Synthesis and evaluation of 2-pyridylbenzothiazole, 2-pyridylbenzoxazole and 2-pyridylbenzofuran derivatives as 11C-PET imaging agents for beta-amyloid plaques.
The syntheses and SAR of new series of beta-amyloid binding agents are reported. The effort to optimize signal-to-background ratios for these ligands are described. Compounds 8, 21 and 30 displayed desirable lipophilicity and pharmacokinetic properties. Compounds 8 and 21 were evaluated with in vitro autoradiographic studies and in vivo in APP/PS1 transgenic mice. It is shown that it was possible to increase the signal-to-background ratios compared to PIB 1, as demonstrated by compounds 8 and 21.
Swahn
Britt-Marie
BM
Department of Medicinal Chemistry, AstraZeneca R&D Södertälje, Södertälje, Sweden. britt-marie.swahn@astrazeneca.com
Wensbo
David
D
Sandell
Johan
J
Sohn
Daniel
D
Slivo
Can
C
Pyring
David
D
Malmström
Jonas
J
Arzel
Erwan
E
Vallin
Michaela
M
Bergh
Margareta
M
Jeppsson
Fredrik
F
Johnson
Allan E
AE
Juréus
Anders
A
Neelissen
Jan
J
Svensson
Samuel
S
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D006207:Half-Life; D051379:Mice; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D001572:Benzofurans; D052160:Benzothiazoles; D001583:Benzoxazoles; D002250:Carbon Radioisotopes