FIELD: chemistry.
SUBSTANCE: invention relates to a compound of formula I having structure (I (a)), or a pharmaceutically acceptable salt thereof, where R1 is selected from a group consisting of H and unsubstituted C1-C4 alkyl; ring A is selected from 5-member heteroaryl having from 1 to 2 heteroatoms selected from nitrogen atoms; where ring A is optionally substituted with: (a) substituents in amount of 1 to 2, selected from a group consisting of a halogen atom, C1-C6 alkyl, C1-C6 halogenalkyl, C3-C6 cycloalkyl, unsubstituted or substituted with 1–2 fluorine atoms, C1-C6 alkoxy, phenyl, isopropenyl, C1-C6 alkyl, substituted with OH, NH-CH2CH2-OCH3 or NH-CH2CF3, and CH2-(C3-C6 cycloalkyl, unsubstituted or substituted with 1–2 fluorine atoms); where in case of substitution of nitrogen atom in ring A substitute is not a halogen atom or not C1-C6 alkoxy; (b) 1 substitute selected from a group consisting of C4-C6 heterocyclyl having 1 heteroatom selected from a group consisting of nitrogen and oxygen atoms, unsubstituted or substituted with C(O)OC(CH3)3, C5 heteroaryl having 2 heteroatoms selected from a group consisting of nitrogen atoms, CH2-(C4-C6 heterocyclyl having from 1 to 2 heteroatoms selected from a group consisting of nitrogen and oxygen atoms, unsubstituted or substituted with 1–2 fluorine atoms), CH2CH2-(C4-C7 heterocyclyl, having from 1 to 2 heteroatoms selected from a group consisting of nitrogen and oxygen atoms, unsubstituted or substituted with 1–2 fluorine atoms); CH2CH2CH2-(C4-C6 heterocyclyl, having from 1 to 2 heteroatoms selected from a group consisting of nitrogen and oxygen atoms, unsubstituted or substituted with 1–2 fluorine atoms); and optionally a second substituent selected from a group consisting of C1-C6 alkyl and C1-C6 alkoxy; or (c) two adjacent substitutes which together form phenyl, C5 heterocyclyl having 1 heteroatom selected from a group consisting of sulfur atoms, or C4-C6 cycloalkyl; Z1 is selected from a group consisting of: C and N, when ring A is 5-member heteroaryl; Z2, Z3 and Z4 each is independently selected from a group consisting of CRZ and NR8; each Rz is independently selected from a group consisting of H, a halogen atom, C1-C6 alkyl, C3-C6 cycloalkyl, CH2(C3-C6 cycloalkyl), C1-C6 halogenalkyl, C1-C6 alkoxy, phenyl, 4–6-member heterocyclyl, having 1 heteroatom selected from a group consisting of nitrogen and oxygen atoms, and 5–6-member heteroaryl, having 2 heteroatoms selected from a group consisting of nitrogen atoms; each R8 or absent, if nitrogen atom, to which it is attached, has three bonds with other atoms, or R8 is selected from a group consisting of C1-C6 alkyl and CH2(C3-C6 cycloalkyl); where Z1 is N only if X is CH2; where, if Z1 is N, at least one of Z2, Z3 or Z4 is CRZ; where, when Z2 and Z3 each is independently selected from CRZ and NR8, Z2 and Z3 together with corresponding substitutes RZ and R8 can form 6-member aryl, 5–6-membered cycloalkyl or 5–6-member heterocyclyl group having 1 heteroatom selected from sulfur; where, when Z3 and Z4 each is independently selected from CRZ and NR8, Z3 and Z4 together with corresponding substitutes RZ and R8 can form 6-member aryl, 5–6-membered cycloalkyl or 5–6-member heterocyclyl group having 1 heteroatom selected from sulfur, or including a SO group2; ring B is tetrazolyl or 5–9-member heteroaryl, having from 1 to 3 heteroatoms selected from a group consisting of nitrogen, oxygen and sulfur atoms; where ring B is optionally substituted with 1 substitute selected from C1-C4 alkyl; ring C is selected from a group consisting of phenyl, 6-member heteroaryl, having from 1 to 2 heteroatoms selected from a group consisting of nitrogen atoms, 3–7-member cycloalkyl and 5–7-member heterocyclyl, having from 1 to 2 heteroatoms selected from a group consisting of nitrogen, oxygen and sulfur atoms; where ring C is optionally substituted with: (a) substitutes in amount of 1 to 2, selected from a group consisting of a halogen atom, C1-C6 alkyl, C1-C6 halogenalkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, cyano and phenyl; where in case of substitution of nitrogen atom in ring C substitute is not a halogen atom, not C1-C6 alkoxy, not C1-C6 haloalkoxy or non-cyano; (b) 1 substitute selected from a group consisting of unsubstituted C5-C6 heteroaryl having from 1 to 2 heteroatoms selected from a group consisting of nitrogen and oxygen atoms; or (c) two adjacent substitutes, which together form C5-C6 heterocyclyl having 1 heteroatom selected from a group consisting of oxygen atoms or C3-C6 cycloalkyl; L is selected from a group consisting of a bond, O, (CH2)m, SN (SN3), or L is absent so that ring B and ring C are condensed; X is selected from a group consisting of O and CH2; m is 1; and n is 1 or 2; provided that, if ring B is tetrazolyl, L is selected from a group consisting of CH2, CH(CH3); and ring C is phenyl. Invention also relates to a pharmaceutical composition which inhibits RIP1 kinase activity on the basis of said compounds.
EFFECT: technical result is obtaining novel compounds and a pharmaceutical composition based thereon, which can be used in medicine for treating or preventing diseases mediated by activity of RIP1 kinase.
21 cl, 8 tbl, 782 ex
| Title | Year | Author | Number |
|---|---|---|---|
| BENZOXAZEPINE PI3K INHIBITORS AND METHODS OF USE | 2010 |
|
RU2600927C2 |
| BENZOXAZEPINE PI3 INHIBITORS AND METHODS OF USE | 2010 |
|
RU2654068C1 |
| METHODS AND COMPOSITIONS FOR TARGETED PROTEIN DEGRADATION | 2020 |
|
RU2820673C2 |
| HETEROARYL COMPOUNDS AS TKB INHIBITORS AND USE THEREOF | 2015 |
|
RU2742122C2 |
| NAPHTHYRIDIN DERIVATIVES AS ANTAGONISTS OF ALPHA V BETA 6 INTEGRIN FOR TREATING, IN PARTICULAR, FIBROTIC DISEASES | 2015 |
|
RU2692775C2 |
| KINASE INHIBITORS | 2013 |
|
RU2637944C2 |
| BENZOXEPIN PI3 INHIBITORS AND METHODS FOR USING THEM | 2010 |
|
RU2557658C2 |
| INHIBITOR COMPOUNDS | 2013 |
|
RU2673079C2 |
| IMIDAZOPYRAZINE OR IMIDAZODIAZEPINE DERIVATIVES, ACTIVE WITH RESPECT TO RECEPTOR CB2 | 2008 |
|
RU2540074C2 |
| INHIBITORS OF AKT ACTIVITY | 2010 |
|
RU2579513C2 |
