Abstract
Melanin-concentrating hormone receptor antagonists containing thieno- and a benzopyridazinone cores were designed and tested as potential anorectic agents. These ligands showed high affinity for the receptor, potent functional activity in vitro, and good oral bioavailabilty in rats. The thiophene analogue exhibited low iv clearance, long half-life, and high brain penetration. In obese rats, the thienopyridazinone demonstrated a dose-dependent reduction in feeding and body weight with doses between 1 and 10 mg kg-1.
MeSH terms
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Animals
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Appetite Depressants / chemical synthesis*
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Appetite Depressants / pharmacokinetics
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Appetite Depressants / pharmacology
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Biological Availability
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Body Weight / drug effects
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Brain / metabolism
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Eating / drug effects
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Half-Life
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Male
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Obesity / drug therapy
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Permeability
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry
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Pyridazines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Somatostatin / antagonists & inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
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Thiophenes / chemical synthesis*
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Thiophenes / pharmacokinetics
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Thiophenes / pharmacology
Substances
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Appetite Depressants
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MCHR1 protein, rat
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Pyridazines
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Receptors, Somatostatin
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Thiophenes
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pyridazine