ARYLALKYNAMIDE DERIVATIVES

Claims

1. A compound of formula (I) or a salt thereof: (Where ring A is phenyl which may be optionally fused with a 5-membered heterocyclyl, a 6-membered heteroaryl containing one or two nitrogen atoms, pyrazolyl or a 6-membered saturated or partially unsaturated heterocyclyl, ring B is phenyl, which may be optionally fused with phenyl or 6-membered heteroaryl containing one or two nitrogen atoms, 6-membered heteroaryl containing one or two nitrogen atoms, pyrazolyl or imidazolyl, R a1 and R a2 independently represent H, C 1-6 alkyl, -OC 1-6 alkyl, -OC 1-6 alkylene-C 2-6 alkenyl, -OC 1-6 alkylene-C 2-6 alkynyl, halogen, halogen-C 1-6 alkyl, -O-halogen-C 1-6 alkyl or -OH, R b1 and R b2independently represent H, C 1-6 alkyl, -O 1-6 alkyl, halogen-C 1-6 alkyl, -O-halo-C 1-6 alkyl, halogen, -C 1-6 alkylene-OH, -C 1-6 alkylene-NR c R d , -C(=O)-NR c R d , -NR c R d , -CN or -OH, R c and R d independently represent H, C 1-6 alkyl, C 3-8 cycloalkyl, -C(=O)-C 1-6 alkyl or -S(=O)2-C 1-6 alkyl, or R c and R d may be optionally linked together to form a 4- to 7-membered saturated heterocyclyl together with the nitrogen atom to which R is attached c and R d , wherein heterocyclyl may be optionally substituted with one or two R e , R e represents C 1-6 alkyl, -OC 1-6 alkyl or halogen, R 1 represents H, optionally substituted with C 1-6alkyl optionally substituted with C 3-8 cycloalkyl, optionally substituted 4-7-membered saturated heterocyclyl, optionally substituted phenyl or optionally substituted heteroaryl, R 2 represents C 1-6 alkyl that is substituted by one or two R 3 , C 3-8 cycloalkyl which is substituted by one or two R 4 , 4-7-membered saturated heterocyclyl, which is substituted with one or two R 5 , or phenyl, which is substituted by one or two R 6 , or R 1 and R 2 are linked together to form a 4-7 membered saturated heterocyclyl with the nitrogen atom to which R is attached 1 and R 2 , wherein the heterocyclyl may be optionally fused with phenyl, and the heterocyclyl and / or fused phenyl may be optionally substituted with one to three R 7 , each R 3 independently represents -OH, -OC 1-6alkyl, -C(=O)-NH2, -C(=O)-NH-C 1-6 alkyl, -C(=O)-N(C 1-6 alkyl)2, -NH2, -NH-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH-C(=O)-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkylene-OH, -NH-S(=O)2-C 1-6 alkylene-C(=O)-OH, -S(=O)2-NH2, -S(=O)2-C 1-6 alkyl or -S(=O)(=NH)-C 1-6 alkyl, each R 4 independently represents -OH, -OC 1-6 alkyl, -C(=O)-NH2, -C(=O)-NH-C 1-6 alkyl, -C(=O)-N(C 1-6 alkyl)2, -NH2, -NH-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH-C(=O)-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkyl, -S(=O)2-NH2, -S(=O)2-C 1-6 alkyl or -S(=O)(=NH)-C 1-6 alkyl, each R 5 independently represents -OH, oxo, or imino, each R 6 independently represents -C(=O)-OH, -S(=O)2-NH2, -S(=O)2-C 1-6 alkyl, -S(=O)(=NH)-C 1-6 alkyl or -NH-S(=O)2-C 1-6 alkyl, and each R 7 independently represents C 1-6 alkyl, -C 1-6 alkylene-OH, -C 1-6 alkylene-C(=O)-OH, C 3-8 cycloalkyl, -OH, -OC 1-6 alkyl, -NH2, -NH-C 1-6 alkyl -N(C 1-6 alkyl)2, -NH-C(=O)-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkyl, -S(=O)2-C 1-6 alkyl, -S(=O)(=NH)-C 1-6 alkyl, -C(=O)-OH, -C(=O)-NH2, -C(=O)-NH-C 1-6 alkyl, -C(=O)-N(C 1-6 alkyl)2, oxo, imino or 4-7-membered saturated heterocyclyl which may be optionally substituted with one or two oxo, provided that the compound of formula (I) is not a compound of formula (II), (III), (IV) or (IVa)).

2. The compound or its salt according to claim 1, characterized in that ring B is phenyl, 6-membered heteroaryl containing one or two nitrogen atoms, or pyrazolyl, R a1 and R a2independently represent H, C 1-6 alkyl, halogen, halogen-C 1-6 alkyl or -O-halo-C 1-6 alkyl, R b1 and R b2 independently represent H, halogen-C 1-6 alkyl or -C 1-6 alkylene-NR c R d , R c and R d independently represent H or C 1-6 alkyl, or R c and R d may be optionally linked together to form a 4- to 7-membered saturated heterocyclyl together with the nitrogen atom to which R is attached c and R d , wherein heterocyclyl may be optionally substituted with one or two R e , R 1 represents H, C 1-6 alkyl, C 3-8 cycloalkyl, 4-7-membered saturated heterocyclyl, optionally substituted phenyl or optionally substituted heteroaryl, R 2 represents C 1-6alkyl that is substituted by one or two R 3 , C 3-8 cycloalkyl which is substituted by one or two R 4 , 4-7-membered saturated heterocyclyl, which is substituted with one or two R 5 , or phenyl, which is substituted by one or two R 6 , or R 1 and R 2 are linked together to form a 4-7 membered saturated heterocyclyl with the nitrogen atom to which R is attached 1 and R 2 , wherein the heterocyclyl may be optionally fused with phenyl, and the heterocyclyl and / or fused phenyl may be optionally substituted with one or two R 7 , each R 3 independently represents -OH, -C(=O)-NH2, -NH-C(=O)-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkyl or -S(=O)2-NH2, each R 4 independently represents -OH, -C(=O)-NH2, -NH-C(=O)-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkyl or -S(=O)2-NH2, each R5 independently represents -OH or oxo, each R 6 independently represents -C(=O)-OH or -S(=O)2-NH2, and each R 7 independently represents C 1-6 alkyl, -C 1-6 alkylene-OH, -C 1-6 alkylene-C(=O)-OH, C 3-8 cycloalkyl, -OH, -NH2, -C(=O)-OH, -C(=O)-NH2, oxo, imino, or 4-7-membered saturated heterocyclyl, which may be optionally substituted with one or two oxo.

3. The compound or its salt according to paragraph 2, characterized in that ring A is phenyl, 6-membered heteroaryl containing one or two nitrogen atoms, pyrazolyl, or 6-membered saturated or partially unsaturated heterocyclyl, ring B represents the formula (V): where X is CH or N, R 1 represents H, C 1-6 alkyl, C 3-8cycloalkyl, 4-7-membered saturated heterocyclyl, phenyl or optionally substituted heteroaryl, R 2 represents C 1-6 alkyl that is substituted by one or two R 3 , C 3-8 cycloalkyl which is substituted by one or two R 4 , or 4-7-membered saturated heterocyclyl, which is substituted with one or two R 5 , or R 1 and R 2 are linked together to form a 4-7 membered saturated heterocyclyl with the nitrogen atom to which R is attached 1 and R 2 , wherein heterocyclyl may be optionally substituted with one or two R 7 , R 4 represents -OH, provided that at least one of R a1 , R a2 , R b1 or R b2 does not represent H.

4. The compound or its salt according to paragraph 3, characterized in that R b1 represents H, Rb2 is a halogen-C 1-6 alkyl, and R 1 and R 2 are linked together to form a 4-7 membered saturated heterocyclyl with the nitrogen atom to which R is attached 1 and R 2 , wherein heterocyclyl may be optionally substituted with one or two R 7 .

