title: Design and synthesis of 4-alkynyl pyrazoles as inhibitors of PDE4: a practical access via Pd/C-Cu catalysis.
abstract: The design and synthesis of 4-alkynyl pyrazole derivatives has led to the identification of new class of PDE4 inhibitors. All these compounds were accessed for the first time via a facile Pd/C-CuI-PPh(3) mediated C-C bond forming reaction between an appropriate pyrazole iodide and various terminal alkynes. In vitro PDE4B inhibitory properties and molecular modeling studies of some of the compounds synthesized indicated that 4-alkynyl pyrazole could be a promising template for the discovery of novel PDE4 inhibitors.
authors.affiliation: Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad 500 046, India.
authors.forename: Dhilli Rao
authors.initials: DR
authors.lastname: Gorja
authors.forename: K
authors.initials: K
authors.lastname: Shiva Kumar
authors.forename: Ajit
authors.initials: A
authors.lastname: Kandale
authors.forename: Chandana Lakshmi T
authors.initials: CL
authors.lastname: Meda
authors.forename: Kishore V L
authors.initials: KV
authors.lastname: Parsa
authors.forename: K
authors.initials: K
authors.lastname: Mukkanti
authors.forename: Manojit
authors.initials: M
authors.lastname: Pal
mesh_terms: D000480:Alkynes / Q000737:chemistry* / Q000494:pharmacology; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002384:Catalysis; D003198:Computer Simulation; D003300:Copper / Q000737:chemistry; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D007454:Iodides / Q000737:chemistry; D008958:Models, Molecular; D010165:Palladium / Q000737:chemistry; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology
chemical_list: D000480:Alkynes; D000928:Antidepressive Agents; D007454:Iodides; D058988:Phosphodiesterase 4 Inhibitors; D011720:Pyrazoles; D010165:Palladium; D003300:Copper; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram