Heteroatom-linked indanylpyrazines are corticotropin releasing factor type-1 receptor antagonists.
Low nanomolar corticotropin releasing factor type-1 (CRF(1)) receptor antagonists containing unique indanylamines were identified from the heteroatom-linked pyrazine chemotype. The most potent indanylpyrazine had a K(i)=11+/-1 nM. The oxygen-linked pyrazinyl derivatives were prepared through a copper-catalyzed coupling of a pyridinone to a bromo- or iodopyrazine.
Corbett
Jeffrey W
JW
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. jeffrey.w.corbett@pfizer.com
Rauckhorst
Mark R
MR
Qian
Fang
F
Hoffman
Robert L
RL
Knauer
Christopher S
CS
Fitzgerald
Lawrence W
LW
D001667:Binding, Competitive / Q000187:drug effects; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007189:Indans / Q000737:chemistry*; D015394:Molecular Structure; D011719:Pyrazines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011728:Pyridones / Q000737:chemistry; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D000099052:CRF Receptor, Type 1
D007189:Indans; D011719:Pyrazines; D011728:Pyridones; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003300:Copper