5-羟基-5H-茚并[1,2-b]吡啶-5-羧酸甲酯 | 97677-73-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 5-羟基-5H-茚并[1,2-b]吡啶-5-羧酸甲酯
• 英文名称: 5-hydroxy-5H-indeno[1,2-b]pyridine-5-carboxylic acid methyl ester
• 英文别名: (RS)-methyl 5H-5-hydroxyindeno<1,2-b>pyridine-5-carboxylate；4-aza-9-hydroxy-9-fluorene carboxylic acid methyl ester；4-aza-9-hydroxyfluorene-9-carboxylic acid methyl ester；5H-Indeno[1,2-b]pyridine-5-carboxylic acid, 5-hydroxy-, methyl ester；methyl 5-hydroxyindeno[1,2-b]pyridine-5-carboxylate
• CAS: 97677-73-1
• 化学式: C₁₄H₁₁NO₃
• 分子量: 241.246
• InChiKey: KGSSVYVWEKTSGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-羟基-5H-茚并[1,2-b]吡啶-5-羧酸甲酯 在 肼 作用下， 反应 0.5h， 以85%的产率得到5-Hydroxy-5H-indeno[1,2-b]pyridine-5-carboxylic acid hydrazide
  参考文献：
  名称：

  9-Hydroxyazafluorenes and Their Use in Thrombin Inhibitors

  摘要：

  Optimization of a previously reported thrombin inhibitor, 9-hydroxy-9-fluorenylcarbonyl-l-prolyl-trans-4-aminocyclohexylmethylamide (1), by replacing the aminocyclohexyl P1 group provided a new lead structure, 9-hydroxy-9-fluorenylcarbonyl-l-prolyl-2-aminomethyl-5-chlorobenzylamide (2), with improved potency (K(i) = 0.49 nM for human thrombin, 2x APTT = 0.37 microM in human plasma) and pharmacokinetic properties (F = 39%, iv T(1/2) = 13 h in dogs). An effective strategy for reducing plasma protein binding of 2 and improving efficacy in an in vivo thrombosis model in rats was to replace the lipophilic fluorenyl group in P3 with an azafluorenyl group. Systematic investigation of all possible azafluorenyl P3 isomers and azafluorenyl-N-oxide analogues of 2 led to the identification of an optimal compound, 3-aza-9-hydroxyfluoren-9(R)-ylcarbonyl-l-prolyl-2-aminomethyl-5-chlorobenzylamide (19b), with high potency (K(i) = 0.40 nM, 2x APTT = 0.18 microM), excellent pharmacokinetic properties (F = 55%, T(1/2) = 14 h in dogs), and complete efficacy in the in vivo thrombosis model in rats (inhibition of FeCl(3)-induced vessel occlusions in six of six rats receiving an intravenous infusion of 10 microg/kg/min of 19b). The stereochemistry of the azafluorenyl group in 19b was determined by X-ray crystallographic analysis of its N-oxide derivative (23b) bound in the active site of human thrombin.

  DOI：

  10.1021/jm049423s
• 作为产物：
  描述：

  5H-茚并[1,2-b]吡啶 在 氧气 、 sodium hydride 、 二甲基亚砜 、 lithium diisopropyl amide 作用下， 反应 7.0h， 生成 5-羟基-5H-茚并[1,2-b]吡啶-5-羧酸甲酯
  参考文献：
  名称：

  Braven, J.; Hanson, R. W.; Smith, N. G., Journal of Heterocyclic Chemistry, 1995, vol. 32, # 3, p. 1051 - 1056

  摘要：

  DOI：

文献信息

• Thrombin inhibitors
  申请人：——

  公开号：US20020119992A1

  公开（公告）日：2002-08-29

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: 1 or a pharmaceutically acceptable salt thereof, e.g. where R 3 is —CH 2 NH 2 , —CH 2 CH 2 NH 2 , or —CH 2 NHC(O)OC(CH 3 ) 3 .

  该发明的化合物在抑制凝血酶和相关血栓闭塞方面具有以下结构： 1 或其药用可接受的盐，例如其中R 3 为—CH 2 NH 2 ，—CH 2 CH 2 NH 2 ，或—CH 2 NHC(O)OC(CH 3 ) 3 。
• Ophthalmic wound healing with aldose reductase inhibitors
  申请人：Alcon Laboratories, Inc.

  公开号：US04717725A1

  公开（公告）日：1988-01-05

  Method of promoting healing of ocular wounds comprising the topical application of an aldose reductase inhibitor; compositions comprising such inhibitors are also disclosed.

  促进眼部伤口愈合的方法包括局部应用醛糖还原酶抑制剂；还公开了包含这些抑制剂的组合物。
• Spiro-tricyclicaromatic succinimide derivatives as inhibitors of aldose
  申请人：Alcon Laboratories, Inc.

  公开号：US04537892A1

  公开（公告）日：1985-08-27

  Disclosed are substituted or unsubstituted planar tricyclic fluorene or nuclear analogs thereof, spiro-coupled to a five-membered ring containing a secondary amide, and the pharmaceutically acceptable salts thereof. These compounds are useful, inter alia, in the treatment of diabetes. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when indicated for, inter alia, long term, prophylactic treatment of the diabetes syndrome.

  本文披露了取代或未取代的平面三环芴或其核类似物，与含有次级酰胺的五元环螺合，并且其药学上可接受的盐。这些化合物在糖尿病治疗中等方面是有用的。还披露了制备这种化合物的方法；包含这种化合物的药物组合物；以及治疗方法，包括在糖尿病综合症的长期、预防性治疗中适时给予这种化合物和组合物。
• Spiro-tricyclicaromatic succinimide derivatives
  申请人：Alcon Laboratories, Inc.

  公开号：US04864028A1

  公开（公告）日：1989-09-05

  Disclosed are substituted or unsubstituted planar tricyclic fluorene or nuclear analogs thereof, spiro-coupled to a five-membered ring containing a secondary amide, and the pharmaceutically acceptable salts thereof. These compounds are useful, inter alia, in the treatment of diabetes. Also disclosed are processes for the preparation of such compounds; pharmaceutical compositions comprising such compounds; and methods of treatment comprising administering such compounds and compositions when indicated for, inter alia, long term, prophylactic treatment of the diabetes syndrome.

  本文披露了替代或未替代的平面三环芴或其核类似物，与含有次级酰胺的五元环螺合，并且其药用盐。这些化合物在治疗糖尿病等方面非常有用。还披露了制备这些化合物的方法；包含这些化合物的药物组合物；以及治疗方法，包括在糖尿病综合征的长期、预防性治疗中适当时给予这些化合物和组合物。
• [EN] BENZYLAMINE DERIVATIVES AND THEIR USE AS THROMBIN INHIBITORS<br/>[FR] DERIVES DE BENZYLAMINE ET LEUR UTILISATION COMME INHIBITEURS DE THROMBINE
  申请人：MERCK & CO INC

  公开号：WO2002050056A1

  公开（公告）日：2002-06-27

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, e.g. where R3 is -CH2NH2, -CH2CH2NH2, or -CH2NHC(O)OC(CH3)3.

  本发明的化合物具有以下结构，或其药学上可接受的盐，例如其中R3为-CH2NH2，-CH2CH2NH2或-CH2NHC（O）OC（CH3）3，对于抑制凝血酶和相关的血栓闭塞非常有用。