P.Trapencieris
Latvian Institute of Organic Synthesis Riga, Aizkraukles iela 21, LV-1006, Latvia
Abstract:
Carbonic anhydrases (CAs) are ubiquitous Zn-containing enzymes and are involved in numerous physiological and pathological processes including respiration and transport of CO2/HCO3- (1). CAII isoform is an bundant, house-keeping enzyme, present in most cells in humans, and differs in amino acid sequence from CAI, CAIX and CAXII, by having Ala in position 65 instead of Ser. The main challenge is to find selective inhibitors with higher affinity to CAI. So far, the only compounds possessing higher affinity for CAI contain ureido or thioureido moieties (2). We tried to find new type inhibitors to CAI active site using quantum chemistry calculations. Binding models for ligand L1 with CAI and CAII different transition states are proposed.
After retrosynthetic analysis ligand L1 was obtained in multistep process from thiophene-3-aldehyde. The key step was the synthesis of thiphene-2-boronic acid and its separation from the corresponding regioisomer.
