(2S)-2-(N-tert-butoxycarbonyl)-amino-N-cyclopentyl-3-(4-cyanophenyl)-N-methylpropanamide | 184771-40-2

• 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: (2S)-2-(N-tert-butoxycarbonyl)-amino-N-cyclopentyl-3-(4-cyanophenyl)-N-methylpropanamide
• 英文别名: tert-butyl N-[(2S)-3-(4-cyanophenyl)-1-[cyclopentyl(methyl)amino]-1-oxopropan-2-yl]carbamate
• CAS: 184771-40-2
• 化学式: C₂₁H₂₉N₃O₃
• 分子量: 371.48
• InChiKey: CUQLISQFJDEUHM-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  82.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-2-(N-tert-butoxycarbonyl)-amino-N-cyclopentyl-3-(4-cyanophenyl)-N-methylpropanamide 在 N-甲基吗啉 、 乙酰氯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (S)-3-(4-cyanophenyl)-N-cyclo-pentyl-N-methyl-2-(5-dimethylamino-naphthalene-1-sulfonylamino)-propionamide
  参考文献：
  名称：

  Structural Modification of an Orally Active Thrombin Inhibitor, LB30057: Replacement of the D-Pocket-binding Naphthyl Moiety

  摘要：

  An amidrazonophenylalanine derivative LB30057 (2) was identified as a potent (K-i = 0.38 nM), selective, and orally active thrombin inhibitor. As a continuation of studies into benzamidrazone-based thrombin inhibitors, we have structurally modified compound 2 by replacing the naphthyl group with a variety of hydrophobic moieties. This study led to discovery of several compounds with significantly enhanced potency in thrombin inhibition without sacrificing selectivity against trypsin and oral absorption. The highest activity was obtained with compound 23 (K-i = 0.045 nM). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00044-3
• 作为产物：
  描述：

  L-4-氰基苯丙氨酸 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 (2S)-2-(N-tert-butoxycarbonyl)-amino-N-cyclopentyl-3-(4-cyanophenyl)-N-methylpropanamide
  参考文献：
  名称：

  Fluorobenzamidrazone thrombin inhibitors: Influence of fluorine on enhancing oral absorption

  摘要：

  LB30057 (1) is a selective and efficacious oral thrombin inhibitor. Fluorine-substitution on the phenylene ring of the benzamidrazone portion in both compound 1 and its derivatives gave, in many cases, enhanced oral absorption in rats while maintaining the intrinsic potency and selectivity. Compound 2 demonstrated a 3-fold increase in absorption. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00412-6

文献信息

• Development of a Scalable Synthetic Route towards a Thrombin Inhibitor, LB30057
  作者：Bong Chan Kim、Sang Yeul Hwang、Tae Hee Lee、Jay Hyok Chang、Hyeong-wook Choi、Kyu Woong Lee、Bo Seung Choi、Young Keun Kim、Jae Hoon Lee、Won Sup Kim、Yeong Soo Oh、Hee Bong Lee、Kyu Young Kim、Hyunik Shin

  DOI：10.1021/op060083p

  日期：2006.9.1

  of methyl tyrosinate to its N,O-bis-trimethylsilyl derivative and subsequent N-selective introduction of naphthalenesulfonyl group provided methyl N-2-naphthalenesulfonyltyrosinate (9). After the phenol group of 9 was triflated to 10, nickel-catalyzed cyanation provided 11 in good yield. The acid chloride 11a was generated via hydrolysis of the ester group followed by the treatment with SOCl2, and then

  描述了朝着LB30057（1）的可扩展的合成路线，其基于使用盐酸酪氨酸甲酯作为起始原料的Chiron方法。酪氨酸甲酯对其N，O-双-三甲基甲硅烷基衍生物的原位保护和随后的萘磺酰基的N-选择性引入提供了N -2-萘磺酰基酪氨酸甲酯（9）。将9的苯酚基团三氟甲基化为10后，镍催化的氰化反应以良好的收率提供11。通过酯基的水解，然后用SOCl 2处理，生成酰基氯11a。，然后与环戊基甲胺偶合，得到酰胺15。形成亚氨酸盐，然后生成酰胺化zone，最后与马来酸形成盐，得到1。
• Process for synthesizing para-and/or meta-substituted cyanophenylalanine derivatives
  申请人：LG Chemical Ltd.

  公开号：EP1043309A1

  公开（公告）日：2000-10-11

  The present invention relates to a process for preparing a useful medicinal intermediate represented by the following formula (1):    in which, R1, A and n are defined as described in the specification, or its stereoisomer, characterized in that a compound represented by the following formula (2):    in which, R, R1, A and n are defined as described in the specification, is reacted with a cyanide in the presence of a nickel catalyst.

  本发明涉及一种制备下列式子（1）所表示的有用药物中间体的方法：   其中，R1，A和n如说明书所述定义，或其立体异构体，其特征在于，在镍催化剂存在下，将下列式子（2）所表示的化合物：   其中，R，R1，A和n如说明书所述定义，与氰化物反应。
• Solid phase synthesis of benzylamine-derived sulfonamide library
  作者：Sang Woong Kim、Chang Yong Hong、Koo Lee、Eun Ju Lee、Jong Sung Koh

  DOI：10.1016/s0960-894x(98)00114-0

  日期：1998.4

  Using solid phase synthesis, a library has been constructed of benzylamine-derived sulfonamides which have strong inhibitory activity against the blood coagulant thrombin. The library compounds were obtained in good yield and high purity; four of these thrombin inhibitors showed nanomolar potency (Ki 600-10 nM). (C) 1998 Elsevier Science Ltd. All rights reserved.
• US6284912B1
  申请人：——

  公开号：US6284912B1

  公开（公告）日：2001-09-04
• Structural Modification of an Orally Active Thrombin Inhibitor, LB30057: Replacement of the D-Pocket-binding Naphthyl Moiety
  作者：Koo Lee、Sang Yeul Hwang、Seongwon Hong、Chang Yong Hong、Chang-Seok Lee、Youseung Shin、Sangsoo Kim、Mikyung Yun、Yung Joon Yoo、Myunggyun Kang、Yeong Soo Oh

  DOI：10.1016/s0968-0896(98)00044-3

  日期：1998.6

  An amidrazonophenylalanine derivative LB30057 (2) was identified as a potent (K-i = 0.38 nM), selective, and orally active thrombin inhibitor. As a continuation of studies into benzamidrazone-based thrombin inhibitors, we have structurally modified compound 2 by replacing the naphthyl group with a variety of hydrophobic moieties. This study led to discovery of several compounds with significantly enhanced potency in thrombin inhibition without sacrificing selectivity against trypsin and oral absorption. The highest activity was obtained with compound 23 (K-i = 0.045 nM). (C) 1998 Elsevier Science Ltd. All rights reserved.