Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. 761446-44-0, formula is C10H17BN2O2, Name is 1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 °C).Pyrazole used as a ligand to prepare organometallic compounds. Category: pyrazoles-derivatives.
Lloyd, Matthew G.;Huckvale, Rosemary;Cheung, Kwai-Ming J.;Rodrigues, Matthew J.;Collie, Gavin W.;Pierrat, Olivier A.;Gatti Iou, Mahad;Carter, Michael;Davis, Owen A.;McAndrew, P. Craig;Gunnell, Emma;Le Bihan, Yann-Vai;Talbot, Rachel;Henley, Alan T.;Johnson, Louise D.;Hayes, Angela;Bright, Michael D.;Raynaud, Florence I.;Meniconi, Mirco;Burke, Rosemary;van Montfort, Rob L. M.;Rossanese, Olivia W.;Bellenie, Benjamin R.;Hoelder, Swen research published 《 Into Deep Water: Optimizing BCL6 Inhibitors by Growing into a Solvated Pocket》, the research content is summarized as follows. We describe the optimization of modestly active starting points to potent inhibitors of BCL6 by growing into a subpocket, which was occupied by a network of five stably bound water mols. Identifying potent inhibitors required not only forming new interactions in the subpocket but also perturbing the water network in a productive, potency-increasing fashion while controlling the physicochem. properties. We achieved this goal in a sequential manner by systematically probing the pocket and the water network, ultimately achieving a 100-fold improvement of activity. The most potent compounds displaced three of the five initial water mols. and formed hydrogen bonds with the remaining two. Compound 25 showed a promising profile for a lead compound with submicromolar inhibition of BCL6 in cells and satisfactory pharmacokinetic (PK) properties. Our work highlights the importance of finding productive ways to perturb existing water networks when growing into solvent-filled protein pockets.
Category: pyrazoles-derivatives, 1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole is a useful research compound. Its molecular formula is C10H17BN2O2 and its molecular weight is 208.07 g/mol. The purity is usually 95%., 761446-44-0.
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics