1,1-dimethylethyl N-(carboxymethyl)-N-(cyclohexylmethyl)carbamate | 143935-49-3

• 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: 1,1-dimethylethyl N-(carboxymethyl)-N-(cyclohexylmethyl)carbamate
• 英文别名: N^α-Boc-N-cyclohexylmethylglycine；Boc-Ncha-OH；tert-Butyl N-(cyclohexylmethyl)-N-(2-hydroxy-2-oxoethyl)carbamate；N-Boc-N-(cyclohexylmethyl)-glycine；2-[cyclohexylmethyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid
• CAS: 143935-49-3
• 化学式: C₁₄H₂₅NO₄
• 分子量: 271.357
• InChiKey: UZFCIFCTRJYIAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl N-(carboxymethyl)-N-(cyclohexylmethyl)carbamate 在 N-甲基吗啉 、 盐酸 、 三甲基乙酰氯 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 66.0h， 生成 (2S)-2-(2-chloroprop-2-enyl)-N-[(1S)-2-cyclohexyl-1-[(4R,5S)-2,2-dimethyl-5-(2-methylpropyl)-1,3-dioxolan-4-yl]ethyl]-N'-(cyclohexylmethyl)-N'-[2-[methyl(2-pyridin-2-ylethyl)amino]-2-oxoethyl]butanediamide
  参考文献：
  名称：

  实用和有效的口服活性肾素抑制剂BILA 2157 BS的合成：酶催化水解在制备手性琥珀酸衍生物中的应用。

  摘要：

  我们已经开发出BILA 2157 BS（一种有效的口服活性肾素抑制剂）的高度收敛和立体选择性合成。合成过程从氨基二醇4开始，经过15个不同的化学步骤（具有多个集成的多步操作），合成中的关键步骤涉及使用对映体特异性，酶催化的取代琥珀酸酯二酯水解，以提供纯手性琥珀酸衍生物。 98％对映体过量（> / = 2.5千克规模）。不需要的对映异构体的再循环是通过碱催化的外消旋作用完成的，从而导致了起始外消旋二酯的高效脱硫。整个序列无需色谱纯化即可进行，并提供具有> 97％均一性的产物。此外，与之前报道的BILA 2157 BS合成相比，

  DOI：

  10.1021/jo990321x
• 作为产物：
  描述：

  在 lithium hydroxide 、 盐酸 作用下， 生成 1,1-dimethylethyl N-(carboxymethyl)-N-(cyclohexylmethyl)carbamate
  参考文献：
  名称：

  实用和有效的口服活性肾素抑制剂BILA 2157 BS的合成：酶催化水解在制备手性琥珀酸衍生物中的应用。

  摘要：

  我们已经开发出BILA 2157 BS（一种有效的口服活性肾素抑制剂）的高度收敛和立体选择性合成。合成过程从氨基二醇4开始，经过15个不同的化学步骤（具有多个集成的多步操作），合成中的关键步骤涉及使用对映体特异性，酶催化的取代琥珀酸酯二酯水解，以提供纯手性琥珀酸衍生物。 98％对映体过量（> / = 2.5千克规模）。不需要的对映异构体的再循环是通过碱催化的外消旋作用完成的，从而导致了起始外消旋二酯的高效脱硫。整个序列无需色谱纯化即可进行，并提供具有> 97％均一性的产物。此外，与之前报道的BILA 2157 BS合成相比，

  DOI：

  10.1021/jo990321x

文献信息

• Antiherpes virus compounds and methods for their preparation and use
  申请人：Boehringer Ingelheim Ltd.

  公开号：US06288091B1

  公开（公告）日：2001-09-11

  This invention relates to methods for inhibiting herpes replication and for treating herpes infection in a mammal by inhibiting the herpes helicase-primase enzyme complex. This invention also relates to thiazolyphenyl derivatives that inhibit the herpes helicase-primase and to pharmaceutical compositions comprising the thiazolylphenyl derivatives, to methods of using and methods of producing the thiazolylphenyl derivatives

  这项发明涉及通过抑制疱疹螺旋酶-引物酶复合物来抑制疱疹复制并治疗哺乳动物体内的疱疹感染的方法。这项发明还涉及抑制疱疹螺旋酶-引物酶的噻唑苯基衍生物，以及包含这些噻唑苯基衍生物的药物组合物，以及使用和生产这些噻唑苯基衍生物的方法。
• Stereoselective synthesis of renin inhibitor BILA 2157 BS
  作者：Bruno Simoneau、Pierre Lavallée、Murray Bailey、Jean-Simon Duceppe、Chantal Grand-Maître、Louis Grenier、William W Ogilvie、Marc-André Poupart、Bounkham Thavonekham

  DOI：10.1139/v99-233

  日期：2000.6.1

  We have developed a convergent and stereoselective synthesis of orally active renin inhibitor BILA 2157 BS. Three building blocks were used to generate the basic skeleton of the inhibitor. The key feature consisted of the late elaboration of the 2-amino-4-thiazolyl heterocycle from a vinylbromide precursor. The synthetic sequence, which required a total of 22 chemical steps, provided 0.6 kg of BILA 2157 BS in 7.3% overall yield.Key words: renin, inhibitor, peptidomimetic, stereoselective synthesis.

