, # 1, p. 27 - 34

  摘要：

  DOI：

文献信息

• Cathepsin S Inhibitor Compounds
  申请人：DENG Gary G.

  公开号：US20120095020A1

  公开（公告）日：2012-04-19

  The present invention provides a compound of Formula (I): or a pharmaceutically acceptable salt thereof. Also, the present invention provides a pharmaceutical composition comprising a compound of Formula (I) or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable diluent or carrier. The present invention further provides methods for treating abdominal aortic aneurysm, plaque instability, atherosclerosis, or autoimmune disorders such as rheumatoid arthritis, psoriasis, and lupus comprising administering a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof or a pharmaceutical composition comprising a compound of Formula (I) or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable diluent or carrier.

  本发明提供了化合物的化学式(I)： 或其药学上可接受的盐。此外，本发明提供了一种包含化合物的药物组合物的制剂(I)或其药学上可接受的盐与药学上可接受的稀释剂或载体。本发明还提供了治疗腹主动脉瘤、斑块不稳定性、动脉粥样硬化或类风湿性关节炎、牛皮癣和红斑狼疮等自身免疫性疾病的方法，包括给予化合物的治疗有效量的化合物的化学式(I)或其药学上可接受的盐或包含化合物的药物组合物的制剂(I)或其药学上可接受的盐和药学上可接受的稀释剂或载体。
• Piperazine compounds
  申请人：Peglion Jean-Louis

  公开号：US20060229318A1

  公开（公告）日：2006-10-12

  A compound selected from those of formula (I): wherein: R 1 , R 2 , R 3 and R 4 , which may be the same or different, each represent an atom or group selected from hydrogen, halogen, alkyl, alkoxy, phenyl and cyano, X represents a bond, an oxygen atom or a group selected from —(CH 2 ) m —, —OCH 2 — and —NR 5 —, wherein m represents 1 or 2, and R 5 is as defined in the description, Y represents an oxygen atom or a group selected from NR 7 and CHR 8 , wherein R 7 and R 8 are as defined in the description, Z represents a nitrogen atom or a CH group, n represents 1 or 2, Ak represents an alkylene chain, Ar represents an aryl or heteroaryl group, its optical isomers, and addition salts thereof with a pharmaceutically acceptable acid. Medical products containing the same which are useful in the treatment of conditions requiring a serotonin reuptake inhibitor and/or NK 1 antagonist.

  从以下化学式（I）中选择的一种化合物：其中：R1、R2、R3和R4，可以相同也可以不同，每个代表从氢、卤素、烷基、烷氧基、苯基和氰基中选择的原子或基团，X代表键，氧原子或从—（CH2）m—、—OCH2—和—NR5—中选择的基团，其中m代表1或2，R5如描述中定义，Y代表氧原子或从NR7和CHR8中选择的基团，其中R7和R8如描述中定义，Z代表氮原子或CH基团，n代表1或2，Ak代表烷基链，Ar代表芳基或杂环芳基，其对映异构体，以及其与药用可接受酸形成的加合盐。含有这种化合物的医疗产品，用于治疗需要选择性5-羟色胺再摄取抑制剂和/或NK1拮抗剂的疾病。
• Tetralinderivate
  申请人：MERCK PATENT GmbH

  公开号：EP0368160A1

  公开（公告）日：1990-05-16

  Neue Tetralinderivate der Formel I worin R¹ bis R⁸ und Z die in Patentanspruch 1 angegebenen Bedeutungen haben, sowie ihre Salze zeigen Wirkungen auf das cardiovas­kuläre System.

  一种式 I 的新型四氢萘衍生物 其中 R¹ 至 R⁸ 和 Z 的含义如权利要求 1 所述、 及其盐类对心血管系统有作用。
• Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm
  作者：Prabhakar K. Jadhav、Matthew A. Schiffler、Kostas Gavardinas、Euibong J. Kim、Donald P. Matthews、Michael A. Staszak、D. Scott Coffey、Bruce W. Shaw、Kenneth C. Cassidy、Richard A. Brier、Yuke Zhang、Robert M. Christie、William F. Matter、Keyun Qing、Jim D. Durbin、Yong Wang、Gary G. Deng

  DOI：10.1021/ml500283g

  日期：2014.10.9

  Cathepsin S (Cat S) plays an important role in many pathological conditions, including abdominal aortic aneurysm (AAA). Inhibition of Cat S may provide a new treatment for AAA. To date, several classes of Cat S inhibitors have been reported, many of which form covalent interactions with the active site Cys25. Herein, we report the discovery of a novel series of noncovalent inhibitors of Cat S through a medium-throughput focused cassette screen and the optimization of the resulting hits. Structure-based optimization efforts led to Cat S inhibitors such as 5 and 9 with greatly improved potency and drug disposition properties. This series of compounds binds to the S2 and S3 subsites without interacting with the active site Cys25. On the basis of in vitro potency, selectivity, and efficacy in a CaC12-induced AAA in vivo model, 5 (LY3000328) was selected for clinical development.
• Aromatic substituent effect on the stereoselectivity of the condensed- and gas-phase acid-induced methanolysis in 2-aryloxiranes derived from 3,4-dihydronaphthalene and trans-1,2,3,4,4a,10a-hexahydrophenanthrene bearing a tertiary benzylic oxirane nucleophilic centre
  作者：Paolo Crotti、Valeria Di Bussolo、Lucilla Favero、Mauro Pineschi、Daniela Sergiampietri、Gabriele Renzi、Massimo Ricciutelli、Graziella Roselli

  DOI：10.1016/s0040-4020(97)00209-3

  日期：1997.4

  The ring-opening reactions with MeOH of the title benzocondensed 2-aryl oxiranes 6 and 7a,b both in the condensed (methanolysis) and in the gas phase were examined, obtaining in all cases a good Hammett-type linear correlation. Results indicate that the secondary or tertiary nature of the benzylic oxirane carbon is not responsible for the different stereochemical behavior so far encountered in different 2-aryl oxirane systems under the same operating conditions. (C) 1997 Elsevier Science Ltd.