3724-26-3Relevant articles and documents
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Alley
, p. 1837 (1975)
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Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A2AReceptor
Amelia, Tasia,Van Veldhoven, Jacobus P. D.,Falsini, Matteo,Liu, Rongfang,Heitman, Laura H.,Van Westen, Gerard J. P.,Segala, Elena,Verdon, Grégory,Cheng, Robert K. Y.,Cooke, Robert M.,Van Der Es, Daan,Ijzerman, Adriaan P.
, p. 3827 - 3842 (2021/05/04)
In this study, we determined the crystal structure of an engineered human adenosine A2A receptor bound to a partial agonist and compared it to structures cocrystallized with either a full agonist or an antagonist/inverse agonist. The interaction between the partial agonist, belonging to a class of dicyanopyridines, and amino acids in the ligand binding pocket inspired us to develop a small library of derivatives and assess their affinity in radioligand binding studies and potency and intrinsic activity in a functional, label-free, intact cell assay. It appeared that some of the derivatives retained the partial agonist profile, whereas other ligands turned into inverse agonists. We rationalized this remarkable behavior with additional computational docking studies.
3-ARYL-5-SUBSTITUTED-ISOQUINOLIN-1-ONE COMPOUNDS AND THEIR THERAPEUTIC USE
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Page/Page column 200, (2015/03/28)
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted- 2/-/-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, e
Bare histidine-serine models: Implication and impact of hydrogen bonding on nucleophilicity
Leclaire, Julien,Mazari, Messaoud,Zhang, Yuan,Bonduelle, Colin,Thillaye Du Boullay, Olivier,Martin-Vaca, Blanca,Bourissou, Didier,De Riggi, Innocenzo,Fortrie, Rémy,Fotiadu, Frédéric,Buono, Gérard
supporting information, p. 11301 - 11309 (2013/09/02)
A new family of 2-hydroxyalk(en/yn)ylimidazoles has been evaluated as serine-histidine bare dyad models for the ring-opening reaction of L-lacOCA, a cyclic O-carboxyanhydride. These models were selected to unravel the implication of intramolecular hydrogen bonding and to substantiate its influence on the nucleophilicity of the alcohol moiety, as it is suspected to occur in enzyme active sites. Although designed to exclusively facilitate the preliminary step of proton transfer during the studied ring-opening reaction, these minimalistic models depicted a measureable increase in reactivity relative to the isolated fragments. A couple of reliable experimental and theoretical methods have been developed to readily monitor the strength of the intramolecular hydrogen bond in dilute solution. Results show that the folded conformers are the most nucleophilic species because of the intramolecular hydrogen bond. Copyright