8-fluoro-dibenzo[b,f]thiepin-3-carboxylic acid-5-oxide | 89825-69-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫平类
• 英文名称: 8-fluoro-dibenzo[b,f]thiepin-3-carboxylic acid-5-oxide
• 英文别名: 8-Fluorodibenzo(b,f)thiepin-3-carboxylic acid-5-oxide；(11R)-3-fluoro-11-oxobenzo[b][1]benzothiepine-9-carboxylic acid
• CAS: 89825-69-4
• 化学式: C₁₅H₉FO₃S
• 分子量: 288.299
• InChiKey: SAHGCTPARQWSQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-fluoro-dibenzo[b,f]thiepin-3-carboxylic acid-5-oxide 、 麻黄碱 生成 (11R)-3-fluoro-11-oxobenzo[b][1]benzothiepine-9-carboxylic acid;(1R,2S)-2-(methylamino)-1-phenylpropan-1-ol
  参考文献：
  名称：

  BELANGER, P. C.;WILLIAMS, H. W. R.;ROKACK, J.

  摘要：

  DOI：
• 作为产物：
  描述：

  3-Cyano-8-fluorodibenzo[b,f]thiepin-5-Oxide 、 溶剂黄146 生成 8-fluoro-dibenzo[b,f]thiepin-3-carboxylic acid-5-oxide
  参考文献：
  名称：

  ROKACH, J.;ROONEY, C. S.;CRAGOE, E. J. ,, JR.

  摘要：

  DOI：

文献信息

• Resolution of substituted dibenzo\x9bb,f!thiepin-3-carboxylic acid-5-oxides \n'
  申请人：Merck & Co., Inc.

  公开号：US04424355A1

  公开（公告）日：1984-01-03

  The present invention is concerned with an improved process for the production of highly active optical isomers of (-) 7 or 8 fluorodibenzo\x9bb,f!thiepin-3-carboxylic acid-5-oxide having the structural \n' formula ##STR1## in which the fluoro substituent replaces a hydrogen in the 7 or 8 position. The two active isomers represented by formula II are S(-)7-fluorodibenzo\x9bb,f!thiepin-3-carboxylic acid-5-oxide and \n' R(-)8-fluorodibenzo\x9bb,f!thiepin-3-carboxylic acid-5-oxide. It is \n' especially concerned with the resolution of the racemic 7 or 8 fluorodibenzo\x9bb,f!thiepin-3-carboxylic acid-5-oxide by first forming and \n' separating diastereomers of said racemic carboxylic acids by salt formation with brucine or ephedrine followed by crystallization and regeneration of the desired (-) isomers and recycling of the (+) isomer by racemization of the regenerated isomer. The compounds obtained in high yield by this process are highly active prostaglandin antagonists which are useful in treating a variety of conditions such as allergic asthma.

  本发明涉及一种改进的制备高活性光学异构体的过程，该异构体为(-)7或8氟代二苯并[b,f]噻吩-3-羧酸-5-氧化物，其结构式为##STR1## 其中氟代取代了7或8位的氢原子。公式II所代表的两个活性异构体为S(-)7-氟代二苯并[b,f]噻吩-3-羧酸-5-氧化物和R(-)8-氟代二苯并[b,f]噻吩-3-羧酸-5-氧化物。本发明特别涉及通过首先与布林或麻黄碱形成盐，然后通过结晶和再生所得到的对映异构体的分离来分离外消旋的7或8氟代二苯并[b,f]噻吩-3-羧酸-5-氧化物，并通过使再生异构体的对映异构体消旋来回收(+ )异构体。通过该过程获得的化合物产率高，是高活性前列腺素拮抗剂，可用于治疗过敏性哮喘等多种疾病。
• Substituted dibenzo(b,f)thiepin-3-carboxylic acid derivatives, their preparation and pharmaceutical compositions containing them
  申请人：Merck & Co., Inc.

  公开号：EP0023078A1

  公开（公告）日：1981-01-28

  8-Fluorodibenzo[b,f] thiepine and 8-hydroxydibenzo[b,f]-thiepin-3-carboxylic acid-5-oxide compounds of formula : where Z is thio, sulfinyl or sulfonyl; and and their pharmaceutically salts are novel. They are used in the treatment and control of allergic conditions such as allergic asthma and are made into pharmaceutical compositions forthat purpose. The compounds are made by hydrolysing the corresponding 3-cyano compounds. The R(-) isomer of 8-fluorodibenzo[b,f] thiepin-3-carboxylic acid-5-oxide is particularly useful as an antiasthmatic.

  式中的 8-氟二苯并[b,f]硫杂卓和 8-羟基二苯并[b,f]硫杂卓-3-羧酸-5-氧化物化合物： 其中 Z 为硫代、亚砜基或磺酰基；以及 及其药用盐是新型化合物。它们可用于治疗和控制过敏性疾病，如过敏性哮喘，并为此制成药物组合物。这些化合物是通过水解相应的 3-氰基化合物制成的。8-氟二苯并[b,f]硫杂卓-3-羧酸-5-氧化物的 R(-)异构体特别适用于抗哮喘。
• Cardiovascular composition
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0166257A2

  公开（公告）日：1986-01-02

  A cardiovascular composition is disclosed which comprises a dibenzo-thiepin compound having the formula wherein: X is a C1-C4 hydrocarbon group, optionally containing O, N or CO; Z is S, SO, S02, CO, CR4R5 wherein R4 and R5 taken together form the group =O or =CHR6 wherein R6 is hydrogen or phenyl; R1 is, e.g., 5-tetrazolyl, 5-tetrazolylmethyl, and wherein m is an integer of from 0 to 4 and R7 is, e.g., hydroxy or loweralkoxy; R2 and R3 can each independently be hydrogen, halogen (F, Cl, Br or I), nitro, loweralkyl, amino, N-loweralkylamino, N,N-diloweralkylamino, loweralkanoyl, hydroxy, loweralkoxy, lower acyloxy, loweralkylthio, trifluoromethylthio, loweralkylsulfinyl, loweralkylsulfonyl, trifluoromethyl, or R2 and R3, when bonded to adjacent carbon atoms, can be joined to form a 5- or 6-membered hydrocarbon ring which can optionally contain a double bond, a carbonyl group, or a hydroxyl group; or a pharmaceutically acceptable salt thereof. The composition can additionally comprise an angiotensin converting enzyme (ACE) inhibitor. These compositions represent a novel therapeutic approach to thromboembolic diseases in man.

  本发明公开了一种心血管组合物，该组合物包含一种二苯并噻吩化合物，其式为 其中X是C1-C4烃基，可选含有O、N或CO； Z是S、SO、S02、CO、CR4R5，其中R4和R5共同形成基团=O或=CHR6，其中R6是氢或苯基； R1是5-四唑基、5-四唑甲基，以及 其中 m 是 0 至 4 的整数，R7 是，例如、羟基或低级烷氧基；低级烷基磺酰基、三氟甲基，或 R2 和 R3 与相邻碳原子结合时可形成 5 或 6 元烃环，该环可选择含有双键、羰基或羟基；或其药学上可接受的盐。组合物还可以包含血管紧张素转换酶（ACE）抑制剂。这些组合物代表了一种治疗人类血栓栓塞性疾病的新方法。
• BELANGER, P. C.;WILLIAMS, H. W. R.;ROKACH, J.
  作者：BELANGER, P. C.、WILLIAMS, H. W. R.、ROKACH, J.

  DOI：——

  日期：——
• US4334077A
  申请人：——

  公开号：US4334077A

  公开（公告）日：1982-06-08