O-(N-吗啉基羰基)-3-苯基乳酸 | 114343-31-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 中文名称: O-(N-吗啉基羰基)-3-苯基乳酸
• 英文名称: 2<(morpholinocarbonyl)oxy>-3-phenylpropanoic acid
• 英文别名: 2(S)-<(4-morpholinylcarbonyl)oxy>-3-phenylpropionic acid；(S)-α-[(4-Morpholinylcarbonyl)oxy]benzenepropanoic acid；(2S)-2-morpholinocarbonyloxy-3-phenylpropionic acid；2(S)-((4-Morpholinyl)carbonyl)oxy-3-phenylpropionic Acid；2(S)-morpholinocarbonyloxy-3-phenylpropionic acid；O-(N-Morpholinocarbonyl)-3-phenyllactic acid；(2S)-2-(morpholine-4-carbonyloxy)-3-phenylpropanoic acid
• CAS: 114343-31-6
• 化学式: C₁₄H₁₇NO₅
• 分子量: 279.293
• InChiKey: RXSSENVGBNPHJJ-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  O-(N-吗啉基羰基)-3-苯基乳酸 、 (S)-2-Amino-N-((1S,2R,3S)-1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexyl)-3-(1H-imidazol-4-yl)-propionamide; hydrochloride 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以35.4%的产率得到Morpholine-4-carboxylic acid (S)-1-[(S)-1-((1S,2R,3S)-1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-2-(1H-imidazol-4-yl)-ethylcarbamoyl]-2-phenyl-ethyl ester
  参考文献：
  名称：

  Renin inhibitors. Dipeptide analogs of angiotensinogen utilizing a structurally modified phenylalanine residue to impart proteolytic stability

  摘要：

  A series of renin inhibitors have been prepared and evaluated for their susceptibility to cleavage by the serine protease chymotrypsin. The compounds were designed by consideration of the structural requirements in the active-site region of renin and chymotrypsin. By systematic alteration of the P3 phenylalanine residue, compounds with varying degrees of renin inhibitory potency and chymotrypsin susceptibility were obtained. Selected analogues from this group were examined in vivo for both their hypotensive effects and metabolic patterns.

  DOI：

  10.1021/jm00120a006
• 作为产物：
  描述：

  L-苯基乳酸甲酯 在 lithium hydroxide 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 18.17h， 生成 O-(N-吗啉基羰基)-3-苯基乳酸
  参考文献：
  名称：

  Renin inhibitors. Dipeptide analogs of angiotensinogen utilizing a structurally modified phenylalanine residue to impart proteolytic stability

  摘要：

  A series of renin inhibitors have been prepared and evaluated for their susceptibility to cleavage by the serine protease chymotrypsin. The compounds were designed by consideration of the structural requirements in the active-site region of renin and chymotrypsin. By systematic alteration of the P3 phenylalanine residue, compounds with varying degrees of renin inhibitory potency and chymotrypsin susceptibility were obtained. Selected analogues from this group were examined in vivo for both their hypotensive effects and metabolic patterns.

  DOI：

  10.1021/jm00120a006

文献信息

• Novel amino acid derivatives possessing renin-inhibitory activities
  申请人：Japan Tobacco Inc.

  公开号：EP0396065A1

  公开（公告）日：1990-11-07

  An amino acid derivative of the general formula: wherein R1 is wherein, R10 is a lower alkyl group and R" is (wherein R111 is a lower alkyl group and n is an integer of 1 to 5) or a lower alkyl group which may be substituted by hydroxy group or methoxyethoxymethoxy group, or R'° and R" are combinedly together with the adjacent nitrogen atom; R12 is a hydrogen atom, CnH2n+1-O-CO- (n is as defined above) or R'3 is a lower alkyl group which may be substituted by substituent(s) selected from HOOC-(H2C)n-O-, R12- NH- (n and R12 are as defined above) and pyridyl group; X is -CH2-, -O- or -NH- and Y is -O- or -NH-; wherein (wherein Z is -0-, -S-, -S(O)-. -S(O)2-, -CH2-, -CH(OH)-, or and a and b are independently an integer of 1 to 4 and the total of a and b is not more than 5) ; R2 is an aralkyl group which may be substituted by lower alkyl group(s); R3 is a hydrogen atom or a lower alkyl group; R4 is a lower alkyl group; and A is hydroxy group and B is a hydrogen atom, or A and B are carbonyl group combinedly together with the adjacent carbon atom, a pharmaceutically acceptable acid addition salt or an ester thereof is described. The compounds of the invention possess inhibitory activities against renin and are useful as an antihypertensive agent.

