916343-75-4Relevant articles and documents
Rational design of inhibitors of the bacterial cell wall synthetic enzyme GlmU using virtual screening and lead-hopping
Doig, Peter,Boriack-Sjodin, P. Ann,Dumas, Jacques,Hu, Jun,Itoh, Kenji,Johnson, Kenneth,Kazmirski, Steven,Kinoshita, Tomohiko,Kuroda, Satoru,Sato, Tomo-O,Sugimoto, Kaori,Tohyama, Katsumi,Aoi, Hiroshi,Wakamatsu, Kazusa,Wang, Hongming
, p. 6256 - 6269 (2014)
An aminoquinazoline series targeting the essential bacterial enzyme GlmU (uridyltransferase) were previously reported (Biochem. J. 2012, 446, 405). In this study, we further explored SAR through a combination of traditional medicinal chemistry and structure-based drug design, resulting in a novel scaffold (benzamide) with selectivity against protein kinases. Virtual screening identified fragments that could be fused into the core scaffold, exploiting additional binding interactions and thus improving potency. These efforts resulted in a hybrid compound with target potency increased by a 1000-fold, while maintaining selectivity against selected protein kinases and an improved level of solubility and protein binding. Despite these significant improvements no significant antibacterial activity was yet observed within this class.
Targeting the heat shock protein 90 dimer with dimeric inhibitors
Kusuma, Bhaskar Reddy,Peterson, Laura B.,Zhao, Huiping,Vielhauer, George,Holzbeierlein, Jeffrey,Blagg, Brian S. J.
scheme or table, p. 6234 - 6253 (2011/10/31)
The design, synthesis, and biological evaluation of conformationally constrained coumermycin A1 analogues are reported. Compounds were evaluated against both breast cancer (SKBr3 and MCF7) and prostate cancer (PC3 mm2, A549, and HT29) cell lines. Non-noviosylated coumermycin A1 analogues that manifest potent antiproliferative activity resulting from Hsp90 inhibition are provided, wherein replacement of the stereochemically complex noviose sugar with readily available piperidine rings resulted in ü100 fold increase in antiproliferative activities as compared to coumermycin A1, producing small molecule Hsp90 inhibitors that exhibit nanomolar activities.
SPIROCHROMANON DERIVATIVES
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Page/Page column 122, (2008/12/07)
The invention relates to a compound of a general formula (I): wherein Ar1 represents a group formed from an aromatic ring selected from a group consisting of benzene, pyrazole, isoxazole, pyridine, indole, 1H-indazole, 1H-furo[2,3-c]pyrazole, 1H-thieno[2,3-c]pyrazole, benzimidazole, 1,2-benzisoxazole, imidazo[1,2-a]pyridine, imidazo[1,5-a]pyridine and 1H-pyrazolo[3,4-b]pyridine, having Ar2, and optionally having one or two or more substituents selected from R3; R1 and R2 each independently represent a hydrogen atom, a halogen atom, a cyano group, a C2-C6 alkenyl group, a C1-C6 alkoxy group, a C2-C7 alkanoyl group, a C2-C7 alkoxycarbonyl group, an aralkyloxycarbonyl group, a carbamoyl-C1-C6 alkoxy group, a carboxy-C2-C6 alkenyl group, or a group of -Q1-N(Ra)-Q2-Rb; or a C1-C6 alkyl group optionally having a substituent; or an aryl or heterocyclic group optionally having a substituent; or a C1-C6 alkyl group or a C2-C6 alkenyl group having the aryl or heterocyclic group; T and U each independently represent a nitrogen atom or a methine group; and V represents an oxygen atom or a sulfur atom. The compound of the invention is useful as therapeutical agents for various ACC-related diseases.
