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

doi:10.1007/s00044-017-2099-z

Cited by 25 publications

(2 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, it was our thought of interest to further investigate any changes in affinity and selectivity towards ARs for a novel series of triazolopyridine derivatives ( 4a–4t ) with 7‐amino (NH 2 ) and 6‐carbonitrile (CN) group, while varying the substitution pattern at the 2‐position of the scaffold with various aryl/hetero‐aryl moieties (Figure ). In continuation of our interest in the search of novel ligands for adenosine receptors (Balakumar et al., ; Chandrasekaran et al., ; Deb et al., ; Kaur et al., ; Kishore, Balakumar, Rao, Roy, & Roy, ; Prasad et al., ; Sirisha et al., ; Veeraswamy et al., ) and in the light of the above‐mentioned literature reports, some novel 5‐oxo[1,2,4]triazolo[1,5‐ a ]pyridine‐6‐carbonitrile derivatives ( 4a–4t ) have been synthesized as potential selective ligands for hA 1 AR.…”

Section: Introductionmentioning

confidence: 98%

7‐Amino‐2‐aryl/hetero‐aryl‐5‐oxo‐5,8‐dihydro[1,2,4]triazolo[1,5‐a]pyridine‐6‐carbonitriles: Synthesis and adenosine receptor binding studies

et al. 2019

Self Cite

View full text Add to dashboard Cite

A series of novel 7-amino-5-oxo-2-substituted-aryl/hetero-aryl-5, 8-dihydro[1,2,4] triazolo[1,5-a]pyridine-6-carbonitriles (4a-4t) was synthesized, characterized and evaluated for their binding affinity and selectivity towards hA 1 , hA 2A , hA 2B and hA 3 adenosine receptors (ARs). Compound 4a with a phenyl ring at 2-position of the triazolo moiety of the scaffold showed high affinity and selectivity for hA 1 AR (K i hA 1 = 0.076 μM, hA 2A = 25.6 μM and hA 3 > 100 μM). Introduction of various electron donating and withdrawing groups at different positions of the phenyl ring resulted in drastic reduction in affinity and selectivity towards all the ARs, except compound 4b with a 4-hydroxyphenyl group at 2-position. Interestingly, the replacement of the phenyl ring with a smaller heterocyclic thiophene ring (π excessive system) resulted in further improvement of affinity for hA 1 AR of compound 4t (K i hA 1 = 0.051 μM, hA 2A = 9.01 μM and hA 3 > 13.9 μM) while retaining the significant selectivity against all other AR subtypes similar to compound 4a. The encouraging results for compounds 4a and 4t indicate that substitution at 2-position of the scaffold with π-excessive systems other than thiophene may lead to even more potent and selective hA 1 AR antagonists. K E Y W O R D SA 1 adenosine receptors, adenosine receptor antagonists, cyanoacetic hydrazides, triazolopyridines

show abstract

Section: Introductionmentioning

confidence: 98%

7‐Amino‐2‐aryl/hetero‐aryl‐5‐oxo‐5,8‐dihydro[1,2,4]triazolo[1,5‐a]pyridine‐6‐carbonitriles: Synthesis and adenosine receptor binding studies

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is known that almost all nitrogen-containing heterocyclic rings exhibit many interesting biological activities, and thus their derivatives have attracted interest in medicinal chemistry due to their properties. 1,2 Some of their interested biological activities include antibacterial, 3 antifungal, 4 antitumor, 4 antioxidant, 5 and anti-inflammatory activities. 3 Therefore, the synthesis of these derivatives has been carried out widely.…”

Section: Introductionmentioning

confidence: 99%