8-(甲氨基)-2-氧代-1,2-二氢喹啉类化合物作为细菌拓扑异构酶 II 抑制剂的先导优化。
Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors.
机构信息
Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-Cho, Kita-Ku, Saitama 331-9530, Japan.
Taisho Pharmaceutical Co., Ltd, 1-403 Yoshino-Cho, Kita-Ku, Saitama 331-9530, Japan.
出版信息
Bioorg Med Chem. 2020 Nov 15;28(22):115776. doi: 10.1016/j.bmc.2020.115776. Epub 2020 Sep 22.
The global increase in multidrug-resistant pathogens has caused severe problems in the treatment of infections. To overcome these difficulties, the advent of a new chemical class of antibacterial drug is eagerly desired. We aimed at creating novel antibacterial agents against bacterial type II topoisomerases, which are well-validated targets. TP0480066 (compound 32) has been identified by using structure-based optimization originated from lead compound 1, which was obtained as a result of our previous lead identification studies. The MIC values of TP0480066 against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and genotype penicillin-resistant Streptococcus pneumoniae (gPRSP) were 0.25, 0.015, and 0.06 μg/mL, respectively. Hence, TP0480066 can be regarded as a promising antibacterial drug candidate of this chemical class.
全球耐多药病原体的增加给感染的治疗带来了严重的问题。为了克服这些困难，人们迫切希望有一种新的化学类别抗菌药物问世。我们的目标是开发针对细菌 II 型拓扑异构酶的新型抗菌剂，这些酶是经过充分验证的靶点。TP0480066（化合物 32）是通过使用源自先导化合物 1 的基于结构的优化方法发现的，该化合物是我们之前的先导化合物鉴定研究的结果。TP0480066 对耐甲氧西林金黄色葡萄球菌（MRSA）、万古霉素耐药肠球菌（VRE）和基因型青霉素耐药肺炎链球菌（gPRSP）的 MIC 值分别为 0.25、0.015 和 0.06 μg/mL。因此，TP0480066 可以被视为该化学类别有前途的抗菌药物候选物。
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