5-arylamino-1,2,4-triazin-6(1H)-one CRF1 receptor antagonists.
A series of 5-arylamino-1,2,4-triazin-6(1H)-ones was synthesized and evaluated as antagonists at the corticotropin releasing factor receptor. Formation of CYP-mediated oxidative reactive metabolites previously observed in a related N(3)-phenylpyrazinone structure was minimized by incorporation of the additional ring nitrogen found in the triazinones.
Schmitz
William D
WD
Neuroscience Discovery Chemistry, Bristol-Myers Squibb Research and Development, Wallingford, CT 06492, USA. william.schmitz@bms.com
Brenner
Allison B
AB
Bronson
Joanne J
JJ
Ditta
Jonathan L
JL
Griffin
Corrine R
CR
Li
Yu-Wen
YW
Lodge
Nicholas J
NJ
Molski
Thaddeus F
TF
Olson
Richard E
RE
Zhuo
Xiaoliang
X
Macor
John E
JE
D000818:Animals; D006801:Humans; D020128:Inhibitory Concentration 50; D010084:Oxidation-Reduction; D011719:Pyrazines; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D000099052:CRF Receptor, Type 1
D011719:Pyrazines; D018019:Receptors, Corticotropin-Releasing Hormone; D014227:Triazines; D000099052:CRF Receptor, Type 1