Regioselective synthesis of 3,4-diaryl-5-unsubstituted isoxazoles, analogues of natural cytostatic combretastatin A4

Regioselective synthesis of 3,4-diaryl-5-unsubstituted isoxazoles, analogues of natural cytostatic combretastatin A4 Full article

Journal

European Journal of Medicinal Chemistry
ISSN: 1768-3254 , E-ISSN: 0223-5234

Output data

Year: 2018, Volume: 146, Pages: 511-518 Pages count : 8 DOI: 10.1016/j.ejmech.2018.01.070

Authors

Chernysheva Natalia B. ¹ , Maksimenko Anna S. ^2,1 , Andreyanov Fedor A. ¹ , Kislyi Victor P. ¹ , Strelenko Yuri A. ¹ , Khrustalev Victor N. ^3,4 , Semenova Marina N. ⁵ , Semenov Victor V. ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991, Moscow, Russian Federation
2	D. I. Mendeleev University of Chemical Technology of Russia, 9 Miusskaya pl., 125047, Moscow, Russian Federation
3	A. N. Nesmeyanov Institute of Organoelement Compounds RAS, 28 Vavilov Street, 119991, Moscow, Russian Federation
4	Faculty of Science, RUDN University, 6 Miklukho-Maklay Street, 117198, Moscow, Russian Federation
5	N. K. Koltzov Institute of Developmental BiologyRAS, 26 Vavilov Street, 119334, Moscow, Russian Federation

4,5-Diarylisoxazoles are potent antiproliferative tubulin-targeting agents. Their isomeric 3,4-diaryl-5-unsubstituted isoxazoles are hardly accessible. The synthesis of 3,4-diaryl-5-unsubstituted isoxazoles 13 was designed based on a condensation of arylbenzaldehydes, arylnitromethanes, and ethoxycarbonylmethylpyridinium bromide followed by a selective one-step transformation of intermediate 3,4-diaryl-5-ethoxycarbonyl-4,5-dihydroisoxazole 2-oxides 8. The orientation of aryl rings in relation to isoxazole heterocycle was confirmed by X-ray crystallography. Targeted compounds were evaluated for antimitotic microtubule destabilizing activity using a phenotypic sea urchin embryo assay. 3-(4-Methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)isoxazole 13e and 13h with a single methoxy substituent were the most potent. Compound 13e showed strong cytotoxicity in NCI60 screen with GI50 for NCI-H522 human lung cancer cell line of 0.023 μM.

Chernysheva N.B. , Maksimenko A.S. , Andreyanov F.A. , Kislyi V.P. , Strelenko Y.A. , Khrustalev V.N. , Semenova M.N. , Semenov V.V.
Regioselective synthesis of 3,4-diaryl-5-unsubstituted isoxazoles, analogues of natural cytostatic combretastatin A4
European Journal of Medicinal Chemistry. 2018. V.146. P.511-518. DOI: 10.1016/j.ejmech.2018.01.070 WOS Scopus OpenAlex

Web of science:	WOS:000427310700040
Scopus:	2-s2.0-85041856515
OpenAlex:	W2792068231

DB	Citing
OpenAlex	34
Scopus	32
Web of science	32