3-(甲基氨基)-n-[(苯基甲氧基)羰基]-l-丙氨酸甲酯 | 138093-73-9

• 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: 3-(甲基氨基)-n-[(苯基甲氧基)羰基]-l-丙氨酸甲酯
• 英文名称: 2-benzyloxycarbonylamino-3-methylamino-propionic acid methyl ester
• 英文别名: (S)-Methyl 2-(((benzyloxy)carbonyl)amino)-3-(methylamino)propanoate；methyl (2S)-3-(methylamino)-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 138093-73-9
• 化学式: C₁₃H₁₈N₂O₄
• 分子量: 266.297
• InChiKey: YZIQHCYMTRFHQW-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  19
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(甲基氨基)-n-[(苯基甲氧基)羰基]-l-丙氨酸甲酯 在 sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 Z-N^βMe-L-A2Pr(Boc)
  参考文献：
  名称：

  Total synthesis of galantin I. Acid-catalyzed cyclization of galantinic acid

  摘要：

  The proposed structure of galantin 1, a peptide antibiotic isolated from Bacillus pulvifaciens as a mixture of congeners (1a with the D-ornithine residue and lb with D-lysine; 1a/1b = 9/1), was shown to be incorrect by total synthesis. The substructure 3a, named galantinic acid, was an artifact, and its correct structure was assumed to be the hydroxylated form, 20a or 20b, by spectroscopic comparisons of synthetic la with natural galantin I. The synthesis of both diastereomers, 4a and 4b, again suggested that the sequence of the spermidine moiety of galantin I should be N5,N8. Finally, the correct structure of galantin I as 5a was confirmed by the synthesis of diastereomers 5a and 5b. The synthesis of 5a was accomplished in a convergent manner by the coupling of the protected forms of the constituent amino acids: D-ornithine, 6b, D-alanine, 23b, 11b, 8c, and 19a. Galantinic acid residue 20a, present in natural galantin 1, was found to undergo cyclization with retention of its C3 configuration under the chemical degradation conditions to give the artifact 3a. In order to elucidate the mode of cyclization of 20a to 3a, the synthesis of 20a and its analogues was accomplished in a stereoselective manner from D-serine. The synthesis was characterized by the stereoselective epoxidation of hydroxymethyl (Z)-allylamine 34 and alpha,beta-unsaturated delta-lactone 39. Acidolysis of 20a, 20b, and their analogues suggested that the stereoselective cyclization of galantinic acid was initiated by the formation of delta-lactone 54, which through the sequence of reactions should afford the artifact 3a.

  DOI：

  10.1021/ja00029a031
• 作为产物：
  描述：

  3-氨基-N-(苄氧基羰基)-L-丙氨酸甲酯 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 14.0h， 生成 3-(甲基氨基)-n-[(苯基甲氧基)羰基]-l-丙氨酸甲酯
  参考文献：
  名称：

  Tripeptide Aldehyde Inhibitors of Human Rhinovirus 3C Protease:  Design, Synthesis, Biological Evaluation, and Cocrystal Structure Solution of P₁ Glutamine Isosteric Replacements

  摘要：

  The investigation of tripeptide aldehydes as reversible covalent inhibitors of human rhinovirus (HRV) 3C protease (3CP) is reported. Molecular models based on the apo crystal structure of HRV-14 3CP and other trypsin-like serine proteases were constructed to approximate the binding of peptide substrates, generate transition state models of P-1-P-1' amide cleavage, and propose novel tripeptide aldehydes. Glutaminal derivatives have limitations since they exist predominantly in the cyclic hemiaminal form. Therefore, several isosteric replacements for the P-1 carboxamide side chain were designed and incorporated into the tripeptide aldehydes. These compounds were found to be potent inhibitors of purified HRV-14 3CP with K(i)s ranging from 0.005 to 0.64 mu M. Several have low micromolar antiviral activity when tested against HRV-14-infected H1-HeLa cells. The N-acetyl derivative 3 was also shown to be active against HRV serotypes 2, 16, and 89. High-resolution cocrystal structures of HRV-8 3CP, covalently bound to compounds 3, 15, and 16, were solved. These cocrystal structures were analyzed and compared with our original HRV-14 3CP-substrate and inhibitor models.

