2-[[2-azaniumyl-3-(4-hydroxyphenyl)propanoyl]amino]acetate

• 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-[[2-azaniumyl-3-(4-hydroxyphenyl)propanoyl]amino]acetate
• 化学式: C11H14N2O4
• mdl: MFCD12972322
• 分子量: 238.24
• InChiKey: HPYDSVWYXXKHRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  5

文献信息

• MACROCYCLES AND MACROCYCLE STABILIZED PEPTIDES
  申请人：Saulnier Mark G.

  公开号：US20130281657A1

  公开（公告）日：2013-10-24

  The invention provides methods of preparing macrocycles including macrocycle stabilized peptides (MSPs). Macrocycles and MSPs are prepared according to nucleophilic capture of an iminoquinomethide type intermediate generated from a suitably substituted 2-amino-thiazol-5-yl carbinol. The preferred nucleophile may be selected from an electron rich aromatic moiety in the case of macrocycles and, in the case of MSPs, at least one amino acid comprises an electron rich aromatic moiety. In addition, the concept can be extended to other related 5-membered heterocyclic systems in place of the thiazole, such as imidazole or oxazole. The conditions for the generation of the corresponding iminoquinomethide type intermediates may be similar or different than the conditions used for the 2-amino-thiazol-5-yl carbinol.

  本发明提供了制备大环化合物的方法，包括稳定大环化肽（MSPs）。根据适当取代的2-氨基噻唑-5-基甲醇生成的亚胺喹啉甲烷型中间体的亲核捕获，制备大环和MSP。在大环的情况下，首选亲核试剂可以从富电子芳香基团中选择，在MSP的情况下，至少有一种氨基酸包含富电子芳香基团。此外，该概念可以扩展到取代噻唑的其他相关5-成员杂环系统，例如咪唑或噁唑。生成相应的亚胺喹啉甲烷型中间体的条件可能与用于2-氨基噻唑-5-基甲醇的条件相似或不同。
• Substituted dipeptides, processes for their preparation and pharmaceutical compositions containing them and their use in the inhibition of enkephalinase
  申请人：SCHERING CORPORATION

  公开号：EP0054862A1

  公开（公告）日：1982-06-30

  The present invention relates to substituted depep- tides which are useful in the inhibition of a natural opiate receptor against known as «enkephalin» Disclosed are substituted dipeptides of the formula: and the pharmaceutically acceptable salts thereof, in which R, is hydrogen; alkyl; halogen loweralkyl; hydroxy lower- alkyl; loweralkoxy loweralkyl; aryloxy loweralkyl; amino loweralkyl; loweralkylamino loweralkyl; di- loweralkyl aminoloweralkyl; acylamino 'oweralkyl; diarylaminoloweralkyl; arylamino loweralkyl; guanidino loweralkyl; heteroaryl; aryl; aralkyl; mercapto loweralkyl; arylthio loweralkyl; loweralkylaralkyl; alkylthio loweralkyl; aralkyloxyalkyl; aralkylthioalkyl; or heteroaryloxyalkyl; wherein the latter 3 radicals may be substituted with halogen, loweralkyl, loweralkoxy, hydroxy, amino, aminomethyl, carboxyl, cyano andior sulfamoyl; or alkenyl substituted by a heterocyclic group or alkyl substituted by a heterocyclic group, the latter two groups optionally being substituted by one or more groups chosen from loweralkyl, hydroxy, loweralkoxy, amino, loweralkylamino, di-loweralkylamino, acylamino, halogeno, halogenoloweralkyl, cyano and/ or sulfonamido; R2 is -COOH, COO-(loweralkyl), -COO-(aryl lower alkyl), -COO aryl, or the group wherein R10 is hydrogen, lower alkyl or benzyl; and R11 is hydroxy, alkoxy, benzyloxy, lower alkyl, aryl or benzyl: R, is hydrogen or iower alkyl: X is wherein q is 0 or 1; R4 and R5 are chosen from the groups defined for R1, in which n is 0 or an integer from 1 to 8 inclusive and m is 2 to 8 inclusive, indolyl (e.g. 3-indolyl), indolylalkyl, (e.g. 3-indolylalkyl), adamantyl (e.g. 1-adamantyl), adamantylmethyl (e.g. 1-adamantylmethyl) and amino methylphenylloweralkyl; y is zero or an integer from 1 to 3; and R6 is chosen from hydroxy, loweralkoxy and the group -NR8R7 in which R8 and R, are independently hydrogen, aralkyl, or loweralkyl which together with the nitrogen atom to which they are attached may form a 4 to 6 membered heterocyclic group, one of whose members may be oxygen or sulphur; Subject to the following proviso: When X is R2 is -COOH, -COO (loweralkyl), -COO (arylloweralkyl) or -COO (aryl), y is zero and R6 is -OH, loweralkoxy, alkylamino, dialkylamino, aralkylamino or diaralkylamino, then R4 is chosen from the group Th-CH2-B- in which «Th» is 2- or 3-thienyl and B is a carbon-carbon bond or a lower alkyl group, the group Naph-CH2-B- in which «Naph» is 1- or 2-naphthyl and B is as defined above, in which n and m are as defined above, adamantyl methyl, unsubstituted or substituted phenyl, or substituted phenylloweralkyl, in which the substituent(s) for the latter two groups is or are chosen from halogen, trifluoromethyl, nitro, loweralkyl and loweralkoxy. Also disclosed are various process for the preparation of the above compounds such as coupling an amino acid A' with an amino acid B'

