摘要 |
<p>FIELD: organic chemistry. SUBSTANCE: invention relates to new antagonists of LHRH of the formula: <EMI ID=0.246 HE=15 WI=78 TI=CHI> or <EMI ID=0.247 HE=15 WI=72 TI=CHI> or <EMI ID=0.248 HE=15 WI=78 TI=CHI>. New antagonists of LHRH of the formula: <EMI ID=0.249 HE=15 WI=78 TI=CHI> where DNal is DArAla where Ar is <EMI ID=0.250 HE=15 WI=30 TI=CHI>; AA is DarAla where Ar is <EMI ID=0.251 HE=12 WI=75 TI=CHI>; AA is DArAla where Ar is <EMI ID=0.252 HE=27 WI=66 TI=CHI> or D -X-<EMI ID=0.253 HE=12 WI=42 TI=CHI>-Ala where X is <EMI ID=0.254 HE=12 WI=24 TI=CHI>; AA is Arg, Tyr or DArAla where Ar is <EMI ID=0.255 HE=12 WI=48 TI=CHI> or D-X-<EMI ID=0.256 HE=12 WI=39 TI=CHI>-Ala where X is <EMI ID=0.257 HE=12 WI=54 TI=CHI>; R and R are CH<SB>3</SB>,CH<SB>3</SB>CH<SB>2</SB>,C<SB>3</SB>H<SB>7</SB>,C<SB>4</SB>H<SB>9</SB>; AA is DArPhe where Ar is <EMI ID=0.258 HE=15 WI=78 TI=CHI> or D-X-<EMI ID=0.259 HE=12 WI=42 TI=CHI>-Ala where X is <EMI ID=0.260 HE=12 WI=54 TI=CHI> or NR<SP>1</SP>R where R and R are CH<SB>3</SB>,CH<SB>3</SB>CH<SB>2</SB>;; AA is Arg or DArAla where Ar is <EMI ID=0.261 HE=15 WI=57 TI=CHI> or X is X-<EMI ID=0.262 HE=12 WI=36 TI=CHI>-Ala where X is <EMI ID=0.263 HE=12 WI=54 TI=CHI> or NR<SP>1</SP>R where R<SP>1</SP>,R is CH<SB>3</SB>,CH<SB>3</SB>CH<SB>2</SB>,C<SB>3</SB>H<SB>7</SB>,C<SB>4</SB>H<SB>9</SB>. These new peptides can be used for treatment of patients with endocrine system sicknesses, cancer and as male and female contraceptives. Invention involves also a method of synthesis of LHRH antagonists. Method involves addition reaction of C-terminal N-protected amino acid to benzhydrolylamine resin, protective group splitting off followed by peptide chain splicing at sequence corresponding to peptide of the formula (IV) under conditions of solid-phase synthesis. Peptide is split off from peptidylpolymer synthesized. Synthesized peptides have value properties, stimulate histamine decreased secretion and can be used in clinical practice. EFFECT: improved method of synthesis, enhanced effectiveness of</p> |