Discovery of (2-(4-Substituted phenyl)quinolin-4-yl)(4-isopropylpiperazin-1-yl)methanone Derivatives as Potent Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors,ChemMedChem

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Discovery of (2-(4-Substituted phenyl)quinolin-4-yl)(4-isopropylpiperazin-1-yl)methanone Derivatives as Potent Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors
ChemMedChem ( IF 3.6 ) Pub Date : 2023-12-06 , DOI: 10.1002/cmdc.202300498
Xiaojing Wang ₁ , Lihui Zhang ₂ , Xue Wang ₃ , Dongqi Zhu ₃ , Guangzhao Xu _{4,

5} , Honggang Li ₆ , Lei Zhang ₁

Affiliation

Inhibition of PCSK9 has been studied for the treatment of hypercholesterolemia. Two human monoclonal antibodies and one siRNA of PCSK9 have been approved by the US FDA to lower LDL−C, but the development of small-molecule PCSK9 inhibitors has not made significant progress. To address this, 33 molecules were designed and synthesized to interfere with the PCSK9/LDLR protein−protein interaction. This study gave rise to novel lead structures useful for the discovery of orally effective hypolipidemic drugs.

中文翻译：

发现 (2-(4-取代苯基)喹啉-4-基)(4-异丙基哌嗪-1-基)甲酮衍生物作为有效的前蛋白转化酶枯草杆菌蛋白酶/Kexin 9 型抑制剂

已研究抑制 PCSK9 用于治疗高胆固醇血症。两种人源单克隆抗体和一种PCSK9 siRNA已被美国FDA批准用于降低LDL−C，但小分子PCSK9抑制剂的开发尚未取得重大进展。为了解决这个问题，设计并合成了 33 个分子来干扰 PCSK9/LDLR 蛋白质-蛋白质相互作用。这项研究产生了新的先导结构，可用于发现口服有效的降血脂药物。

更新日期：2023-12-06

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