  本发明涉及可用于抑制被称为 "脑啡肽 "的天然阿片受体的取代二肽。 本发明公开了式中的取代二肽： 及其药学上可接受的盐类，其中 R，是氢；烷基；卤素低级烷基；羟基低级烷基；低级烷氧基低级烷基；芳氧基低级烷基；氨基低级烷基；低级烷基氨基低级烷基；二低级烷基氨基低级烷基；酰氨基低级烷基；二芳基氨基低级烷基；芳基氨基低级烷基；胍基低级烷基；杂芳基；芳基；芳烷基；巯基低级烷基；芳硫基低级烷基；低级芳烷基；烷硫基低级烷基；芳氧基烷基；芳硫基烷基；或杂芳氧基烷基；其中后三个基团可被卤素、低级烷基、低级烷氧基、羟基、氨基、氨甲基、羧基、氰基和/或氨基磺酰基取代；或被杂环基团取代的烯基或被杂环基团取代的烷基，后两个基团可任选被一个或多个选自低级烷基、羟基、低级烷氧基、氨基、低级烷基氨基、二低级烷基氨基、酰氨基、卤素、卤代低级烷基、氰基和/或氨基磺酰基的基团取代； R2 是-COOH、COO-（低级烷基）、-COO-（芳基低级烷基）、-COO 芳基或以下基团 其中 R10 是氢、低级烷基或苄基；以及 R11 是羟基、烷氧基、苄氧基、低级烷基、芳基或苄基： R 是氢或低级烷基： X 是 其中 q 为 0 或 1； R4 和 R5 选自 R1 定义的基团、 其中 n 为 0 或 1 至 8 的整数，m 为 2 至 8 的整数；吲哚基（如 3-吲哚基）、吲哚烷基（如 3-吲哚烷基）、金刚烷基（如 1-金刚烷基）、金刚烷甲基（如 1-金刚烷甲基）和氨基甲基苯基烷基； y 为零或 1 至 3 的整数；以及 R6 选自羟基、低级烷氧基和基团-NR8R7，其中 R8 和 R 独立为氢、芳烷基或低级烷基，它们与所连接的氮原子一起可形成 4 至 6 个成员的杂环基团，其中一个成员可以是氧或硫； 但须符合以下但书：当 X 为 R2为-COOH、-COO（低级烷基）、-COO（芳基低级烷基）或-COO（芳基），y为零，R6为-OH、低级烷氧基、烷基氨基、二烷基氨基、芳基氨基或二芳基氨基、则 R4 选自以下基团：Th-CH2-B-，其中 "Th "为 2-或 3-噻吩基，B 为碳-碳键或低级烷基；Naph- -B-，其中 "Naph "为 1-或 2-萘基，B 如上定义、 金刚烷基甲基、未取代或取代的苯基或取代的苯基低级烷基，其中后两个基团的取代基是或选自卤素、三氟甲基、硝基、低级烷基和低级烷氧基。 还公开了制备上述化合物的各种工艺，如将氨基酸 A'与氨基酸 B'偶联
• Substituted dipeptides, methods for their production, pharmaceutical compositions containing them, method for making such pharmaceutical compositions
  申请人：SCHERING CORPORATION

  公开号：EP0103077A2

  公开（公告）日：1984-03-21

  Dipeptides are disclosed having the formula in which R,, R2, R3, R4, R5 and R6 are various substituents, p is 0,1 or 2 and the asterisks indicate chiral centres. The compounds inhibit the aciton of enkephalinase in mammals. Pharmaceutical compositions containing the above compounds are described.

  已公开的二肽具有如下式子 其中 R、R2、R3、R4、R5 和 R6 为各种取代基，p 为 0、1 或 2，星号表示手性中心。 这些化合物可抑制哺乳动物体内脑啡肽酶的活性。 描述了含有上述化合物的药物组合物。
• 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-( )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 CH-，Ya 是 -NH2 或 -NCO。
• Enkephalinase B inhibitors, their preparation, and pharmaceutical compositions containing the same
  申请人：SANKYO COMPANY LIMITED

  公开号：EP0177366A2

  公开（公告）日：1986-04-09

  Propioxatins A and B, which have the formula: wherein R represents a hydrogen atom or a methyl goup, can be prepared by cultivating a suitable strain of Kitasatosporia, e.g. Kitasatosporia sp. SANK 60684 (FERM-P 7581) They can be salified to give pharmaceutically acceptable salts. The compounds are active as enkephalinase B inhibitors and are thus capable of enhancing enkephalin activity in vivo.

  这些化合物具有脑啡肽酶 B 抑制剂的活性，因此能够增强脑啡肽在体内的活性。