Synthesis of benzoylpyrimidines as antagonists of the corticotropin-releasing factor-1 receptor.
A series of benzoylpyrimidines derived from the anilinepyrimidine CRF(1) antagonists were synthesized. Several synthetic routes were developed to explore the SAR of this series of compounds. Compounds such as 8d (K(i) = 15 nM) exhibited high binding affinities at the human CRF(1) receptor.
Webb
Thomas R
TR
Department of Medicinal Chemistry and Department of Pharmacology, Neurocrine Bioscience, Inc., 10555 Science Center Drive, San Diego, CA 92121, USA.
Moran
Terry
T
Huang
Charles Q
CQ
McCarthy
James R
JR
Grigoriadis
Dimitri E
DE
Chen
Chen
C
D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003001:Cloning, Molecular; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D000099052:CRF Receptor, Type 1
D001565:Benzoates; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1