Date of Award

Fall 2003

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry & Biochemistry

Program/Concentration

Chemistry

Committee Director

Roy L. Williams

Committee Member

P. Blackmore

Committee Member

Y. Dobrydneva

Call Number for Print

Special Collections LD4331.C45 M32 2003

Abstract

Studies have shown that 2-aminoethoxydiphenyl borate (2-APB) inhibits thrombin-mediated influx of Ca2 + through store-operated calcium channels in human platelets. Based on this molecule, two sets (boron analogues and the non-boron analogues) were synthesized and characterized by IR, NMR and CHN analysis and evaluated in human platelets to block thrombin-induced [Ca2+] elevation.

The synthesis of the non-boron compounds was performed in a simple one step process. According to the literature, some of these compounds were synthesized previously by a complicated two-step process.

All the compounds synthesized were tested for biological activity and the results showed that they did not have any enhanced biological activity as calcium channel blockers compared to 2-APB.

(R)(+)-2-amino-3-phenyl propoxy diphenyl borate and (S)(-)2-amino-3- phenyl propoxy diphenyl borate (structure 12) boron containing compounds were synthesized specifically to detect for stereospecificity of 2-APB derivatives to inhibit calcium influx channel. Biological activity of these compounds demonstrated that they have potency and efficacy similar to that of 2-APB.

Addition of (R)(+)2-amino-3-phenyl-1-propanol and (S)(-)2-amino-3- phenyl-1-propanol substituents to the boroxazolidine ring of 2-APB resulted in a similar inhibitory activity. This result indicates that R and S substituents are not involved in binding to the Ca2 + channel.

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DOI

10.25777/5zmj-kd42

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