α-[(Diethoxyphosphinyl)methyl]benzenepropanoic acid | 95272-47-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: α-[(Diethoxyphosphinyl)methyl]benzenepropanoic acid
• 英文别名: benzyl 3-(diethoxyphosphoryl)-2(R,S)-propionic acid；2(R,S)-benzyl-3-diethoxyphosphorylpropionic acid；2-Benzyl-3-(diethoxyphosphinyl)propionic acid；2-benzyl-3-diethoxyphosphorylpropanoic acid
• CAS: 95272-47-2
• 化学式: C₁₄H₂₁O₅P
• 分子量: 300.292
• InChiKey: OPMNUPKKGGXJHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,4S,5S)-5-[(S)-2-Amino-3-(1H-imidazol-4-yl)-propionylamino]-6-cyclohexyl-4-hydroxy-2-isopropyl-hexanoic acid butylamide 、 α-[(Diethoxyphosphinyl)methyl]benzenepropanoic acid 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， 生成 (2S,4S,5S)-5-[[(2S)-2-[(2-benzyl-3-diethoxyphosphorylpropanoyl)amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-N-butyl-6-cyclohexyl-4-hydroxy-2-propan-2-ylhexanamide
  参考文献：
  名称：

  Synthesis and biological activity of some transition-state inhibitors of human renin

  摘要：

  A series of renin inhibitors containing the dipeptide transition state mimics (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-7-methyloctanoic acid (Leu (OH)/Val) and (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-6-cyclohexylhexanoic acid (CHa /(OH)/Val) was prepared. A structure-activity study with Boc-Phe-His-Leu (OH)/Val-Ile-His-NH2 (8a) as starting material led to N-[(2S)-2-[(tert-butylsulfonyl)methyl]-3-phenylpropionyl]-His-Cha (OH)/ Val- NHC4H9-n (8i) which has the length of a tetrapeptide and contains only one natural amino acid. Compound 8i had an IC50 of 2 x 10(-9) M against human renin and showed high enzyme specificity; IC50 values against the related aspartic proteinases pepsin and cathepsin D were (8 x 10(-6) and 3 x 10(-6) M, respectively). In salt-depleted marmosets, 8i inhibited plasma renin activity PRA and lowered blood pressure for up to 2 h after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00117a027
• 作为产物：
  描述：

  乙基2-苄基丙烯酸酯 在 氢氧化钾 、 sodium ethanolate 作用下， 以 乙醇 、 水 为溶剂， 反应 28.0h， 生成 α-[(Diethoxyphosphinyl)methyl]benzenepropanoic acid
  参考文献：
  名称：

  Synthesis and biological activity of some transition-state inhibitors of human renin

  摘要：

  A series of renin inhibitors containing the dipeptide transition state mimics (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-7-methyloctanoic acid (Leu (OH)/Val) and (2S,4S,5S)-5-amino-4-hydroxy-2-isopropyl-6-cyclohexylhexanoic acid (CHa /(OH)/Val) was prepared. A structure-activity study with Boc-Phe-His-Leu (OH)/Val-Ile-His-NH2 (8a) as starting material led to N-[(2S)-2-[(tert-butylsulfonyl)methyl]-3-phenylpropionyl]-His-Cha (OH)/ Val- NHC4H9-n (8i) which has the length of a tetrapeptide and contains only one natural amino acid. Compound 8i had an IC50 of 2 x 10(-9) M against human renin and showed high enzyme specificity; IC50 values against the related aspartic proteinases pepsin and cathepsin D were (8 x 10(-6) and 3 x 10(-6) M, respectively). In salt-depleted marmosets, 8i inhibited plasma renin activity PRA and lowered blood pressure for up to 2 h after oral administration of a dose of 10 mg/kg.

  DOI：

  10.1021/jm00117a027

文献信息

• N-morpholino derivatives and their use as anti-hypertensive agents
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05055466A1

  公开（公告）日：1991-10-08

  Compounds of the formula ##STR1## are disclosed. These compounds are inhibitors of renin and therefore useful as cardiovascular agents.

