Benzimidazole derivatives as novel nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Part 2: Benzimidazole-5-sulfonamides.
The 2-cyclopropyl substituted benzimidazole 2 has been used as a starting point for further optimization of an LHRH antagonist series. SAR studies revealed that a tert-butyl urea fragment connected through a simple carbon chain would improve activity. Further modification of the benzylsulfonamide moiety led to the discovery of 23 (IC(50): 4.2 nM).
Li
Yingfu
Y
Department of Chemistry, Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto 619-0216, Japan.
Kataoka
Mikayo
M
Tatsuta
Miyuki
M
Yasoshima
Kayo
K
Yura
Takeshi
T
Urbahns
Klaus
K
Kiba
Atsushi
A
Yamamoto
Noriyuki
N
Gupta
Jang B
JB
Hashimoto
Kentaro
K
D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology; D014508:Urea
D001562:Benzimidazoles; D013449:Sulfonamides; D007987:Gonadotropin-Releasing Hormone; D014508:Urea