(S,S)-1-(pyrrolidine-2-carbonyl)-pyrrolidine-2-carboxylic acid benzylamide | 202932-83-0

• 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,S)-1-(pyrrolidine-2-carbonyl)-pyrrolidine-2-carboxylic acid benzylamide
• 英文别名: L-Prolinamide, L-prolyl-N-(phenylmethyl)-；(2S)-N-benzyl-1-[(2S)-pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide
• CAS: 202932-83-0
• 化学式: C₁₇H₂₃N₃O₂
• 分子量: 301.389
• InChiKey: HGDPOFYRDGIIPZ-GJZGRUSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S,S)-1-(pyrrolidine-2-carbonyl)-pyrrolidine-2-carboxylic acid benzylamide 、 2-甘油磷酸二钠 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 1-{(2E,4S)-2,5-dimethyl-4-[methyl(N-methyl-3-phenyl-L-valyl-3-methyl-L-valyl)amino]hex-3-enoyl}-L-prolyl-N-benzyl-L-prolinamide
  参考文献：
  名称：

  Hybrids of the Hemiasterlin Analogue Taltobulin and the Dolastatins Are Potent Antimicrotubule Agents

  摘要：

  The targeting of microtubules is an important mechanism for cancer chemotherapy. However, there is still a need for improved antimicrotubule agents. A number of seemingly structurally disparate peptidic natural products inhibit tubulin polymerization by binding to a region of the tubulin heterodimer close to the vinca binding site. An analogue of the naturally occurring tripeptide hemiasterlin, taltobulin (HTI-286, 3), has advanced to clinical trials. Structure-activity relationship studies of 3 have revealed critical structural elements necessary for antimicrotubule activity that correspond to comparable groups in the amino terminus tripeptide region of the dolastatins. To investigate the structural relationship between the hemiasterlins and the more complex dolastatins, hybrid compounds composed of 3 and the carboxy terminus dipeptides of dolastatin 10, or the dolastatin 15 analogue cemadotin, were synthesized. The resulting hybrid compounds were potent antimicrotubule agents, thus establishing a structural relationship between the hemiasterlins and the dolastatins. This relationship may be useful in the design of analogues having improved activity in resistant cell lines expressing the P-glycoprotein transporter, for establishing structural relationships with other classes of peptidic antimicrotubule agents, or for modeling studies of the tubulin binding site of these agents.

  DOI：

  10.1021/ja053663v

文献信息

• DOLASTATIN PENTAPEPTIDE DERIVATIVES AND THEIR USE AS ANTITUMOR AGENTS
  申请人：BASF AKTIENGESELLSCHAFT

  公开号：EP0915908A1

  公开（公告）日：1999-05-19
• US5741892A
  申请人：——

  公开号：US5741892A

  公开（公告）日：1998-04-21
• [EN] DOLASTATIN PENTAPEPTIDE DERIVATIVES AND THEIR USE AS ANTITUMOR AGENTS<br/>[FR] DERIVES DE PENTAPEPTIDES DE DOLASTATINE UTILISES COMME AGENTS ANTITUMORAUX
  申请人：BASF AKTIENGESELLSCHAFT

  公开号：WO1998004581A1

  公开（公告）日：1998-02-05

  (EN) The present invention provides anti-tumor peptides of the Formula (I), A-B-N(CH3)-CHD-CH(OCH3)-CH2CO-Pro-Pro-K, and the acid salts thereof. A is an amino acid residue of the formula (CH3)2N-CHX-CO, wherein X is a normal or branched alkyl group. B is an amino acid residue selected from the group consisting of valyl, isoleucyl, leucyl, and 2-t-butylglycyl. D is a normal or branched C3-C4-alkyl group. K is a t-butoxy group or a substituted amino group. An additional embodiment of the present invention is a method for treating a malignancy in a mammal, such as a human, comprising administering to the mammal an effective amount of a compound or compounds of Formula (I) in a pharmaceutically acceptable composition.(FR) La présente invention concerne des peptides antitumoraux de la formule (I) suivante : Formule I, A-B-N(CH3)-CHD-CH(OCH3)-CH2CO-Pro-Pro-K, et des sels acides desdits peptides. Dans la formu le, A représente un résidu aminoacide de la formule (CH3)2N-CHX-CO, dans laquelle X représente un groupe alkyle normal ou ramifié; B représente un résidu aminoacide sélectionné dans le groupe comprenant valyle, isoleucyle, leucyle et 2-t-butylglycyle; D représente un groupe C3-C4-alkyle normal ou ramifié; K représente un groupe t-butoxy ou un groupe amino substitué. Un mode de réalisation supplémentaire de la présente invention consiste à administrer à un mammifère une dose efficace d'un composé ou de composés de la formule I dans une composition phamaceutiquement acceptable.
• Hybrids of the Hemiasterlin Analogue Taltobulin and the Dolastatins Are Potent Antimicrotubule Agents
  作者：Arie Zask、Joshua Kaplan、Sylvia Musto、Frank Loganzo

  DOI：10.1021/ja053663v

  日期：2005.12.1

  The targeting of microtubules is an important mechanism for cancer chemotherapy. However, there is still a need for improved antimicrotubule agents. A number of seemingly structurally disparate peptidic natural products inhibit tubulin polymerization by binding to a region of the tubulin heterodimer close to the vinca binding site. An analogue of the naturally occurring tripeptide hemiasterlin, taltobulin (HTI-286, 3), has advanced to clinical trials. Structure-activity relationship studies of 3 have revealed critical structural elements necessary for antimicrotubule activity that correspond to comparable groups in the amino terminus tripeptide region of the dolastatins. To investigate the structural relationship between the hemiasterlins and the more complex dolastatins, hybrid compounds composed of 3 and the carboxy terminus dipeptides of dolastatin 10, or the dolastatin 15 analogue cemadotin, were synthesized. The resulting hybrid compounds were potent antimicrotubule agents, thus establishing a structural relationship between the hemiasterlins and the dolastatins. This relationship may be useful in the design of analogues having improved activity in resistant cell lines expressing the P-glycoprotein transporter, for establishing structural relationships with other classes of peptidic antimicrotubule agents, or for modeling studies of the tubulin binding site of these agents.