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
We present an experimental circuit realization of a simple jerk equation with modulus nonlinearity and study the chaotic behaviour as a function of a variable control parameter. The third order differential equation has been realized using commonly available opamps and the nonlinearity using a pair of diodes. The experiments indicate that chaotic behaviour indeed emerges through the period doubling route as the parameter is changed. This work is instructive to show students the phase plots as a function of the control parameter and determine the Feigenbaum constant.
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