PH23769A - Renin inhibitors containing statine or derivatives thereof - Google Patents

Abstract

Polypeptides of formula (I) and their salts are new. R-W-W'-NH-CHR2-CHR3-CH2-COR1 (I) W = Phe, His, Leu, Tyr, 1-naphthyl-Ala or 2-phenylmethyl 2-phenylmethylpropionylene; W' = Phe, His, Leu, Tyr or Nle; when W = Phe and W' = His, then the peptide link between W and W' may be replaced by -CH(1-4C)Alkyl-NH-; R = H, amino-protecting acyl of molecular wt. up to 500, or Pro or pGlu both amino protected; R2 = H, 1-6C alkyl, Ph, 4-7C cycloalkyl, Ph-(1-3C)alkyl or 5-10C cycloalkylalkyl; R3 = OH, NH2, NHR9, NHCOR9, OR9 or OCOR9; R9 = 1-4C alkyl; R1 = A-E-B; a gp. of formula (II); NH2; 1-4C alkoxy; 5-benzylipiperazin-1-yl; 1,2,3,4-tetrahydroquinolin-1-yl or -2-yl; 1,2,3,4-tetrahydro-3-aminocarbonyl isoquinolin-2-yl or the corresp. 3-methoxycarbonyl gp.; 1,2,3,4,5,6,7,8-decahydro-3-methoxycarbonyl isoquinolin-2-yl; 2-methoxycarbonylpyrrolidin -1-yl; 2-aminocarbonylpyrrolindin-1-yl; 4-phenylmethylpiperidin-1-yl; Pro-B; or Lys-B; -X-NH-CHZ-(CH2)n-Q-CHZ1-(CH2)m-Y (II) A = Lys or Pro or when R3 = NH2, Ile; E = Phe, Gly, Ala, Val, Leu, Ile, Lys, Orn, Arg, Asp opt. gamma-esterified or Glu opt. delta-esterified; B = OR4, NR4R5, glutamic acid (-OR4)2, glutamic acid (-OR4)(-NR4R5) or glutamic acid (-NR4R5)2; R4, R5 = H, 1-4C alkyl, Ph-(1-3C)alkyl or 5-10C cycloalkylalkyl; X = absent or Ala, Ile, Lys, Pro, Orn, Arg, N-(1-4C alkyl)- or N,N-(di-(1-4C) alkyl)-Lys or -Orn; Z, Z1 = H, 1-6C alkyl, 4-7C cycloalkyl, 5-10C cycloalkylalkyl or Ph-(1-3C)alkyl; n, m = 0-6; Q = CH2, CH=CH, O, NH, CH(OH) or CO; Y = Me, Ph, COOR6, CONR6R7, NH2, benzyloxycarbonylamino, CO-glutamic acid (-OR6)2, CO-glutamic acid (OR6)(NR6R7) or CO-glutamic acid (-NR6R7); R6, R7 = H, 1-4C alkyl, Ph-(1-3C)alkyl or 5-10C cycloalkylalkyl.