Edafiogho I O, Moore J A, Farrar V A, Nicholson J M, Scott K R
Department of Medicinal Chemistry, College of Pharmacy and Pharmacal Sciences, Howard University, Washington, DC 20059.
J Pharm Sci. 1994 Jan;83(1):79-84. doi: 10.1002/jps.2600830119.
The objective of this work was to design enaminone esters that would possess potential medicinal properties. The reaction between beta-hydroxyketo esters and primary or secondary amines yielded secondary or tertiary enaminone esters, respectively. The UV spectra of the enaminone esters were determined in acidic, alkaline, and neutral media; the spectra have a hypsochromic shift in acidic media in comparison with neutral media. The enaminone esters provided nucleophilic and electrophilic sites for a variety of reactions. Thus, the enaminone esters were converted into enaminone amides and O-alkylation products exclusively. Although the enaminone esters were generally resistant to reduction by metal hydrides, one unhindered enaminone ester was reduced to an alcohol with sodium borohydride. Another enaminone ester reacted with guanidine to give the corresponding quinazolinone. Due to the variety of nucleophilic and electrophilic sites in the enaminone system, enaminone esters possess a great potential as reaction intermediates and medicinal compounds. Preliminary evaluations of the enaminone esters revealed a histaminergic effect, uterine relaxant properties, and anticonvulsant activity.
这项工作的目的是设计具有潜在药用特性的烯胺酮酯。β-羟基酮酯与伯胺或仲胺之间的反应分别生成仲烯胺酮酯或叔烯胺酮酯。在酸性、碱性和中性介质中测定了烯胺酮酯的紫外光谱；与中性介质相比，光谱在酸性介质中有蓝移。烯胺酮酯为各种反应提供了亲核和亲电位点。因此，烯胺酮酯仅转化为烯胺酮酰胺和O-烷基化产物。虽然烯胺酮酯通常对金属氢化物的还原具有抗性，但一种无位阻的烯胺酮酯被硼氢化钠还原为醇。另一种烯胺酮酯与胍反应生成相应的喹唑啉酮。由于烯胺酮体系中存在多种亲核和亲电位点，烯胺酮酯作为反应中间体和药用化合物具有很大的潜力。对烯胺酮酯的初步评估显示出组胺能效应、子宫松弛特性和抗惊厥活性。
