No abstract

The Na+/H+ exchanger isoform 1 (NHE-1) attracts ongoing attention as a validated drug target for the management of cardiovascular and ocular diseases owing to cytoprotective, anti-ischemic and anti-inflammatory properties of NHE-1 inhibitors. Herein we report novel NHE-1 inhibitors realized via functionalization of N1-alkyl quinazoline-2,4(1H,3H)-dione and quinazoline-4(3H)-one with N-acylguanidine or 3-acyl(5-amino-1,2,4-triazole) side chain. Lead compounds show activity in a nanomolar range. Their pharmacophoric features were elucidated with neural network modeling. Several compounds combine NHE-1 inhibition with antiplatelet activity. Compound 6b reduces intraocular pressure in rats and effectively inhibits the formation of glycated proteins. Compounds 3e and 3i inhibit pro-inflammatory activation of murine macrophages, LPS-induced interleukin-6 secretion and also exhibit antidepressant activity similar to amiloride. Hence, novel compounds represent an interesting starting point for the development of agents against cardiovascular diseases, thrombotic events, excessive inflammation, long-term diabetic complications and glaucoma.

No abstract

No abstract

No abstract

No abstract

Taking into account the structure-activity relationship established previously for imidazobenzimidazole derivatives with high hemorheological activity, several new 9-R-2-halogenophenyl-substituted imidazo-[1,2-a]benzimidazoles with C 2 fluoro-, chloro-, dichloro-, or bromo-phenyl radicals have been synthesized. All substances were tested in vitro for various types of pharmacological activity characteristic of this class of drugs including hemorheological, antiplatelet, antiarrhythmic, antioxidant; 5-HT 2 -, 5-HT 3 -, P2Y 1 -, and H 1 -antagonist; and k-opioid-agonist.

No abstract