(S)-2-amino>-3-(4-biphenylyl)propionic acid | 147862-23-5

• 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: (S)-2-amino>-3-(4-biphenylyl)propionic acid
• 英文别名: (S)-2-(dimethylphosphonomethylamino)-3-(4-biphenylyl)-propionic acid；(2S)-2-(dimethoxyphosphorylmethylamino)-3-(4-phenylphenyl)propanoic acid
• CAS: 147862-23-5
• 化学式: C₁₈H₂₂NO₅P
• 分子量: 363.35
• InChiKey: FPNAACGXHSNRHH-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-amino>-3-(4-biphenylyl)propionic acid 在 氢溴酸 、 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 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 (S)-[(S)-3-Biphenyl-4-yl-2-(phosphonomethyl-amino)-propionylamino]-phenyl-acetic acid
  参考文献：
  名称：

  De Lombaert; Erion; Tan, Journal of Medicinal Chemistry, 1994, vol. 37, # 4, p. 498 - 511

  摘要：

  DOI：
• 作为产物：
  描述：

  (S)-4-phenylphenylalanine benzyl ester 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 20.0h， 生成 (S)-2-amino>-3-(4-biphenylyl)propionic acid
  参考文献：
  名称：

  De Lombaert; Erion; Tan, Journal of Medicinal Chemistry, 1994, vol. 37, # 4, p. 498 - 511

  摘要：

  DOI：

文献信息

• Phosphono/biaryl substituted amino acid derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US05250522A1

  公开（公告）日：1993-10-05

  The present invention relates to the N-phosphonomethyl-biaryl substituted amino acid derivatives of formula I ##STR1## wherein X represents a direct bond, C.sub.1-4 -alkylene or C.sub.2 -C.sub.4 -alkenylene; R and R' represent independently hydrogen, carbocyclic aryl, 6-tetrahydronaphthyl, 5-indanyl, .alpha.-(trichloromethyl, carboxyl, esterified carboxyl or amidated carboxyl)substituted-(lower alkyl or aryl-lower alkyl), acyloxymethyl optionally monosubstituted on methyl carbon by C.sub.1-20 -alkyl, by C.sub.5 -C.sub.7 -cycloalkyl, by aryl or by aryl-lower alkyl; R.sub.1 represents monocyclic carbocyclic or monocyclic heterocyclic aryl; COR.sub.3 represents carboxyl or carboxyl derivatized in form of a pharmaceutically acceptable ester; R.sub.2 and R.sub.4 represent hydrogen, lower alkyl, trifluoromethyl, lower alkoxy or halogen; and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; methods for preparation of said compounds and for the preparation of intermediates; and methods of treating disorders in mammals which are responsive to the inhibition of neutral endopeptidases by administration of said compounds to mammals in need of such treatment.

  本发明涉及公式I的N-磷酸甲基-联苯基取代氨基酸衍生物，其中X代表直接键，C.sub.1-4-烷基或C.sub.2-C.sub.4-烯基; R和R'分别独立表示氢、环烷基芳基、6-四氢萘基、5-茚基、α-(三氯甲基、羧基、酯化羧基或酰胺化羧基)取代-(较低烷基或芳基-较低烷基)、酰氧甲基在甲基碳上选择性地单取代C.sub.1-20-烷基、C.sub.5-C.sub.7-环烷基、芳基或芳基-较低烷基; R.sub.1表示单环芳基或单环杂环芳基; COR.sub.3表示羧基或以药学上可接受的酯形式衍生的羧基; R.sub.2和R.sub.4表示氢、较低烷基、三氟甲基、较低烷氧基或卤素;及其药学上可接受的盐;包含所述化合物的制药组合物;制备所述化合物和中间体的方法;以及通过将所述化合物用于需要此类治疗的哺乳动物的治疗中，抑制中性内肽酶的方法。
• Phosphono/biaryl substituted dipetide derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US05294632A1

  公开（公告）日：1994-03-15

  The invention relates to the N-phosphonomethyl-biaryl substituted dipeptide derivatives of formula I ##STR1## and tetrazole derivatives of the formula Ia ##STR2## wherein A represents a direct bond, lower alkylene, phenylene or cyclohexylene; m represents 1 or zero, provided that m represents 1 when A is a direct bond; R.sub.2 represents hydrogen, hydroxy, lower alkyl, aryl-lower alkyl, C.sub.5 -C.sub.7 -cycloalkyl-lower alkyl, amino-lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, lower alkoxy-lower alkyl, aryl-lower alkylthio-lower alkyl or aryl-lower alkoxy-lower alkyl; biaryl represents phenyl substituted by carbocyclic or heterocyclic aryl; and pharmaceutically acceptable mono-, di- or tri-ester derivatives thereof in which one, two or three of the acidic hydroxy groups of the carboxyl and/or phosphono functional groups are esterified in form of a mono-, di- or tri-pharmaceutically acceptable ester; and pharmaceutically acceptable amide derivatives thereof wherein the carboxyl group is derivatized in form of a pharmaceutically acceptable amide; and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; methods for the preparation of said compounds and for the preparation of intermediates; and methods of treating disorders in mammals which are responsive to the inhibition of neutral endopeptidases by administration of said compounds to mammals in need of such treatment.

  本发明涉及式I的N-磷酸甲基-双芳基取代二肽衍生物##STR1##和式Ia的四唑衍生物##STR2##其中A代表直接键，较低的烷基，苯基或环己基; m表示1或零，但当A为直接键时，m表示1; R.sub.2表示氢，羟基，较低的烷基，芳基-较低的烷基，C.sub.5-C.sub.7-环烷基-较低的烷基，氨基-较低的烷基，羟基-较低的烷基，较低的烷基硫醇-较低的烷基，较低的烷氧-较低的烷基，芳基-较低的烷基硫醇-较低的烷基或芳基-较低的烷氧-较低的烷基; 双芳基代表被碳环或杂环芳基取代的苯基; 以及其药学上可接受的单酯，二酯或三酯衍生物，其中羧酸和/或磷酸功能团的一个，两个或三个酸性羟基以单一，二重或三重药学上可接受的酯的形式酯化; 其药学上可接受的酰胺衍生物，其中羧基以药学上可接受的酰胺衍生物的形式衍生化; 以及其药学上可接受的盐; 包括上述化合物的制药组合物; 制备上述化合物和中间体的方法; 以及通过向需要此类治疗的哺乳动物管理所述化合物来抑制中性内肽酶并治疗哺乳动物的障碍的方法。
• Phosphono substituted tetrazole derivatives as ECE inhibitors
  申请人：Ciba-Geigy Corporation

  公开号：US05550119A1

  公开（公告）日：1996-08-27

  The present invention relates to the N-phosphonomethyl substituted compounds of formula ##STR1##

  本发明涉及式子为##STR1##的N-磷酸甲基取代化合物。
• Phosphono/biaryl substituted dipeptide derivatives
  申请人：CIBA-GEIGY AG

  公开号：EP0511940A2

  公开（公告）日：1992-11-04

  Novel N-phosphonomethyl-biaryl substituted dipeptide derivatives of formula I wherein R and R' represent independently hydrogen, carbocyclic aryl, 6-tetrahydronaphthyl, 5-indanyl, acyloxymethyl or acyloxymethyl monosubstituted on methyl carbon by C1-C2o-alkyl, by C5-C7-cycloalkyl, by aryl or by aryl-lower alkyl ; A represents a direct bond, lower alkylene, phenylene or cyclohexylene ; m represents 1 or zero, provided that m represents 1 when A is a direct bond ; R1 represents phenyl, phenyl substituted by one to three substituents selected from lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, halogen, cyano, trifluoromethyl, lower alkanoylamino or lower alkoxycarbonyl, naphthyl, naphthyl substituted by lower alkyl, lower alkoxy or halogen, thienyl, thienyl substituted by lower alkyl, furanyl, furanyl substituted by lower alkyl, pyridyl, pyridyl substituted by lower alkyl, halogen or cyano, pyrrolyl or N-lower alkylpyrrolyl ; R2 represents hydrogen, hydroxy, lower alkyl, aryl-lower alkyl, C5-C7-cycloalkyl-lower alkyl, amino-lower alkyl, hydroxy-lower alkyl, lower alkylthio-lower alkyl, lower alkoxy-lower alkyl, aryl-lower alkylthio-lower alkyl or aryl-lower alkoxy-lower alkyl ; COR3 represents carboxyl or carboxyl derivatized in form of a pharmaceutically acceptable ester or amide ; and pharmaceutically acceptable salts thereof are useful as neutral endopeptidase (NEP) inhibitors. Suitable methods for their be manufacture are described.

  式 I 的新颖 N-膦酰甲基-叔丁基取代二肽衍生物 其中 R 和 R'独立地代表氢、碳环芳基、6-四氢萘基、5-茚基、酰氧基甲基或在甲基碳上被 C1-C2o- 烷基、C5-C7-环烷基、芳基或芳基-低级烷基单取代的酰氧基甲基；A 代表直接键、低级亚烷基、亚苯基或环己基；m 代表 1 或 0，但当 A 为直接键时，m 代表 1；R1 代表苯基、被选自低级烷基、羟基、低级烷氧基、低级烷酰氧基、卤素、氰基、 三氟甲基、低级烷酰胺基或低级烷氧基羰基的一至三个取代基取代的苯基、萘基被低级烷基、低级烷氧基或卤素取代的萘基，噻吩基，被低级烷基取代的噻吩基，呋喃基，被低级烷基取代的呋喃基，吡啶基，被低级烷基、卤素或氰基取代的吡啶基，吡咯基或 N-低级烷基吡咯基；R2代表氢、羟基、低级烷基、芳基-低级烷基、C5-C7-环烷基-低级烷基、氨基-低级烷基、羟基-低级烷基、低级烷硫基-低级烷基、低级烷氧基-低级烷基、芳基-低级烷硫基-低级烷基或芳基-低级烷氧基-低级烷基；COR3代表羧基或以药学上可接受的酯或酰胺形式衍生的羧基；其药学上可接受的盐可用作中性内肽酶（NEP）抑制剂。本文介绍了制造它们的适当方法。
• PHOSPHONO SUBSTITUTED TETRAZOLE DERIVATIVES
  申请人：CIBA-GEIGY AG

  公开号：EP0660840A1

  公开（公告）日：1995-07-05