title: Design and synthesis of 3,5-disubstituted-1,2,4-oxadiazoles as potent inhibitors of phosphodiesterase4b2.
abstract: 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 IC(50)  = 5.28 μm). 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.
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani, Rajasthan, India. dalipk@bits-pilani.ac.in
authors.forename: Dalip
authors.initials: D
authors.lastname: Kumar
authors.forename: Gautam
authors.initials: G
authors.lastname: Patel
authors.forename: Lalitha
authors.initials: L
authors.lastname: Vijayakrishnan
authors.forename: Sunanda G
authors.initials: SG
authors.lastname: Dastidar
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ray
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008958:Models, Molecular; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D010069:Oxadiazoles; D058988:Phosphodiesterase 4 Inhibitors; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4