1-[M-CARBOXAMIDO(HETERO)ARYL-METHYL]-HETEROCYCLYL-CARBOXAMIDE DERIVATIVES Russian patent published in 2018 - IPC C07D211/62 C07D401/12 C07D401/14 C07D405/12 C07D409/12 C07D413/12 C07D417/12 C07D471/08 A61K31/445 A61K31/4523 A61K31/4545 A61P29/00 A61P35/00 

FIELD: chemistry.

SUBSTANCE: invention relates to 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide compounds of formula (I) (I), in which Ar¹ represents a phenylene group or a 5- or 6-member heteroarylene group, which is a 5-6 member monocyclic or bicyclic aromatic ring containing from one to a maximum of four heteroatoms, each of which is independently selected from oxygen, nitrogen and sulfur; wherein -CHR⁴- and -NH-CO-X-R³ groups in Formula (I) are joined in a meta-arrangement to ring carbon atoms Ar¹; wherein said phenylene or a 5- or 6-member heteroarylene is independently unsubstituted or monosubstituted, wherein the substituent is selected from a group consisting of (C_1-4)alkyl, (C_1-4)alkoxy, halogen, (C_1-3)fluoroalkyl and (C_1-3)fluoroalkoxy; X is • direct bond; • -(C_1-4)alkylene- which is optionally monosubstituted, wherein the substituent is hydroxy; • -(C_3-6)cycloalkylene-; • -CH₂-O-, whereby oxygen is bonded to R³; or • -CH=CH-; R³ represents • aryl or 5-10 member heteroaryl, which represents a 5-10 member monocyclic or bicyclic aromatic ring containing from one to a maximum of four heteroatoms, each of which is independently selected from oxygen, nitrogen and sulfur; wherein said aryl or 5-10 member heteroaryl is independently unsubstituted, mono-, di- or trisubstituted, wherein the substituents are independently selected from a group consisting of (C_1-4)alkyl; (C_1-4)alkoxy; (C_1-3)fluoroalkyl; (C_1-3)fluoroalkoxy; halogen; cyano; (C_3-6)cycloalkyl; -CO-(C_1-4)alkoxy; -SO₂-(C_1-4)alkyl; and -NR⁶R⁷, wherein R⁶ and R⁷ are independently hydrogen or (C_1-3)alkyl, or R⁶ and R⁷ together with the nitrogen atom, to which they are attached form a 5- or 6-member ring selected from pyrrolidinyl, morpholinyl, piperidinyl and piperazinyl, optionally substituted on the free nitrogen atom with (C_1-4)alkyl; where if the 5-10 member heteroaryl is pyridine, then such a pyridine may additionally be present in the form of a corresponding N-oxide; • or, if X is a direct bond or a methylene group, R³ in addition, can be a > partially aromatic bicyclic ring system consisting of a phenyl ring, which is fused with a 4-6 member saturated carbocyclic ring optionally containing one or two heteroatoms independently selected from nitrogen and oxygen; wherein said ring system is optionally mono- or disubstituted with (C_1-4)alkyl or halogen; > (C_3-8)cycloalkyl, the cycloalkyl optionally having a ring oxygen atom, and wherein said cycloalkyl is optionally substituted with up to four methyl groups; • or, if X is a direct bond, R³ in addition, can be (C_2-6)alkyl; • or, if X is -CH=CH-, R³ can also be hydrogen, (C_1-4)alkyl or (dimethylamino)methyl; R¹ represents • (C_1-6)alkyl which is optionally monosubstituted (C_1-4)alkoxy or hydroxy; • (C_2-3)fluoroalkyl; • (C_3-8)cycloalkyl or (C_3-8)cycloalkyl-(C_1-3)alkyl; wherein the corresponding (C_3-8)cycloalkyl groups may optionally contain a ring oxygen atom; where (C_3-8)cycloalkyl or (C_3-8)cycloalkyl-(C_1-3)alkyl is independently unsubstituted or substituted as follows: > (C_3-8)cycloalkyl group is mono- or disubstituted, wherein the substituents are independently selected from a group consisting of (C_1-4)alkyl, fluoro, hydroxy-methyl, hydroxy and cyano; or > (C_1-3)alkyl group is monosubstituted with hydroxy; • aryl-(C_1-4)alkyl- or 5- or 6-member heteroaryl-(C_1-4)alkyl-, which is a 5-6 member monocyclic or bicyclic aromatic ring containing from one to up to four heteroatoms, each of which is independently selected from oxygen, nitrogen and sulfur; wherein said 5- or 6-member monocyclic or bicyclic aromatic ring is linked to the rest of the molecule via a (C_1-4)alkylene group, wherein the aryl or 5- or 6-member heteroaryl is independently unsubstituted, mono- or disubstituted, where the substituents are independently selected from a group consisting of (C_1-4)alkyl, (C_1-4)alkoxy, halogen, cyano, (C_1-3)fluoroalkyl and (C_1-3)fluoroalkoxy (in particular (C_1-4)alkyl, (C_1-4)alkoxy, halogen and (C_1-3)fluoroalkyl); or • 1,2,3,4-tetrahydronaphthalenyl or an indanyl group which are attached to the rest of the molecule via a carbon atom that is part of a non-aromatic ring; and R² is hydrogen or (C_1-3)alkyl; or R¹ and R² together with the nitrogen atom to which they are attached, are an azetidine, pyrrolidine, piperidine, morpholine or azepane ring, wherein said rings are independently unsubstituted, or mono- or disubstituted, wherein the substituents are independently selected from a group consisting of fluoro and methyl; R⁴ is hydrogen or (C_1-3)alkyl; and • R^5a is hydrogen, methyl or fluoro; R^5b is hydrogen; and p is an integer 0, 1 or 2; or • R^5a is hydrogen; R^5b is methyl; and p is an integer 1.

EFFECT: use as CXCR7 receptor modulators.

15 cl, 5 tbl, 8 ex