title: Stimulation of cortical bone formation with thienopyrimidine based inhibitors of Notum Pectinacetylesterase.
abstract: A group of small molecule thienopyrimidine inhibitors of Notum Pectinacetylesterase are described. We explored both 2-((5,6-thieno[2,3-d]pyrimidin-4-yl)thio)acetic acids and 2-((6,7-thieno[3,2-d]pyrimidin-4-yl)thio)acetic acids. In both series, highly potent, orally active Notum Pectinacetylesterase inhibitors were identified.
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: 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: Qiang
authors.initials: Q
authors.lastname: Han
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, 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: AGE
authors.lastname: Wilson
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: Lexicon Pharmaceuticals, 350 Carter Road, Princeton, NJ 08540, United States.
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Lombardo
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; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004950:Esterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010012:Osteogenesis / Q000187:drug effects*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011743:Pyrimidines; C476003:thienopyrimidine; D004950:Esterases; C000596390:Notum protein, human; C000611122:Notum protein, mouse
keywords: Femur cortical bone thickness; Notum Pectinacetylesterase; Osteoporosis; SAR; Thienopyrimidine