TY - JOUR T1 - 2-Aminoethoxydiphenyl Borate as a Prototype Drug for a Group of Structurally Related Calcium Channel Blockers in Human Platelets JF - Molecular Pharmacology JO - Mol Pharmacol SP - 247 LP - 256 DO - 10.1124/mol.105.015701 VL - 69 IS - 1 AU - Yuliya Dobrydneva AU - Christopher J. Abelt AU - Beth Dovel AU - Celina M. Thadigiri AU - Roy L. Williams AU - Peter F. Blackmore Y1 - 2006/01/01 UR - http://molpharm.aspetjournals.org/content/69/1/247.abstract N2 - We have synthesized a series of 2-aminoethoxydiphenyl borate (2-APB, 2,2-diphenyl-1,3,2-oxazaborolidine) analogs and tested their ability to inhibit thrombin-induced Ca2+ influx in human platelets. The analogs were either synthesized by adding various substituents to the oxazaborolidine ring (methyl, dimethyl, tert-butyl, phenyl, methyl phenyl, and pyridyl) or increasing the size of the oxazaborolidine ring to seven- and nine-membered rings. NMR analysis of the boron-containing analogs suggests that each of them exist as a ring structure through the formation of an N→B coordinate bond (except for the hexyl analog). The possibility that these boron-containing compounds formed dimers was also considered. All compounds dose-dependently inhibited thrombin-induced Ca2+ influx in human platelets, with the 2,2-diphenyl-1,3,2-oxazaborolidine-5-one derivative having the weakest activity at 100 μM, whereas the (S)-4-benzyl and (R)-4-benzyl derivatives of 2-APB were approximately 10 times more potent than the parent 2-APB. Two nonboron analogs (3-methyl and 3-tert-butyl 2,2-diphenyl-1,3-oxazolidine) were synthesized; they had approximately the same activity as 2-APB, and this implies that the presence of boron was not necessary for inhibitory activity. All of the compounds tested were also able to inhibit thrombin-induced calcium release. We concluded that extensive modifications of the oxazaborolidine ring in 2-APB can be made, and Ca2+-blocking activity was maintained. ER -