SYNTHESIS AND EVALUATION OF NEW LOCAL ANTIINFLAMMATORY STEROIDS

皮质类固醇在治疗炎症性疾病中的使用 主要是因为它们的系统性抑制作用 肾上腺功能和免疫系统。若要克服此限制，请使用 已集中努力合成局部活性抗炎药物 根据前药物概念，类固醇没有全身性不良反应。 在这种方法中，代谢不稳定的官能团，烷基 强效皮质类固醇的不同战略位置的羧酸盐，有 被介绍给了。减少这种类固醇的全身不良反应 前药归因于酯功能迅速水解成一种 进入循环系统时不活跃的类固醇酸。因此， 真正的禁药只在局部起作用。有人提议合成一个新的群体 并从以下方面对其进行综合评价 它们的局部和全身药理活性。为了进一步描绘 新类固醇的作用方式及其受体结合 特性、对垂体肾上腺功能、糖原的影响 将研究前列腺素和弹性蛋白酶的沉积、释放。 这些研究的结果将产生对结构的有价值的见解 局部抗炎药物最大分离度的特点 来自系统性不良影响的活动，以及这些新的行动模式 类固醇，承诺提供坚实的理性基础 不含全身激素的新型高效抗炎激素的研究进展 副作用。

The use of corticosteroids in the treatment of inflammatory conditions has been limited primarily due to their systemic suppressive effects on the adrenal function and the immune system. To overcome this limitation, a focused effort has been made to synthesize locally active antiinflammatory steroids without systemic adverse effects based on the antedrug concept. In this approach, metabolically labile functional groups, alkyl carboxylates at various strategic positions of potent corticosteroids, have been introduced. The reduced systemic adverse effects of this steroidal antedrug are ascribed to rapid hydrolysis of the ester function into an inactive steroid acid upon entry into the circulation system. Thus the true antedrug acts only locally. It is proposed to synthesize a new group of steroidal antedrugs and evaluate them comprehensively with respect to their local and systemic pharmacological activity. To further delineate the mode of action of the new steroids, their receptor binding characteristics, effects on pituitary adrenal function, glycogen deposition, liberation of prostanoids and elastase will b studied. Results of these studies will yield valuable insight into the structural characteristics for the maximum separation of local anti-inflammatory activity from systemic adverse effects, and mode of action of these new steroids with the promise of providing a solid rational basis for development of new potent anti-inflammatory steroids devoid of systemic side effects.