  公开了式##STR1##的化合物。这些化合物是肾素抑制剂，因此可用作心血管药物。
• Novel 5-amino-4-hydroxyvaleryl derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US04727060A1

  公开（公告）日：1988-02-23

  Compounds of the formula ##STR1## in which R.sub.1 represents hydrogen or acyl, A represents an optionally N-alkylated .alpha.-amino acid residue which is bonded N-terminally to R.sub.1 and C-terminally to the group --NR.sub.2 --, R.sub.2 represents hydrogen or lower alkyl, R.sub.3 represents hydrogen, lower alkyl, optionally etherified or esterified hydroxy-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, bicycloalkyl-lower alkyl, tricycloalkyl-lower alkyl, aryl or aryl-lower alkyl, R.sub.4 represents hydroxy or etherified or esterified hydroxy, R.sub.5 represents lower alkyl having 2 or more carbon atoms, optionally etherified or esterified hydroxy-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, bicycloalkyl, bicycloalkyl-lower alkyl, tricycloalkyl, tricycloalkyl-lower alkyl, aryl, aryl-lower alkyl, optionally substituted carbamoyl, optionally substituted amino, optionally substituted hydroxy or optionally substituted mercapto and R.sub.6 represents substituted amino, and salts of such compounds having salt-forming groups inhibit the blood pressure-increasing action of the enzyme renin and can be used as antihypertensives.

  式为##STR1##的化合物，其中R.sub.1代表氢或酰基，A代表一个可选的N-烷基化的α-氨基酸残基，其N-末端与R.sub.1和C-末端与--NR.sub.2--基团连接，R.sub.2代表氢或较低的烷基，R.sub.3代表氢、较低烷基、可选地醚化或酯化的羟基较低烷基、环烷基、环烷基较低烷基、双环烷基较低烷基、三环烷基较低烷基、芳基或芳基较低烷基，R.sub.4代表羟基或醚化或酯化的羟基，R.sub.5代表具有2个或更多碳原子的较低烷基、可选地醚化或酯化的羟基较低烷基、环烷基、环烷基较低烷基、双环烷基、双环烷基较低烷基、三环烷基、三环烷基较低烷基、芳基、芳基较低烷基、可选地取代的氨基甲酰基、可选地取代的氨基、可选地取代的羟基或可选地取代的巯基，R.sub.6代表取代的氨基，以及具有形成盐的基团的这类化合物的盐，抑制肾素酶增加血压的作用，可用作降压药。
• Pharmaceutical amides, and preparation, formulations and use of thereof
  申请人：The Wellcome Foundation Ltd.

  公开号：US04423242A1

  公开（公告）日：1983-12-27

  Compounds of the general formula ##STR1## wherein Ph is a phenyl group which is optionally substituted by one or more substituents selected from halo (i.e. fluoro, chloro, bromo or iodo), C.sub.1-4 alkyl, amino, C.sub.1-4 alkylamino, di-C.sub.1-4 alkylamino, nitro, sulphonyl, aminosulphonyl, trihalomethyl, carboxy, C.sub.1-4 alkoxycarbonyl, amido, C.sub.1-4 alkylamido C.sub.1-4 alkoxy, C.sub.2-4 alkenyl, cyano, aminomethyl or methylsulphonyl; R.sup.a and R.sup.b, which may be the same or different, each represents a hydrogen or alkali metal (e.g. sodium or lithium) atom or a C.sub.1-4 (e.g. ethyl) group; m is 0 or 1; Y is a group of formula: --NH--CH.sub.2 --CO-- or a group of formula: ##STR2## where R.sup.1 is hydrogen or methyl; R.sup.2 is alkyl of 1 to 3 carbon atoms or is methylthiomethyl; and Z is --OR.sup.3 or --NR.sup.4 R.sup.5 where R.sup.3, R.sup.4 and R.sup.5 are each hydrogen or alkyl of 1 to 4 carbon atoms (i.e. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or t-butyl) and R.sup.3 can further be phenylalkyl having 1 to 3 carbon atoms in the alkylene moiety thereof, or phenyl; and basic salts thereof. These compounds have an advantageous enkephalinase inhibitory activity which renders the compounds useful in medical therapy, e.g. to prolong and/or potentiate in a mammal, the effects of endogenous or exogenous enkephalins. The latter includes synthetic enkepalin analogues.

  一般式为##STR1##的化合物，其中Ph是苯基，可选地取代为一个或多个取代基，所选取代基包括卤素（即氟、氯、溴或碘）、C.sub.1-4烷基、氨基、C.sub.1-4烷基氨基、二-C.sub.1-4烷基氨基、硝基、磺酰基、氨基磺酰基、三卤甲基、羧基、C.sub.1-4烷氧基羰基、酰胺基、C.sub.1-4烷基酰胺基、C.sub.1-4烷氧基、C.sub.2-4烯基、氰基、氨甲基或甲磺酰基；R.sup.a和R.sup.b，可以相同也可以不同，分别代表氢或碱金属（例如钠或锂）原子或C.sub.1-4（例如乙基）基团；m为0或1；Y是公式：--NH--CH.sub.2 --CO--或公式：##STR2##的基团，其中R.sup.1是氢或甲基；R.sup.2是1至3个碳原子的烷基或甲基硫代甲基；Z是--OR.sup.3或--NR.sup.4 R.sup.5，其中R.sup.3、R.sup.4和R.sup.5分别是氢或1至4个碳原子的烷基（即甲基、乙基、正丙基、异丙基、正丁基、异丁基或叔丁基），并且R.sup.3还可以是具有1至3个碳原子的烷基链的苯基烷基，或苯基；以及它们的盐。这些化合物具有有利的脑啡肽酶抑制活性，使得这些化合物在医疗治疗中有用，例如在哺乳动物中延长和/或增强内源性或外源性脑啡肽的效果，后者包括合成的脑啡肽类似物。
• Pharmaceutical compounds, and preparation, formulations and use thereof
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0075334A2

