8-CARBAMOYL-2-(2,3-DI-SUBSTITUTED PYRID-6-YL)-1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES AS APOPTOSIS-INDUCING AGENTS FOR CANCER TREATMENT Russian patent published in 2017 - IPC C07D401/14 C07D417/14 C07D513/04 C07D471/04 C07D487/04 A61K31/4725 A61K31/4188 A61P35/00 

Abstract RU 2625315 C2

FIELD: pharmacology.

SUBSTANCE: invention relates to organic chemistry, namely a heterocyclic compound of formula (I) or to a therapeutically acceptable salt thereof, where X is benzo[d]thiazolyl, thiazolo[5,4-b]pyridinyl, thiazolo[4,5-c]pyridinyl, imidazo[1,2-a]pyridinyl, thiazolo[5,4-c]pyridinyl, thiazolo[4,5-b]pyridinyl, imidazo[1,2-a]pyrazinyl or imidazo[ 1,2-b]pyridazinyl; Y1 means pyrrolyl, pyrazolyl, triazolyl or pyridinyl; where Y1 is optionally substituted with 1 or 2 substituents independently selected from R5, CN and Cl; L1 is selected from (CR6R7)q, (CR6R7)s-O-(CR6R7)r, (CR6R7)s-S-(CR6R7)r, (CR6R7)s-S(O)2-(CR6R7)r and (CR6R7)s-NR6A-(CR6R7)r; Y2 means mono- or tricyclic C8-C10-cycloalkyl, spiro[2.5]octyl, spiro[3.5]nonyl, oxatricyclo[3.3.1.13,7]decyl or azabicyclo[3.2.1]octyl; where Y2 is optionally substituted with 1, 2 or 3 substituents independently selected from R8, OR8, SO2R8, CO(O)R8, OH and Br; Z1 is selected from , R1 and R3 are absent; R2 is deuterium or C1-C6-alkyl; R5 is C1-C6-alkyl; R6A is selected from hydrogen and C1-C6-alkyl; each R6 and R7 are hydrogen; R8 is selected from the group consisting of C1-C3-alkyl, morpholinyl and dioxydothiomorpholinyl; where R8, meaning C1-C6-alkyl, is optionally substituted with a substituent selected from R16, OR16, SO2R16 and NHR16; Rk is selected from C1-C6-alkyl, morpholinyl, cyclopropyl and C1-haloalkyl; R16 Is selected from C1-C4-alkyl, phenyl, morpholinyl and tetrahydropyranyl; where R16, meaning C1-C4-alkyl, is optionally substituted with 1 substituent selected from OCH3, OCH2CH2OCH3 and OCH2CH2NHCH3; q is 1 or 2; s, m and p is 0; r is 0 or 1; N is 0, 1, or 2. The invention also relates to specific compounds, pharmaceutical compositions based on these compounds and a method for treatment of these diseases.

EFFECT: new heterocyclic compounds are obtained, that are useful for treatment of some cancers.

16 cl, 3 tbl, 86 ex

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RU 2 625 315 C2

Authors

Vang Li

Douerti Dzhordzh

Van Silu

Tao Chzhi-Fu

Branko Milan

Kanzer Aaron R.

Uendt Majkl D.

Sun Syaokhun

Frej Robin

Khansen Todd M.

Sallivan Dzherard M.

Dzhadd Endryu

Sauers Endryu

Dates

2017-07-13Published

2012-10-11Filed