(S)-1-((R)-2-Amino-3-phenyl-propionyl)-pyrrolidine-2-carboxylic acid (4-guanidino-butyl)-amide | 80079-63-6

• 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)-1-((R)-2-Amino-3-phenyl-propionyl)-pyrrolidine-2-carboxylic acid (4-guanidino-butyl)-amide
• 英文别名: (2S)-1-[(2R)-2-amino-3-phenylpropanoyl]-N-[4-(diaminomethylideneamino)butyl]pyrrolidine-2-carboxamide
• CAS: 80079-63-6
• 化学式: C₁₉H₃₀N₆O₂
• 分子量: 374.486
• InChiKey: FWGBPNKASCASNV-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙酰氯 、 (S)-1-((R)-2-Amino-3-phenyl-propionyl)-pyrrolidine-2-carboxylic acid (4-guanidino-butyl)-amide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (2S)-1-[(2R)-2-acetamido-3-phenylpropanoyl]-N-[4-(diaminomethylideneamino)butyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Molecular design and structure–Activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664

  摘要：

  A series of structurally novel small molecule inhibitors of human alpha -thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha -thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00667-9
• 作为产物：
  描述：

  Boc-D-苯丙氨酸 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (S)-1-((R)-2-Amino-3-phenyl-propionyl)-pyrrolidine-2-carboxylic acid (4-guanidino-butyl)-amide
  参考文献：
  名称：

  Molecular design and structure–Activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664

  摘要：

  A series of structurally novel small molecule inhibitors of human alpha -thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha -thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00667-9

文献信息

• Sulfonamido heterocyclic thrombin inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0601459A2

  公开（公告）日：1994-06-15

  Sulfonamido heterocyclic thrombin inhibitors are provided which have the structure wherein G is including all stereoisomers thereof and salts thereof, wherein n is 0, I or 2 or 3; m is 0, I, 2 or 3; Y is NH or S; p is 0, I or 2, Q is a single bond or A is aryl, cycloalkyl, azacycloalkyl or azaheteroalkyl; R is hydrogen, hydroxyalkyl, aminoalkyl, alkyl, cycloalkyl, amidoalkyl, arylalkyl, alkenyl, aryl, alkynyl, arylalkoxyalkyl, or an amino acid side chain; R1 and R2 are independently hydrogen, lower alkyl, cycloalkyl, aryl, hydroxy, alkoxy, keto, thioketal, thioalkyl, thioaryl, amino or alkylamino; or R1 and R2 can be taken together with the carbons to which they are attached to form a cycloalkyl, aryl or heteroaryl ring; R3 is lower alkyl, aryl, arylalkyl, heteroaryl, quinolinyl or tetrahydroquinolinyl; and R4 can be guanidine, amidine or aminomethyl; where A includes a hetero atom, R4 is amidino; otherwise it may be any of the R4 moieties set out above.

  提供的磺酰胺杂环凝血酶抑制剂具有以下结构 其中 G 是 包括其所有立体异构体及其盐类，其中n是0、I或2或3；m是0、I、2或3；Y是NH或S；p是0、I或2，Q是单键或 A 是芳基、环烷基、偶氮环烷基或杂杂环烷基； R 是氢、羟烷基、氨基烷基、烷基、环烷基、氨基烷基、芳烷基、烯基、芳基、炔基、芳烷氧基烷基或氨基酸侧链； R1 和 R2 独立地为氢、低级烷基、环烷基、芳基、羟基、烷氧基、酮基、硫代酮基、硫代烷基、硫代芳基、氨基或烷基氨基；或 R1 和 R2 可与它们所连接的碳一起形成环烷基、芳基或杂芳基环； R3 是低级烷基、芳基、芳烷基、杂芳基、喹啉基或四氢喹啉基；以及 R4 可以是胍基、脒基或氨甲基；在 A 包括杂原子的情况下，R4 是脒基； 否则可以是上述任何 R4 分子。
• US5583146A
  申请人：——

  公开号：US5583146A

  公开（公告）日：1996-12-10
• Molecular design and structure–Activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664
  作者：Jagabandhu Das、S.David Kimball、Steven E. Hall、Wen-Ching Han、Edwin Iwanowicz、James Lin、Robert V. Moquin、Joyce A. Reid、John S. Sack、Mary F. Malley、Chiehying Y. Chang、Saeho Chong、David B. Wang-Iverson、Daniel G.M. Roberts、Steven M. Seiler、William A. Schumacher、Martin L. Ogletree

  DOI：10.1016/s0960-894x(01)00667-9

  日期：2002.1

  A series of structurally novel small molecule inhibitors of human alpha -thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha -thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models. (C) 2001 Elsevier Science Ltd. All rights reserved.