Helquats with heteroaromatic substituents, preparation thereof, and use thereof as G-quadruplex stabilizers

0499710 - ÚOCHB 2019 RIV eng P - Patentový dokument
Teplý, Filip - Hájek, Miroslav - Kužmová, Erika - Kozák, Jaroslav - Komárková, Veronika - Hubálková, Pavla - Reyes Gutierrez, Paul Eduardo - Jirásek, Michael - Sonawane, Manoj R. - Joshi, Vishwas - Severa, Lukáš - Novotná, J.
Helquats with heteroaromatic substituents, preparation thereof, and use thereof as G-quadruplex stabilizers.
2018. Vlastník: Ústav organické chemie a biochemie AV ČR, v. v. i. - Vysoká škola chemicko-technologická v Praze. Datum udělení patentu: 27.06.2018. Číslo patentu: EP3148997
Grant CEP: GA MŠMT LO1302
Institucionální podpora: RVO:61388963
Klíčová slova: helquats * G-quadruplex * diseases
Obor OECD: Organic chemistry
https://worldwide.espacenet.com/publicationDetails/originalDocument?CC=EP&NR=3148997B1&KC=B1&FT=D&ND=4&date=20180627&DB=&locale=en_EP#

The invention provides helquat derivatives of general formula I, wherein substituents R1 and R2 are independently selected from a group comprising H and C1 to C4 alkyl, up to three pairs of adjacent atoms in positions 1 and 2, 3 and 4, 1'and 2', 3' and 4' are possibly bridged with link S and, simultaneously, one to four atoms with an even descriptor (i.e., 2, 4, 2', 4') are substituted with substituent R3 of general formula II, wherein R4 is substituted or unsubstituted heteroaryl, S1,2, S1´,2´, S3,4 and S3´, 4´ is a link formed by a hydrocarbon chain of 3 to 6 carbon atoms, preferably a carbon chain of 4 carbon atoms, wherein the structure of the individual links S is mutually independent, and T1 and T2 are links that bridge atoms N5 with C8 and N5 with C8´, where the link is a hydrocarbon chain of 2 to 5 carbon atoms, preferably 2 or 3 carbon atoms, wherein the structure of the individual links T is mutually independent, and anions (X1)- and (X2)- are independent salt anions and preferably pharmaceutically acceptable salts. The helquat derivatives are useful as medicaments in the treatment of diseases related to increased cellular proliferation, such as oncologic diseases, and in the treatment requiring affecting of G-quadruplex, preferably at telomeres or in gene promoters.
Trvalý link: http://hdl.handle.net/11104/0292024