title: Novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one derivatives as potential inhibitors of chorismate mutase.
abstract: A series of novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one (DHPM) derivatives were designed, synthesized and evaluated in vitro as potential inhibitors of chorismate mutase (CM). All these compounds were prepared via a multi-component reaction (MCR) involving sequential I2-mediated Biginelli reaction followed by Cu-free Sonogashira coupling. Some of them showed promising inhibitory activities when tested at 30μM. One compound showed dose dependent inhibition of CM with IC50 value of 14.76±0.54μM indicating o-alkynylphenyl substituted DHPM as a new scaffold for the discovery of promising inhibitors of CM.
authors.affiliation: Center for Pharmaceutical Sciences, Institute of Science and Technology, Jawaharlal Nehru Technological University, Hyderabad 500 085, Andhra Pradesh, India.
authors.forename: V
authors.initials: V
authors.lastname: Mallikarjuna Rao
authors.forename: P
authors.initials: P
authors.lastname: Mahesh Kumar
authors.forename: D
authors.initials: D
authors.lastname: Rambabu
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Kapavarapu
authors.forename: S
authors.initials: S
authors.lastname: Shobha Rani
authors.forename: Parimal
authors.initials: P
authors.lastname: Misra
authors.forename: Manojit
authors.initials: M
authors.lastname: Pal
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D002826:Chorismate Mutase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C507290:3,4-dihydropyridopyrimidin-2(1H)-one; D000480:Alkynes; D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D002826:Chorismate Mutase
keywords: Alkyne; Chorismate mutase; Iodine; Palladium; Pyrimidinone