1-咪唑基羰氧基取代的四氢喹啉和吡啶：细胞色素P450血栓素A2抑制作用的合成与评估

1-Imidazolylcarbonyloxy-substituted tetrahydroquinolines and pyridines: synthesis and evaluation of P450 TxA2 inhibition.

作者信息

Hartmann R W, Frotscher M

机构信息

Pharmaceutical and Medicinal Chemistry, Universität des Saarlandes, Saarbrücken, Germany.

出版信息

Arch Pharm (Weinheim). 1999 Oct;332(10):358-62. doi: 10.1002/(sici)1521-4184(199910)332:10<358::aid-ardp358>3.0.co;2-d.

DOI:10.1002/(sici)1521-4184(199910)332:10<358::aid-ardp358>3.0.co;2-d

PMID:10575369

Abstract

The title compounds are derived from our model describing structural requirements for strong P450 TxA2 inhibition. In the present paper the syntheses of the 1-imidazolylcarbonyloxy-substituted tetrahydroquinolines 1, 3, and 4, tetrahydro-naphthalene 2 and 3-ethylpyridines 5 and 6 are described. Using our P450 TxA2 inhibition assay, 1-6 were tested for enzyme inhibitory activity. Compound 1 (5-(1-imidazolylcarbonyloxy)-5,6,7,8-tetrahydroquinoline) turned out to be the most active derivative showing a potency similar to the reference compound dazoxiben (IC50 values 1.6 and 1.1 microM).

摘要

标题化合物源自我们描述对细胞色素P450血栓素A2强抑制作用结构要求的模型。本文描述了1-咪唑基羰氧基取代的四氢喹啉1、3和4、四氢萘2以及3-乙基吡啶5和6的合成。使用我们的细胞色素P450血栓素A2抑制试验，对1-6进行了酶抑制活性测试。化合物1（5-(1-咪唑基羰氧基)-5,6,7,8-四氢喹啉）是活性最高的衍生物，其效力与参考化合物达唑氧苯相似（IC50值分别为1.6和1.1微摩尔）。