Abstract
In the present study, we have synthesized and tested novel pyridopyrrolo- and pyrrolobenzoxazepine derivatives, as novel and selective peripheral type benzodiazepine receptor (PBR) ligands, and their ability to modulate steroid biosynthesis has been investigated. A subset of new ligands bind the PBR (rat brain and testis) with picomolar affinity, representing the most potent ligands that have been identified to date, and elicited effects on endogenous rate of steroidogenesis in MA10 Leydig cells, having similar potency and effect as PK11195. Several compounds, differently substituted at C-7, were used as molecular yardsticks to probe the spatial dimension of the lipophilic pocket L4 in the receptor binding site.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Azepines / chemical synthesis*
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Azepines / chemistry
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Azepines / pharmacology
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Binding Sites
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Binding, Competitive
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Cell Line
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Cerebral Cortex / metabolism
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Hydrogen Bonding
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In Vitro Techniques
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Ligands
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Male
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Mitochondria / drug effects
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Mitochondria / metabolism
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Molecular Probes / chemical synthesis*
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Molecular Probes / chemistry
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Molecular Probes / pharmacology
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Oxazepines / chemical synthesis
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Oxazepines / chemistry
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Oxazepines / pharmacology
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Progesterone / biosynthesis
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Rats
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Receptors, GABA-A / drug effects*
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Steroids / biosynthesis*
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Structure-Activity Relationship
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Testis / cytology
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Testis / ultrastructure
Substances
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Azepines
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Ligands
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Molecular Probes
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Oxazepines
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Receptors, GABA-A
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Steroids
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Progesterone