(4-t-Butyloxycarbonyl-3,3-dimethyl)butanoylphenylalanine Benzyl Ester | 114359-47-6

• 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: (4-t-Butyloxycarbonyl-3,3-dimethyl)butanoylphenylalanine Benzyl Ester
• 英文别名: tert-butyl 3,3-dimethyl-5-oxo-5-[[(2S)-1-oxo-3-phenyl-1-phenylmethoxypropan-2-yl]amino]pentanoate
• CAS: 114359-47-6
• 化学式: C₂₇H₃₅NO₅
• 分子量: 453.579
• InChiKey: NBPHMIYLNQQSOE-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-t-Butyloxycarbonyl-3,3-dimethyl)butanoylphenylalanine Benzyl Ester 生成 (4-t-Butyloxycarbonyl-3,3-dimethyl)butanoylphenylalanine
  参考文献：
  名称：

  LULY, JAY R.;DELLARIA, JOSEPH;FUNG, ANTHONY K. L.;KEMPF, DALE J.;PLATTNER+

  摘要：

  DOI：
• 作为产物：
  描述：

  3,3-Dimethylglutaric Acid Mono t-Butyl Ester 生成 (4-t-Butyloxycarbonyl-3,3-dimethyl)butanoylphenylalanine Benzyl Ester
  参考文献：
  名称：

  LULY, JAY R.;DELLARIA, JOSEPH;FUNG, ANTHONY K. L.;KEMPF, DALE J.;PLATTNER+

  摘要：

  DOI：

文献信息

• 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。
• Functionalized peptidyl aminodiols and -triols
  申请人：ABBOTT LABORATORIES

  公开号：EP0230266A2

  公开（公告）日：1987-07-29

  The invention relates to renin inhibiting compounds of the formula wherein A is hydrogen; loweralkyl; arylalkyl; OR₈ or SR₈ wherein R₈ is hydrogen, loweralkyl or aminoalkyl; NR₉R₁₀ wherein R₉ and R₁₀ are independently selected from hydrogen, loweralkyl, aminoalkyl, cyanoalkyl and hydroxyalkyl; wherein B is NH, alkylamino, S, O, CH₂ or CHOH and R₁₁ is loweralkyl, cycloalkyl, aryl, arylalkyl, alkoxy, alkenyloxy, hydroxyalkoxy, dihydroxyalkoxy, arylalkoxy, arylalkoxyalkyl, amino, alkylamino, dialkylamino, (hydroxyalkyl)(alkyl)amino, (dihydroxy­alkyl)(alkyl)amino, carboxylic acid-substituted alkyl, alkoxycarbonylalkyl, aminoalkyl, N-protected aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, (N-protected)­ alkyl)aminoalkyl, (heterocyclic)alkyl or a substituted or unsubstituted heterocyclic; R₁ is loweralkyl, cycloalkylmethyl, benzyl, α-methylbenzyl, α, α-di­methylbenzyl, 4-methoxybenzyl, halobenzyl, (1-naphthyl)­methyl, (2-naphthyl)methyl, (4-imidazoyl)methyl, phenethyl, phenoxy, thiophenoxy or anilino; provided if R₁ is phenoxy, thiophenoxy or anilino, B is CH₂ or CHOH or A is hydrogen; R₃ is loweralkyl, benzyl or heterocyclic ring-substituted methyl; R₄ is lower­alkyl, cycloalkyl- methyl or benzyl; R₂, R₅ and R₆ are independently hydrogen or loweralkyl; X is O, NH or S; R₇ is hydrogen, loweralkyl, alkanoyl, alkylsulfonyl. wherein R₁₂ and R₁₃ are independently hydrogen or loweralkyl, n is 0-2 and R₁₄ is substituted or unsubstituted penyl or heterocyclic; or XR₇ together are loweralkylsulfonyl, N₃ or Cl, and pharmaceutically acceptable salts thereof.

  本发明涉及式中的肾素抑制化合物 其中 A 是氢；低级烷基；芳基烷基；OR₈或 SR₈，其中 R₈ 是氢、低级烷基或氨基烷基；NR₉R₁₀，其中 R₉ 和 R₁₀ 独立选自氢、低级烷基、氨基烷基、氰基烷基和羟基烷基； 其中 B 是 NH、烷基氨基、S、O、CH₂ 或 CHOH，R₁₁ 是低级烷基、环烷基、芳基、芳烷基、烷氧基、烯氧基、羟基烷氧基、二羟基烷氧基、芳基烷氧基、芳基烷氧基烷基、氨基、烷基氨基、二烷基氨基、(羟基烷基)(烷基)氨基、(二羟基烷基)(烷基)氨基、(二羟基烷基)(烷基)氨基、羧酸取代的烷基、烷氧羰基烷基、氨基烷基、N-保护氨基烷基、烷基氨基烷基、二烷基氨基烷基、(N-保护)烷基)氨基烷基、(杂环)烷基或取代或未取代的杂环；R₁ 是低级烷基、环烷基甲基、苄基、α-甲基苄基、α、α-二甲基苄基、4-甲氧基苄基、卤代苄基、(1-萘基)甲基、(2-萘基)甲基、(4-咪唑酰基)甲基、苯乙基、苯氧基、噻吩氧基或苯胺基；如果 R₁ 是苯氧基、噻吩氧基或苯胺基，则 B 是 CH₂ 或 CHOH 或 A 是氢；R₃ 是低级烷基、苄基或杂环取代的甲基；R₄ 是低级烷基、环烷基-甲基或苄基；R₂、R₅ 和 R₆ 独立地是氢或低级烷基；X 是 O、NH 或 S；R₇ 是氢、低级烷基、烷酰基、烷基磺酰基。 其中 R₁₂ 和 R₁₃ 独立地为氢或低级烷基，n 为 0-2 且 R₁₄ 为取代或未取代的戊基或杂环；或 XR₇ 一起为低级烷基磺酰基、N₃ 或 Cl 及其药学上可接受的盐。
• Renin-inhibiting peptidyl heterocycles
  申请人：ABBOTT LABORATORIES

  公开号：EP0307837A2

  公开（公告）日：1989-03-22

  A renin inhibiting compound of the formula: wherein A is a substituent; W is C=O, CHOH or NR₂ wherein R₂ is hydrogen or loweralkyl; U is C=O, CH₂ or NR₂ wherein R₂ is hydrogen or loweralkyl, with the proviso that when W is CHOH then U is CH₂ and with the proviso that U is C=O or CH₂ when W is NR₂; V is CH, C(OH) or C(halogen) with the proviso that V is CH when U is NR₂; R₁ is loweralkyl, cycloalkylalkyl, benzyl, (alpha, alpha)-dimethylbenzyl, 4-methoxybenzyl, halobenzyl, 4-hydroxybenzyl, (1-naphthyl)methyl, (2-naphthyl)methyl, (unsubstituted heterocyclic)methyl, (substituted heterocyclic)methyl, phenethyl, 1-benzyloxyethyl, phenoxy, thiophenoxy or anilino, provided that B is CH₂ or CHOH or A is hydrogen when R₁ is phenoxy, thiophenoxy or anilino; R₃ is loweralkyl, loweralkenyl, ((alkoxy)alkoxy)alkyl, carboxyalkyl, (thioalkoxy)alkyl, azidoalkyl, aminoalkyl, (alkyl)aminoalkyl, dialkylaminoalkyl, (alkoxy)(alkyl)aminoalkyl, (alkoxy)aminoalkyl, benzyl or heterocyclic ring substituted methyl; R₄ is loweralkyl, cycloalkylmethyl or benzyl; R₅ is OH or NH₂; and Z is a substituent. Also disclosed are compositions for and a method of treating hypertension, methods of making the renin inhibiting compounds and intermediates useful in making the renin inhibiting compounds.

  一种式的肾素抑制化合物： 其中 A 是取代基；W 是 C=O、CHOH 或 NR₂，其中 R₂ 是氢或低级烷基；U 是 C=O、CH₂ 或 NR₂，其中 R₂ 是氢或低级烷基，但当 W 是 CHOH 时，U 是 CH₂，当 W 是 NR₂ 时，U 是 C=O 或 CH₂；V 是 CH、C(OH) 或 C(卤素)，但当 U 是 NR₂ 时，V 是 CH；(取代杂环)甲基、苯乙基、1-苄氧基乙基、苯氧基、噻吩氧基或苯胺基，但当 R₁ 为苯氧基、噻吩氧基或苯胺基时，B 为 CH₂ 或 CHOH 或 A 为氢；R₃ 是低级烷基、低级烯基、((烷氧基)烷氧基)烷基、羧基烷基、(硫代烷氧基)烷基、叠氮烷基、氨基烷基、(烷基)氨基烷基、二烷基氨基烷基、(烷氧基)(烷基)氨基烷基、(烷氧基)氨基烷基、苄基或杂环取代的甲基；R₄ 是低级烷基、环烷基甲基或苄基；R₅ 是 OH 或 NH₂；Z 是取代基。 还公开了治疗高血压的组合物和方法、制造肾素抑制化合物的方法以及制造肾素抑制化合物的中间体。
• PEPTIDE ANALOGS
  申请人：DELLARIA, Joseph

  公开号：EP0258289A1

  公开（公告）日：1988-03-09