title: Discovery and structure-activity relationships of a novel series of benzopyran-based K(ATP) openers for urge urinary incontinence.
abstract: A novel series of benzopyran derivatives were synthesized and evaluated as K(ATP) channel openers. Structure-activity relationships were investigated around 4-position of the benzopyran nucleus. Optimization of 4-substituent with some heterocyclic rings led to compound 13b bearing a benzo[d]isoxazol-3-one moiety as a potent and selective K(ATP) channel opener in vitro. In two anesthetized rat models of myogenic bladder overactivity, compound 13b was found to inhibit spontaneous bladder contractions.
authors.affiliation: Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, LLC, 665 Stockton Drive, Exton, PA 19341, USA. xzhang5@prdus.jnj.com
authors.forename: Xuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Qiu
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Li
authors.forename: Sheela
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Morgan
authors.initials: M
authors.lastname: Woods
authors.forename: Patricia
authors.initials: P
authors.lastname: Kraft
authors.forename: Scott G
authors.initials: SG
authors.lastname: Lundeen
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sui
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D004195:Disease Models, Animal; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists*; D051381:Rats; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D053202:Urinary Incontinence, Urge / Q000188:drug therapy*
chemical_list: D001578:Benzopyrans; D024661:Potassium Channels, Inwardly Rectifying