Waszkowycz, Bohdan; Smith, Kate M.; McGonagle, Alison E.; Jordan, Allan M.; Acton, Ben; Fairweather, Emma E.; Griffiths, Louise A.; Hamilton, Niall M.; Hamilton, Nicola S.; Hitchin, James R.; Hutton, Colin P.; James, Dominic I.; Jones, Clifford D.; Jones, Stuart; Mould, Daniel P.; Small, Helen F.; Stowell, Alexandra I. J.; Tucker, Julie A.; Waddell, Ian D.; Ogilvie, Donald J. published their research in Journal of Medicinal Chemistry on December 13 ,2018. The article was titled 《Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides》.Synthetic Route of C5H8N2O The article contains the following contents:
DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone 8a, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design. 1-Oxetan-3-ylmethyl derivatives 33d and 35d were selected for preliminary investigations in vivo. X-ray crystal structures help rationalize the observed structure-activity relationships of these novel inhibitors. After reading the article, we found that the author used (3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7Synthetic Route of C5H8N2O)
(3-methyl-1H-pyrazol-5-yl)methanol(cas: 29004-73-7) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Synthetic Route of C5H8N2O
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics