Synthesis and biological activity of fluoro-substituted pyrrolo[2,3-d]pyrimidines: the development of potential positron emission tomography imaging agents for the corticotropin-releasing hormone type 1 receptor.
A series of fluoro-substituted 4-(dialkylamino)pyrrolo[2,3-d]pyrimidines was synthesized and their binding affinity for corticotropin-releasing hormone type 1 receptor (CRHR1) was investigated. Compounds 11a and 11b possessed very high CRHR1 affinity (Ki=3.5, 0.91 nM, respectively). They are promising candidates for the development of 18F-containing nonpeptide PET radioligands for CRHR1.
Hsin
L W
LW
Laboratory of Medicinal Chemistry, NIDDK, NIH, Bethesda, MD 20892, USA.
Webster
E L
EL
Chrousos
G P
GP
Gold
P W
PW
Eckelman
W C
WC
Contoreggi
C
C
Rice
K C
KC
D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D003287:Contrast Media / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D005461:Fluorine / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry; D011869:Radioligand Assay; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D003287:Contrast Media; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D005461:Fluorine