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.
Keywords:
Femur cortical bone thickness; Notum Pectinacetylesterase; Osteoporosis; SAR; Thienopyrimidine.
Copyright © 2016 Elsevier Ltd. All rights reserved.
MeSH terms
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Animals
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Esterases / antagonists & inhibitors*
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Esterases / metabolism
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Femur / anatomy & histology
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Femur / drug effects*
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Femur / growth & development
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Humans
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Mice
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Molecular Structure
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Osteogenesis / drug effects*
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Pyrimidines / chemical synthesis
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Structure-Activity Relationship
Substances
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Enzyme Inhibitors
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Pyrimidines
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thienopyrimidine
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Esterases
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Notum protein, human
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Notum protein, mouse