  通用公式的氨基酸衍生物： 其中R1为 其中，R10为较低的烷基基团，R"为 （其中R111为较低的烷基基团，n为1至5的整数）或者可以被羟基或甲氧乙氧甲氧基取代的较低烷基基团，或者R'°和R"与相邻的氮原子 结合在一起； R12为氢原子，CnH2n+1-O-CO-（n如上定义）或者 R'3为可以被HOOC-(H2C)n-O-、R12-NH-（n和R12如上定义）和吡啶基取代的较低烷基基团； X为-CH2-、-O-或-NH-，Y为-O-或-NH-；其中 （其中Z为-0-、-S-、-S(O)-、-S(O)2-、- -、-CH(OH)-， 或 a和b分别独立为1至4的整数，且a和b的总和不超过5）； R2为可以被较低烷基基团取代的芳基烷基基团； R3为氢原子或较低烷基基团； R4为较低烷基基团； A为羟基，B为氢原子，或者A和B与相邻的碳原子结合在一起，描述了一种药学上可接受的酸盐或其酯。本发明的化合物具有对肾素的抑制活性，并可用作降压药。
• Renin-inhibiting functionalized peptidyl aminodiols and - triols
  申请人：ABBOTT LABORATORIES

  公开号：EP0341602A2

  公开（公告）日：1989-11-15

  A renin inhibiting compound of the formula: or a pharmaceutically acceptable salt, ester or prodrug thereof.

  一个公式为的抑制肾素的化合物： 或其药用可接受的盐、酯或前药。
• Peptidyl difluorodiol renin inhibitors
  申请人：ABBOTT LABORATORIES

  公开号：EP0416393A1

  公开（公告）日：1991-03-13

  A renin inhibiting compound of the formula: wherein A is a functional group; W is (1) -C(O)-, (2) -CH(OH)- or (3) -N(R₂)- wherein R₂ is hydrogen or loweralkyl; U is (1) -C(O)-, (2) -CH₂- or (3) -N(R₂)- wherein R₂ is hydrogen or lower alkyl, with the proviso that when W is -CH(OH)- then U is -CH₂- and with the proviso that U is -C(O)- or -CH₂- when W is -N(R₂)-; V is (1) -CH-, (2) -C(OH)- or (3) -C(halogen)- with the proviso that v is -CH-­when U is -N(R₂)-; Q is -CH(R₁)- or -C(=CHR1a)- wherein R₁ is (1) loweralkyl, (2) cycloalkylalkyl, (3) arylalkyl, (4) (heterocyclic)alkyl, (5) 1-benzyloxyethyl, (6) phenoxy, (7) thiophenoxy or (8) anilino, provided that B is -CH₂- or -CH(OH)- or A is hydrogen when R₁ is phenoxy, thiophenoxy or anilino and R1a is aryl or heterocyclic; R₃ is a functional group; R₄ is (1) loweralkyl, (2) cycloalkylmethyl or (3) benzyl; R₅ is -CH(OH)- or -C(O)-; R₆ is -CH(OH)- or -C(O)-; and Z is (1) lower alkyl, (2) aryl, (3) arylalkyl, (4) cycloalkyl, (5) cycloalkylalkyl, (6) heterocyclic or (7) (heterocyclic)alkyl; or a pharmaceutically acceptable salt, ester or prodrug thereof.

