(R)-N-(2,2-dimethylpropyl)-3-{(2S,3S)-3-[(2S)-2-amino-3,3-dimethylbutanoylamino]-2-hydroxy-4-phenylbutanoyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxamide | 1061338-75-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (R)-N-(2,2-dimethylpropyl)-3-{(2S,3S)-3-[(2S)-2-amino-3,3-dimethylbutanoylamino]-2-hydroxy-4-phenylbutanoyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
• CAS: 1061338-75-7
• 化学式: C₂₇H₄₄N₄O₄S
• 分子量: 520.737
• InChiKey: GAXROAKAEIYWEE-UWHLTILDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.29
• 重原子数：
  36.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  124.76
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (R)-N-(2,2-dimethylpropyl)-3-{(2S,3S)-3-[(2S)-2-amino-3,3-dimethylbutanoylamino]-2-hydroxy-4-phenylbutanoyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxamide 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 KNI-10754
  参考文献：
  名称：

  Maintaining potent HTLV-I protease inhibition without the P3-cap moiety in small tetrapeptidic inhibitors

  摘要：

  The human T cell lymphotropic/leukemia virus type 1 (HTLV-I) causes adult T cell lymphoma/leukemia. The virus is also responsible for chronic progressive myelopathy and several inflammatory diseases. To stop the manufacturing of new viral components, in our previous reports, we derived small tetrapeptidic HTLV-I protease inhibitors with an important amide-capping moiety at the P-3 residue. In the current study, we removed the P-3-cap moiety and, with great difficulty, optimized the P-3 residue for HTLV-I protease inhibition potency. We discovered a very potent and small tetrapeptidic HTLV-I protease inhibitor (KNI-10774a, IC50 = 13 nM). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.048
• 作为产物：
  描述：

  (2S,3S)-3-tert-butoxycarbonylamino-2-hydroxy-4-phenylbutanoic acid 在 盐酸 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 (R)-N-(2,2-dimethylpropyl)-3-{(2S,3S)-3-[(2S)-2-amino-3,3-dimethylbutanoylamino]-2-hydroxy-4-phenylbutanoyl}-5,5-dimethyl-1,3-thiazolidine-4-carboxamide
  参考文献：
  名称：

  Design and synthesis of several small-size HTLV-I protease inhibitors with different hydrophilicity profiles

  摘要：

  The human T cell leukemia/lymphotropic virus type 1 (HTLV-I) is clinically associated with adult T cell leukemia/lymphoma, HTLV-I associated myelopathy/tropical spastic paraparesis, and a number of other chronic inflammatory diseases. To stop the replication of the virus, we developed highly potent tetrapeptidic HTLV-I protease inhibitors. In a recent X-ray crystallography study, several of our inhibitors could not form co-crystal complexes with the protease due to their high hydrophobicity. In the current study, we designed, synthesized and evaluated the HTLV-I protease inhibition potency of compounds with hydrophilic end-capping moieties with the aim of improving pharmaceutic and pharmacokinetic properties. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.066

文献信息

• Locking the two ends of tetrapeptidic HTLV-I protease inhibitors inside the enzyme
  作者：Meihui Zhang、Jeffrey-Tri Nguyen、Henri-Obadja Kumada、Tooru Kimura、Maosheng Cheng、Yoshio Hayashi、Yoshiaki Kiso

  DOI：10.1016/j.bmc.2008.05.052

  日期：2008.7

  Adult T-cell leukemia and tropical spastic paraparesis/ HTLV-I-associated myelopathy are only some of the more common end results of an infection with a human T-cell leukemia virus type 1 (HTLV-I). Expanding from our previous reports, we synthesized all different permutations of tetrapeptidic HTLV-I protease inhibitors using at least eight P3-cap and five P(1)'-cap moieties. The inhibitors exhibited over 97% inhibition against HIV-1 protease and a wide range of inhibitory activity against HTLV-I protease. (c) 2008 Elsevier Ltd. All rights reserved.
• Truncation and non-natural amino acid substitution studies on HTLV-I protease hexapeptidic inhibitors
  作者：Jeffrey-Tri Nguyen、Meihui Zhang、Henri-Obadja Kumada、Ayako Itami、Keiji Nishiyama、Tooru Kimura、Maosheng Cheng、Yoshio Hayashi、Yoshiaki Kiso

  DOI：10.1016/j.bmcl.2007.10.066

  日期：2008.1

  The culprit behind adult T-cell leukemia, myelopathy/tropical paraparesis, and a plethora of inflammatory diseases is the human T-cell leukemia virus type 1 (HTLV-1). We recently unveiled a potent hexapeptidic HTLV-1 protease inhibitor, KNI-10166, composed mostly of natural amino acid residues. Herein, we report the derivation of potent tetrapeptidic inhibitor KNI-10516, possessing only non-natural amino acid residues. (C) 2007 Elsevier Ltd. All rights reserved.