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PubMed1995

Renin inhibitors containing nicotinic or isonicotinic acid at the N-terminus. Part V.

Four new compounds: Nic-Phe/4-OMe/-MePhe-Sta-epsilonAhx-OMe/23/,Nic-Phe/4-OMe/-MePhe- Sta-epsilonAhx-Iaa/24/,iNic-Phe/4-OMe/-MeLeu-Sta-ep silonAhx-OMe/29/ and iNic-Phe/4-OMe/-MeLeu-Sta-epsilonAhx-Iaa/30/ have been synthesized in search after renin inhibitors of improved biological properties. Their stability against chymotrypsin activity, solubility in water at pH 7.4, 6.9 and 2.0, partition coefficient and activity in vitro were determined. All synthesized inhibitors are resistant to enzymatic degradation, all are very good soluble in water at pH 2.0, poorly soluble at pH 6.9 and insoluble at pH 7.4. Partition coefficients go up together with increase of pH worth of buffer. IC50 of obtained inhibitors 23,24,29 and 30 is 3 x 10(-4),7.5 x 10(-4),4 x 10(5) and 4 x 10(-3)M/1 respectively.

Amino Acid Sequence↗