piperidine amide of L-phenyllactic acid | 130316-83-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: piperidine amide of L-phenyllactic acid
• 英文别名: 1(S)-(N-Piperidinylcarbonyl)-2-phenylethanol；(2S)-2-hydroxy-3-phenyl-1-piperidin-1-ylpropan-1-one
• CAS: 130316-83-5
• 化学式: C₁₄H₁₉NO₂
• 分子量: 233.31
• InChiKey: OFFGVDUKXBSJEK-ZDUSSCGKSA-N

物化性质

• 沸点：
  420.5±38.0 °C(Predicted)
• 密度：
  1.144±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  piperidine amide of L-phenyllactic acid 在 N-甲基吗啉 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 反应 21.75h， 生成 (S)-2-((S)-1-Benzyl-2-oxo-2-piperidin-1-yl-ethoxy)-hexanoic acid ((1S,2R,3S)-1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexyl)-amide
  参考文献：
  名称：

  Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement

  摘要：

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.

  DOI：

  10.1021/jm00088a006
• 作为产物：
  描述：

  哌啶 、 L-(-)-3-苯基乳酸 在 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 piperidine amide of L-phenyllactic acid
  参考文献：
  名称：

  Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement

  摘要：

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.

  DOI：

  10.1021/jm00088a006

文献信息

• Non-peptide renin inhibitors
  申请人：ABBOTT LABORATORIES

  公开号：EP0364804A1

  公开（公告）日：1990-04-25

  A renin inhibiting compound of the formula: wherein A is a substituent; R1 is hydrogen, loweralkyl, substituted loweralkyl or loweralkenyl; X is CH2, CHOH, C(O), O, S, S(O), S02, NH, N(O) or -P(O)O-; R3 is loweralkyl, loweralkenyl or substituted loweralkyl; and T is mimic of the Leu-Val cleavage site of angiotensinogen; or a pharmaceutically acceptable salt, ester or prodrug thereof.

  式中的肾素抑制化合物： 其中 A 是取代基；R1 是氢、低级烷基、取代的低级烷基或低级烯基；X 是 CH2、CHOH、C(O)、O、S、S(O)、S02、NH、N(O)或-P(O)O-；R3 是低级烷基、低级烯基或取代的低级烷基；T 是血管紧张素原的 Leu-Val 裂解位点的模拟物；或其药学上可接受的盐、酯或原药。
• NON-PEPTIDE RENIN INHIBITORS
  申请人：ABBOTT LABORATORIES

  公开号：EP0437508A1

  公开（公告）日：1991-07-24
• [EN] NON-PEPTIDE RENIN INHIBITORS
  申请人：——

  公开号：WO1990003971A1

  公开（公告）日：1990-04-19

  [FR] L'invention concerne un composé d'inhibition de la rénine ayant la formule (I), dans laquelle A est un substituant; R1 représente hydrogène, alkyl inférieur, alkyl inférieur substitué ou alkényl inférieur; X représente CH2, CHOH, C(O), O, S, S(O), SO2, NH, N(O) ou -P(O)O-; R3 représente un alkyl inférieur, un alkényl inférieur ou un alkyl inférieur substitué; et T est une mimique du site de clivage Leu-Val de l'angiotensinogène; ou un sel, un ester ou un promédicament pharmaceutiquement acceptable de celui-ci.
  [EN] A renin inhibiting compound of formula (I), wherein A is a substituent; R1? is hydrogen, loweralkyl, substituted loweralkyl or loweralkenyl; X is CH2?, CHOH, C(O), O, S, S(O), SO2?, NH, N(O) or -P(O)O-; R3? is loweralkyl, loweralkenyl or substituted loweralkyl; and T is mimic of the Leu-Val cleavage site of angiotensinogen; or a pharmaceutically acceptable salt, ester or prodrug thereof.
• Nonpeptide renin inhibitors employing a novel 3-aza (or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement
  作者：William R. Baker、Anthony K. L. Fung、Hollis D. Kleinert、Herman H. Stein、Jacob J. Plattner、Yoek Lin Armiger、Stephen L. Condon、Jerome Cohen、David A. Egan

  DOI：10.1021/jm00088a006

  日期：1992.5

  A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4-di-alkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4-butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha-amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides.