Abstract
2-Amino-4-azaindoles have been identified as a structurally novel class of BK(Ca) channel openers. Their synthesis from 2-chloro-3-nitropyridine is described together with their in vitro properties assessed by 86Rb(+) efflux and whole-cell patch-clamp assays using HEK293 cells stably transfected with the BK(Ca) alpha subunit. In vitro functional characterization of BK(Ca) channel opening activity was also assessed by measurement of relaxation of smooth muscle tissue strips obtained from Landrace pig bladders. The preliminary SAR data indicate the importance of steric bulk around the 2-amino substituent.
MeSH terms
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Amines / chemical synthesis*
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Amines / chemistry
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Amines / pharmacology*
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Animals
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Aza Compounds / chemical synthesis
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Aza Compounds / chemistry
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Aza Compounds / pharmacology
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Calcium / metabolism
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Cell Line
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Humans
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In Vitro Techniques
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Indoles / chemical synthesis*
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Indoles / chemistry
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Indoles / pharmacology*
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Muscle Relaxation / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Potassium Channels, Calcium-Activated / drug effects*
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Potassium Channels, Calcium-Activated / metabolism
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Structure-Activity Relationship
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Swine
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Transfection
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Urinary Bladder / drug effects*
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Urinary Bladder / metabolism
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Urinary Bladder Diseases / drug therapy
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Urination Disorders / drug therapy
Substances
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Amines
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Aza Compounds
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Indoles
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Potassium Channels, Calcium-Activated
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Calcium