%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