Abstract
Optimisation of urea (5), identified from high throughput screening and subsequent array chemistry, has resulted in the identification of pyridine carboxamide (33) which is a potent motilin receptor agonist possessing favourable physicochemical and ADME profiles. Compound (33) has demonstrated prokinetic-like activity both in vitro and in vivo in the rabbit and therefore represents a promising novel small molecule motilin receptor agonist for further evaluation as a gastroprokinetic agent.
MeSH terms
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Animals
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Carbon / chemistry*
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Chemistry, Pharmaceutical / methods
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Drug Design
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Gastrins / chemistry
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Humans
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Inhibitory Concentration 50
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Kinetics
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Models, Chemical
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Pyridines / chemical synthesis
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Pyridines / chemistry*
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Pyridines / pharmacology
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Rabbits
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Rats
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Receptors, Gastrointestinal Hormone / agonists*
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Receptors, Gastrointestinal Hormone / chemistry
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Receptors, Neuropeptide / agonists*
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Receptors, Neuropeptide / chemistry
Substances
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GSK326416
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Gastrins
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Pyridines
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Receptors, Gastrointestinal Hormone
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Receptors, Neuropeptide
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motilin receptor
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Carbon