Retroisosteric dipeptide, preparation thereof and use thereof as renin inhibitor in drug

PURPOSE: To provide a novel compound (salt) composed of a retroisosteric dipeptide having a specific structure, having high selectivity to human renin and good oral efficacy and useful for an antihypertensive agent or the like as the renin inhibitor. CONSTITUTION: An isoxazolidine compound represented by formula I [wherein R 1 and R 2 are each (substituted) 1-8C alkyl; Z is 1-10C alkoxycarbonyl or an amino protective group; and V is a group removable by hydrogenolysis such as benzyl] is reduced by hydrogenolysis accompanied by ring-opening to form an amino alcohol represented by formula II which is then condensed with a compound of the formula: HO-L-M-Y [wherein L and M are each a direct bond or a group of formula III (wherein R 3 is H, 1-8C alkyl, or phenyl; R 4 and R 5 are each a 3-8-membered heterocyclic ring having up to 4 hetero atoms such as N, O and S; and (p) is 0, 1 or 2); Y is H, acyl or the like] in the presence of a dehydrating agent and/or a base. Subsequently, the protective group is removed and the substance thus obtained is reacted with a compound of the formula, X-A-B-D-OH (wherein X is H or the same as defined with Z; and A, B and D are each the same as defined with L) to obtain a compound of formula IV. COPYRIGHT: (C)1995,JPO