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2-Amino[1,2,4]triazolo[1,5-c]quinazolines were identified as potent adenosine receptor (AR) antagonists. Synthetic strategies were devised to gain access to a broad range of derivatives including novel polyheterocyclic compounds. Potent and selective A AR antagonists were discovered, including 3,5-diphenyl[1,2,4]triazolo[4,3-c]quinazoline (17, K human A AR 1.16 nm) and 5'-phenyl-1,2-dihydro-3'H-spiro[indole-3,2'-[1,2,4]triazolo[1,5-c]quinazolin]-2-one (20, K human A AR 6.94 nm). In addition, multitarget antagonists were obtained, such as the dual A /A antagonist 2,5-diphenyl[1,2,4]triazolo[1,5-c]quinazoline (13 b, K human A AR 51.6 nm, human A AR 11.1 nm), and the balanced pan-AR antagonists 5-(2-thienyl)[1,2,4]triazolo[1,5-c]quinazolin-2-amine (11 c, K human A AR 131 nm, A AR 32.7 nm, A AR 150 nm, A AR 47.5 nm) and 9-bromo-5-phenyl[1,2,4]triazolo[1,5-c]quinazolin-2-amine (11 q, K human A AR 67.7 nm, A AR 13.6 nm, A AR 75.0 nm, A AR 703 nm). In many cases, significantly different affinities for human and rat receptors were observed, which emphasizes the need for caution in extrapolating conclusions between different species.

Eprosartan mesylate (EM), an angiotensin II antagonist, is used as an antihypertensive drug. Its poor (13%) bioavailability is limited by its solubility rather than metabolism (hepatic CYP450). The hydrogen bond interactions between EM and pharmaceutical coformers involving carboxylic−carboxylic or carboxylic−amino interactions have been considered as the basis for the formation of cocrystals. A liquid-assisted grinding method was successfully employed. These cocrystals were characterized on the basis of their unique thermal (differential scanning calorimetry) and spectroscopic (Fourier transform infrared spectroscopy FTIR) profiles. They were confirmed by powder X-ray diffraction studies and characteristic vibrational modes in Raman spectra. The cocrystals prepared using succinic, p-aminobenzoic, and salicylic acids exhibited markedly high solubility (30−60-fold) compared to that of the pure drug (EM). In vitro dissolution studies also showed impressive dissolution profiles (50%), suggesting that they favor an increase in the oral bioavailability of EM.