290299-52-4Relevant academic research and scientific papers
Improving the solubility of anti-proliferative thieno[2,3-b]quinoline-2-carboxamides
Haverkate, Natalie A.,van Rensburg, Michelle,Kumara, Sisira,Reynisson, Jóhannes,Leung, Euphemia,Pilkington, Lisa I.,Barker, David
supporting information, (2021/03/16)
Thieno[2,3-b]pyridines are a class of compounds known for their potent anti-proliferative activities against a range of human cancer cell lines. In this research, a number of strategies to generate analogues that have improved aqueous solubility whilst retaining the potent anti-proliferative actions, compared to previously-explored compounds in this class, were made. Herein we report the synthesis of 80 novel compounds, comprising two series, all based on the thieno[2,3-b]pyridine core structure. Overall, it was found that introducing alternative heterocycles did not notably improve the solubility or retain anti-proliferative activity seen in previously-reported analogues. However, pleasingly it was discovered, that the best strategy for improving the solubility was the alteration of the appended alkyl ring to introduce polar groups such as alcohols, ketones and substituted amine groups. In addition to this finding, we have discovered a thieno[2,3-b]pyridine, 15e, with greater aqueous solubility that has ever been seen for this class of compounds that is also a potent inhibitor of cancer cell growth, with IC50′s in the nanomolar range. This new lead structure will form the basis of future explorations into this class of compounds.
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.
Synthesis of thieno[2,3-b][1,6]naphthyridines and pyrimido[4',5':4,5] thieno[2,3-b][1,6]naphthyridines
Abdel-Wadood, Fatma K.,Abdel-Monem, Maisa I.,Fahmy, Atiat M.,Geies, Ahmed A.
scheme or table, p. 89 - 94 (2009/07/18)
3-Cyano-6-methyl-5,6,7,8-tetrahydro[1,6]naphthyridine-2(1H)-thione (3a) and 3-cyano-6-methyl-4-(2'-thienyl)-5,6,7,8-tetrahydro[1,6]naphthyridine-2(1H)- thione (3b) were reacted with a-halo compounds to give the intermediates 4a-j which upon refluxing in ethanolic sodium ethoxide afforded the thieno[2,3-b][1,6]naphthyridine derivatives 5a-l. Further annellation of pyridine and pyrimidine rings to the remaining free bond of the fused thiophene ring was achieved, providing tetrahydro-pyrido[2',3':4,5]- and -pyrimido[4',5':4,5]-thieno[2,3-b][1,6]naphthyridines. Some of the synthesised compounds were screened against different strains of bacteria.
