2(R)-amino-N-(3-phenylpropyl)propanamide | 99952-51-9

• 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: 2(R)-amino-N-(3-phenylpropyl)propanamide
• 英文别名: N-(3-phenylpropyl)-D-alaninamide；D-Ala-NH-(CH2)3-Ph；(2R)-2-amino-N-(3-phenylpropyl)propanamide
• CAS: 99952-51-9
• 化学式: C₁₂H₁₈N₂O
• 分子量: 206.288
• InChiKey: BTOXZNNDLGGUIC-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2(R)-amino-N-(3-phenylpropyl)propanamide 生成 2(R)-<(cyclopropylmethyl)amino>-N-(3-phenylpropyl)propanamide
  参考文献：
  名称：

  PITZELE, BARNETT S.;HANSEN, DONALD W. (JR);HAMILTON, ROBERT W.;PLIPAUSKAS+

  摘要：

  DOI：
• 作为产物：
  描述：

  phenylmethyl [1R-methyl-2-oxo-2-[(3-phenylpropyl)amino]ethyl]carbamate 生成 2(R)-amino-N-(3-phenylpropyl)propanamide
  参考文献：
  名称：

  HANSEN, DONALD W.;MAZUR, ROBERT H.;PILIPAUSKAS, DANIEL R.

  摘要：

  DOI：

文献信息

• Substituted tyrosil alanine dipeptide amides
  申请人：G.D. Searle & Co.

  公开号：EP0154234A2

  公开（公告）日：1985-09-11

  The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: and the pharmaceutically acceptable acid addition salts thereof wherein R, represents straight or branched lower alkyl having 1 to 4 carbons; R2 represent hydrogen, hydroxy, -OCO2R1 substituent or lower alkyl having 1 to 4 carbons; R3 represents a hydrogen or lower alkyl having 1 to 6 carbons; R4 and R5 may be the same or different and represent hydrogen or lower alkyl having 1 to 6 carbons; n is 1 to 6; X represents a hydrogen, hydroxy or OCO2R1 substituent; A represents a cyclohexyl, phenyl or phenyl substituted with one or more lower alkyls containing 1 to 6 carbons, one or more amino, hydroxy, halogen, nitro or lower alkoxy substituent having 1 to 6 carbons; V represents the asymmetric carbon that may be racemic or have the D or L configuration; W represents the asymmetric carbon when R4 and R5 are not the same that may optionally be racemic or have the D or L configuration. These compounds are useful as analgesic and/or antihypertensive agents.

  本发明涉及式如下的新型取代酪氨丙氨酸二肽酰胺： 及其药学上可接受的酸加成盐 其中 R，代表具有 1 至 4 个碳原子的直链或支链低级烷基； R2 代表氢、羟基、-OCO2R1 取代基或具有 1 至 4 个碳原子的低级烷基； R3 代表氢或具有 1 至 6 个碳原子的低级烷基； R4 和 R5 可以相同或不同，代表氢或含 1 至 6 个碳原子的低级烷基； n 为 1 至 6； X 代表氢、羟基或 OCO2R1 取代基； A 代表环己基、苯基或被一个或多个含 1 至 6 个碳原子的低级烷基、一个或多个氨基、羟基、卤素、硝基或 1 至 6 个碳原子的低级烷氧基取代的苯基； V 代表不对称碳，可以是外消旋的，或具有 D 或 L 构型； W 代表 R4 和 R5 不相同时的不对称碳，可选择外消旋或具有 D 或 L 构型。这些化合物可用作镇痛剂和/或抗高血压剂。
• N-terminally substituted dipeptide amides No. 2
  申请人：G.D. Searle & Co.

  公开号：EP0213481A2

  公开（公告）日：1987-03-11

  This invention encompasses compounds of the formula and the pharmaceutically acceptable acid addition salts thereof wherein R¹ is lower alkoxy or -O-(CH₂)n-phenyl where the phenyl may be optionally substituted with halogen, -NO₂, -CN, -NH₂ or lower alkyl wherein n is 1 to 4; R² and R³ represent lower alkyl, halogen, lower alkoxy or one of R² or R³ is hydrogen and the other is lower alkyl, lower alkoxy, or halogen; R⁴, R⁵, R⁷, R⁸, and R⁹ represent hydrogen or lower alkyl, R⁶ represents hydrogen, lower alkyl, lower alkenyl, or -(CH₂)m-cycloalkyl wherein m is 1 to 4 and the cycloalkyl has 3 to 8 carbon atoms; R¹⁰ is -(CH₂)p-phenyl wherein p is 1 to 4; and v represents an asymmetric carbon that may be racemic or have the D or L Configuration; w represents an asymmetric carbon when R⁷ and R⁸ are not the same that may be racemic or have the D or L configuration. This invention also encompasses compounds where R¹ is hydroxy, provided at least one of R⁴, R⁵, R⁶ or R⁹ is lower alkyl. The compounds of this invention are useful analgesic agents.

  本发明包括以下式子的化合物 及其药学上可接受的酸加成盐 其中 R¹ 为低级烷氧基或-O-(CH₂)n-苯基，其中苯基可任选被卤素、-NO₂、-CN、-NH₂ 或低级烷基取代，其中 n 为 1 至 4；R² 和 R³ 代表低级烷基、卤素、低级烷氧基，或 R² 或 R³ 中的一个为氢，另一个为低级烷基、低级烷氧基或卤素；R⁴、R⁵、R⁷、R⁸ 和 R𠞙 代表氢或低级烷基，R⁶ 代表氢、低级烷基、低级烯基或-(CH₂)m-环烷基，其中 m 为 1 至 4，环烷基具有 3 至 8 个碳原子；R¹⁰ 是-(CH₂)对苯基，其中 p 为 1 至 4；当 R⁷和 R⁸ 不相同时，w 代表不对称碳，它可能是外消旋的或具有 D 或 L 构型。本发明还包括 R¹ 为羟基的化合物，条件是 R⁴、R⁵、R⁶ 或 R⁹ 中至少有一个是低级烷基。本发明的化合物是有用的镇痛剂。
• Substituted dipeptide amides
  申请人：G.D. Searle & Co.

  公开号：EP0215297A2

  公开（公告）日：1987-03-25

  The invention relates to novel substituted tyrosyl alanine dipeptide amides of the formula: and the pharmaceutically acceptable acid addition salts thereof wherein R' is hydrogen, lower alkyl, hydroxy, -OCO2 lower alkyl, lower alkoxy, -O(CH2)n- phenyl with the phenyl optionally substituted by halogen, -NO2, -CN, -NH2 or lower alkyl wherein n is 1 to 4; R2 and R' represent lower alkyl, halogen, or lower alkoxy, or either one of R2 or R3 is hydrogen and the other is lower alkyl, lower alkoxy or halogen; R4. R5, R6, R', R8, and R' may be the same or different and represent hydrogen or lower alkyl; and R10 is selected from the group consisting of -(ALK)X where ALK represents alkylene, thioalkylene, oxyalkylene, having 1 to 5 carbon atoms; alkenylene and alkynylene having 2 to 4 carbon atoms; and X represents pyridyl, pyrimidinyl, 9H-fluoren-9-yl, diphenylmethyl, thienyl, carboxy, lower alkoxy carbonyl, substituted phenyl wherein the phenyl substituent is amino, hydroxy, halogen, nitro, methylenedioxy, lower alkyl, carboxy, lower alkoxycarbonyl, lower alkoxy, carboxamide, diloweral- kylamino or X represents phenyl when ALK is not alkylene; or R'° is where p and q are independently 1 to 4; or R9 and R10 together with N is where r and t are independently 1 to 4; v represents an asymmetric carbon that may be racemic or have the D or L configuration; w represents an asymmetric carbon when R7 and R8 are not the same that may be racemic or have the D or L configuration. These compounds are useful as analgesic and/or antihypertensive compounds.

  本发明涉及式中的新型取代酪氨丙氨酸二肽酰胺： 及其药学上可接受的酸加成盐 其中R'是氢、低级烷基、羟基、-OCO2 低级烷基、低级烷氧基、-O(CH2)n-苯基，苯基可任选被卤素、-NO2、-CN、-NH2或低级烷基取代，其中n为1至4；R2和R'代表低级烷基、卤素或低级烷氧基，或者R2或R3中的一个为氢，另一个为低级烷基、低级烷氧基或卤素；R4.R5、R6、R'、R8 和 R' 可以相同或不同，代表氢或低级烷基；以及 R10 选自以下组成的组-(ALK)X 其中 ALK 代表具有 1 至 5 个碳原子的亚烷基、硫代烷基、氧代烷基；具有 2 至 4 个碳原子的烯基和炔基；X代表吡啶基、嘧啶基、9H-芴-9-基、二苯基甲基、噻吩基、羧基、低级烷氧基羰基、取代苯基，其中苯基取代基为氨基、羟基、卤素、硝基、亚甲基二氧基、低级烷基、羧基、低级烷氧基羰基、低级烷氧基、羧酰胺、稀释酰基氨基，或者当ALK不是亚烷基时，X代表苯基；或者R'°为 其中 p 和 q 独立地为 1 至 4；或 R9 和 R10 与 N 一起为 其中 r 和 t 独立地为 1 至 4； v 代表不对称碳，可以是外消旋体或具有 D 或 L 构型； 当 R7 和 R8 不相同时，w 代表一个不对称碳，它可能是外消旋的或具有 D 或 L 构型。这些化合物可用作镇痛剂和/或抗高血压化合物。
• Pitzele; Hamilton; Kudla, Journal of Medicinal Chemistry, 1994, vol. 37, # 7, p. 888 - 896
  作者：Pitzele、Hamilton、Kudla、Tsymbalov、Stapelfeld、Savage、Clare、Hammond、Hansen Jr.

  DOI：——

  日期：——
• Preparation and opioid activity of analogs of the analgesic dipeptide 2,6-dimethyl-L-tyrosyl-N-(3-phenylpropyl)-D-alaninamide
  作者：Nizal S. Chandrakumar、Peter K. Yonan、Awilda Stapelfeld、Michael Savage、Elaine Rorbacher、Patricia C. Contreras、Donna Hammond

  DOI：10.1021/jm00080a005

  日期：1992.1

  A number of analogues of the recently disclosed analgesic dipeptide 2,6-dimethyl-L-tyrosyl-D-alanine-phenylpropylamide (SC-39566,2) were prepared. These analogues contained oxymethylene, aminomethylene, ketomethylene, bismethylene, and trans double bond (including vinyl fluoride) isosteric replacements for the amide bond between the D-alanine and phenylpropylamine units in 2. These compounds were tested in opioid binding assays and in the mouse writhing assay for analgesic activity. Though not as potent as 2, the oxymethylene, and trans double bond isosteres showed analgesic activity. The aminomethylene analogues also showed binding activity in subnanomolar concentrations at the mu-receptor. The amide bond between 2,6-dimethyl-L-tyrosine and D-alanine units seems to be critical for opioid activity.