Velagapudi, Uday Kiran; Langelier, Marie-France; Delgado-Martin, Cristina; Diolaiti, Morgan E.; Bakker, Sietske; Ashworth, Alan; Patel, Bhargav A.; Shao, Xuwei; Pascal, John M.; Talele, Tanaji T. published the artcile< Design and Synthesis of Poly(ADP-ribose) Polymerase Inhibitors: Impact of Adenosine Pocket-Binding Motif Appendage to the 3-Oxo-2,3-dihydrobenzofuran-7-carboxamide on Potency and Selectivity>, Name: 4-(Thiazol-2-yl)benzaldehyde, the main research area is PARP inhibitor anticancer drug crystal structure adenosine breast cancer.
Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of anticancer drugs that block the catalytic activity of PARP proteins. Optimization of our lead compound 1 ((Z)-2-benzylidene-3-oxo-2,3-dihydrobenzofuran-7-carboxamide; PARP-1 IC50 = 434 nM) led to a tetrazolyl analog (51, IC50 = 35 nM) with improved inhibition. Isosteric replacement of the tetrazole ring with a carboxyl group (60, IC50 = 68 nM) gave a promising new lead, which was subsequently optimized to obtain analogs with potent PARP-1 IC50 values (4-197 nM). PARP enzyme profiling revealed that the majority of compounds are selective toward PARP-2 with IC50 values comparable to clin. inhibitors. X-ray crystal structures of the key inhibitors bound to PARP-1 illustrated the mode of interaction with analog appendages extending toward the PARP-1 adenosine-binding pocket. Compound 81, an isoform-selective PARP-1/-2 (IC50 = 30 nM/2 nM) inhibitor, demonstrated selective cytotoxic effect toward breast cancer gene 1 (BRCA1)-deficient cells compared to isogenic BRCA1-proficient cells.
Journal of Medicinal Chemistry published new progress about Antitumor agents. 198904-53-9 belongs to class thiazole, and the molecular formula is C10H7NOS, Name: 4-(Thiazol-2-yl)benzaldehyde.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica