H-Thr-OiPr hydrochloride | 1235740-47-2

• 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: H-Thr-OiPr hydrochloride
• 英文别名: (2S,3R)-Isopropyl 2-amino-3-hydroxybutanoate hydrochloride；propan-2-yl (2S,3R)-2-amino-3-hydroxybutanoate;hydrochloride
• CAS: 1235740-47-2
• 化学式: C₇H₁₅NO₃*ClH
• 分子量: 197.662
• InChiKey: WTNKLHOYNYGZOQ-IBTYICNHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.07
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  72.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  H-Thr-OiPr hydrochloride 、 甲基丙烯酰氯 在 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 16.0h， 以79%的产率得到Nα-(methacryloyl)-threonine isopropyl ester
  参考文献：
  名称：

  Synthesis and characterization of tailorable biodegradable thermoresponsive methacryloylamide polymers based on l-serine and l-threonine alkyl esters

  摘要：

  A series of monomers based on the methyl, ethyl, and isopropyl esters of N-alpha-(methacryloyl)-serine and -threonine were synthesized, and used in an AIBN-initiated radical polymerization reaction to yield polymers with an M-n ranging between 6.6 and 23.8 kDa. The newly synthesized polymers showed LCST behavior in aqueous solution that could be tailored by subtle variations of the hydrophobicity of the monomers to obtain a broad range of cloud points between 1.5 and >100 degrees C. According to HPLC, the hydrolytic t(1/2)-values (pH 7.4 at 37 degrees C) of the monomers were found to be 5, 12, and 40 days of the methyl, ethyl, and isopropyl esters, respectively, while the hydrolysis rate of poly[M-alpha-(methacryloyl)-Ser-OMe] and poly[N-alpha-(methacryloyl)-Thr-Ome] was found to be significantly lower compared to the corresponding monomers. In order to obtain thermoresponsive nanoparticles, N-alpha-(methacryloyl)-Thr-OEt was polymerized with (PEG monomethyl ether 5000)(2)-ABCPA as macroinitiator to yield an amphiphilic block co-polymer, poly[N-alpha-(methacryloyl)-Thr-OEt]-b-(PEG monomethyl ether 5000), which forms particles of 300 nm at a temperature higher than its cloud point of 24 degrees C. Incubation at physiological conditions induced ester hydrolysis resulting in a destabilization of the particles making these particles suitable for drug delivery purposes. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.polymer.2010.04.010
• 作为产物：
  描述：

  (2S,3R)-isopropyl 2-amino-3-hydroxybutanoate 4-methylbenzenesulfonate 在 水 、 sodium carbonate 、 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 以33.5 g的产率得到H-Thr-OiPr hydrochloride
  参考文献：
  名称：

  [EN] BENZIMIDAZOLE DERIVATIVES AS BROMODOMAIN INHIBITORS
  [FR] DÉRIVÉS DE BENZIMIDAZOLE COMME INHIBITEURS DES BROMODOMAINES

  摘要：

  式（I）的化合物及其盐：其中R1、R2、R3、R4在此处定义。已发现式（I）的化合物及其盐能够抑制BET家族的溴结构域蛋白与例如乙酰化赖氨酸残基的结合，因此可能在治疗中发挥作用，例如在治疗自身免疫和炎症性疾病（如类风湿性关节炎）和癌症方面。

  公开号：

  WO2016146738A1

文献信息

• [EN] CRYSTALLINE HYDRATE OF THE COMPOUND (2S,3R)-ISOPROPYL 2-(((2-(1,5-DIMETHYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL)-1-((TETRAHYDRO-2H-PYRAN-4-YL)METHYL)-1H-BENZO[D]IMIDAZOL-5-YL)METHYL)AMINO)-3-HYDROXYBUTANOATE EDISYLATE<br/>[FR] HYDRATE CRISTALLIN DU COMPOSÉ (2S,3R)-ISOPROPYL 2-(((2-(1,5-DIMÉTHYL-6-OXO-1,6-DIHYDROPYRIDIN-3-YL)-1-((TÉTRAHYDRO-2H-PYRAN-4-YL)MÉTHYL)-1H-BENZO[D]IMIDAZOL-5-YL)MÉTHYL)AMINO)-3-HYDROXYBUTANOATE ÉDISYLATE
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2018041946A1

