Abstract
To search for neutral sphingomyelinase inhibitors we designed and synthesized hydrolytically stable analogues of sphingomyelin. The novel compounds 8 and 9 which were replaced the phosphodiester moiety of sphingomyelin with the carbamate moiety showed inhibitory activity with an IC(50) value of micro M on neutral sphingomyelinase in rat brain microsomes. Compound 8i showed a selective neutral sphingomyelinase inhibitory activity.
MeSH terms
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Animals
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Brain / metabolism
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Carbamates / chemistry
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Carbamates / pharmacology
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Inhibitory Concentration 50
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Microsomes / enzymology
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Phosphodiesterase Inhibitors / chemical synthesis
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Phosphodiesterase Inhibitors / chemistry*
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Phosphodiesterase Inhibitors / pharmacology*
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Rats
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Sphingomyelin Phosphodiesterase / antagonists & inhibitors*
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Sphingomyelin Phosphodiesterase / metabolism
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Sphingomyelins / chemical synthesis
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Sphingomyelins / chemistry*
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Sphingomyelins / pharmacology*
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Structure-Activity Relationship
Substances
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Carbamates
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Phosphodiesterase Inhibitors
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Sphingomyelins
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Sphingomyelin Phosphodiesterase