125366-05-4Relevant academic research and scientific papers
STEREOCHEMISTRY OF ELECTROPHILIC ANNELATION OF 2-ALLYL- (AND 2-CYCLOHEXEN-1-YL)THIO-1,5-NAPHTHYRIDINES TO THIAZOLO-1,5-NAPHTHYRIDINIUM SALTS
Shestopalov, A. M.,Nesterov, V. N.,Sharanin, Yu. A.,Litvinov, V. P.,Mortikov, V. Yu.,et al.
, p. 467 - 473 (1989)
Methods have been developed for the synthesis of 3-cyano-5,8-ethano-5,6,7,8-tetrahydro-1,5-naphthyridine-2(1H)-thione and 2-allyl- (and 2-cyclohexen-1-yl)thio-1,5-naphthyridines, and their structures have been studied.X-ray diffraction examination has shown that these compounds contain a disordered contact between the free electron pair of the pyridine nitrogen and the ?-bond of the allyl grouping, so that they react stereoselectively with halogens to give thiazolo-1,5-naphthyridinium salts.
3-Amino-thieno[2,3-b]pyridines as microtubule-destabilising agents: Molecular modelling and biological evaluation in the sea urchin embryo and human cancer cells
Eurtivong, Chatchakorn,Semenov, Victor,Semenova, Marina,Konyushkin, Leonid,Atamanenko, Olga,Reynisson, Jóhannes,Kiselyov, Alex
, p. 658 - 664 (2016/12/27)
A series of 3-amino-thieno[2,3-b]pyridines was prepared and tested in a phenotypic sea urchin embryo assay to identify potent and specific molecules that affect tubulin dynamics. The most active compounds featured a tricyclic core ring system with a fused cycloheptyl or cyclohexyl substituent and unsubstituted or alkyl-substituted phenyl moiety tethered via a carboxamide. Low nano-molar potency was observed in the sea urchin embryos for the most active compounds (1–5) suggestive of a microtubule-destabilising effect. The molecular modelling studies indicated that the tubulin colchicine site is inhibited, which often leads to microtubule-destabilisation in line with the sea urchin embryo results. Finally, the identified hits displayed a robust growth inhibition (GI50of 50–250?nM) of multidrug-resistant melanoma MDA-MB-435 and breast MDA-MB-468 human cancer cell lines. This work demonstrates that for the thieno[2,3-b]pyridines the most effective mechanism of action is microtubule-destabilisation initiated by binding to the colchicine pocket.