  DOI：

  10.1021/jm980071x

文献信息

• Discovery of an Orally Active Series of Isoxazoline Glycoprotein IIb/IIIa Antagonists
  作者：Chu-Biao Xue、John Wityak、Thais M. Sielecki、Donald J. Pinto、Douglas G. Batt、Gary A. Cain、Michael Sworin、Arlene L. Rockwell、John J. Roderick、Shuaige Wang、Michael J. Orwat、William E. Frietze、Lori L. Bostrom、Jie Liu、C. Anne Higley、F. Wayne Rankin、A. Ewa Tobin、George Emmett、George K. Lalka、Jean Y. Sze、Susan V. Di Meo、Shaker A. Mousa、Martin J. Thoolen、Adrienne L. Racanelli、Elizabeth A. Hausner、Thomas M. Reilly、William F. DeGrado、Ruth R. Wexler、Richard E. Olson

  DOI：10.1021/jm960799i

  日期：1997.6.1

  Using isoxazoline XR299 (1a) as a starting point for the design of highly potent, long-duration GPIIb/IIIa antagonists, the effect of placing lipophilic substituents at positions alpha and beta to the carboxylate moiety was evaluated. Of the compounds studied, it was found that the n-butyl carbamate 24u exhibited superior potency and duration of ex vivo antiplatelet effects in dogs. Replacement of

  使用异恶唑啉XR299（1a）作为设计高效，长效GPIIb / IIIa拮抗剂的起点，评估了将亲脂性取代基置于羧酸酯部分的α和β处的效果。在所研究的化合物中，发现氨基甲酸正丁酯24u在狗中表现出优异的效力和离体抗血小板作用的持续时间。用可替代的碱性基团取代苯并胺丁-4-基部分，消除异恶唑啉立体中心，并改变异恶唑啉环的方向，导致效力和/或作用时间降低。
• Aryl-substituted alicylic compound and medical composition comprising the same
  申请人：——

  公开号：US20040106622A1

  公开（公告）日：2004-06-03

  An aryl-substituted alicyclic compound of the formula (I): 1 wherein U is 1,4,5,6-tetrahydropyrimidin-2-yl, etc., A is phenylene, etc., B is piperidine-1,4-diyl, etc., Z is —CONH—, etc., R 3 is hydrogen, etc., R 5 is hydrogen, aryl, etc., R 6 is a mono-substituted amino (e,g., benzyloxycarbonylamino), R 7 is hydrogen, etc., and a process for preparation thereof, and a pharmaceutical composition containing the same. The compound of the present invention has a high selectivity for &agr;v&bgr;3 integrin, and exhibits a potent inhibitory activity thereto, and hence, it is useful as a preventive or/and a therapeutic agent for a disease in which &agr;v&bgr;3 integrin is involved.

  公式（I）的芳基取代脂环化合物：其中U为1,4,5,6-四氢嘧啶-2-基等，A为苯基等，B为哌啶-1,4-二基等，Z为—CONH—等，R3为氢等，R5为氢、芳基等，R6为单取代氨基（例如苄氧羰基氨基），R7为氢等。本发明还涉及一种制备该化合物的方法，以及含有该化合物的制药组合物。本发明化合物对αvβ3整合素有高度选择性，并表现出强大的抑制活性，因此，它可用作预防或治疗αvβ3整合素参与的疾病的药物。
• [EN] ACRYLAMIDE DERIVATIVES AS VLA-1 INTEGRIN ANTAGONISTS AND USES THEREOF<br/>[FR] DERIVES D'ACRYLAMIDE SERVANT D'ANTAGONISTES DE L'INTEGRINE VLA-1, ET LEURS UTILISATIONS
  申请人：ICOS CORP

  公开号：WO2005016883A3

  公开（公告）日：2005-04-14
• ARYL-SUBSTITUTED ALICYCLIC COMPOUND AND MEDICAL COMPOSITION COMPRISING THE SAME
  申请人：Dainippon Sumitomo Pharma Co., Ltd.

  公开号：EP1371646B1

  公开（公告）日：2010-05-19
• US7176199B2
  申请人：——

  公开号：US7176199B2

  公开（公告）日：2007-02-13