N-α-(1-ethoxycarbonyl-3-phenylpropyl)-L-lysyl-L-proline | 85955-62-0

• 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: N-α-(1-ethoxycarbonyl-3-phenylpropyl)-L-lysyl-L-proline
• 英文别名: (2S)-1-[(2S)-6-amino-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]hexanoyl]pyrrolidine-2-carboxylic acid
• CAS: 85955-62-0
• 化学式: C₂₃H₃₅N₃O₅
• 分子量: 433.548
• InChiKey: AWWHRFHKCVLCJX-WMEOFMBSSA-N

物化性质

• 沸点：
  641.6±55.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  31
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  7

文献信息

• Process for preparation of carboxyalkyldipeptide derivatives
  申请人：Merck & Co., Inc.

  公开号：EP0079521A1

  公开（公告）日：1983-05-25

  A process for the preparation of carboxyalkyldipeptide compounds of the Formula is described wherein R6 is hydroxy, loweralkoxy, or amino; R, R2 and R7 are hydrogen or loweralkyl; R3 is, e.g., hydrogen, or loweralkyl, R' is, e.g., hydrogen, or alkyl of from 1 to 20 carbon atoms, R4 is hydrogen or loweralkyl, R5 is, e.g., hydrogen, or loweralkyl, and, R4 and R5 may be connected together to form an alyklene bridge of from 2 to 4 carbon atoms. The process comprises reacting a compound of the Formula with a dipeptide (or protected dipeptide) of the Formula and an alkali metal cyanide or a trimethylsilycyanide, to form an amino nitrile compound of the Formula followed by hydrolysis. These compounds are useful as converting enzyme inhibitors and as antihypertensive agents.

  描述了一种制备Formula的羧基烷基二肽化合物的过程，其中R6为羟基、低烷氧基或氨基；R、R2和R7为氢或低烷基；R3为氢、低烷基等；R'为氢、1-20碳原子的烷基等；R4为氢或低烷基；R5为氢、低烷基等，R4和R5可以连接在一起形成2-4个碳原子的烷基桥。该过程包括将Formula的化合物与Formula的二肽（或保护的二肽）和碱金属氰化物或三甲基硅氰化物反应，形成Formula的氨基腈化合物，然后进行水解。这些化合物可用作转化酶抑制剂和降压剂。
• Carboxyalkyl dipeptide derivatives, process for preparing them and pharmaceutical composition containing them
  申请人：Merck & Co., Inc.

  公开号：EP0012401A1

  公开（公告）日：1980-06-25

  Carboxyalkyl dipeptide derivatives and related compounds which are useful as antihypertensives, and having the formulae: wherein R and R6 are the same or different and are hydroxy, alkoxy, alkenoxy, dialkylamino alkoxy, acylamino alkoxy, acyloxy alkoxy, aryloxy, alkyloxy, substituted aryloxy or substituted aralkoxy wherein the substituent is methyl, halo, or niethoxy, amino, alkylamino, dialkylamino, aralkylamino or hydroxyamino; R1 is hydrogen, alkyl of from 1 to 20 carbon atoms, including branched, cyclic and unsaturated alkyl groups; substituted alkyl wherein the substituent is halo, hydroxy, alkoxy, aryloxy amino, alkylamino, dialkylamino, acylamino, arylamino, guanidino, imidazolyl, indolyl, mercapto, alkylthio, arylthio, carboxy, carboxamido, carbalkoxy, phenyl, substituted phenyl wherein the substituent is alkyl, alkoxy or halo; aralkyl or heteroaralkyl, aralkenyl or heteroaralkenyl, substituted aralkyl, substituted heteroaralkyl, substituted aralkenyl or substituted hetereoaralkenyl, wherein the substituent is halo or dihalo, alkyl, hydroxy, alkoxy, amino, aminomethyl, acylamino, dialkylamino, alkylamino, carboxyl, haloalkyl, cyano or sulfonamido, aralkyl or hetereoaralkyl substituted on the alkyl portion by amino or acylamino; R2 and R7 are hydrogen or alkyl; R3 is hydrogen, alkyl, phenylalkyl, aminomethylphenyl- alkyl, hydroxyphenylalkyl, hydroxyalkyl, acetylaminoalkyl, acylaminoalkyl, acylaminoalkyl aminoalkyl, dimethyl- aminoalkyl, haloalkyl, guanidinoalkyl, imidazolylalkyl, indolylalkyl, mercaptoalkyl and aikylthioalkyl; R4 is hydrogen or alkyl; R5 is hydrogen, alkyl, phenyl, phenylalkyl, hydroxyphenylalkyl, hydroxyalkyl, aminoalkyl, guanidinoalkyl, imidazolylalkyl, indolylalkyl, mercaptoalkyl or alkylthioalkyl; R and R5 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms, an alkylene bridge of from 2 to 3 carbon atoms and one sulphur atom, an alkylene bridge of from 3 to 4 carbon atoms containing a double bond or an alkylene bridge as above, substituted with hydroxy, alkoxy or alkyl and the pharmaceutically acceptable salts thereof.

