Montmorillonite K-10 mediated green synthesis of cyano pyridines: Their evaluation as potential inhibitors of PDE4.
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.
Custom Pharmaceutical Services, Dr. Reddy's Laboratories Limited, Bollaram Road Miyapur, Hyderabad 500 049, India.
T
T
Ram Reddy
G
G
Rajeshwar Reddy
L
L
Srinivasula Reddy
Subbarao
S
Jammula
Y
Y
Lingappa
Ravikumar
R
Kapavarapu
Chandana Lakshmi T
CL
Meda
Kishore V L
KV
Parsa
Manojit
M
Pal
D001546:Bentonite / Q000737:chemistry; D002384:Catalysis; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D055772:Green Chemistry Technology / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D058988:Phosphodiesterase 4 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared
D058988:Phosphodiesterase 4 Inhibitors; D011725:Pyridines; C503188:montmorillonite K-10; D001546:Bentonite; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4