Synthesis and Evaluation of Novel [1,2,4]Triazolo[5,1-c][1,2,4]-triazines and Pyrazolo[5,1-c][1,2,4]triazines as Potential Antidiabetic Agents.

Inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme activity and prevention of advanced glycation end (AGE) products formation represents a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In the frames of this research study, several triazolo- and pyrazolotriazines were synthesized and evaluated as inhibitors of AGE products formation, DPP4, glycogen phosphorylase and α-glucosidase activities, as well as AGE cross-link breakers. From the two considered classes of heterocyclic compounds, the pyrazolotriazines showed the highest potency as antiglycating agents and DPP4 inhibitors.

Study of μ- and δ-Opioid Activities in Agents with Various κ-Receptor Selectivity.

A putative opioid agonist RU-1205 was ineffective within in vitro model of electrically induced contractions of rat ileum assessing the μ- and δ-opioid receptor pathways, while morphine inhibited these contractions in a dose-dependent and naloxone-reversible manners with EC=2.6×10 M. In vivo experiments revealed no significant effects of RU-1205 on respiration and gastrointestinal tract contractile activity.

STUDYING THE PHYSICAL DEPENDENCE ON AND TOLERANCE TO THE ANTINOCICEPTIVE EFFECT OF RU-1205 SUBSTANCE.

We have studied the physical dependence on and tolerance to the analgesic activity of compound RU-1205. It is established that this compound does not cause side effects typical of morphine and butorphanol including the development of withdrawal syndrome upon naloxone provocation and tolerance to analgesic activity upon 14-day administration.

[Pharmacokinetic and analgesic properties of tabletized dosage form of RU-1205-new imidazobenzimidazole derivative with kappa agonist activity].

The pharmacokinetic properties of a new imidazobenzimidazole derivative, compound RU-1205, were studied after peroral administration to rabbits at a dose of 50 mg/kg as a parent substance and in coated tablet dosage form. It was found that RU-1205 tablets are characterized by high values of the relative bioavailability (105.3 +/- 11.

[The absolute bioavailability of benzimidazole derivative RU-1205 in rats].

Pharmacokinetics of morpholinoethylimidazobenzimidazole derivative RU-1205 with kappa-agonist activity have been studied. The pharmacokinetic parameters were determined upon intravenous (10 mg/kg), peroral, and subcutaneous (50 mg/kg) administration. It is established that RU-1205 substance has high bioavailability (44.