Discovery of potent α1L-adrenoceptor agonists: Design and synthesis of bicyclic derivatives. Issue 16 (15th August 2015)

• Record Type: Journal Article
• Authors: Suzuki, Shinya; Okano, Tsubasa; Horiuchi, Rie; Hareyama, Nana; Amikura, Kazutoshi; Yamamoto, Naoyoshi; Yoshizawa, Yoshitaka; Yagi, Mai; Serizawa, Kanako; Hayashi, Ryoji
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 16(2015)
• Page Start: 3368
• Page End: 3372
• Publication Date: 2015-08-15
• Subjects: GROKJWIZNNIFHU-UHFFFAOYSA-N -- SLRPDPCBTCROEE-UHFFFAOYSA-N -- WTENIACMOBFYEM-UHFFFAOYSA-N -- COORKIPQLUGFRA-UHFFFAOYSA-N -- HSTAEZZQOHLNOM-UHFFFAOYSA-N -- QPXAZXHIRJCAJL-UHFFFAOYSA-N -- XEMJEEKINKETKM-UHFFFAOYSA-N -- NQXJCQGOKFNKHA-UHFFFAOYSA-N; CHO Chinese hamster ovary -- EC50 half maximal effective concentration -- DCE 1, 2-dichloroethane -- DMF dimethylformamide -- DMSO dimethyl sulfoxide -- NA noradrenaline -- NBS N-bromosuccinimide -- PMB 4-methoxybenzyl ether -- SUI stress urinary incontinence -- TosMIC toluenesulfonylmethyl isocyanide -- TFA trifluoroacetic acid -- THF tetrahydrofuran -- TMS trimethylsilyl; Drug discovery -- Adrenoceptor agonist -- Stress urinary incontinence; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.05.049
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We aimed to create a novel and potent α1L -adrenoceptor agonist because such agonists are possible drug candidates for stress urinary incontinence. We used ligand-based drug design and evaluated the α1L -adrenoceptor agonist activity of the designed compounds. Among them, tetrahydroquinoline derivative50 showed the most potent activity (ratio of noradrenaline half maximal effective concentration, 0.0028) and effectively induced contraction of rat bladder neck.