  可用作抗高血压药的羧烷基二肽衍生物及相关化合物，其式如下 其中 R 和 R6 相同或不同，并且是羟基、烷氧基、烯氧基、二烷基氨基烷氧基、酰氨基烷氧基、酰氧基烷氧基、芳氧基、烷氧基、取代的芳氧基或取代的烷氧基，其中取代基是甲基、卤代或二乙氧基、氨基、烷基氨基、二烷基氨基、芳基氨基或羟基氨基； R1 是氢、1 至 20 个碳原子的烷基，包括支链、环状和不饱和烷基； 取代基为卤素、羟基、烷氧基、芳氧基氨基、烷基氨基、二烷基氨基、酰基氨基、芳基氨基、胍基、咪唑基、吲哚基、巯基、烷硫基、芳硫基、羧基、羧酰胺基、羰基烷氧基、苯基、取代基为烷基、烷氧基或卤素的取代苯基；芳烷基或杂烷基、芳烯基或杂芳烯基、取代的芳烷基、取代的杂烷基、取代的芳烯基或取代的对位芳烯基，其中取代基为卤代或二卤代、烷基、羟基、烷氧基、氨基、氨甲基、酰氨基、二烷基氨基、烷基氨基、羧基、卤代烷基、氰基或磺酰氨基，烷基部分被氨基或酰氨基取代的芳烷基或对位芳烷基； R2 和 R7 是氢或烷基； R3 是氢、烷基、苯基烷基、氨甲基苯基烷基、羟基苯基烷基、羟基烷基、乙酰氨基烷基、酰氨基烷基、酰氨基烷基氨基烷基、二甲基氨基烷基、卤代烷基、胍基烷基、咪唑基烷基、吲哚基烷基、巯基烷基和烷硫基烷基； R4 是氢或烷基 R5 是氢、烷基、苯基、苯基烷基、羟苯基烷基、羟基烷基、氨基烷基、胍基烷基、咪唑基烷基、吲哚基烷基、巯基烷基或硫代烷基； R 和 R5 可连接在一起，形成 2 至 4 个碳原子的亚烷基桥、2 至 3 个碳原子和一个硫原子的亚烷基桥、含有双键的 3 至 4 个碳原子的亚烷基桥或被羟基、烷氧基或烷基取代的上述亚烷基桥及其药学上可接受的盐。
• Carboxyalkyl dipeptides, processes for their production and pharmaceutical compositions containing them
  申请人：SCHERING CORPORATION

  公开号：EP0088350A1

  公开（公告）日：1983-09-14

  The compounds of the present invention are compounds of the formula and the pharmaceutically acceptable esters and salts thereof wherein R' and R2 independently are hydrogen or lower alkyl; the group is one of the structures II to VIII specified in the description, one of R3, R4 and R5 is a group Z-(CH2)0-6-' wherein Z is selected from Z' to Z10 being as defined in the description and the other of the groups R3, R4 and R5 are as also defined. The compounds are useful as antihypertensive agents, in the treatment of congestive heart failure and glaucoma. Their preparation and pharmaceutical compositions are disclosed.

  本发明的化合物是如下式的化合物 及其药学上可接受的酯和盐 其中 R' 和 R2 分别为氢或低级烷基；基团 是描述中规定的结构 II 至 VIII 之一，R3、R4 和 R5 中的一个是基团 Z-(CH2)0-6-'，其中 Z 选自描述中定义的 Z' 至 Z10，基团 R3、R4 和 R5 中的另一个也如定义。这些化合物可用作降压药、治疗充血性心力衰竭和青光眼。已公开了它们的制备方法和药物组合物。
• Prostaglandin antagonists
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0140784A2