  我们已经开发出一种具有收敛性和立体选择性的口服活性肾素抑制剂BILA 2157 BS的合成方法。使用了三种构建模块来生成抑制剂的基本骨架。关键特征是从乙烯溴化物前体中晚期修饰2-氨基-4-噻唑基杂环。这种合成序列总共需要22个化学步骤，提供了0.6公斤的BILA 2157 BS，总产率为7.3%。关键词：肾素、抑制剂、肽类模拟物、立体选择性合成。
• Discovery of non-peptidic P 2 –P 3 butanediamide renin inhibitors with high oral efficacy
  作者：Bruno Simoneau、Pierre Lavallée、Paul C. Anderson、Murray Bailey、Gary Bantle、Sylvie Berthiaume、Catherine Chabot、Gulrez Fazal、Ted Halmos、William W. Ogilvie、Marc-André Poupart、Bounkham Thavonekham、Zhili Xin、Diane Thibeault、Gordon Bolger、Maret Panzenbeck、Raymond Winquist、Grace L. Jung

  DOI：10.1016/s0968-0896(98)00265-x

  日期：1999.3

  A new series of non-peptidic renin inhibitors having a 2-substituted butanediamide moiety at the P-2 and P-3 positions has been identified. The optimized inhibitors have IC50 values of 0.8 to 1.4 nM and 2.5 to 7.6 nM in plasma renin assays at pH 6.0 and 7.4, respectively. When evaluated in the normotensive cynomolgus monkey model, two of the most potent inhibitors were orally active at a dose as low as 3 mg/kg. These potent renin inhibitors are characterized by oral bioavailabilities of 40 and 89% in the cynomolgus monkey. Inhibitor 3z (BILA 2157 BS) was selected as candidate for pre-development. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Bradykinin Receptor Antagonists Containing N-Substituted Amino Acids:  <i>In Vitro</i> and <i>in Vivo</i> B₂ and B₁ Receptor Antagonist Activity
  作者：Val S. Goodfellow、Manoj V. Marathe、Karen G. Kuhlman、Timothy D. Fitzpatrick、David Cuadrado、Wendy Hanson、John S. Zuzack、Sherman E. Ross、Maciej Wieczorek、Michael Burkard、Eric T. Whalley

  DOI：10.1021/jm950716i

  日期：1996.1.1

  We report a systematic probing of the structural requirements of the bradykinin (BK) type 2 (B-2) receptor for antagonist activity by incorporating N-Alkyl-amino acid residues at positions 7 and 8 of a potent antagonist sequence. Compound 1 (D-Arg(0)-Arg(1)-Pro(2)-Hyp(3)-Gly(4)-Thi(5)-Ser(6)- D-Tic(7)-N-Chg(8)-Arg(9), CP-0597)(1,2) is a potent (pA(2) = 9.3, rat uterus; pK(i) = 9.62, binding, human receptor clone) Bz receptor antagonist devoid of in vitro B-1 antagonist activity (rabbit aorta). Compound 1 exhibits high potency (ED(50) = 29.2 pmol/kg/min, iv, rabbit) and duration of action when tested in models for in vivo B-2 antagonist activity. Although devoid of activity in a classic B-1 isolated tissue assay, B-1 antagonist activity for 1 was demonstrated in vivo, in a LPS-treated, inducible BK1 receptor rabbit blood pressure model (ED(50) = 1.7 nmol/kg/min). D-Arg(0) of 1 can be formally replaced by an achiral arginine surrogate, without significant loss in antagonist potency on rat uterus (compound 11, B-2 pA(2) = 9.1). Antagonist 13 (Hyp(2), NChg(8)), pK(i) = 10.2, and agonist 4 (N-methylcyclohexyl-Gly(8)), pK(i) = 10.1, also exhibited substantial binding to guinea pig ileum membrane receptors as well as a human Bz receptor clone. Very minor structural changes in the N-alkyl amino acid residues in positions 7 and 8 can modify the activity of this class of compounds from being extremely potent antagonists to tight binding partial or full agonists. These studies have resulted in a series of compounds containing inexpensive amino acid residues but which produce broad spectrum BK receptor blocking potency and exceptional in vivo duration of action.
• BRADYKININ ANTAGONIST PEPTIDES INCORPORATING N-SUBSTITUTED GLYCINES
  申请人：CORTECH, INC.

  公开号：EP0813544B1

  公开（公告）日：2004-10-27