Browsing by Author "Adams, Mortimer Hilary"

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    The synthesis of prodrugs and novel analogues of Beta-sympathomimetic bronchodilators
    (University of the Western Cape, 1998) Adams, Mortimer Hilary; Ameer, Farouk; Green, Ivan R.
    Prodrugs are reversible derivatives of active drugs destined to undergo chemical or enzymatic transformation to the active drug after administration in order that the active drug may subsequently elicit the desired pharmacological response . In synthesizing a prodrug, the physico chemical properties of a drug are altered by suitable functionalisation of an appropriate appendage of the drug molecule such that some barrier or problem may be circumvented or obviated in totality. Prodrugs of bronchodilators have been prod used with the aim of reducing enzymatic degradation, improving their bio-availability and, displaying a marked separation between their desirable bronchodilator and undesirable cardiovascular activities. Chlorphentermine (II), a lung accurnulating arnine, was used as a carrier molecule in novel prodrugs which potentially possess these attributes. Model prodrugs viz. CPE (20) and CPETA (t4), consisting of chlorpltentennine (ll) connected through a propionic ester link to ethanol and etafedrine (13), respectively, were synthesized by reacting the alcohols with acryloyl chloride and the resultant acrylates subsequently reacted with chlorphentennine (II). CPA (21), the prodmg hydrolysis product of CPE (20), was also synthesized. Closely related analoEres of CPETA (t4) narnely PETA (15) and CPAP' (16) were then synthesized. PETA (15) was synthesized by the condensation of methylamino- I -phenylpropane (phentenrtine) and etaf-edrine ( I 3).