上呼吸道刺激的定量构效关系

QSAR for upper-respiratory tract irritation.

作者信息

Roberts D W

出版信息

Chem Biol Interact. 1986 Mar;57(3):325-45. doi: 10.1016/0009-2797(86)90007-4.

Abstract

A recent paper by Muller and Greff (Fd. Chem. Toxicol., 22 (1984) 661) presents QSAR equations for upper respiratory tract irritation by compounds falling into various chemical families. In the present paper the relationships are analysed further. It is found that a general QSAR equation, covering a diverse range of structures, correlates the biological activity reported by Muller and Greff with a single physicochemical parameter, TB'. The parameter TB' is the boiling point at atmospheric pressure (TB), adjusted for compounds with Trouton constants different from 22 cal deg-1 mol-1: TB' = (Tr X TB/22) + 40(1 - Tr/22) where Tr is the Trouton constant. Some of the compounds studied were found to be more irritant than predicted by the general equation: their enhanced activity can be rationalised in terms of their chemical reactivity as electrophiles, their metabolism to electrophiles, or their hydrolysis to more irritant products.

摘要

穆勒和格雷夫最近发表的一篇论文（《食品化学毒理学》，22 (1984) 661）给出了各类化学族化合物对上呼吸道刺激性的定量构效关系（QSAR）方程。在本文中，对这些关系进行了进一步分析。结果发现，一个涵盖多种结构的通用QSAR方程将穆勒和格雷夫报道的生物活性与单一物理化学参数TB'关联起来。参数TB'是在大气压下的沸点（TB），对于特鲁顿常数不同于22 cal deg⁻¹ mol⁻¹的化合物进行了校正：TB' = (Tr × TB/22) + 40(1 - Tr/22)，其中Tr是特鲁顿常数。研究发现，一些化合物的刺激性比通用方程预测的更强：它们增强的活性可以从其作为亲电试剂的化学反应性、它们代谢成亲电试剂或它们水解成更具刺激性的产物方面进行解释。