A new class of potent nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists: design and synthesis of 2-phenylimidazo[1,2-a]pyrimidin-5-ones.
The design and synthesis of a new class of nonpeptide luteinizing hormone-releasing hormone (LHRH) receptor antagonists, the 2-phenylimidazo[1,2-a]pyrimidin-5-ones, is reported. Among compounds described in this study, we identified the potent antagonist 15b with nanomolar in vitro functional antagonism. The result might suggest that the heterocyclic 5-6-ring system possessing a pendant phenyl group attached to the five-membered ring is the important structural feature for a scaffold of small molecule LHRH antagonists.
Sasaki
Satoshi
S
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., 10 Wadai, Tsukuba, 300-4293, Ibaraki, Japan. sasaki_satoshi@takeda.co.jp
Imaeda
Toshihiro
T
Hayase
Yoji
Y
Shimizu
Yoshiaki
Y
Kasai
Shizuo
S
Cho
Nobuo
N
Harada
Masataka
M
Suzuki
Nobuhiro
N
Furuya
Shuichi
S
Fujino
Masahiko
M
D001667:Binding, Competitive / Q000187:drug effects; D015195:Drug Design; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011966:Receptors, LHRH / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
D011744:Pyrimidinones; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone