酰腙类化合物作为药物。

N-Acylhydrazones as drugs.

作者信息

Thota Sreekanth, Rodrigues Daniel A, Pinheiro Pedro de Sena Murteira, Lima Lídia M, Fraga Carlos A M, Barreiro Eliezer J

机构信息

National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswaldo Cruz - Ministério da Saúde, Av. Brazil 4036 - Prédio da Expansão, 8° Andar - Sala 814, Manguinhos, 21040-361 Rio de Janeiro, RJ, Brazil; Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), PO Box 68023, 21941-902 Rio de Janeiro, RJ, Brazil.

Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), PO Box 68023, 21941-902 Rio de Janeiro, RJ, Brazil.

出版信息

Bioorg Med Chem Lett. 2018 Sep 15;28(17):2797-2806. doi: 10.1016/j.bmcl.2018.07.015. Epub 2018 Jul 9.

DOI:10.1016/j.bmcl.2018.07.015

PMID:30006065

Abstract

Over the last two decades, N-acylhydrazone (NAH) has been proven to be a very versatile and promising motif in drug design and medicinal chemistry. Herein, we discuss the current and future challenges in the emergence of bioactive NAH-based scaffolds and to developing strategies to overcome the failures in drug discovery. The NAH-related approved drugs nitrofurazone, nitrofurantoin, carbazochrome, testosterone 17-enanthate 3-benzilic acid hydrazine, nifuroxazide, dantrolene, and azumolene are already used as therapeutics in various countries. PAC-1 is an NAH-based therapeutic agent that entered clinical trials in 2015. Another NAH-derived scaffold, LASSBio-294, is in preclinical trials. This review highlights the detailed comprehensive assessment and therapeutic landscape of bioactive NAH motif scaffolds in preclinical and clinical studies published to date and their promise and associated challenges in current and future drug discovery of NAH-based drugs that will progress to clinical use.

摘要

在过去二十年中，酰腙（NAH）已被证明是药物设计和药物化学中一种非常通用且有前景的结构单元。在此，我们讨论基于生物活性NAH的支架出现过程中的当前和未来挑战，以及开发策略以克服药物发现中的失败。与NAH相关的已批准药物呋喃西林、呋喃妥因、卡巴克络、睾酮17-庚酸3-二苯乙醇酸肼、硝呋齐特、丹曲林和阿祖莫林已在各国用作治疗药物。PAC-1是一种基于NAH的治疗剂，于2015年进入临床试验。另一种源自NAH的支架LASSBio-294正在进行临床前试验。本综述重点介绍了迄今为止已发表的临床前和临床研究中生物活性NAH基序支架的详细综合评估和治疗前景，以及它们在当前和未来将进入临床应用的基于NAH的药物发现中的前景和相关挑战。