title: 4H-Thieno[3,2-c]chromene based inhibitors of Notum Pectinacetylesterase.
abstract: A group of small molecule thienochromenes inhibitors of Notum Pectinacetylesterase are described. We developed SAR on three series based on carbon, oxygen and sulfur replacement of the 5-position. In each series, highly potent Notum Pectinacetylesterase inhibitors were identified.
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Han
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Pabba
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Barbosa
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Ross
authors.initials: R
authors.lastname: Mabon
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Healy
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Gardyan
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Terranova
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Brommage
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
authors.forename: Andrea Y
authors.initials: AY
authors.lastname: Thompson
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
authors.forename: James M
authors.initials: JM
authors.lastname: Schmidt
authors.affiliation: Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
authors.forename: Alan G E
authors.initials: AG
authors.lastname: Wilson
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Xu
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States. Electronic address: james.tarver2@gmail.com.
authors.forename: James E
authors.initials: JE
authors.lastname: Tarver
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Carson
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004950:Esterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005269:Femur / Q000502:physiology; D006207:Half-Life; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D010024:Osteoporosis / Q000188:drug therapy / Q000503:physiopathology; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D001578:Benzopyrans; D004791:Enzyme Inhibitors; D004950:Esterases; C000596390:Notum protein, human
keywords: Femur cortical bone thickness; Notum Pectinacetylesterase; Osteroporosis; SAR; Thienochromene