| 摘要 |
Carboxyalkyl peptides of formula (R8)y-CR1R2-X- (CH2)m-CR3R7-C(:O)-NR4 -C(R10)xR6-C(:O)R6 (I) are new. (x, y, and m are 0 or 1; X is S, O, NH or NCH3; R10 is H, CH3, F, Cl, or Br; R2 is e.g. COOY, COSY, CH2SY etc.; Y is H, phenyl, benzyl or 1-5C alkyl; R4 and R5 form a ring contg. N and C to which they are respectively attached, opt. mono- or di-substd.; R6 is NH2, -OM, or -SM; M is H, 1-3C alkyl, anion or ester gp. hydrolysable in vitro; R7 is H, Me opt. halo-, hydroxy-, amino- or mercapto-substd.; R8 is e.g. H, opt. substd. Me, amino, CH2=CHCH2, isobutyl, 2-3C hydroxyalkyl, 2-3C mercaptoalkyl (acetylthio)ethyl, benzamido, acetamido, phthaloyl aminoalkylene etc.; R1 and R3 are opt. the same and are e.g. mono-N-substd. 2-4C alkylene, (substd.) hydroxyphenyl, mercapto-, phenyl-alkylthio-, phenylthio or benzyloxy-alkylene, alkoxyphenyl, alkoxybenzyl, hydroxy- or mercaptophenoxy benzyl, substd. NH2- or NO2-alkylene, (thio)guanidino alkylene, substd. aryl, (substd.) vinyl, unsubstd. heterocyclic gp.; R1 and R2 may form lactone ring with -CH gp. etc.). (I) are inhibitors of angiotensin, converting enzyme and are more stable than 'Captopril' (RTM) and less likely to induce D-penicillinamine-like adverse side effects. Useful as antihypertensives, their daily dose is 0.03-20 mg/kg. |
