Comfort A Boateng, Ashley N Nilson, Rebekah Placide, Mimi L Pham, Franziska M Jakobs, Noelia Boldizsar, Scot McIntosh, Leia S Stallings, Ivana V Korankyi, Shreya Kelshikar, Nisha Shah, Diandra Panasis, Abigail Muccilli, Maria Ladik, Brianna Maslonka, Connor McBride, Moises Ximello Sanchez, Ebrar Akca, Mohammad Alkhatib, Julianna Saez, Catherine Nguyen, Emily Kurtyan, Jacquelyn DePierro, Raymond Crowthers, Dylan Brunt, Alessandro Bonifazi, Amy Hauck Newman, Rana Rais, Barbara S Slusher, R Benjamin Free, David R Sibley, Kent D Stewart, Chun Wu, Scott E Hemby, Thomas M Keck
Pharmacological targeting of the dopamine D4 receptor (D4 R)─expressed in brain regions that control cognition, attention, and decision-making─could be useful for several neuropsychiatric disorders including substance use disorders (SUDs). This study focused on the synthesis and evaluation of a novel series of benzothiazole analogues designed to target D4 R. We identified several compounds with high D4 R binding affinity ( Ki ≤ 6.9 nM) and >91-fold selectivity over other D2 -like receptors (D2 R, D3 R) with diverse partial agonist and antagonist profiles...
August 30, 2023: Journal of Medicinal Chemistry