Abstract
Synthesis and structure-activity relationship (SAR) studies on 5-trifluoromethylpyrido[4,3-d]pyrimidin-4(3H)-ones, a novel class of calcium receptor antagonists is described with particular emphasis on optimization of the pharmacokinetic/pharmacodynamic parameters required for a short duration of action compound. Orally-active compounds were identified which displayed the desired animal pharmacology (rapid and transient stimulation of parathyroid hormone) essential for bone anabolic effects.
MeSH terms
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Administration, Oral
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Anabolic Agents / administration & dosage
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Anabolic Agents / chemistry*
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Anabolic Agents / pharmacokinetics
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Animals
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Male
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Parathyroid Hormone / metabolism
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Pyrimidinones / administration & dosage
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Pyrimidinones / chemistry*
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Pyrimidinones / pharmacokinetics
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Rats
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Rats, Sprague-Dawley
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Receptors, Calcium-Sensing / antagonists & inhibitors*
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Receptors, Calcium-Sensing / metabolism
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Structure-Activity Relationship
Substances
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Anabolic Agents
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Parathyroid Hormone
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Pyrimidinones
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Receptors, Calcium-Sensing