Synthesis and theoretical studies on energetics of novel N- and O- perfluoroalkyl triazole tagged thienopyrimidines--their potential as adenosine receptor ligands.
A series of novel N- and O- perfluoroalkyl triazole tagged thienopyrimidines 6a-c and 7a-d was synthesized in two steps from thienopyrimidin-4-ones 2 through O- and N-propargylated regioisomers 3a-i and 4a-i respectively. Compound 2 was reacted with propargyl bromide to form O- and N-propargylated regioisomers 3 and 4 in definite proportions. Each regioisomer was separated and independently subjected to [3+2] cycloaddition using perfluoroalkyl azides through Click reaction under Sharpless conditions and obtained exclusively anti product in each case. The formation of two regioisomers in the first step and single anti addition product in the next step could be explained based on computational studies carried out at B3LYP/6-31G(d) level of theory. Results of Fukui function indices at the reactive centers are in accordance with the observations. On evaluation of the synthesized molecules for their binding affinities towards adenosine receptors, 4d and 4f were found to be selective to A1 over A2A receptors.
Sirisha
B
B
Fluoroorganic Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India.
Narsaiah
B
B
Yakaiah
T
T
Gayatri
G
G
Sastry
G Narahari
GN
Prasad
M Raghu
MR
Rao
A Raghuram
AR
D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D003500:Cyclization; D015195:Drug Design; D008024:Ligands; D008958:Models, Molecular; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014230:Triazoles / Q000737:chemistry*
D008024:Ligands; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D014230:Triazoles; C476003:thienopyrimidine