(S,S)-2,4-dibenzylglutaric anhydride | 105226-92-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (S,S)-2,4-dibenzylglutaric anhydride
• 英文别名: trans-2,4-dibenzyl glutaric anhydride；(3S,5S)-3,5-dibenzyloxane-2,6-dione
• CAS: 105226-92-4
• 化学式: C₁₉H₁₈O₃
• 分子量: 294.35
• InChiKey: NJPQOFBKNPKUPP-IAGOWNOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S,S)-2,4-dibenzylglutaric anhydride 在 吡啶 、 水 、 乙酸酐 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 甲苯 为溶剂， 反应 18.0h， 生成 N-<(S,S)-2,4-dibenzyl-4-carboxybutyryl>-(S)-leucine
  参考文献：
  名称：

  Enkephalinase inhibitors. 1. 2,4-Dibenzylglutaric acid derivatives

  摘要：

  The synthesis of two new series of dicarboxylic acid dipeptides and two sulfhydryl-containing inhibitors are described. The in vitro enkephalinase inhibition data and some in vivo analgesic data are presented for these compounds. For the dibenzylglutaric acid series structure-activity relationships and in vivo analgesic activity are discussed. The reverse amides, i.e., 4-amino-2,4-dibenzylbutyric acid derivatives, are also discussed. Two sulfhydryl-containing inhibitors showed good in vivo potency in the mouse jump-latency hot-plate test after peripheral administration at moderate low doses.

  DOI：

  10.1021/jm00132a005
• 作为产物：
  描述：

  (S,S)-2,4-dibenzylglutaric acid 在 甲苯 作用下， 以 乙酰氯 为溶剂， 反应 3.0h， 生成 (S,S)-2,4-dibenzylglutaric anhydride
  参考文献：
  名称：

  Certain n-substituted butyramide derivatives

  摘要：

  本发明涉及一种化合物，其化学式为##STR1##其中X和Y独立地表示羟甲基;氰基;羧基;功能修饰的羧基，所述功能修饰的羧基选自酯化羧基，氨基甲酰基和N-取代氨基甲酰基; 5-四唑基; 2-噁唑基，4,5-二氢-2-噁唑基，或每个所述基团均被低烷基取代; R和R.sub.o独立地表示低烷基，(C.sub.3-C.sub.7)-环烷基-低烷基或芳基-低烷基; A表示亚甲基; 或A表示被低烷基，被低烷硫基-低烷基，被芳基-低烷硫基-低烷基，被芳基硫基-低烷基，羟基-低烷基，酰氧基-低烷基，低烷氧基-低烷基，烷氧基-低烷基，芳氧基-低烷基，氨基-低烷基，酰胺基-低烷基，鸟氨酸基-低氨基-低烷基，(C.sub.3-C.sub.7)-环烷基，(C.sub.3-C.sub.7)-环烷基-低烷基，芳基或芳基-低烷基取代的亚甲基取代; 具有自由羧基的任何所述化合物的药学上可接受的酯和酰胺衍生物; 药学上可接受的盐; 合成方法; 其药物组成物; 以及作为内肽酶抑制剂的用途。

  公开号：

  US05166212A1

文献信息

• N-substituted butyramide derivatives useful for treatment of conditions
  申请人：Ciba-Geigy Corporation

  公开号：US04939261A1

  公开（公告）日：1990-07-03

  Disclosed are compounds of the formula ##STR1## wherein X and Y independently represent hydroxymethyl; cyano; carboxy; functionally modified carboxy selected from esterified carboxy, carbamoyl, and N-substituted carbamoyl; 5-tetrazolyl; 2-oxazolyl, 4,5-dihydro-2-oxazolyl, 2-imidazolyl or 4,5-dihydro-2-imidazolyl or any said grouping substituted by lower alkyl; R and R.sub.0 independently represent hydrogen, lower alkyl, (C.sub.3 -C.sub.7)-cycloalkyl-lower alkyl, or aryl-lower alkyl in which aryl represents phenyl, pyridyl, thienyl, furyl, biphenyl or naphthyl, each unsubstituted or mono- or di-substituted by halogen, lower alkyl, hydroxy, acyloxy, lower alkoxy, trifluoromethyl or cyano; A represents straight chain (C.sub.2 -C.sub.5)-alkylene; or A represents straight chain (C.sub.2 -C.sub.5)-alkylene substituted by lower alkyl, by lower alkylthio-lower alkyl, by hydroxy-lower alkyl, by acyloxy-lower alkyl, by lower alkoxy-lower alkyl, by amino or acyl-amino, by amino-lower alkyl, by acylamino-lower alkyl, by (C.sub.3 -C.sub.7)-cycloalkyl, by (C.sub.3 -C.sub.7)-cycloalkyl-lower alkyl, by aryl or aryl-lower alkyl in which aryl represents phenyl or phenyl mono- or disubstituted by halogen, lower alkyl, lower alkoxy, hydroxy, acyloxy, trifluoromethyl or cyano; or A represents phenylene or cyclohexylene; pharmaceutically acceptable prodrug derivatives of any said compounds having a free carboxy group; pharmaceutically acceptable salts of any said compounds with a salt-forming group; methods for synthesis; pharmaceutical compositions thereof; and use thereof as enkephalinase inhibitors.

