(S,E)-2-(5,7-dichloro-2-(3-(furan-2-yl)acryloyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(thiophene-2-carboxamido)propanoic acid | 1250829-09-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S,E)-2-(5,7-dichloro-2-(3-(furan-2-yl)acryloyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(thiophene-2-carboxamido)propanoic acid
• 英文别名: (2S)-2-[[5,7-dichloro-2-[(E)-3-(furan-2-yl)prop-2-enoyl]-3,4-dihydro-1H-isoquinoline-6-carbonyl]amino]-3-(thiophene-2-carbonylamino)propanoic acid
• CAS: 1250829-09-4
• 化学式: C₂₅H₂₁Cl₂N₃O₆S
• 分子量: 562.43
• InChiKey: WHGBQVUQKROPLI-QWNKOJSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 (S,E)-2-(5,7-dichloro-2-(3-(furan-2-yl)acryloyl)-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(thiophene-2-carboxamido)propanoic acid
  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

• Compositions and methods for treatment of diabetic retinopathy
  申请人：NOVARTIS AG

  公开号：US10960087B2

  公开（公告）日：2021-03-30

  The present invention provides compounds and methods for the treatment of diabetic retinopathy. In particular, LFA-1 antagonists are described herein to be used in the treatment of diabetic retinopathy. One aspect of the invention provides for diagnosis of diabetic retinopathy and administration of a LFA-1 antagonist, after the patient is diagnosed with diabetic retinopathy.

  本发明提供了用于治疗糖尿病视网膜病变的化合物和方法。特别是，本文描述了用于治疗糖尿病视网膜病变的 LFA-1 拮抗剂。本发明的一个方面提供了糖尿病视网膜病变的诊断，以及在患者被诊断为糖尿病视网膜病变后给予 LFA-1 拮抗剂。
• COMPOSITIONS AND METHODS FOR TREATMENT OF DIABETIC RETINOPATHY
  申请人：SARcode Bioscience Inc.

  公开号：EP2209371B1

  公开（公告）日：2017-01-04
• COMPOSITIONS AND METHODS FOR TREATMENT OF EYE DISORDERS
  申请人：Burnier John

  公开号：US20100092541A1

  公开（公告）日：2010-04-15

  The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.
• Compositions and Methods for Treatment
  申请人：BURNIER John

  公开号：US20110165229A1

  公开（公告）日：2011-07-07

  The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.
• Compositions and Methods for Treatment of Eye Disorders
  申请人：Gadek Thomas

  公开号：US20120232019A1

  公开（公告）日：2012-09-13

  The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.