N-取代氨基羟基吡啶作为潜在的非阿片类镇痛剂。

N-substituted aminohydroxypyridines as potential non-opioid analgesic agents.

作者信息

Viaud M C, Jamoneau P, Bizot-Espiard J G, Pfeiffer B, Renard P, Caignard D H, Adam G, Guillaumet G

机构信息

Université d'Orléans Laboratoire de Chimie Bioorganique et Analytique (L.C.B.A.), URA CNRS n.499, Orléans, France.

出版信息

Bioorg Med Chem. 1995 Jul;3(7):929-37. doi: 10.1016/0968-0896(95)00080-z.

DOI:10.1016/0968-0896(95)00080-z

PMID:7582970

Abstract

A series of new N-substituted aminohydroxypyridines have been synthesized, pharmacologically evaluated and compared with their N-substituted oxazolopyridone analogs. The compound with the maximal combination of safety and analgesic efficacy was 3-[2-[4-(4-fluorophenyl)-1-piperazinyl]ethyl]amino-2-hydroxypyridine (compound 10a), with ED50 values 0.4 mg kg-1 po (mouse: phenylquinone writhing test) and 0.5 mg kg-1 po (rat: acetic acid writhing test). Compound 10a possesses a potent non-opioid antinociceptive activity with moderate anti-inflammatory properties.

摘要

一系列新的N-取代氨基羟基吡啶已被合成、进行药理评估并与其N-取代恶唑并吡啶酮类似物进行比较。安全性和镇痛效果最佳组合的化合物是3-[2-[4-(4-氟苯基)-1-哌嗪基]乙基]氨基-2-羟基吡啶（化合物10a），其ED50值为0.4 mg kg-1口服（小鼠：苯醌扭体试验）和0.5 mg kg-1口服（大鼠：醋酸扭体试验）。化合物10a具有强效的非阿片类抗伤害感受活性以及适度的抗炎特性。