- Design and Synthesis of 3,5-Disubstituted-1,2,4-Oxadiazoles as Potent Inhibitors of Phosphodiesterase4B2
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A series of 3,5-disubstituted-1,2,4-oxadiazoles has been prepared and evaluated for phosphodiesterase inhibition (PDE4B2). Among the prepared 3,5-disubstituted-1,2,4-oxadiazoles, compound 9a is the most potent inhibitor (PDE4B2 IC50=5.28μm). Structure-activity relationship studies of 3,5-disubstituted-1,2,4-oxadiazoles revealed that substituents 3-cyclopentyloxy-4-methoxyphenyl group at 3-position and cyclic ring bearing heteroatoms at 5-position are important for activity. Molecular modeling study of the 3,5-disubstituted-1,2,4-oxadiazoles with PDE4B has shown similar interactions of 3-cyclopentyloxy-4-methoxyphenyl group; however, heteroatom ring is slightly deviating when compared to Piclamilast. 3-(3-Cyclopentyloxy-4-methoxyphenyl)-5-(piperidin-4-yl)-1,2,4-oxadiazole (9a) exhibited good analgesic and antiinflammatory activities in formalin-induced pain in mice and carrageenan-induced paw edema model in rat.
- Kumar, Dalip,Patel, Gautam,Vijayakrishnan, Lalitha,Dastidar, Sunanda G.,Ray, Abhijit
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scheme or table
p. 810 - 818
(2012/06/18)
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- 6-phenyltetrahydro-1,3-oxazin-2-one derivative and pharmaceutical composition containing the same
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A 6-phenyltetrahydro-1,3-oxazin-2-one derivative having the formula (I): wherein, R1is an unsubstituted or substituted C1to C8alkyl group; an unsubstituted or substituted C3to C7cycloalkyl group;, etc
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- COMPOUNDS CONTAINING PHENYL LINKED TO ARYL OR HETEROARYL BY AN ALIPHATIC- OR HETEROATOM-CONTAINING LINKING GROUP
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This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase
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- Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic-or heteroatom-containing linking group
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This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.
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