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Chemical Structure| 17969-22-1 Chemical Structure| 17969-22-1

Structure of 17969-22-1

Chemical Structure| 17969-22-1

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Product Citations

Gaofenngwe Nkomba ; Gisella Terre’Blanche ; Helena D. Janse van Rensburg ; Lesetja J. Legoabe ;

Abstract: Due to the implication of adenosine in seizure suppression, adenosine-based therapies such as adenosine receptor (AR) agonists have been investigated. This study aimed at investigating thieno[2,3-b]pyridine derivatives as non-nucleoside A1 agonists that could be used in pharmaco-resistant epilepsy (PRE). Compound 7c (thieno[2,3-b]pyridine derivative), displayed good binding affinity to the rA1 AR (Ki = 61.9 nM). This could be a breakthrough for further investigation of this heterocyclic scaffold as potential ligand. In silico evaluation of this compound raised bioavailability concerns but performed well on drug-likeness tests. The effect of intramolecular cyclisation that occurs during synthesis of thieno[2,3-b]pyridines from the lead compounds, amino-3,5-dicyanopyridine derivatives (6a-s) in relation to AR binding was also evaluated. A significant loss of activity against rA1/rA2A ARs with cyclisation was revealed. Amino-3,5-dicyanopyridines exhibited greater affinity towards rA1 ARs (Ki < 10 nM) than rA2A. Compound 6c had the best rA1 affinity (Ki = 0.076 nM). Novel compounds (6d, 6k, 6l, 6m, 6n, 6o, 6p) were highly selective towards rA1 AR (Ki between 0.179 and 21.0 nM). Based on their high selectivity for A1 ARs, amino-3,5-dicyanopyridines may be investigated further as AR ligands in PRE with the right structural optimisations and formulations.

Keywords: Amino-3,5-dicyanopyridines ; Thieno[2,3-b]pyridines ; Intramolecular cyclisation ; Adenosine A1/A2A receptors ; Epilepsy

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Product Details of [ 17969-22-1 ]

CAS No. :17969-22-1
Formula : C10H7Cl2NS
M.W : 244.14
SMILES Code : ClC1=CC=C(C2=NC(CCl)=CS2)C=C1
MDL No. :MFCD00047057

Safety of [ 17969-22-1 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H312-H315-H318-H332-H335
Precautionary Statements:P261-P264-P270-P271-P280-P302+P352-P304+P340-P305+P351+P338-P310-P330-P332+P313-P362-P403+P233-P405-P501
Class:8
UN#:3261
Packing Group:
 

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