New Tetrazolopyridine-Acetohydrazide, Bis-3-(phenylamino)-5-pyridinyl-oxadiazolethione and Thiazolocoumarin Derivatives: Synthesis and Characterization

Abstract

In the present endeavor the aetohydrazide derivatives and diacylhydrazine derivatives were synthesized and characterized. The key intermediate 2-(5-(pyridin-3/4-yl)-2H-tetrazol-2-yl)acetohydrazide was reacted with substituted-benzaldehydes and acid chlorides to give two classes of compounds: (i) N΄-(Substituted-benzylidene)-2-(5-(pyridin-3/4-yl)-2H-tetrazol-2-yl) acetohydrazides (ii) Substituted-N΄-(2-(5-(pyridin-3/4-yl)-2H-tetrazol-2-yl)acetyl)benzohydrazides The acetohydrazides were screened for their in vivo antidiabetic activity and most of the derivatives have effective role in lowering plasma glucose, exerting potential of being good antidiabetic agents. Tetrazolo-pyridine-diacylhydrazines were tested for their inhibitory activity against nucleotide pyrophosphatase (hNPP1 & hNPP3) and the results show that NPP1 and NPP3 reveal differential susceptibility to benzohydrazide inhibitors. Some of the newly-synthesized analogues are selective inhibitors of NPP1 while some others selectively retard the activity of NPP3. The derivatives with IC50 values lesser than or closer to Suramin, (standard used) may have potential application in the treatment of neurodegenerative, cancer and metastatic diseases. In addition, Mannich bases act as important biologically-active compounds with high medicinal value, therefore a series of bis Mannich bases type derivatives were synthesized and characterized. Benzidine, 5-(pyridin-4-yl)-1,3,4-oxadiazole-2(3H)-thione and substitutedbenzaldehydes were reacted in 1:2:2 molar ratio giving 3,3΄-(4,4΄{[1,1-Biphenyl)-4,4΄-diylbis(azanediyl)]bis(substitutedphenyl)methylene)]bis(5-thioxo-4,5-dihydro-1,3,4-oxadiazol-4,2-diyl)}bis(4-pyridine) by means of simple and easy procedure. Coumarin and thiazole derivatives are well-known for their wide range of fluorescent and medicinal applications. Some new series of 3-thiazolyl-coumarins were designed containing both these important nuclei in a single structural unit, synthesized and characterized. The intermediate 3-(2-Bromoacetyl)-2H-chromen-2-one led to two different series of 3-thiazolylcoumarins: (i) 3-(2-(Substituted phenylamino)thiazol-4-yl)-2H-chromen-2-ones (ii) (ii) 3(2-(2-(Substitutedbenzylidene)hydrazinyl)thiazol-4-yl-2H-chromen-2-ones The second series was tested against acetylcholinesterase and butyrylcholinesterase and their structure–activity relationship was established. Studies tagged them as the potential inhibitors of cholinesterase (acetylcholinesterase and butyrylcholinesterase). The docking studies showed that these synthesized compounds possess better interaction patterns with butyrylcholinesterase over acetylcholinesterase. The main objective of the present investigation was to develop new potent and selective compounds, which might be further optimized to prevent the progression of the Alzheimer’s disease