  公开（公告）日：1985-05-08

  This invention deals with the compounds of the formulae: wherein Z is thio, sulfinyl, or sulfonyl; R1 and R2 are independently hydrogen, halogen, amino, C1 to C4 alkyl, C1 to C4 alkylthio, C1 to C4 alkoxy, thiol, C, to C4 alkylsulfinyl, C1 to C4 alkylsulfonyl, trifluoromethyl, trifluoromethylthio, cyano, nitro, aralkyl, hydroxyalkyl, C1 to C4 alkylamino, dialkylamino wherein each alkyl group has 1 to 4 carbons, or R1 and R2 are joined together to form a polymethylene chain of 3 or 4 carbon atoms, with or without a hydroxy or keto functionality; X is O, N-R3, wherein R3 is hydrogen, C1 to C4 alkyl, aryl, hydroxy, C1 to C4 alkoxy, C1 to C5 acyloxy, amino, C1 to C4 alkylamino or dialkylamino wherein each alkyl group has 1 to 4 carbons; or a group of the formula: wherein each Y is independently O or S or NR6 wherein R6 is H, C1 to C4 alkyl, lower alkanoyl, benzoyl, trifluoroacetyl or CN; and R4 and R5 are each independently hydrogen or C1 to C4 alkyl and the broken line between R4 and R5 represents an optional bond when R4 and R5 are not hydrogen; and the pharmaceutically acceptable salts thereof. These compounds are useful for antagonizing the activity of prostaglandins in a mammal.

  本发明涉及式中的化合物： 式中 Z 是硫代、亚砜基或磺酰基； R1 和 R2 独立地为氢、卤素、氨基、C1 至 C4 烷基、C1 至 C4 烷硫基、C1 至 C4 烷氧基、硫醇、C, 至 C4 烷基亚磺酰基、C1 至 C4 烷基磺酰基、三氟甲基、三氟甲基硫代、氰基、硝基、芳烷基、羟基烷基、C1 至 C4 烷基氨基、二烷基氨基，其中 C1 至 C4 烷基为卤素、羟烷基、C1 至 C4 烷基氨基、二烷基氨基，其中每个烷基具有 1 至 4 个碳原子，或 R1 和 R2 连接在一起形成 3 或 4 个碳原子的多亚甲基链，具有或不具有羟基或酮官能团； X 是 O、N-R3，其中 R3 是氢、C1 至 C4 烷基、芳基、羟基、C1 至 C4 烷氧基、C1 至 C5 乙酰氧基、氨基、C1 至 C4 烷基氨基或二烷基氨基（其中每个烷基具有 1 至 4 个碳原子）；或式中的基团： 其中每个 Y 独立地为 O 或 S 或 NR6，其中 R6 为 H、C1 至 C4 烷基、低级烷酰基、苯甲酰基、三氟乙酰基或 CN；R4 和 R5 独立地为氢或 C1 至 C4 烷基，当 R4 和 R5 不是氢时，R4 和 R5 之间的断线代表任选键；及其药学上可接受的盐。 这些化合物可用于拮抗哺乳动物体内前列腺素的活性。
• Cardiovascular composition
  申请人：MERCK FROSST CANADA INC.

  公开号：EP0166257A2

  公开（公告）日：1986-01-02

  A cardiovascular composition is disclosed which comprises a dibenzo-thiepin compound having the formula wherein: X is a C1-C4 hydrocarbon group, optionally containing O, N or CO; Z is S, SO, S02, CO, CR4R5 wherein R4 and R5 taken together form the group =O or =CHR6 wherein R6 is hydrogen or phenyl; R1 is, e.g., 5-tetrazolyl, 5-tetrazolylmethyl, and wherein m is an integer of from 0 to 4 and R7 is, e.g., hydroxy or loweralkoxy; R2 and R3 can each independently be hydrogen, halogen (F, Cl, Br or I), nitro, loweralkyl, amino, N-loweralkylamino, N,N-diloweralkylamino, loweralkanoyl, hydroxy, loweralkoxy, lower acyloxy, loweralkylthio, trifluoromethylthio, loweralkylsulfinyl, loweralkylsulfonyl, trifluoromethyl, or R2 and R3, when bonded to adjacent carbon atoms, can be joined to form a 5- or 6-membered hydrocarbon ring which can optionally contain a double bond, a carbonyl group, or a hydroxyl group; or a pharmaceutically acceptable salt thereof. The composition can additionally comprise an angiotensin converting enzyme (ACE) inhibitor. These compositions represent a novel therapeutic approach to thromboembolic diseases in man.

  本发明公开了一种心血管组合物，该组合物包含一种二苯并噻吩化合物，其式为 其中X是C1-C4烃基，可选含有O、N或CO； Z是S、SO、S02、CO、CR4R5，其中R4和R5共同形成基团=O或=CHR6，其中R6是氢或苯基； R1是5-四唑基、5-四唑甲基，以及 其中 m 是 0 至 4 的整数，R7 是，例如、羟基或低级烷氧基；低级烷基磺酰基、三氟甲基，或 R2 和 R3 与相邻碳原子结合时可形成 5 或 6 元烃环，该环可选择含有双键、羰基或羟基；或其药学上可接受的盐。组合物还可以包含血管紧张素转换酶（ACE）抑制剂。这些组合物代表了一种治疗人类血栓栓塞性疾病的新方法。