Benzimidazole derivatives as novel nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Part 2: Benzimidazole-5-sulfonamides

Yingfu Li; Mikayo Kataoka; Miyuki Tatsuta; Kayo Yasoshima; Takeshi Yura; Klaus Urbahns; Atsushi Kiba; Noriyuki Yamamoto; Jang B Gupta; Kentaro Hashimoto

doi:10.1016/j.bmcl.2004.10.090

Benzimidazole derivatives as novel nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Part 2: Benzimidazole-5-sulfonamides

Bioorg Med Chem Lett. 2005 Feb 1;15(3):805-7. doi: 10.1016/j.bmcl.2004.10.090.

Authors

Yingfu Li¹, Mikayo Kataoka, Miyuki Tatsuta, Kayo Yasoshima, Takeshi Yura, Klaus Urbahns, Atsushi Kiba, Noriyuki Yamamoto, Jang B Gupta, Kentaro Hashimoto

Affiliation

¹ Department of Chemistry, Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto 619-0216, Japan.

PMID: 15664861
DOI: 10.1016/j.bmcl.2004.10.090

Abstract

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).

MeSH terms

Benzimidazoles / chemical synthesis*
Benzimidazoles / pharmacology*
Gonadotropin-Releasing Hormone / antagonists & inhibitors*
Humans
Inhibitory Concentration 50
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / pharmacology
Urea

Substances

Benzimidazoles
Sulfonamides
Gonadotropin-Releasing Hormone
Urea