Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor

Fyfe, Tim J.; Kellam, Barrie; Mistry, Shailesh N.; Scammells, Peter J.; Lane, J. Robert; Capuano, Ben

doi:10.1016/j.ejmech.2019.01.061

All Outputs (3)

Structure-Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D2 Receptor (2019)
Journal Article
Fyfe, T. J., Kellam, B., Sykes, D. A., Capuano, B., Scammells, P. J., Lane, J. R., …Mistry, S. N. (2019). Structure-Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D2 Receptor. Journal of Medicinal Chemistry, 62(21), 9488-9520. https://doi.org/10.1021/acs.jmedchem.9b00864

Haloperidol is a typical antipsychotic drug (APD) associated with an increased risk of extrapyramidal side-effects (EPS) and hyperprolactinemia relative to atypical APDs such as clozapine. Both drugs are dopamine D2 receptor (D2R) antagonists, with c... Read More about Structure-Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D2 Receptor.

Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole (2019)
Journal Article
Klein Herenbrink, C., Verma, R., Lim, H. D., Kopinathan, A., Keen, A., Shonberg, J., …Lane, J. R. (2019). Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole. ACS Chemical Biology, 14(8), 1780-1792. https://doi.org/10.1021/acschembio.9b00342

Partial agonists of the dopamine D2 receptor (D2R) have been developed to treat the symptoms of schizophrenia without causing the side effects elicited by antagonists. The receptor-ligand interactions that determine the intrinsic efficacy of such dru... Read More about Molecular Determinants of the Intrinsic Efficacy of the Antipsychotic Aripiprazole.

Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor (2019)
Journal Article
Fyfe, T. J., Kellam, B., Mistry, S. N., Scammells, P. J., Lane, J. R., & Capuano, B. (2019). Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor. European Journal of Medicinal Chemistry, 168, 474-490. https://doi.org/10.1016/j.ejmech.2019.01.061

We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like N... Read More about Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor.