2-(butylsulfinyl)-4-(2-isopropyl-1-methyl-1H-imidazol-5-yl)-6-(thiazol-2-yl)thieno[2,3-b]pyridin-3-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 2-(butylsulfinyl)-4-(2-isopropyl-1-methyl-1H-imidazol-5-yl)-6-(thiazol-2-yl)thieno[2,3-b]pyridin-3-amine
• 英文别名: 2-Butylsulfinyl-4-(3-methyl-2-propan-2-ylimidazol-4-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine；2-butylsulfinyl-4-(3-methyl-2-propan-2-ylimidazol-4-yl)-6-(1,3-thiazol-2-yl)thieno[2,3-b]pyridin-3-amine
• 化学式: C₂₁H₂₅N₅OS₃
• 分子量: 459.66
• InChiKey: ASBMONXKYLRPGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  162
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  butyl(chloromethyl)sulfane 在 双氧水 、 溶剂黄146 、 三乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.58h， 生成 2-(butylsulfinyl)-4-(2-isopropyl-1-methyl-1H-imidazol-5-yl)-6-(thiazol-2-yl)thieno[2,3-b]pyridin-3-amine
  参考文献：
  名称：

  Inhibitors of 15-Prostaglandin Dehydrogenase To Potentiate Tissue Repair

  摘要：

  The enzyme 15-prostaglandin dehydrogenase (15-PGDH) catalyzes the first step in the degradation of prostaglandins including PGE2. It is a negative regulator of tissue repair and regeneration in multiple organs. Accordingly, inhibitors of 15-PGDH are anticipated to elevate in vivo levels of PGE2 and to promote healing and tissue regeneration. The small molecule SW033291 (1) inhibits 15-PGDH with K-i = 0.1 nM in vitro, doubles PGE2 levels in vivo, and shows efficacy in mouse models of recovery from bone marrow transplantation, ulcerative colitis, and partial hepatectomy. Here we describe optimized variants of 1 with improved solubility, druglike properties, and in vivo activity.

  DOI：

  10.1021/acs.jmedchem.7b00271

文献信息

• [EN] COMPOSITIONS AND METHODS OF MODULATING SHORT-CHAIN DEHYDROGENASE ACTIVITY<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE MODULATION DE L'ACTIVITÉ DE LA DÉSHYDROGÉNASE À CHAÎNE COURTE
  申请人：UNIV CASE WESTERN RESERVE

  公开号：WO2015065716A1

  公开（公告）日：2015-05-07

  Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors described herein.

  调节15-PGDH活性的化合物和方法，调节组织前列腺素水平，治疗希望调节15-PGDH活性和/或前列腺素水平的疾病、疾病障碍或病况，包括本文所描述的15-PGDH抑制剂。
• [EN] INHIBITORS OF SHORT-CHAIN DEHYDROGENASE ACTIVITY FOR TREATING FIBROSIS<br/>[FR] INHIBITEURS DE L'ACTIVITÉ DE LA DÉSHYDROGÉNASE À CHAÎNE COURTE POUR LE TRAITEMENT DE LA FIBROSE
  申请人：UNIV CASE WESTERN RESERVE

  公开号：WO2016144958A1

  公开（公告）日：2016-09-15

  A method of treating or preventing a fibrotic disease, disorder or condition includes administering to a subject in need of treatment a 15-PGDH inhibitor.

  治疗或预防纤维化疾病、紊乱或状况的方法包括向需要治疗的对象施用15-PGDH抑制剂。
• [EN] INHIBITORS OF SHORT-CHAIN DEHYDROGENASE ACTIVITY FOR PROMOTING NEUROGENESIS AND INHIBITING NERVE CELL DEATH<br/>[FR] INHIBITEURS DE L'ACTIVITÉ DÉSHYDROGÉNASE À CHAÎNE COURTE POUR FAVORISER LA NEUROGENÈSE ET INHIBER LA MORT DES CELLULES NERVEUSES
  申请人：UNIV CASE WESTERN RESERVE

  公开号：WO2018017582A1

  公开（公告）日：2018-01-25

  A method of promoting neuroprotection in a subject from axonal degeneration, neuronal cell death, and/or glia cell damage after injury, augmenting neuronal signaling underlying learning and memory, stimulating neuronal regeneration after injury, and/or treating a disease, disorder, and/or condition of the nervous system in a subject in need thereof includes administering to the subject a therapeutically effective amount of a 15-PGDH inhibitor.

  在需要的受试者中，促进神经保护的方法包括向受试者施用治疗有效量的15-PGDH抑制剂，以防止轴突退化、神经细胞死亡和/或胶质细胞损伤，增强学习和记忆的神经信号传导，刺激受伤后的神经再生，以及/或治疗神经系统的疾病、紊乱和/或状况。
• Inhibitors of short-chain dehydrogenase activity for modulating hematopoietic stem cells and hematopoiesis
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US10420752B2

  公开（公告）日：2019-09-24

  A method of modulating hematopoietic stem cells and hematopoiesis includes administering to a subject in need thereof a 15-PGDH inhibitor.

  一种调节造血干细胞和造血的方法包括向有需要的受试者施用 15-PGDH 抑制剂。
• Compositions and methods of modulating short-chain dehydrogenase activity
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US10869871B2

  公开（公告）日：2020-12-22

  Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors described herein.

  调节 15-PGDH 活性、调节组织前列腺素水平、治疗疾病、疾病紊乱或希望调节 15-PGDH 活性和/或前列腺素水平的条件的化合物和方法包括本文所述的 15-PGDH 抑制剂。