| 摘要 |
New butyramide derivatives corresponding to formula (I), 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 Ro independently represent lower alkyl, (C3-C7)-cycloalkyl-lower alkyl, or aryl-lower alkyl in which aryl represents phenyl, pyridyl, thienyl, furyl, biphenylyl or naphthyl, each unsubstituted or mono- or di-substituted by halogen, lower alkyl, hydroxy, acyloxy, lower alkoxy, trifluoromethyl or cyano; A represents straight chain (C2-C5)-alkylene; or A represents straight chain (C2-C5)-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 acylamino, by amino-lower alkyl, by acylamino-lower alkyl, by (C3-C7)-cycloalkyl, by (C3-C7)-cycloalkyl-lower alkyl, by aryl or aryl-lower alkyl in which aryl represents phenyl or phenyl mono- or di-substituted by halogen, lower alkyl, lower alkoxy, hydroxy, acyloxy, trifluoromethyl or cyano; or A represents phenylene or cyclohexylene; or pharmaceutically acceptable prodrug derivatives of any said compounds having a free carboxy group; or pharmaceutically acceptable salts of any said compounds with a salt-forming group; processes for the manufacture of these compounds; pharmaceutical compositions comprising said compounds; and their use as pharmaceutical agents or for the manufacture of pharmaceutical preparations. The compounds of the invention exhibit valuable pharmacological properties, particularly potentiation of enkephalins by virtue of their ability to inhibit the enkephalin degrading enzyme enkephalinase. The foregoing attributes render the N-substituted butyramide derivatives of this invention particularly useful when administered, alone or in combination, to mammals e.g. for the treatment of conditions responsive to inhibition of enkephalinase, namely as analgesic, anticonvulsant, psychotropic (particularly antidepressant and neuroleptic), cardiovascular (particularly antihypertensive), as well as antiinflammatory agents. |
