[({2-(R)-[4-(benzyloxycarbonylamino-imino-methyl)-benzylcarbamoyl]-indan-2-ylcarbamoyl}-cyclohexyl-methyl)-amino]-acetic acid benzyl ester | 907185-73-3

• 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: [({2-(R)-[4-(benzyloxycarbonylamino-imino-methyl)-benzylcarbamoyl]-indan-2-ylcarbamoyl}-cyclohexyl-methyl)-amino]-acetic acid benzyl ester
• 英文别名: Benzyl {[(1R)-2-({2-[({4-[{(benzyloxycarbonyl)-amino}-(imino)-methyl]-benzyl}-amino)-carbonyl]-indan-2-yl}-amino)-1-cyclohexyl-2-oxoethyl]-amino}-acetate；benzyl 2-[[(1R)-1-cyclohexyl-2-oxo-2-[[2-[[4-(N-phenylmethoxycarbonylcarbamimidoyl)phenyl]methylcarbamoyl]-1,3-dihydroinden-2-yl]amino]ethyl]amino]acetate
• CAS: 907185-73-3
• 化学式: C₄₃H₄₇N₅O₆
• 分子量: 729.876
• InChiKey: ZOWGHBGXFJGJJD-KXQOOQHDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  54
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  161
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [({2-(R)-[4-(benzyloxycarbonylamino-imino-methyl)-benzylcarbamoyl]-indan-2-ylcarbamoyl}-cyclohexyl-methyl)-amino]-acetic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以97%的产率得到({(R)-[2-(4-Carbamimidoyl-benzylcarbamoyl)-indan-2-ylcarbamoyl]-cyclohexyl-methyl}-amino)-acetic acid
  参考文献：
  名称：

  Low Molecular Weight Activated Protein C Inhibitors as a Potential Treatment for Hemophilic Disorders

  摘要：

  The synthesis and evaluation of inhibitors of activated protein C (aPC) are reported. This serine protease is partly responsible for the degradation of factor VIIIa, involved in the regulation of bleeding in hemophilia A. Benzamidine-containing derivatives were found to be potent aPC inhibitors, some of them showing selectivity against the procoagulant protease thrombin. Moreover, compound 1 significantly restored the generation of thrombin in hemophiliac plasma.

  DOI：

  10.1021/jm0606950
• 作为产物：
  描述：

  {[4-({[2-(R)-(2-amino-2-cyclohexyl-acetylamino)indane-2-carbonyl]-amino}-methyl)-phenyl]-imino-methyl}-carbamic acid benzyl ester 、 2-溴乙酸苄酯 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 1.5h， 以11.4 g的产率得到[({2-(R)-[4-(benzyloxycarbonylamino-imino-methyl)-benzylcarbamoyl]-indan-2-ylcarbamoyl}-cyclohexyl-methyl)-amino]-acetic acid benzyl ester
  参考文献：
  名称：

  Low Molecular Weight Activated Protein C Inhibitors as a Potential Treatment for Hemophilic Disorders

  摘要：

  The synthesis and evaluation of inhibitors of activated protein C (aPC) are reported. This serine protease is partly responsible for the degradation of factor VIIIa, involved in the regulation of bleeding in hemophilia A. Benzamidine-containing derivatives were found to be potent aPC inhibitors, some of them showing selectivity against the procoagulant protease thrombin. Moreover, compound 1 significantly restored the generation of thrombin in hemophiliac plasma.

  DOI：

  10.1021/jm0606950

文献信息

• Novel amino acid derivatives, method for production thereof and pharmaceutical compositions comprising said derivative
  申请人：De Nanteuil Guillaume

  公开号：US20050085517A1

  公开（公告）日：2005-04-21

  Compound of formula (I): wherein: R 1 represents aryl, heteroaryl or alkyl which is optionally substituted, or a group of formula —(CO)—CR 6 R 7 NR 8 R 9 wherein R 6 , R 7 , R 8 and R 9 are as defined in the description, R 2 represents hydrogen or alkyl, R 3 represents hydrogen or optionally substituted alkyl, R 4 represents a saturated or unsaturated, 7- to 15-membered bicyclic system or optionally substituted alkyl, or R 3 and R 4 , together with the carbon atom carrying them, form a saturated or unsaturated, 3- to 18-membered, mono-, bi- or tri-cyclic system optionally containing one or more hetero atoms selected from O, S and N and optionally substituted, n represents zero, 1 or 2, Ar represents aryl or heteroaryl, R 5 represents amino, guanidino, cyano or amidino which is optionally substituted, its optical isomers, and also addition salts thereof with a pharmaceutically acceptable acid. Medicinal products containing the same which are useful in pathological conditions involving activated protein C.

  化合物的分子式（I）如下所示：其中：R1代表芳基、杂环芳基或烷基，可以选择性地被取代，或者是下述分子式的基团—(CO)—CR6R7NR8R9，其中R6、R7、R8和R9如描述中定义，R2代表氢或烷基，R3代表氢或可选择性取代的烷基，R4代表饱和或不饱和的7至15环双环系统或可选择性取代的烷基，或者R3和R4与携带它们的碳原子一起形成饱和或不饱和的3至18环的单环、双环或三环系统，该系统可以选择性地含有一个或多个来自O、S和N的杂原子，并且可以被取代，n代表零、1或2，Ar代表芳基或杂环芳基，R5代表氨基、胍基、氰基或酰胺基，可以选择性地被取代，其光学异构体，以及与药学上可接受的酸形成的相应的盐。含有这些化合物的药物制剂在涉及活化蛋白C的病理状况中是有用的。
• Low Molecular Weight Activated Protein C Inhibitors as a Potential Treatment for Hemophilic Disorders
  作者：Guillaume De Nanteuil、Philippe Gloanec、Suzette Béguin、Peter L. A. Giesen、H. Coenraad Hemker、Philippe Mennecier、Alain Rupin、Tony J. Verbeuren

  DOI：10.1021/jm0606950

  日期：2006.8.1

  The synthesis and evaluation of inhibitors of activated protein C (aPC) are reported. This serine protease is partly responsible for the degradation of factor VIIIa, involved in the regulation of bleeding in hemophilia A. Benzamidine-containing derivatives were found to be potent aPC inhibitors, some of them showing selectivity against the procoagulant protease thrombin. Moreover, compound 1 significantly restored the generation of thrombin in hemophiliac plasma.