l-isoleucyl-L-tryptophan methyl ester | 54793-69-0

• 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: l-isoleucyl-L-tryptophan methyl ester
• 英文别名: methyl (2S)-2-[[(2S,3S)-2-amino-3-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoate
• CAS: 54793-69-0
• 化学式: C₁₈H₂₅N₃O₃
• 分子量: 331.415
• InChiKey: KJXQTLXKXSATBX-UVBJJODRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  97.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  l-isoleucyl-L-tryptophan methyl ester 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.67h， 生成
  参考文献：
  名称：

  New hydroxyethylamine HIV protease inhibitors that suppress viral replication

  摘要：

  The synthesis of analogues of AcSerLeuAsn[Phe-HEA-Pro]IleValOMe (1, JG-365; where HEA stands for the hydroxyethylamine unit 2), a tight-binding inhibitor of HIVP, are reported. Systematic modification of the P3 and P3' regions of the inhibitors has led to smaller HIVP inhibitors that inhibit viral replication in HIV-infected and SIV-infected cell cultures. Six aliphatic and/or aromatic derivatives were prepared by replacing residues in the P3 regions of BocLeuAsn[Phe-HEA-Pro]IleValOMe. Aromatic side chains at P3 gave better inhibitors than aliphatic side chains. The better inhibitors in this series contained a beta-naphthylalanine or a biphenyl unit at P3. A second series of HIVP inhibitors were obtained by converting the P3 group into acyl groups. CbzAsn[Phe-HEA-Pro]IlePheOMe and Qua-Asn-[Phe-HEA-Pro]-Ile-Phe-OMe (where Qua = quinolin-2-ylcarbonyl) are potent HIVP inhibitors with K(i) values equal to 1.0 and 0.1 nM, respectively. The inhibition constants were determined by using the continuous fluorometric assay developed by Toth and Marshall. The activities of the protease inhibitors for inhibition of SIV replication were determined in vitro using CEMX174 cells. Inhibition of HIV infection was determined essentially as reported by Pauwels and co-workers. The anti-HIV assay was carried out in culture using CEM cell (a CD4+ lymphocyte line) infected with virus strain HTLV-IIIb with a multiplicity of infection of 0.1. Several analogues inhibited the cytopathic effect at concentrations of 0.1-0.8 mug/mL. These results establish that good inhibitors of HIV protease that inhibit viral replication in infected lymphocytes in in vitro cell assays can be obtained from JG-365 when the AcSerLeu unit is replaced by aromatic acyl derivatives.

  DOI：

  10.1021/jm00099a008
• 作为产物：
  描述：

  L-色氨酸甲酯盐酸盐 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.67h， 生成 l-isoleucyl-L-tryptophan methyl ester
  参考文献：
  名称：

  New hydroxyethylamine HIV protease inhibitors that suppress viral replication

  摘要：

  The synthesis of analogues of AcSerLeuAsn[Phe-HEA-Pro]IleValOMe (1, JG-365; where HEA stands for the hydroxyethylamine unit 2), a tight-binding inhibitor of HIVP, are reported. Systematic modification of the P3 and P3' regions of the inhibitors has led to smaller HIVP inhibitors that inhibit viral replication in HIV-infected and SIV-infected cell cultures. Six aliphatic and/or aromatic derivatives were prepared by replacing residues in the P3 regions of BocLeuAsn[Phe-HEA-Pro]IleValOMe. Aromatic side chains at P3 gave better inhibitors than aliphatic side chains. The better inhibitors in this series contained a beta-naphthylalanine or a biphenyl unit at P3. A second series of HIVP inhibitors were obtained by converting the P3 group into acyl groups. CbzAsn[Phe-HEA-Pro]IlePheOMe and Qua-Asn-[Phe-HEA-Pro]-Ile-Phe-OMe (where Qua = quinolin-2-ylcarbonyl) are potent HIVP inhibitors with K(i) values equal to 1.0 and 0.1 nM, respectively. The inhibition constants were determined by using the continuous fluorometric assay developed by Toth and Marshall. The activities of the protease inhibitors for inhibition of SIV replication were determined in vitro using CEMX174 cells. Inhibition of HIV infection was determined essentially as reported by Pauwels and co-workers. The anti-HIV assay was carried out in culture using CEM cell (a CD4+ lymphocyte line) infected with virus strain HTLV-IIIb with a multiplicity of infection of 0.1. Several analogues inhibited the cytopathic effect at concentrations of 0.1-0.8 mug/mL. These results establish that good inhibitors of HIV protease that inhibit viral replication in infected lymphocytes in in vitro cell assays can be obtained from JG-365 when the AcSerLeu unit is replaced by aromatic acyl derivatives.

  DOI：

  10.1021/jm00099a008

文献信息

• Anthraquinone derivatives and preparation thereof
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0405421A2

  公开（公告）日：1991-01-02

  A compound of the formula: wherein R¹ is hydrogen, hydroxy or acyloxy, R² is hydrogen or acyl, R³ is acyl, R⁴ is hydrogen or acyl, R⁵ is hydrogen or acyl, R⁶ is hydrogen or acyl, and R⁷ is hydrogen or acyl, and pharmaceutically acceptable salt thereof, processes for the preparation and pharmaceutical compositions comprising them as an active ingredient in association with a pharmaceutically acceptabel, substantially non-toxic carrier or excipient. The invention also comprises biologically pure cultures of the microorganisms Streptomyces sp. No. 89009 (FERM BP-2475) and Pseudomonas cepacia No. 97 (FERM BP-2945).

  式中的化合物： 其中 R¹ 是氢、羟基或酰氧基、 R² 是氢或酰基 R³ 是酰基 R⁴ 是氢或酰基、 R⁵ 是氢或酰基、 R⁶ 是氢或酰基，以及 R⁷ 是氢或酰基、 及其药学上可接受的盐、制备工艺和药物组合物，其中包含它们作为活性成分与药学上可接受的、基本上无毒的载体或赋形剂。本发明还包括微生物链霉菌（Streptomyces sp.
• Selective Removal of Fluorenylmethoxycarbonyl (FMOC) Groups Under Mild Conditions
  作者：Jianjun Jiang、Wen-Ren Li、Madeleine M. Joullié

  DOI：10.1080/00397919408013818

  日期：1994.1

  N-Fluorenylmethoxycarbonyl groups may be removed by potassium fluoride/18-crown-6 in the presence of methyl, ethyl, tert-butyl, benzyl, and p-methoxybenzyl esters.
• US5187195A
  申请人：——

  公开号：US5187195A

  公开（公告）日：1993-02-16