  公开（公告）日：1983-03-30

  Compounds of the general formula wheren Ph is a phenyl group which is optionally substituted by one or more substituents selected from halo (i.e. fluoro, chloro, bromo or iodo), C1-4alkyl, amino, C1-4alkylamino, di-C1-4alkylamino, nitro, sulphonyl, aminosulphonyl, trihalomethyl, carboxy, C1-4alkoxycarbonyl, amido, C1-4alky(amido C1-4alkoxy, C2-4alkenyl, cyano, aminomethyl or methylsulphonyl; R' und Rb, which may be the same or different, each represents a hydrogen or alkali metal (eg. sodium or lithium) atom or a C1-4 (eg. ethyl) group; m is 0 or 1; Y is a group of formula: or a group of formula: where R' is hydrogen or methyl; R2 is alkyl of 1 to 3 carbon atoms or is methylthiomethyl; and Z is -OR3 or -NR4Rs where R3, R4 and R5 are each hydrogen or alkyl of 1 to 4 carbon atoms (ie. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or t-butyl) and R3 can further be phenylalkyl having 1 to 3 carbon atoms in the alkylene moiety thereof, or phenyl; and basic salts thereof. These compounds have an advantageous enkephalinase inhibitor activity which renders the compounds useful in medical therapy, eg. to prolong and/or potentiate in a mammal, the effects of endogenous or exogenous enkephalins. The latter includes synthetic enkephalin analogues.

  通式如下的化合物 其中 Ph 是苯基，可任选被一个或多个取代基取代，这些取代基选自卤代（即C1-4烷基、氨基、C1-4烷基氨基、二-C1-4烷基氨基、硝基、磺酰基、氨磺酰基、三卤甲基、羧基、C1-4烷氧基羰基、氨基、C1-4烷氧基、C2-4烯基、氰基、氨甲基或甲基磺酰基；R'和 Rb 可以相同或不同，各自代表氢原子或碱金属（如钠或锂）原子或 C1-4（如乙烯基）原子。m为 0 或 1； Y 是式中的基团 或式 其中 R' 是氢或甲基； R2 是 1 至 3 个碳原子的烷基或甲硫基；以及 Z是-OR3或-NR4Rs，其中R3、R4和R5各自是氢或1至4个碳原子的烷基（即甲基、乙基、正丙基、异丙基、正丁基、异丁基或叔丁基），R3还可以是在其亚烷基中具有1至3个碳原子的苯基烷基或苯基；以及它们的碱式盐。这些化合物具有良好的脑啡肽酶抑制剂活性，可用于医学治疗，例如延长和/或增强哺乳动物体内的内源性或外源性脑啡肽的作用。后者包括合成的脑啡肽类似物。
• Phosphorous containing compounds as inhibitors of enkephalinases
  申请人：SCHERING CORPORATION

  公开号：EP0117429A1

  公开（公告）日：1984-09-05

  Compounds having the general formula in which W is R' or OR', R' being hydrogen, alkyl, phenyl or benzyl Xis-(CH2)P-CHR3 or CHR3-(CH2)p- R33 is chosen from various substituents, or Z is chosen from various of organic groups, and R2 forms, with the carbonyl group to which it is attached, carboxy or various esterified carboxy groups or is the group -NR8R9. The compounds inhibit the activity of enkephalinases. Intermediates of formula are disclosed in which Wa is alkoxy, phenoxy or benzyloxy Xa is CH2CH-, and Ya is -NH2 or -NCO.

  具有通式的化合物，其中 W 是 R'或 OR'，R'是氢、烷基、苯基或苄基，Xis-(CH2)P-CHR3 或 CHR3-(CH2)p- R33 可从各种取代基中选择，或 Z 可从各种有机基团中选择，R2 与所连接的羰基形成羧基或各种酯化羧基，或为基团 -NR8R9。 这些化合物可抑制脑啡肽酶的活性。 公开了式中的中间体，其中 Wa 是烷氧基、苯氧基或苄氧基，Xa 是 CH2CH-，Ya 是 -NH2 或 -NCO。