Zwitterionic uracil derivatives as potent GnRH receptor antagonists with improved pharmaceutical properties.
A novel series of potent zwitterionic uracil GnRH antagonists were discovered that showed reduced liability for CYP3A4 enzyme inhibition.
Regan
Colin F
CF
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12780 El Camino Real, San Diego, CA 92130, USA.
Guo
Zhiqiang
Z
Chen
Yongsheng
Y
Huang
Charles Q
CQ
Chen
Mi
M
Jiang
Wanlong
W
Rueter
Jaimie K
JK
Coon
Timothy
T
Chen
Chen
C
Saunders
John
J
Brown
Michael S
MS
Betz
Steve F
SF
Struthers
R Scott
RS
Yang
Chun
C
Wen
Jenny
J
Madan
Ajay
A
Zhu
Yun-Fei
YF
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D051544:Cytochrome P-450 CYP3A / Q000737:chemistry*; D015195:Drug Design; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry; D006801:Humans; D007477:Ions; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry
D007477:Ions; D010455:Peptides; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D014498:Uracil; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human