Abstract
The first enantioselective synthesis of (D)-2-tert-butoxycarbonylamino-5,5-difluoro-5-phenyl-pentanoic acid 3 was achieved. The incorporation of the titled compound into growth hormone secretagogue (GHS) compounds resulted in new analogs 10 and 16, both of which had significantly increased in vitro potency. The compound 10 also showed improved in vivo efficacy as well as pharmacokinetic properties in rat models.
MeSH terms
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Administration, Oral
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Animals
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Area Under Curve
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Biological Availability
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Carbamates / pharmacology
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Chemistry, Pharmaceutical / methods
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Drug Design
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Growth Hormone / metabolism*
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Indoles / pharmacology
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Models, Chemical
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Pentanoic Acids / chemical synthesis*
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Pentanoic Acids / chemistry
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Pentanoic Acids / pharmacology
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Peptide Hormones / chemistry
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Rats
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Spiro Compounds / pharmacology
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Stereoisomerism
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Tetrazoles / pharmacology
Substances
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(D)-2-tert-butoxycarbonylamino-5,5-difluoro-5-phenyl-pentanoic acid
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4-(hydroxybutyl)carbamic acid 2-(5-(1-(2-amino-2-methylpropionylamino)-2-benzyloxyethyl)tetrazol-1-yl)ethyl ester
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Carbamates
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Indoles
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Pentanoic Acids
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Peptide Hormones
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Spiro Compounds
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Tetrazoles
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Growth Hormone
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ibutamoren mesylate