title: Pd-mediated functionalization of polysubstituted pyrroles: their evaluation as potential inhibitors of PDE4.
abstract: Novel polysubstituted pyrroles have been designed and accessed via a one-pot multicomponent reaction followed by Pd-mediated C-C bond forming reactions. All the compounds synthesized were tested for their PDE4B inhibitory properties in vitro and two of them obtained via Heck reaction showed significant inhibition. The docking results suggested that these alkenyl derivatives containing ester moiety interact well with the PDE4B protein in silico where the ester carbonyl oxygen played a key role. The pyrrole framework presented here could be a new template for the identification of small molecule based novel inhibitors of PDE4. The single crystal X-ray data of a representative compound is presented.
authors.affiliation: Custom Pharmaceutical Services, Dr. Reddy's Laboratories Limited, Bollaram Road Miyapur, Hyderabad 500049, India.
authors.forename: T
authors.initials: T
authors.lastname: Bhaskar Kumar
authors.forename: Ch
authors.initials: Ch
authors.lastname: Sumanth
authors.forename: S
authors.initials: S
authors.lastname: Vaishaly
authors.forename: M
authors.initials: M
authors.lastname: Srinivasa Rao
authors.forename: K B
authors.initials: KB
authors.lastname: Chandra Sekhar
authors.forename: Chandana Lakshmi T
authors.initials: CL
authors.lastname: Meda
authors.forename: Ajit
authors.initials: A
authors.lastname: Kandale
authors.forename: D
authors.initials: D
authors.lastname: Rambabu
authors.forename: G
authors.initials: G
authors.lastname: Rama Krishna
authors.forename: C
authors.initials: C
authors.lastname: Malla Reddy
authors.forename: K
authors.initials: K
authors.lastname: Shiva Kumar
authors.forename: Kishore V L
authors.initials: KV
authors.lastname: Parsa
authors.forename: Manojit
authors.initials: M
authors.lastname: Pal
mesh_terms: D000818:Animals; D002384:Catalysis; D002460:Cell Line; D018360:Crystallography, X-Ray; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D008958:Models, Molecular; D010165:Palladium / Q000737:chemistry; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D058988:Phosphodiesterase 4 Inhibitors; D011758:Pyrroles; D010165:Palladium; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4