FIELD: chemistry.
SUBSTANCE: invention relates to a compound of formula (I) or pharmaceutically acceptable salts thereof, which can activate the nuclear factor Nrf2. In formula (I), R1 and R2 each independently denote H or C1-C6-alkyl; or R1 and R2 together with the carbon with which they are bonded form C3-C6-cycloalkyl; R3 denotes C1-C6-alkyl or C6-C10-aryl; R4 means NR7C(O)R8 or CONR9R10; or R3 and R4 together with the carbon to which they are bonded form C3-C8-cycloalkyl or 3–8-membered saturated or unsaturated heterocyclic ring containing from 1 to 3 heteroatoms independently selected from the group consisting of O and N, where said C3-C8-cycloalkyl and 3–8-membered saturated or unsaturated heterocyclic ring are optionally substituted with 1–4 substitutes R12; R7 denotes H or C1-C6-alkyl; R8 denotes H, C1-C6-alkyl, C3-C8-cycloalkyl, C6-C10-aryl or 3–9-membered saturated or unsaturated heterocyclic ring containing from 1 to 3 heteroatoms independently selected from a group comprising O, S and N; where said C1-C6-alkyl, C3-C8-cycloalkyl, C6-C10-aryl and 3–9-membered saturated or unsaturated heterocyclic ring are optionally substituted with 1–4 substitutes R13; R9 denotes C1-C6-alkyl; R10 denotes C1-C6-alkyl; each R12 is independently selected from a group comprising: (1) C1-C6-alkyl, (2) halogen, (3) oxo group, (4) -(CH2)pC3-C6-cycloalkyl, (5) -(CH)pC6-C10-aryl, (6) -(CH2)phet, where het denotes 3–9-membered saturated or unsaturated heterocyclic ring containing from 1 to 4 heteroatoms independently selected from a group consisting of O and N, (7) -(CH2)p-OR14, (8) -(CH2)p-NR15R16, (9) -(CH2)p-C(O)R19, (10) -(CH2)p-S(O)nR19 and (11) -(CH2)p-C(O)OR20; where said C1-C6-alkyl, C3-C6-cycloalkyl, C6-C10-aryl and 3–9-membered heterocyclic ring are each independently substituted with one or more substitutes selected from a group comprising halogen, hydroxyl, C1-C6-alkyl and -OC1-C6-alkyl, and where said C1-C6-alkyl and -OC1-C6-alkyl are optionally substituted with one or more halogens or one or more hydroxyls; or two substitutes R12 on adjacent atoms of C3-C8-cycloalkyl or 3–8-membered saturated or unsaturated heterocyclic ring together with ring atoms, with which they are bonded, form a fused bicyclic ring system, which is optionally substituted with one or more substitutes R21; R13 denotes halogen, C1-C6-alkyl, -OC1-C6-alkyl or C6-C10-aryl, where in each case said C1-C6-alkyl is independently optionally substituted with one or more halogens and where said C6-C10-aryl is optionally substituted with 1–4 substitutes selected from halogen, hydroxyl or C1-C6-alkyl; R14 denotes H or C1-C6-alkyl; R15 denotes H or C1-C6-alkyl; R16 denotes C6-C10-aryl; R19 and R20 independently denote H, C1-C6-alkyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C6-C12-aryl or 5–10-membered heteroaryl, containing from 1 to 3 heteroatoms independently selected from a group consisting of O, S and N, where said C1-C6-alkyl, C2-C6-alkynyl, C3-C6-cycloalkyl, C6-C12-aryl and 5–10-membered heteroaryl are all optionally independently substituted with one or more substitutes R27; R21 is independently selected from a group consisting of H, halogen, hydroxyl, C1-C6-alkyl and -OC1-C6-alkyl, where said C1-C6-alkyl and -OC1-C6-alkyl are all optionally independently substituted with one or more substitutes selected from the group consisting of halogen, hydroxyl and -OC1-C6-alkyl; R27 denotes halogen, hydroxyl, nitrile, C1-C6-alkyl, -O-C1-C6-alkyl, -SC1-C6-alkyl, C(O)NHC1-C6-alkyl, C3-C6-cycloalkyl, C6-C10-aryl, -O-C6-C10-aryl, -O-C1-C2-alkyl-C6-C10-aryl or 5–8-member heteroaryl containing from 1 to 3 heteroatoms independently selected from the group consisting of O, S and N, where in each case said C1-C6-alkyl, C3-C6-cycloalkyl, C6-C10-aryl and 5–8-membered heteroaryl are independently substituted with one or more substitutes selected from the group consisting of halogen, hydroxyl, nitrile, C1-C6-alkyl, -OC1-C6-alkyl and -N(C1-C6-alkyl)2, where said C1-C6-alkyl and -OC1-C6-alkyl are all independently substituted with one or more halogens; m is 0, 1 or 2; each n is independently 0, 1 or 2 and each p is independently 0, 1 or 2. Invention also relates to a pharmaceutical composition containing said compound.
EFFECT: cyclic cyanoenone derivatives as KEAP1 modulators are disclosed.
14 cl, 33 tbl, 951 ex
| Title | Year | Author | Number |
|---|---|---|---|
| 1,1,1-TRIFLUORO-3-HYDROXYPROPANE-2-YLCARBAMATE DERIVATIVES AS MAGL INHIBITORS | 2018 |
|
RU2720203C1 |
| COMPOUND WITH A CYCLIC STRUCTURE | 2018 |
|
RU2795119C2 |
| SPIRO-FUSED PIPERIDINE DERIVATIVES FOR APPLICATION AS INHIBITORS OF EXTERNAL MEDULLAR LAYER POTASSIUM CHANNEL | 2013 |
|
RU2642066C2 |
| MODULATORS OF NUCLEAR RECEPTORS | 2016 |
|
RU2715897C2 |
| BICYCLIC HETEROCYCLIC SPIROCOMPOUNDS | 2010 |
|
RU2506266C2 |
| BICYCLIC CONDENSED HETEROARYL OR ARYL COMPOUNDS AS IRAK4 MODULATORS | 2016 |
|
RU2684324C1 |
| N-ALKOXY-4,4-DIOXYPOLYALKYLPIPERIDINE COMPOUNDS WITH GLYCIDYL OR ALKYLCARBONYL GROUPS AS FUNCTIONAL INITIATING AGENTS FOR REGULATED RADICAL POLYMERIZATION | 2001 |
|
RU2281281C2 |
| HETEROCYCLIC SPIRO COMPOUNDS AS MAGL INHIBITORS | 2018 |
|
RU2726631C1 |
| DIHYDROPYRIDAZINE-3,5-DIONE DERIVATIVE | 2014 |
|
RU2662832C2 |
| NOVEL BENZOTHIAZINONE DERIVATIVES AND USE THEREOF AS ANTIBACTERIAL AGENTS | 2006 |
|
RU2395508C1 |
