Novel renin inhibitors containing a non-peptide aminoalkanoyl moiety at P1-P1' position.

Six novel potential renin inhibitors have been designed and synthesized. All these inhibitors contained an unnatural aminoalkanoyl moiety at the central position P1- P1' of the molecule, which is attacked by renin. The moiety consists of pseudodipeptidic units, transition state analogues of a natural dipeptide of the parent substance: 4-amino-3-hydroxybutanoic acid (AHBA), 4-amino-5-(4-ethoxyphenyl)-3-hydroxypentanoic acid (AEPHPA), 4-amino-5-cyclohexyl-3-hydroxypentanoic acid (ACHPA) or 4-amino-3-hydroxynonanoic acid (AHNA). An unnatural moiety, 4-methoxyphenylalanylhistydyl (Phe(4-OMe)-His) has been introduced at the P3-P2 position of the obtained compounds. Five compounds contain isoamylamide of 6-aminohexanoic acid (epsilon-Ahx-laa) at the P2'-P3' position. One of designed inhibitors has been obtained in the form of an ethyl ester. The in vitro renin inhibitory activity of all synthesized compounds is contained within the range 10(-6) - 10(-8) M. The compound in the form of an ethyl ester has proven to be the most active (IC50 = 1.3 x 10(-8) M) but also susceptible to enzymatic degradation. The other five inhibitors were stable to chymotrypsin.

Determination of oxazepam and diazepam in body fluids by HPLC.

A reversed-phase high-performance liquid chromatography method for determination of benzodiazepine derivatives has been developed. Oxazepam and diazepam was determined in serum and oxazepam in urine.

Qualitative and quantitative analysis of 2-methyl-3(2-pyridyl-methyl)-3H-pyrido-[2,3-D]-pyrimidin-4-on dihydrochloride.

Qualitative and quantitative methods for analysis of 2-methyl-3(2-pyridyl-methyl)-3H-pyrido-[2,3-d]-pyrimidin-4-on dihydrochloride were developed. Qualitative analysis included characteristic reactions, chromatographic investigations, interpretation of IR and UV spectra and quantitative analysis included spectrophotometric, argentometric and alkalimetric methods.