5,7-Dichloro-1,2,3,4-tetrahydroisoquinolin-6-ol | 876108-97-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 5,7-Dichloro-1,2,3,4-tetrahydroisoquinolin-6-ol
• 英文别名: 5,7-dichloro-1,2,3,4-tetrahydroisoquinolin-6-ol
• CAS: 876108-97-3
• 化学式: C₉H₉Cl₂NO
• 分子量: 218.083
• InChiKey: SBDDVAHCMMAZHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  32.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5,7-Dichloro-1,2,3,4-tetrahydroisoquinolin-6-ol 、 二碳酸二叔丁酯 在 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 5,7-二氯-6-羟基-3,4-二氢异喹啉-2(1H)-羧酸叔丁酯
  参考文献：
  名称：

  Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists

  摘要：

  This letter describes the discovery of a novel series of tetrahydroisoquinoline (THIQ)-derived small molecules that potently inhibit both human T-cell migration and super-antigen induced T-cell activation through disruption of the binding of integrin LFA-1 to its receptor, ICAM-1. In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester (6t) demonstrates good oral bioavailability in both mouse and rat. Either intravenous administration of 6q or oral administration of its ethyl ester (6t) produced a significant reduction of neutrophil migration in a thioglycollate-induced murine peritonitis model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.145
• 作为产物：
  描述：

  N-BOC-6-羟基-3,4-二氢异喹啉 在 磺酰氯 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 5,7-Dichloro-1,2,3,4-tetrahydroisoquinolin-6-ol
  参考文献：
  名称：

  Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists

  摘要：

  This letter describes the discovery of a novel series of tetrahydroisoquinoline (THIQ)-derived small molecules that potently inhibit both human T-cell migration and super-antigen induced T-cell activation through disruption of the binding of integrin LFA-1 to its receptor, ICAM-1. In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester (6t) demonstrates good oral bioavailability in both mouse and rat. Either intravenous administration of 6q or oral administration of its ethyl ester (6t) produced a significant reduction of neutrophil migration in a thioglycollate-induced murine peritonitis model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.06.145

文献信息

• [EN] LFA-1 INHIBITOR AND POLYMORPH THEREOF<br/>[FR] INHIBITEUR DE LFA-1 ET POLYMORPHE DE CELUI-CI
  申请人：SARCODE BIOSCIENCE INC

  公开号：WO2014018748A1

  公开（公告）日：2014-01-30

  Methods of preparation and purification of a compound, intermediates thereof, a polymorph thereof, and related compounds are disclosed. Formulations and uses thereof in the treatment of LFA -1 mediated diseases are also disclosed.

  公开了化合物的制备和纯化方法、其中间体、多晶型及相关化合物。还公开了该化合物的制剂以及在治疗LFA-1介导疾病中的用途。
• LFA-1 INHIBITOR AND METHODS OF PREPARATION AND POLYMORPH THEREOF
  申请人：SARcode Bioscience Inc.

  公开号：US20180118726A1

  公开（公告）日：2018-05-03

  Methods of preparation and purification of a compound of Formula I, intermediates thereof, a polymorph thereof, and related compounds are disclosed. Formulations and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed.

  本发明公开了制备和纯化I式化合物、其中间体、其多晶形式及相关化合物的方法。同时，还公开了该化合物在治疗LFA-1介导的疾病中的配方和用途。
• PREPARATION OF LFA-1 INHIBITOR AND POLYMORPH THEREOF
  申请人：Novartis AG

  公开号：EP3715345A2

  公开（公告）日：2020-09-30

  Methods of preparation and purification of a compound, intermediates thereof, a polymorph thereof, and related compounds are disclosed. Formulations and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed.

  公开了一种化合物、其中间体、其多晶型以及相关化合物的制备和纯化方法。还公开了治疗 LFA-1 介导的疾病的制剂及其用途。
• LFA-1 inhibitor and methods of preparation and polymorph thereof
  申请人：NOVARTIS PHARMACEUTICALS CORPORATION

  公开号：US10906892B2

  公开（公告）日：2021-02-02

  Methods of preparation and purification of a compound of Formula I, intermediates thereof, a polymorph thereof, and related compounds are disclosed. Formulations and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed.

  公开了式 I 化合物、其中间体、其多晶型以及相关化合物的制备和纯化方法。还公开了其治疗 LFA-1 介导的疾病的制剂和用途。
• US9085553B2
  申请人：——

  公开号：US9085553B2

  公开（公告）日：2015-07-21