  揭示了以下式的化合物##STR1##其中X和Y分别代表羟甲基；氰基；羧基；从酯化羧基，氨基甲酰基和N-取代氨基甲酰基中选择的功能修饰羧基；5-四唑基；2-噁唑基，4,5-二氢-2-噁唑基，2-咪唑基或4,5-二氢-2-咪唑基或任何由较低烷基取代的所述基团；R和R.sub.0分别代表氢，较低烷基，(C.sub.3 -C.sub.7)-环烷基-较低烷基，或芳基-较低烷基，其中芳基代表苯基，吡啶基，噻吩基，呋喃基，联苯基或萘基，每个未取代或经卤素，较低烷基，羟基，酰氧基，较低烷氧基，三氟甲基或氰基单取代或双取代；A代表直链(C.sub.2 -C.sub.5)-烷基；或A代表由较低烷基，由较低烷硫基-较低烷基，由羟基-较低烷基，由酰氧基-较低烷基，由较低烷氧基-较低烷基，由氨基或酰胺基，由氨基-较低烷基，由酰胺基-较低烷基，由(C.sub.3 -C.sub.7)-环烷基，由(C.sub.3 -C.sub.7)-环烷基-较低烷基，由芳基或芳基-较低烷基取代的直链(C.sub.2 -C.sub.5)-烷基取代；其中芳基代表苯基或经卤素，较低烷基，较低烷氧基，羟基，酰氧基，三氟甲基或氰基单取代或双取代的苯基；或A代表苯亚甲基或环己亚甲基；具有游离羧基的任何所述化合物的药学上可接受的前药衍生物；具有盐形成基团的任何所述化合物的药学上可接受的盐；合成方法；其制药组合物；以及作为脑啡肽酶抑制剂的用途。
• Certain N-substituted butyramide derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US05021430A1

  公开（公告）日：1991-06-04

  Disclosed are compound of the formula ##STR1## wherein X and Y independently represent hydroxymethyl; cyano; carboxy; functionally modified carboxy selected from esterified carboxy, carbamoyl, and N-substituted carbamoyl; 5-tetrazolyl; 2-oxazolyl, 4,5-dihydro-2-oxazolyl, or each said grouping substituted by lower alkyl; R and R.sub.o independently represent lower alkyl, (C.sub.3 -C.sub.7)-cycloalkyl-lower alkyl, or aryl-lower alkyl; A represents methylene; or A represents methylene substituted by lower alkyl, by lower alkylthio-lower alkyl, by aryl-lower alkylthio-lower alkyl, by arylthio-lower alkyl, by hydroxy-lower alkyl, by acyloxy-lower alkyl, by lower alkoxy-lower alkyl, by aryl-lower alkyloxy-lower alkyl, by aryloxy-lower alkyl, by amino-lower alkyl, by acylamino-lower alkyl, by guanidino-lower alkyl, by (C.sub.3 -C.sub.7)-cycloalkyl, by (C.sub.3 -C.sub.7)-cycloalkyl-lower alkyl, by aryl or aryl-lower alkyl; pharmaceutically acceptable ester and amide derivatives of any said compounds having a free carboxy group; pharmaceutically acceptable salts; methods for synthesis; pharmaceutical compositions thereof; and use thereof as endopeptidase inhibitors.

  本发明揭示了公式##STR1##的化合物，其中X和Y独立地表示羟甲基；氰基；羧基；功能修饰的羧基，所述功能修饰的羧基被选择为酯化羧基，氨基甲酰基或N-取代的氨基甲酰基；5-四唑基；2-噁唑基，4,5-二氢-2-噁唑基，或所述各个基团被较低的烷基取代；R和R.sub.o独立地表示较低的烷基，（C.sub.3-C.sub.7）-环烷基-较低的烷基，或芳基-较低的烷基；A表示亚甲基；或A表示被较低的烷基，被较低的烷基硫基-较低的烷基，被芳基-较低的烷基硫基-较低的烷基，被芳基硫基-较低的烷基，被羟基-较低的烷基，被酰氧基-较低的烷基，被较低的烷氧基-较低的烷基，被芳基-较低的烷氧基-较低的烷基，被芳氧基-较低的烷基，被氨基-较低的烷基，被酰胺基-较低的烷基，被鸟氨酸基-较低的烷基，被（C.sub.3-C.sub.7）-环烷基，被（C.sub.3-C.sub.7）-环烷基-较低的烷基，被芳基或芳基-较低的烷基取代的亚甲基；任何具有自由羧基的所述化合物的药学上可接受的酯和酰胺衍生物；药学上可接受的盐；合成方法；其制药组合物；以及其作为内肽酶抑制剂的用途。
• Dicarboxylic Acid Dipeptide Neutral Endopeptidase Inhibitors
  作者：Gary M. Ksander、Raj D. Ghai、Reynalda deJesus、Clive Diefenbacher、Andrew Yuan、Carol Berry、Yumi Sakane、Angelo Trapani

  DOI：10.1021/jm00010a014

  日期：1995.5

  The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described. In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50 = 5.0 nM) in vitro and in vivo. Blood levels of 21a were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys. Free drug concentrations were 10-1500 times greater than the inhibitory constant for NEP over the course of a 6 h experiment. A good correlation of free drug concentrations was obtained when comparing values determined by the ex vivo analysis to those calculated from direct HPLC measurements. Plasma atrial natriuretic factor (exogenous) levels were elevated in rats and dogs after oral administration of 19a. Urinary volume and urinary sodium excretion were also potentiated in anesthetized dogs treated with 21a.
• KSANDER, GARY M.;DIEFENBACHER, CLIVE G.;YUAN, ANDREW M.;CLARK, F.;SAKANE,+, J. MED. CHEM., 32,(1989) N2, C. 2519-2526
  作者：KSANDER, GARY M.、DIEFENBACHER, CLIVE G.、YUAN, ANDREW M.、CLARK, F.、SAKANE,+

  DOI：——

  日期：——
• N-SUBSTITUTED BUTYRAMIDE DERIVATIVES
  申请人：CIBA-GEIGY AG

  公开号：EP0185079A1

  公开（公告）日：1986-06-25