  公开（公告）日：2018-03-08

  The present invention relates to a crystalline hydrate of the compound (2S,3R)-isopropyl 2-(((2-(l,5-dimethyl-6-oxo-l,6-dihydropyridin-3-yl)-l-((tetrahydro-2H-pyran-4-yl)methyl)-1H-benzo[d]imidazol-5-yl)methyl)amino)-3-hydroxybutanoate edisylate and to its use in the treatment of various disorders for which a BET inhibitor is indicated, in particular inflammatory and autoimmune diseases, and cancers. Processes for the manufacture of this crystalline form and pharmaceutical compositions comprising the crystalline form are also disclosed and form part of the present invention.

  本发明涉及化合物(2S,3R)-异丙基2-(((2-(1,5-二甲基-6-氧代-1,6-二氢吡啶-3-基)-1-((四氢-2H-吡喃-4-基)甲基)-1H-苯并[d]咪唑-5-基)甲基)氨基)-3-羟基丁酸二乙酸盐的结晶水合物，以及其在治疗各种需要BET抑制剂的疾病中的用途，特别是炎症性和自身免疫疾病以及癌症。本发明还揭示了制备该结晶形式的工艺和包含该结晶形式的药物组合物，并构成本发明的一部分。
• Benzimidazole derivatives as bromodomain inhibitors
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

  公开号：US10442786B2

  公开（公告）日：2019-10-15

  Compounds of formula (I) and salts thereof: wherein R1, R2, R3, R4 are defined herein. Compounds of formula (I) and salts thereof have been found to inhibit the binding of the BET family of bromodomain proteins to, for example, acetylated lysine residues and thus may have use in therapy, for example in the treatment of autoimmune and inflammatory diseases, such as rheumatoid arthritis; and cancers.

  式 (I) 化合物及其盐类： 其中 R1、R2、R3、R4 在本文中定义。已发现式（I）化合物及其盐类可抑制 BET 家族溴域蛋白与乙酰化赖氨酸残基等的结合，因此可用于治疗，例如治疗自身免疫性和炎症性疾病，如类风湿性关节炎；以及癌症。
• Crystalline hydrate of the compound (2S,3R)-isopropyl 2-(((2-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-benzo[D]imidazol-5- yl)methyl)amino)-3-hydroxybutanoate edisylate
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

  公开号：US10676466B2

  公开（公告）日：2020-06-09

  The present invention relates to a crystalline hydrate of the compound (2S,3R)-isopropyl 2-(((2-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-benzo[d]imidazol-5-yl)methyl)amino)-3-hydroxybutanoate edisylate and to its use in the treatment of various disorders for which a BET inhibitor is indicated, in particular inflammatory and autoimmune diseases, and cancers. Processes for the manufacture of this crystalline form and pharmaceutical compositions comprising the crystalline form are also disclosed and form part of the present invention.

  本发明涉及化合物(2S,3R)-异丙基 2-(((2-(1,5-二甲基-6-氧代-1、 2-((2-(1,5-二甲基-6-氧代-1,6-二氢吡啶-3-基)-1-((四氢-2H-吡喃-4-基)甲基)-1H-苯并[d]咪唑-5-基)甲基)氨基)-3-羟基丁酸乙二酯的结晶水合物，并涉及其在治疗 BET 抑制剂适用的各种疾病，特别是炎症和自身免疫性疾病以及癌症中的用途。 本发明还公开了这种结晶形式的制造工艺和包含这种结晶形式的药物组合物，并构成本发明的一部分。
• BENZIMIDAZOLE DERIVATIVES AS BROMODOMAIN INHIBITORS
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3271349B1

  公开（公告）日：2019-05-15
• EP3507286A1
  申请人：——

  公开号：EP3507286A1

  公开（公告）日：2019-07-10