Synthesis and Evaluation of Adenosine Antagonist Activity of a Series of [1,2,4]Triazolo[1,5-c]quinazolines

Abstract

A series of [1,2,4]triazolo[1,5-c]quinazolines were prepared in satisfactory yields by reaction of some derivatives of 2-aminobenzohydrazide with several hydrochlorides of aromatic amidines, and their binding affinities for the recombinant human adenosine A2A and A2B receptors were determined. None of the new compounds showed noteworthy affinity for these receptors, though a very high affinity for the A2A receptor and, consequently, a high level of A2A/A2B selectivity was revealed for one of the synthesized compounds.

Synthesis of novel 1-alkyl-8-substituted-3-(3-methoxypropyl) xanthines as putative A2B receptor antagonists

“…26 These compounds showed moderate-to-low affinity for human A 2A and A 2B receptors expressed. The affinity values of compounds that did not fully displace specific radioligand binding are given only in terms of displacement percentage.…”

“…The affinity (pK i or displacement percentage) values of the 1-ethyl-3-(3-methoxypropyl)-9-susbtituted xanthine derivatives 15a-15m at cloned human adenosine receptors expressed in HeLa (A 2A and A 3 ), and HEK-293 (A 2B ) cells, and at rat A 1 receptors, are given in Table 2 26 1-Ethyl-3-(3-methoxypropyl)-9-subtituted xanthine derivatives showed moderate-to-high affinity at human A 2B receptors with selectivity over A 2A receptors of up to 33.8-fold (compound 15d). The affinity at rat A 1 and human A 3 receptors for most of these compounds showed lower pK i values than those observed at A 2B receptors.…”

2-(Azolyl)anilines: methods of synthesis, cyclocondensations, and biological properties

“…Thus, 2-(4,5-dihydro-1H-imidazol-2-yl)aniline (43) was synthesized in xylene with the yield of 93%. phenyl]amine (48) and its regioisomer 2-(2H-indazol-2-yl)-aniline (49). It is important to note that structure of the starting aniline significantly affected the ratio of isomers.…”

Synthesis of Diverse Azolo[c]quinazolines by Palladium(II)‐ Catalyzed Aerobic Oxidative Insertion of Isocyanides

“…[4] Triazolo [c]quinazolines containing an unsubstituted 5-amino group (2, R 3 = H) are easily obtained in this manner, but direct substitution of the exocyclic amino group is not possible via this nonconvergent approach. In contrast, mono-alkylated amino groups are typically installed by nucleophilic displacement of an appropriate leaving group by an amine, requiring more synthetic steps.…”