Synthesis and antibacterial evaluation of macrocyclic diarylheptanoid derivatives

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:26

Article

Lin, Hao¹  Bruhn, David F.^2,3  Maddox, Marcus M.²  Singh, Aman P.²  Lee, Richard E.²  Sun, Dianqing¹ 

[1] Univ Hawaii Hilo, Daniel K Inouye Coll Pharm, Dept Pharmaceut Sci, 34 Rainbow Dr, Hilo, HI 96720 USA

[2] St Jude Childrens Res Hosp, Dept Chem Biol & Therapeut, 262 Danny Thomas Pl,MS 1000, Memphis, TN 38105 USA

[3] Avista Pharma Solut, 3501 Trictr Blvd,Suite C, Durham, NC 27713 USA

关键词: Antituberculosis;    Antibacterial;    Diarylheptanoid;    Macrocycle;    SAR;   

DOI  :  10.1016/j.bmcl.2016.06.075

来源: Elsevier

【 摘 要 】

Bacterial infections, caused by Mycobacterium tuberculosis and other problematic bacterial pathogens, continue to pose a significant threat to global public health. As such, new chemotype antibacterial agents are desperately needed to fuel and strengthen the antibacterial drug discovery and development pipeline. As part of our antibacterial research program to develop natural product-inspired new antibacterial agents, here we report synthesis, antibacterial evaluation, and structure-activity relationship studies of an extended chemical library of macrocyclic diarylheptanoids with diverse amine, amide, urea, and sulfonamide functionalities. Results of this study have produced macrocyclic geranylamine and 4-fluorophenethylamine substituted derivatives, exhibiting moderate to good activity against M. tuberculosis and selected Gram-positive bacterial pathogens. (C) 2016 Elsevier Ltd. All rights reserved.

【 授权许可】

Free