89181-79-3Relevant academic research and scientific papers
A facile and novel synthesis of N2-, C6-substituted pyrazolo[3,4- d ]pyrimidine-4 carboxylate derivatives as adenosine receptor antagonists
Venkatesan,Paira,Cheong,Federico,Klotz,Spalluto,Pastorin
, p. 784 - 798 (2015/02/05)
An efficient synthetic procedure was adopted to synthesize a series of new molecules containing the pyrazolo[3,4-d]pyrimidine (PP) scaffold, which have been evaluated as promising human adenosine receptor (AR) antagonists. The effect of substitutions at t
Discovery of simplified N2-substituted pyrazolo[3,4-d]pyrimidine derivatives as novel adenosine receptor antagonists: Efficient synthetic approaches, biological evaluations and molecular docking studies
Venkatesan, Gopalakrishnan,Paira, Priyankar,Cheong, Siew Lee,Vamsikrishna, Kosaraju,Federico, Stephanie,Klotz, Karl-Norbert,Spalluto, Giampiero,Pastorin, Giorgia
, p. 1751 - 1765 (2014/03/21)
In the present study, a molecular simplification approach was employed to design novel bicyclic pyrazolo[3,4-d]pyrimidine (PP) derivatives from tricyclic pyrazolo[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines (PTP) as promising human A3 adenosine receptor (hA3AR) antagonists. All the target compounds were synthesized using novel and efficient synthetic schemes and the structure-activity relationship studies of these PPs were explored through the synthesis of a series of PTP analogues with various substituents. Substituents with different lipophilicity and steric hindrance (e.g., alkyl and aryl-alkyl) functions were introduced at N2 position of the pyrazole ring, while acyl groups with different electronic properties were introduced at C 6 position of the bicyclic nucleus to probe both electronic and positional effects. Most of the synthesized derivatives of the PP series presented good affinity at the hA3AR, as indicated by the low micromolar range of Ki values and among them, compound 63 with N 2 neopentyl substituents showed most potent hA3AR affinity with Ki value of 0.9 μM and high selectivity (hA 1AR/hA3AR = >111 & hA2AAR/hA 3AR = >111) towards other adenosine receptor subtypes. Interestingly, small isopropyl groups at N2 position displayed high affinity at another receptor subtype (hA2AAR, e.g., compound 55, with Ki hA2AAR = 0.8 μM), while they were less favorable at the hA3AR. Molecular docking analysis was also performed to predict the possible binding mode of target compounds inside the hA3AR and hA2AAR. Overall, PP derivatives represent promising starting points for new AR antagonists.
AZOLOPYRIDINE AND AZOLOPYRIMIDINE COMPOUNDS AND METHODS OF USE THEREOF
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Page/Page column 134, (2012/03/26)
Provided herein are azolopyridine and azolopyrimidine compounds for treatment of JAK kinase mediated diseases, including JAK2 kinase-, JAK3 kinase- or TYK2 kinase-mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.
