An efficient and green synthesis of functionalized cyano pyridines has been achieved via montmorillonite K-10 mediated multi-component reaction in a chemo- and regioselective manner. The four-component reaction of β-keto ester, arylaldehyde, malononitrile and an alcohol provided a variety of pyridine derivatives and montmorillonite K-10 was found to be a reusable catalyst. The potential of this operationally simple methodology has been demonstrated in further structure elaboration of a compound synthesized via C-C bond forming reactions under Suzuki, Sonogashira and Heck conditions. Some of the cyano pyridines synthesized showed PDE4B inhibitory properties in vitro and good interactions with PDE4B protein in silico suggesting cyano pyridine scaffold as a potential template for the discovery of novel PDE4 inhibitors.