  一种肾素抑制化合物的化学式：其中A是一个功能基团；W是(1) -C(O)-，(2) -CH(OH)-或(3) -N(R₂)-，其中R₂是氢或较低烷基；U是(1) -C(O)-，(2) -CH₂-或(3) -N(R₂)-，其中R₂是氢或较低烷基，但当W为-CH(OH)-时，则U为-CH₂-，并且当U为-N(R₂)-时，U为-C(O)-或-CH₂-；V是(1) -CH-，(2) -C(OH)-或(3) -C(卤素)-，但当U为-N(R₂)-时，V为-CH-；Q是-CH(R₁)-或-C(=CHR1a)-，其中R₁是(1) 较低烷基，(2) 环烷基烷基，(3) 芳基烷基，(4) (杂环)烷基，(5) 1-苄氧乙基，(6) 苯氧基，(7) 噻吩氧基或(8) 氨基苯基，前提是当R₁是苯氧基、噻吩氧基或氨基苯基时，B是-CH₂-或-CH(OH)-，或A是氢，而R1a是芳基或杂环；R₃是一个功能基团；R₄是(1) 较低烷基，(2) 环烷基甲基或(3) 苄基；R₅是-CH(OH)-或-C(O)-；R₆是-CH(OH)-或-C(O)-；Z是(1) 较低烷基，(2) 芳基，(3) 芳基烷基，(4) 环烷基，(5) 环烷基烷基，(6) 杂环或(7) (杂环)烷基；或其药学上可接受的盐、酯或前药。
• New Histidyl amino acid derivatives, and pharmaceutical composition
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04921855A1

  公开（公告）日：1990-05-01

  A compound of the formula: ##STR1## wherein R.sup.1 is lower alkyl optionally substituted with a substituent selected from the group consisting of acyl, hydroxy, lower alkoxy, aryl, lower alkylthio and a group of the formula: ##STR2## in which R.sup.5 is hydrogen or acyl and R.sup.6 is hydrogen or lower alkyl; aryl; or amino optionally substituted with substituent(s) selected from the group consisting of lower alkyl and acyl; and R.sup.2 is hydrogen or lower alkyl; or R.sup.1 and R.sup.2 are taken together with the attached nitrogen atom to form a heterocyclic group optionally substituted with substituent(s) selected from the group consisting of lower alkyl, hydroxy(lower )alkyl, lower alkoxy(lower)alkyl, acyl(lower)alkyl, oxo and acyl; R.sup.3 is hydrogen or lower alkyl; and R.sup.4 is lower alkyl; and its pharmaceutically acceptable salt, processes for the preparation thereof and pharmaceutical composition comprising the same.

  该化合物的化学式如下：##STR1##其中R.sup.1是选择自酰基、羟基、较低烷氧基、芳基、较低烷硫基和化学式组成的取代基的较低烷基，其中R.sup.5是氢或酰基，R.sup.6是氢或较低烷基；芳基；或氨基，可选择地带有来自较低烷基和酰基的取代基，R.sup.2是氢或较低烷基；或R.sup.1和R.sup.2与相连的氮原子一起形成可选择地带有来自较低烷基、羟基(较低)烷基、较低烷氧基(较低)烷基、酰基(较低)烷基、氧代基和酰基的取代基的杂环基；R.sup.3是氢或较低烷基；R.sup.4是较低烷基；以及其药学上可接受的盐、其制备方法和包含其的药物组合物。
• Amino acid derivatives, processes for the preparation thereof and
  申请人：Ujisawa Pharmaceutical Co., Ltd.

  公开号：US05223489A1

  公开（公告）日：1993-06-29

  A compound of the formula: ##STR1## wherein R.sup.1 is lower alkyl optionally substituted aryl; or amino optionally substituted; and R.sup.2 is hydrogen or lower alkyl; or R.sup.1 and R.sup.2 are taken together with the attached nitrogen atom to form a heterocyclic group optionally substituted; R.sup.3 is hydrogen or lower alkyl; and R.sup.4 is lower alkyl; and its pharmaceutically acceptable salt, processes for the preparation thereof and pharmaceutical composition comprising the same

  一种化合物的公式：##STR1##其中R.sup.1是低碳基可选择取代芳基; 或氨基可选择取代; R.sup.2是氢或低碳基; 或R.sup.1和R.sup.2与所连接的氮原子一起形成可选择取代的杂环基团; R.sup.3是氢或低碳基; R.sup.4是低碳基; 以及其药学上可接受的盐，其制备方法和包含该化合物的药物组成物。