1256952-72-3Relevant academic research and scientific papers
Synthesis and adenosine receptors binding studies of new fluorinated analogues of pyrido[2,3-d]pyrimidines and quinazolines
Chandrasekaran, Balakumar,Deb, Pran Kishore,Kachler, Sonja,Akkinepalli, Raghuram Rao,Mailavaram, Raghuprasad,Klotz, Karl-Norbert
, p. 756 - 767 (2017/11/03)
A series of new fluorine containing pyrido[2,3-d]pyrimidines and imidazo[1,2-c]pyrido[3,2-e]pyrimidines along with a series of bioisosteric fluorinated quinazolines were synthesised following appropriate synthetic schemes and characterised by spectral analytical means. X-ray crystal structure of the key precursor 1 (2-amino-3-cyano-4-trifluoro-methyl-6-phenyl-pyridine) was also determined to gain insight into its reactivity. Binding affinity data of all the compounds for adenosine receptors (ARs) showed that pyrido[2,3-d]pyrimidine scaffold with free amino (NH2) group at 2- and 4-position (2a) exhibited the maximum binding affinity for hA3 AR with similar affinity for the hA1 and somewhat lower affinity for hA2A ARs resulting in a compound with no A3 selectivity vs. A1 and moderate selectivity vs. A2A AR (Ki hA1 = 0.62 μM, hA2A = 3.59 μM and hA3 = 0.42 μM). Interestingly, the replacement of both the amino groups with carbonyl (C=O) groups (compound 4) resulted in significantly improved affinity for hA1 AR but with moderate selectivity against hA2A and hA3 ARs (Ki hA1 = 0.17 μM, hA2A = 0.67 μM and hA3 =0.68 μM). In case of fluorinated quinazolines, only compound 18a showed remarkable affinity for hA1 AR with significant selectivity against hA2A and hA3 ARs (Ki hA1 = 0.73 μM, hA2A CloseSPigtSPi 30 μM and hA3 = 9.27 μM). The preliminary results of these compounds demonstrate that the fluorinated pyrido[2,3-d]pyrimidine and imidazo[1,2-c]pyrido[3,2-e]pyrimidine can be considered as promising scaffolds for further optimisation in search of potential antagonists with better affinity and selectivity towards hA1 and hA3 ARs.
Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines
Balakumar,Lamba,Pran Kishore,Lakshmi Narayana,Venkat Rao,Rajwinder,Raghuram Rao,Shireesha,Narsaiah
experimental part, p. 4904 - 4913 (2010/11/18)
A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies.
