32320-41-5Relevant academic research and scientific papers
Computational modeling and target synthesis of monomethoxy-substituted o-diphenylisoxazoles with unexpectedly high antimitotic microtubule destabilizing activity
Stroylov, Victor S.,Svitanko, Igor V.,Maksimenko, Anna S.,Kislyi, Victor P.,Semenova, Marina N.,Semenov, Victor V.
, (2020)
The ability of monomethoxy-substituted o-diphenylisoxazoles 2a-d to interact with the colchicine site of tubulin was predicted using computational modeling, docking studies, and calculation of binding affinity. The respective molecules were synthesized in high yields by three steps reaction using easily available benzaldehydes, acetophenones, and arylnitromethanes as starting material. The calculated antitubulin effect was confirmed in vivo in a sea urchin embryo model. Compounds 2a and 2c showed high antimitotic microtubule destabilizing activity compared to that of CA4. Isoxazole 2a also exhibited significant cytotoxicity against human cancer cells in NCI60 screen. For the first time, isoxazole-linked CA4 derivatives 2a and 2c with only one methoxy substituent were identified as potent antimitotic microtubule destabilizing agents. These molecules could be considered as promising structures for further optimization.
Effective Synthesis of 3,4-Diaryl-isoxazole-5-carboxamides and their Antiproliferative Properties
Maksimenko, Anna S.,Kislyi, Victor P.,Chernysheva, Natalia B.,Strelenko, Yuri A.,Zubavichus, Yan V.,Khrustalev, Victor N.,Semenova, Marina N.,Semenov, Victor V.
, p. 4260 - 4270 (2019/07/12)
A simple scalable procedure for the synthesis of 3,4-diaryl-isoxazole-5-carboxamides 6 under mild conditions from readily available material was developed. The targeted compounds 6, structural analogues of heat shock protein inhibitors, were obtained by the rearrangement of intermediate 3,4-diaryl-5-carboxamido-isoxazoline N-oxides 5. In contrast to carboxamido-isoxazoline oxides 5, base-catalyzed recyclization of 3,4-diaryl-5-(ethoxycarbonyl)isoxazoline N-oxides 9c unexpectedly yielded 5-hydroxy-1,2-oxazin-6-ones 17c instead of ethyl 3,4-diaryl-isoxazole-5-carboxylates 10. Crystal and molecular structure of 4-(2,5-dimethoxy-3,4-methylenedioxyphenyl)-5-hydroxy-3-phenyl-6H-1,2-oxazin-6-one 17c was established by single-crystal X-ray diffraction study. In a phenotypic sea urchin embryo assay, carboxamide 6f showed moderate antimitotic antitubulin activity compared to 5-unsubstituted 3,4-diarylisoxazoles 15, which featured strong microtubule destabilizing effect.
Regioselective synthesis of 3,4-diaryl-5-unsubstituted isoxazoles, analogues of natural cytostatic combretastatin A4
Chernysheva, Natalia B.,Maksimenko, Anna S.,Andreyanov, Fedor A.,Kislyi, Victor P.,Strelenko, Yuri A.,Khrustalev, Victor N.,Semenova, Marina N.,Semenov, Victor V.
, p. 511 - 518 (2018/02/15)
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 arylb
Synthesis of 3,4-diaryl-5-carboxy-4,5-dihydroisoxazole 2-oxides as valuable synthons for anticancer molecules
Chernysheva, Natalia B.,Maksimenko, Anna S.,Andreyanov, Fedor A.,Kislyi, Victor P.,Strelenko, Yuri A.,Khrustalev, Victor N.,Semenova, Marina N.,Semenov, Victor V.
, p. 6728 - 6735 (2017/10/25)
The convenient regioselective scalable synthesis of 3,4-diaryl-5-carboxy-4,5-dihydroisoxazole 2-oxides was developed based on a condensation of simple starting materials (arylbenzaldehydes, arylnitromethanes, and ethoxycarbonylmethylpyridinium bromide) un
