Abstract
A focused SAR study around the previously reported selective 5-HT(7) receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A.
MeSH terms
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Animals
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Blood-Brain Barrier
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Heterocyclic Compounds
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Indoles
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Phenols / chemical synthesis
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Phenols / pharmacokinetics*
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Phenols / pharmacology
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Protein Binding
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Pyrrolidines / chemical synthesis
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Pyrrolidines / pharmacokinetics*
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Pyrrolidines / pharmacology
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Rats
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Receptors, Serotonin / chemistry*
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Serotonin Antagonists / chemical synthesis*
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Serotonin Antagonists / pharmacokinetics*
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Serotonin Antagonists / pharmacology
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Structure-Activity Relationship
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Sulfonamides / pharmacokinetics
Substances
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Heterocyclic Compounds
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Indoles
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Phenols
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Pyrrolidines
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Receptors, Serotonin
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SB 269970
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SB-656104-A
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Serotonin Antagonists
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Sulfonamides
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serotonin 7 receptor