Synthesis and biological evaluation of indolylglyoxylamide bisphosphonates, antimitotic microtubule-targeting derivatives of indibulin with improved aqueous solubility

Synthesis and biological evaluation of indolylglyoxylamide bisphosphonates, antimitotic microtubule-targeting derivatives of indibulin with improved aqueous solubility Full article

Journal

Bioorganic & Medicinal Chemistry Letters
ISSN: 1464-3405 , E-ISSN: 0960-894X

Output data

Year: 2020, Volume: 30, Number: 23, Article number : 127635, Pages count : DOI: 10.1016/j.bmcl.2020.127635

Authors

Brel Valery K. ¹ , Artyushin Oleg I. ¹ , Chuprov-Netochin Roman N. ² , Leonov Sergey V. ² , Semenova Marina N. ³ , Semenov Victor V. ⁴

Affiliations

1	A. N. Nesmeyanov Institute of Organoelement Compounds, 28 Vavilov Street, 119991 Moscow, Russian Federation
2	Moscow Institute of Physics and Technology (State University), Institutskiy per. 9, Dolgoprudny, Moscow Region 141701, Russian Federation
3	N. K. Kol’tsov Institute of Developmental Biology, Russian Academy of Sciences, Vavilov Street, 26, 119334 Moscow, Russian Federation
4	N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect, 47, 119991 Moscow, Russian Federation

Reactions of 3-tert-butyl-8-methylpyrazolo[5,1-c][1,2,4]triazine with lithium phenyldimethylsilanide and triphenylsilanide in THF media at −85 to −60 °C led to the formation of the silicon C(4)-addition products in high yields. Aromatic 3-tert-butyl-8-methyl-4-(triphenylsilyl)pyrazolo[5,1-c][1,2,4]triazine has been synthesized by oxidation of the corresponding 1,4-dihydro derivative using NBS/Et3N in pentane at −30 to −15 °C. Preferential N(1)-nucleophilic additions of silanides were observed for the sterically hindered 3,4-di-R-8-methylpyrazolo[5,1-c][1,2,4]triazines (R = t-Bu, Ph3Si). Novel C–Si derivatives of 1,2,4-triazines, as well as some other isolated compounds were characterized by IR, 1H, 13C, 29Si NMR, HRMS data and X-ray crystallography.

Brel V.K. , Artyushin O.I. , Chuprov-Netochin R.N. , Leonov S.V. , Semenova M.N. , Semenov V.V.
Synthesis and biological evaluation of indolylglyoxylamide bisphosphonates, antimitotic microtubule-targeting derivatives of indibulin with improved aqueous solubility
Bioorganic & Medicinal Chemistry Letters. 2020. V.30. N23. 127635 . DOI: 10.1016/j.bmcl.2020.127635 WOS Scopus OpenAlex

Web of science:	WOS:000595004500006
Scopus:	2-s2.0-85094585589
OpenAlex:	W3094353657

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