Abstract
Gonadotropin releasing hormone (GnRH) plays an important role in the biology of reproduction. The use of GnRH receptor antagonists has been reported in the literature for the treatment of breast, ovarian, and prostate cancers. In this article, we report the synthesis, in vitro characterization, pharmacokinetics, and pharmacodynamics of an orally bioavailable, potent, small molecule GnRH receptor antagonist N-{4,6-dimethoxy-2-[(3-morpholin-4-ylpropyl)amino]pyrimidin-5-yl}-5-[3,3,6-trimthyl-2,3-dihydro-1H-inden-5-yl)oxy]-2-furamide (compound 1).
MeSH terms
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Administration, Oral
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Animals
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Biological Availability
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Humans
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In Vitro Techniques
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Indenes / chemical synthesis*
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Indenes / chemistry
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Indenes / pharmacology
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Inositol Phosphates / biosynthesis
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Male
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Morpholines / chemical synthesis*
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Morpholines / chemistry
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Morpholines / pharmacology
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Orchiectomy
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Pituitary Gland / metabolism
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
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Receptors, LHRH / antagonists & inhibitors*
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
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Testis / drug effects
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Testis / metabolism
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Testosterone / antagonists & inhibitors
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Testosterone / metabolism
Substances
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Indenes
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Inositol Phosphates
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Morpholines
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N-(4,6-dimethoxy-2-((3-morpholin-4-ylpropyl)amino)pyrimidin-5-yl)-5-(3,3,6-trimethyl-2,3-dihydro-1H-inden-5-yloxy)-2-furamide
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Pyrimidines
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Receptors, LHRH
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Recombinant Proteins
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Testosterone