Halogen-aromatic π interactions modulate inhibitor residence times was written by Heroven, Christina;Georgi, Victoria;Ganotra, Gaurav K.;Brennan, Paul;Wolfreys, Finn;Wade, Rebecca C.;Fernandez-Montalvan, Amaury E.;Chaikuad, Apirat;Knapp, Stefan. And the article was included in Angewandte Chemie, International Edition in 2018.Formula: C11H13IN4O4 The following contents are mentioned in the article:
Prolonged drug residence times may result in longer-lasting drug efficacy, improved pharmacodynamic properties, and “kinetic selectivity” over off-targets with high drug dissociation rates. However, few strategies have been elaborated to rationally modulate drug residence time and thereby to integrate this key property into the drug development process. Herein, we show that the interaction between a halogen moiety on an inhibitor and an aromatic residue in the target protein can significantly increase inhibitor residence time. By using the interaction of the serine/threonine kinase haspin with 5-iodotubercidin (5-iTU) derivatives as a model for an archetypal active-state (type I) kinase-inhibitor binding mode, we demonstrate that inhibitor residence times markedly increase with the size and polarizability of the halogen atom. The halogen-aromatic π interactions in the haspin-inhibitor complexes were characterized by means of kinetic, thermodn., and structural measurements along with binding-energy calculations This study involved multiple reactions and reactants, such as (2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4Formula: C11H13IN4O4).
(2R,3R,4S,5R)-2-(4-Amino-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (cas: 24386-93-4) belongs to tetrahydrofuran derivatives. THF (Tetrahydrofuran) is water-miscible and has a low viscosity making it a highly versatile solvent used in a variety of industries. THF can also be synthesized by catalytic hydrogenation of furan. This allows certain sugars to be converted to THF via acid-catalyzed digestion to furfural and decarbonylation to furan, although this method is not widely practiced. THF is thus derivable from renewable resources.Formula: C11H13IN4O4
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem