(S)-苄基2-((S)-2-(叔丁氧基羰基氨基)-4-甲基戊酰胺基)-3-苯基丙酸 | 140834-91-9

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 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
• 中文名称: (S)-苄基2-((S)-2-(叔丁氧基羰基氨基)-4-甲基戊酰胺基)-3-苯基丙酸
• 英文名称: Boc-D-Leu-Phe-OBzl
• 英文别名: Boc-(R)-Leu-Phe-OBn；(S)-Benzyl 2-((r)-2-((tert-butoxycarbonyl)amino)-4-methylpentanamido)-3-phenylpropanoate；benzyl (2S)-2-[[(2R)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoyl]amino]-3-phenylpropanoate
• CAS: 140834-91-9
• 化学式: C₂₇H₃₆N₂O₅
• 分子量: 468.593
• InChiKey: IKZFNIAMQFYRSM-PKTZIBPZSA-N

物化性质

• 沸点：
  629.5±55.0 °C(Predicted)
• 密度：
  1.114±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-苄基2-((S)-2-(叔丁氧基羰基氨基)-4-甲基戊酰胺基)-3-苯基丙酸 在 盐酸 、 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 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 Boc-Gln-D-Leu-Phe-OBzl
  参考文献：
  名称：

  Studies on neurokinin antagonists. 1. The design of novel tripeptides possessing glutaminyl-D-tryptophylphenylalanine sequence as substance P antagonists

  摘要：

  To discover a novel and low molecular weight substance P (SP) antagonist we postulated that the essential binding domain of peptide ligands was only a small portion in the whole structure. On the basis of this assumption, we selected the known octapeptide SP antagonist D-Pro-Gln-Gln-D-Trp-Phe-D-Trp-D-Trp-Phe-NH2 (1) as a lead and synthesized its fragment tripeptides which were evaluated for their activity to block H-3-SP binding on guinea pig lung membranes. The protected tripeptide N(alpha)-[N(alpha)-[N(alpha)-(tert-butyloxycarbonyl)-L-glutaminyl]-N1-formyl-D-tryptophyl]-L-phenylalanine benzyl ester [Boc-Gln-D-Trp(CHO)-Phe-OBzl (4a)], corresponding to the Gln-D-Trp-Phe part of 1, exhibited 7-fold potent inhibitory activity in comparison with 1. Studies on structure-activity relationships revealed that the D-tryptophan, L-phenylalanine, and benzyl ester were quite important to maintain the high binding affinity. It was also indicated that 4a antagonized the SP-induced contraction of isolated guinea pig trachea strips (IC50 = 4.7 x 10(-6) M).

  DOI：

  10.1021/jm00089a011
• 作为产物：
  描述：

  BOC-D-亮氨酸 、 L-苯丙氨酸苄酯对甲苯磺酸盐 在 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 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以93.9%的产率得到(S)-苄基2-((S)-2-(叔丁氧基羰基氨基)-4-甲基戊酰胺基)-3-苯基丙酸
  参考文献：
  名称：

  Studies on neurokinin antagonists. 1. The design of novel tripeptides possessing glutaminyl-D-tryptophylphenylalanine sequence as substance P antagonists

  摘要：

  To discover a novel and low molecular weight substance P (SP) antagonist we postulated that the essential binding domain of peptide ligands was only a small portion in the whole structure. On the basis of this assumption, we selected the known octapeptide SP antagonist D-Pro-Gln-Gln-D-Trp-Phe-D-Trp-D-Trp-Phe-NH2 (1) as a lead and synthesized its fragment tripeptides which were evaluated for their activity to block H-3-SP binding on guinea pig lung membranes. The protected tripeptide N(alpha)-[N(alpha)-[N(alpha)-(tert-butyloxycarbonyl)-L-glutaminyl]-N1-formyl-D-tryptophyl]-L-phenylalanine benzyl ester [Boc-Gln-D-Trp(CHO)-Phe-OBzl (4a)], corresponding to the Gln-D-Trp-Phe part of 1, exhibited 7-fold potent inhibitory activity in comparison with 1. Studies on structure-activity relationships revealed that the D-tryptophan, L-phenylalanine, and benzyl ester were quite important to maintain the high binding affinity. It was also indicated that 4a antagonized the SP-induced contraction of isolated guinea pig trachea strips (IC50 = 4.7 x 10(-6) M).

  DOI：

  10.1021/jm00089a011

文献信息

• The greening of peptide synthesis
  作者：Stefan B. Lawrenson、Roy Arav、Michael North

  DOI：10.1039/c7gc00247e

  日期：——

  Both couplings and deprotections for solution- and solid-phase peptide synthesis can be carried out in the polar aprotic solvent propylene carbonate.

  用于溶液和固相肽合成的偶联和脱保护均可在极性非质子传递溶剂碳酸亚丙酯中进行。
• [EN] AN IMPROVED PROCESSES FOR THE PREPARATION OF CARFILZOMIB OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF<br/>[FR] PROCÉDÉ PERFECTIONNÉ DE PRÉPARATION DE CARFILZOMIB OU DE SELS PHARMACEUTIQUEMENT ACCEPTABLES DE CELUI-CI
  申请人：LAURUS LABS PRIVATE LTD

  公开号：WO2016185450A1

  公开（公告）日：2016-11-24

  The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.

  本发明涉及一种改进的制备卡菲唑胺或其药学上可接受的盐的工艺。本发明还涉及一种制备卡菲唑胺非晶态形式的工艺。
• PROCESSES FOR THE PREPARATION OF CARFILZOMIB OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
  申请人：LAURUS LABS LIMITED

  公开号：US20190284231A1

  公开（公告）日：2019-09-19

  The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.

  本发明涉及一种改进的制备卡非索米或其药学上可接受的盐的方法。本发明还涉及一种制备卡非索米非晶态的方法。
• Acylated nonadepsipeptides
  申请人：Von Nussbaum Franz

  公开号：US20050075281A1

  公开（公告）日：2005-04-07

  The invention relates to nonadepsipeptides and process for their preparation, and to their use for producing medicaments for the treatment and/or prophylaxis of diseases, in particular bacterial infectious diseases.

  本发明涉及非脂肪酰二肽类化合物及其制备方法，以及它们用于生产治疗和/或预防疾病，特别是细菌感染性疾病的药物的用途。
• Processes for the preparation of carfilzomib or pharmaceutically acceptable salts thereof
  申请人：LAURUS LABS PRIVATE LIMITED

  公开号：US10364269B2

  公开（公告）日：2019-07-30

  The present invention relates to an improved process for the preparation of carfilzomib or a pharmaceutically acceptable salt thereof. The present invention also relates to a process for the preparation of amorphous form of carfilzomib.

  本发明涉及一种制备卡非佐米或其药学上可接受的盐的改进工艺。本发明还涉及一种制备无定形卡非佐米的工艺。