55240-51-2Relevant articles and documents
Structure-Activity Relationship for the Picolinamide Antibacterials that Selectively Target Clostridioides difficile
Speri, Enrico,Qian, Yuanyuan,Janardhanan, Jeshina,Masitas, Cesar,Lastochkin, Elena,De Benedetti, Stefania,Wang, Man,Schroeder, Valerie A.,Wolter, William R.,Oliver, Allen G.,Fisher, Jed F.,Mobashery, Shahriar,Chang, Mayland
, p. 991 - 995 (2021/05/27)
Clostridioides difficile is a leading health threat. This pathogen initiates intestinal infections during gut microbiota dysbiosis caused by oral administration of antibiotics. C. difficile is difficult to eradicate due to its ability to form spores, which are not susceptible to antibiotics. To address the urgent need for treating recurrent C. difficile infection, antibiotics that selectively target C. difficile over common gut microbiota are needed. We herein describe the class of picolinamide antibacterials which show potent and selective activity against C. difficile. The structure-activity relationship of 108 analogues of isonicotinamide 4, a compound that is equally active against methicillin-resistant Staphylococcus aureus and C. difficile, was investigated. Introduction of the picolinamide core as exemplified by analogue 87 resulted in exquisite potency and selectivity against C. difficile. The ability of the picolinamide class to selectively target C. difficile and to prevent gut dysbiosis holds promise for the treatment of recurrent C. difficile infection.
Discovery of benzoylsulfonohydrazides as potent inhibitors of the histone acetyltransferase KAT6A
Leaver, David J.,Cleary, Benjamin,Nguyen, Nghi,Priebbenow, Daniel L.,Lagiakos, H. Rachel,Sanchez, Julie,Xue, Lian,Huang, Fei,Sun, Yuxin,Mujumdar, Prashant,Mudududdla, Ramesh,Varghese, Swapna,Teguh, Silvia,Charman, Susan A.,White, Karen L.,Katneni, Kasiram,Cuellar, Matthew,Strasser, Jessica M.,Dahlin, Jayme L.,Walters, Michael A.,Street, Ian P.,Monahan, Brendon J.,Jarman, Kate E.,Sabroux, Helene Jousset,Falk, Hendrik,Chung, Matthew C.,Hermans, Stefan J.,Parker, Michael W.,Thomas, Tim,Baell, Jonathan B.
, p. 7146 - 7159 (2019/08/28)
A high-throughput screen for inhibitors of the histone acetyltransferase, KAT6A, led to identification of an aryl sulfonohydrazide derivative (CTX-0124143) that inhibited KAT6A with an IC50 of 1.0 μM. Elaboration of the structure-activity relationship and medicinal chemistry optimization led to the discovery of WM-8014 (97), a highly potent inhibitor of KAT6A (IC50 = 0.008 μM). WM-8014 competes with acetyl-CoA (Ac-CoA), and X-ray crystallographic analysis demonstrated binding to the Ac-CoA binding site. Through inhibition of KAT6A activity, WM-8014 induces cellular senescence and represents a unique pharmacological tool.
NOVEL FAP INHIBITORS
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Paragraph 0456; 0457; 0458; 0459, (2014/12/09)
The present invention relates to novel inhibitors having high selectivity and specificity for FAP (fibroblast activation protein). Said inhibitors are useful as a human and/or veterinary medicine, in particular for the treatment and/or prevention of FAP-related disorders such as but not limited to proliferative disorders.
