Dihydropyrimidinone-isatin hybrids as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
A novel series of substituted N-(2-(2,3-dioxoindolin-1-yl)acetyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide was designed, synthesized and evaluated for in vitro Reverse Transcriptase (RT) inhibitory activity. This series is a combination of peculiar structural features from leading scaffolds of [(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and oxyindole. In vitro screening led to identification of two hybrids (9c and 9d) possessing higher RT inhibitory activity than the standard rilpivirine. Docking study was performed to study the binding orientations of synthesized hybrids towards RT enzyme.
Jaipur National University, Jagatpura, Jaipur, India; Sinhgad Institute of Pharmacy, Narhe, Pune, India. Electronic address: titikshdevale@gmail.com.
Titiksh L
TL
Devale
National Chemical Laboratory (NCL), Pune, India. Electronic address: jkparikh1@gmail.com.
Jignesh
J
Parikh
Sinhgad Institute of Pharmacy, Narhe, Pune, India. Electronic address: miniyarpankaj@gmail.com.
Pankaj
P
Miniyar
Jaipur National University, Jagatpura, Jaipur, India. Electronic address: sharmapankaj_73@yahoo.co.in.
Pankaj
P
Sharma
Jaipur National University, Jagatpura, Jaipur, India. Electronic address: jnupharmacyresearch@gmail.com.
Birendra
B
Shrivastava
Faculty of Pharmacy, The Maharaja Sayajirao University of Baroda, Vadodara, India. Electronic address: prashant_murumkar@yahoo.com.
Prashant
P
Murumkar
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007510:Isatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D019380:Anti-HIV Agents; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors; D007510:Isatin; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
G-score; Hybrid approach; Microwave assisted synthesis; Molecular docking; NNRTI