TY - JOUR

T1 - Synthesis and Properties of 6-Aryl-4-azidocinnolines and 6-Aryl-4-(1,2,3-1H-triazol-1-yl)cinnolines

AU - Danilkina, Natalia A.

AU - Bukhtiiarova, Nina S.

AU - Govdi , Anastasia I.

AU - Vasileva, Anna A.

AU - Rumyantsev, Andrey M.

AU - Volkov, Artemii A.

AU - Sharaev, Nikita I.

AU - Povolotskiy, Alexey V.

AU - Boyarskaya, Irina A.

AU - Kornyakov, Ilya V.

AU - Tokareva, Polina V.

AU - Balova, Irina A.

N1 - Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - An efficient approach towards the synthesis of 6-aryl-4-azidocinnolines was developed with the aim of exploring the photophysical properties of 6-aryl-4-azidocinnolines and their click reaction products with alkynes, 6-aryl-4-(1,2,3-1H-triazol-1-yl)cinnolines. The synthetic route is based on the Richter-type cyclization of 2-ethynyl-4-aryltriazenes with the formation of 4-bromo-6-arylcinnolines and nucleophilic substitution of a bromine atom with an azide functional group. The developed synthetic approach is tolerant to variations of functional groups on the aryl moiety. The resulting azidocinnolines were found to be reactive in both CuAAC with terminal alkynes and SPAAC with diazacyclononyne, yielding 4-triazolylcinnolines. It was found that 4-azido-6-arylcinnolines possess weak fluorescent properties, while conversion of the azido function into a triazole ring led to complete fluorescence quenching. The lack of fluorescence in triazoles could be explained by the non-planar structure of triazolylcinnolines and a possible photoinduced electron transfer (PET) mechanism. Among the series of 4-triazolylcinnoline derivatives a compound bearing hydroxyalkyl substituent at triazole ring was found to be cytotoxic to HeLa cells.

AB - An efficient approach towards the synthesis of 6-aryl-4-azidocinnolines was developed with the aim of exploring the photophysical properties of 6-aryl-4-azidocinnolines and their click reaction products with alkynes, 6-aryl-4-(1,2,3-1H-triazol-1-yl)cinnolines. The synthetic route is based on the Richter-type cyclization of 2-ethynyl-4-aryltriazenes with the formation of 4-bromo-6-arylcinnolines and nucleophilic substitution of a bromine atom with an azide functional group. The developed synthetic approach is tolerant to variations of functional groups on the aryl moiety. The resulting azidocinnolines were found to be reactive in both CuAAC with terminal alkynes and SPAAC with diazacyclononyne, yielding 4-triazolylcinnolines. It was found that 4-azido-6-arylcinnolines possess weak fluorescent properties, while conversion of the azido function into a triazole ring led to complete fluorescence quenching. The lack of fluorescence in triazoles could be explained by the non-planar structure of triazolylcinnolines and a possible photoinduced electron transfer (PET) mechanism. Among the series of 4-triazolylcinnoline derivatives a compound bearing hydroxyalkyl substituent at triazole ring was found to be cytotoxic to HeLa cells.

KW - Alkynes

KW - Azides

KW - Cinnolines

KW - CuAAC

KW - Cycloalkynes

KW - Cytotoxicity

KW - Fluorescence

KW - Richter cyclization

KW - Suzuki coupling

KW - Triazoles

KW - ONE-POT SYNTHESIS

KW - alkynes

KW - CINNOLINES

KW - SOLID-PHASE

KW - triazoles

KW - AZIDE

KW - fluorescence

KW - BIOLOGICAL EVALUATION

KW - PDE10A INHIBITORS

KW - DERIVATIVES

KW - cytotoxicity

KW - cinnolines

KW - cycloalkynes

KW - CLICK CHEMISTRY

KW - azides

KW - FLUORESCENCE

KW - ANTIMICROBIAL ACTIVITY

UR - https://www.mdpi.com/1420-3049/24/13/2386

UR - http://www.mendeley.com/research/synthesis-properties-6aryl4azidocinnolines-6aryl41231htriazol1ylcinnolines

UR - http://www.scopus.com/inward/record.url?scp=85068957032&partnerID=8YFLogxK

U2 - 10.3390/molecules24132386

DO - 10.3390/molecules24132386

M3 - Article

VL - 24

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 13

M1 - 2386

ER -