%0 Journal Article %A Singh, Prachi %A Shrestha, Stal %A Cortes-Salva, Michelle Y. %A Jenko, Kimberly J. %A Zoghbi, Sami S. %A Morse, Cheryl L. %A Innis, Robert B. %A Pike, Victor W. %D 2018 %T 3‑Substituted 1,5-Diaryl‑1H‑1,2,4-triazoles as Prospective PET Radioligands for Imaging Brain COX‑1 in Monkey. Part 1: Synthesis and Pharmacology %U https://acs.figshare.com/articles/journal_contribution/3_Substituted_1_5-Diaryl_1_i_H_i_1_2_4-triazoles_as_Prospective_PET_Radioligands_for_Imaging_Brain_COX_1_in_Monkey_Part_1_Synthesis_and_Pharmacology/6508895 %R 10.1021/acschemneuro.8b00102.s001 %2 https://acs.figshare.com/ndownloader/files/11973479 %K PET radioligands %K drug development %K 3- methoxy %K 18 F %K direct-acting positron emission tomography %K neuroinflammatory states %K imaging COX %K carbon -11 %K Pharmacology Cyclooxygenase %K proinflammatory thromboxanes %K 3- fluoromethoxy substituent %K fluorine -18 %K triazole %K 109.8 min %K radioligand development %K hydroxy precursors %K Prospective PET Radioligands %K carboxyl group %K 20.4 min %X Cyclooxygenase-1 (COX-1) is a key enzyme in the biosynthesis of proinflammatory thromboxanes and prostaglandins and is found in glial and neuronal cells within brain. COX-1 expression is implicated in numerous neuroinflammatory states. We aim to find a direct-acting positron emission tomography (PET) radioligand for imaging COX-1 in human brain as a potential biomarker of neuroinflammation and for serving as a tool in drug development. Seventeen 3-substituted 1,5-diaryl-1H-1,2,4-triazoles were prepared as prospective COX-1 PET radioligands. From this set, three 1,5-(4-methoxyphenyl)-1H-1,2,4-triazoles, carrying a 3-methoxy (5), 3-(1,1,1-trifluoroethoxy) (20), or 3-fluoromethoxy substituent (6), were selected for radioligand development, based mainly on their high affinities and selectivities for inhibiting human COX-1, absence of carboxyl group, moderate computed lipophilicities, and scope for radiolabeling with carbon-11 (t1/2 = 20.4 min) or fluorine-18 (t1/2 = 109.8 min). Methods were developed for producing [11C]­5, [11C]­20, and [d2-18F]6 from hydroxy precursors in a form ready for intravenous injection for prospective evaluation in monkey with PET. %I ACS Publications