Ceskoslovenska Akademie Ved

Tomislav Barth

Karel Jost

Linda Servitova

Alena Machova

Joseph H Cort

Michal Lebl

Frantisek Brtnik

Zdenko Prochazka

Jana Skopkova

Jirina Slaninova

Zdenek Veznik

Ivan Krejci

Frantisek Sorm

Hans Vilhardt

Lenka Maletinska

Bela Kupkova

Petr Simek

Miroslava Zertova

Ivo Blaha

Jirina Slantinova

Jiri Velek

Pavel Hrbas

Analogues of 8-D-homoarginine vasopressin were prepared with the general formula ##STR1## where X is L-O-methyltyrosine, L-p-ethylphenylalanine, D-p-ethylphenylalanine, L-p-methylphenylalanine or D-methylphenylalanine and R is cysteine or .beta.-mercaptopropionic acid. These vasopressin analogues exhibited an increased affinity to uterus receptors for oxytocin, where they acted as ocytocin antagonists. Moreover, the analogues of deamino vasopressin have a significantly reduced antidiuretic activity in comparison with [8-D-arginine]vasopressin.

Analogues of 8-D-homoarginine vasopressin

The invention pertains to analogs of neurohypophysial hormones evidencing inhibition effects of the chemical formula I ##STR1## where A is CH.sub.3 CO or H, V is a residue of penicilamine or cysteine, B is CH.sub.3 or H, X is a residue of isoleucine or phenylalanine, Y is a residue of penicilamine or cysteine, and Z is a residue of leucine or lysine. These analogues evidence inhibition effects towards certain biological activities of neurohypophysial hormones.

Analogs of neurohypophysial hormones with inhibition effects

Analogs of neurohypophysial hormones with inhibition properties are described. The hormones are of the formula ##STR1## wherein in all chiral amino acids are of the L-series and the aromatic amino acid in the position 2, indicated with an asterisk, is of the D-series, and where R.sup.1 and R.sup.2 are hydrogen or a methyl group, R.sup.3 is hydrogen, an amino group, or a triglycylamine grouping, R.sup.4 is hydrogen, a methyl, ethyl or ethoxy group, R.sup.5 is S--CH.sub.2 or S--S group, X.sup.1 is a residue of isoleucine or phenylalanine, X.sup.2 is a residue of leucine or lysine, and X.sup.3 is a glycinamide residue or a hydroxyl group. These compounds exhibit inhibition effects towards the uterotonic and pressor activity of natural hormones. The common structural feature of all these analogues is the presence of an aromatic hydrophobic D-amino acid in the position 2.

Analogs of neurohypophysial hormones

Vasopressin analogs of the formula ##STR1## wherein R.sup.1 is H, R.sup.2 is CH.sub.2 S and R.sup.3 is D-Arg,

Analogs of vasopressin

The use of long-acting oxytocin analogs, characterized chemically by replacement of the disulfide bridge by a thioether bridge, in safely increasing the milk products in mammals is disclosed. Of particular importance in the use of these compounds is the safety factor, that is, the absence of dangerous side effects at dosage levels required for increasing lactation. An increase in milk production can be accomplished with one or, at most, two single injections.

Method for increasing the milk let down in mammals

The use of long-acting oxytocin analogs, characterized chemically by replacement of the disulfide bridge by a thioether bridge, in safely inducing labor in mammals is disclosed. Of particular importance in the use of these compounds is the safety factor, that is, the absence of uterine tetany, dangerous to both mother and fetus, at dosage levels required for induction of complete labor. Induction of complete labor can be accomplished with one or, at most, two single injections.

Long-acting oxytocin analogs for use in inducing and accelerating labor

Stepwise synthesis in solution and cyclization by means of active esters or another method suitable for peptide bond formation were used to prepare analogues of deamino-vasopressin with the disulphide bridge altered to the thioether group. In sequence position 8 of the peptide chain the analogs differed by the nature of basic amino acid. Typical vasopressin-like activities, mainly antidiuretic, were very high in these analogs; of particular importance will be their haemodynamic activity.

Novel analogs of deamino-vasopressin with a modified disulfide bridge

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Roztoky, Czechoslovakia

Tomislav Barth