5. The compound or its salt according to paragraph 3, characterized in that ring A is phenyl, R a1 , R a2 and R b1 represent H, R b2 is a halogen-C 1-6 alkyl, R 1 represents H, R 2 represents C 1-6 alkyl that is substituted by one or two R 3 , or R 1 and R 2 are linked to each other to form azetidinyl, pyrrolidinyl, piperidinyl, or thiomorpholinyl together with the nitrogen atom to which R is attached 1 and R2 , wherein azetidinyl, pyrrolidinyl, piperidinyl or thiomorpholinyl may be optionally substituted with one or two R 7 , each R 3 independently represents -OH or -C(=O)-NH2, and each R 7 independently represents -C 1-6 alkylene-OH, -OH, -C(=O)-NH2, oxo or imino.

6. A compound or its salt according to claim 1, characterized in that it is a compound selected from the following group: N 2 -{3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-inoyl}-L-serinamide, 1-[(3R,4R)-3,4-dihydroxypyrrolidin-1-yl]-3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-yn-1-one, 1-{3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-inoyl}piperidine-4-carboxamide, 1-[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]-3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-yn-1-one, 1-[3,3-bis(hydroxymethyl)azetidin-1-yl]-3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-yn-1-one, N-[(2R)-2,3-dihydroxypropyl]-3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-ynamide, N-[(2S)-2,3-dihydroxypropyl]-3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-ynamide, 1-[(3S,4S)-3,4-dihydroxypyrrolidin-1-yl]-3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-yn-1-one, (3R)-1-{3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-inoyl}pyrrolidine-3-carboxamide, 1-[(3R,4S)-3,4-dihydroxypyrrolidin-1-yl]-3-[6-phenyl-5-(trifluoromethyl)pyridin-3-yl]prop-2-yn-1-one, and 1-imino-4-{3-[2-(trifluoromethyl)[1,1'-biphenyl]-4-yl]prop-2-inoyl}-1λ 6 -thiomorpholin-1-one.

7. A pharmaceutical composition comprising a compound or a salt thereof according to claim 1 and one or more pharmaceutically acceptable excipients.

8. A STING inhibitor comprising a compound or a salt thereof according to claim 1.

9. The pharmaceutical composition according to claim 7, characterized in that it is a pharmaceutical composition for the treatment of an autoimmune disease, a neurodegenerative disease, type I interferonopathy and / or another STING-mediated disease.

10. Use of a compound or a salt thereof according to claim 1 for the manufacture of a pharmaceutical composition for the treatment of an autoimmune disease, a neurodegenerative disease, type I interferonopathy and / or another STING-mediated disease.

11. Use of a compound or a salt thereof according to claim 1 for the treatment of an autoimmune disease, a neurodegenerative disease, type I interferonopathy and / or another STING-mediated disease.

12. A compound or salt thereof according to claim 1 for use in the treatment of an autoimmune disease, a neurodegenerative disease, type I interferonopathy and / or another STING-mediated disease.

13. A method for treating an autoimmune disease, a neurodegenerative disease, type I interferonopathy and / or another STING-mediated disease, comprising administering to a subject an effective amount of a compound or a salt thereof according to claim 1.

14. Use of a compound of formula (I) or a salt thereof for the manufacture of a pharmaceutical composition for the treatment of an autoimmune disease, a neurodegenerative disease, type I interferonopathy and / or another STING-mediated disease, characterized in that ring A is phenyl which may be optionally fused with a 5-membered heterocyclyl, a 6-membered heteroaryl containing one or two nitrogen atoms, pyrazolyl or a 6-membered saturated or partially unsaturated heterocyclyl, ring B is phenyl, which may be optionally fused with phenyl or 6-membered heteroaryl containing one or two nitrogen atoms, 6-membered heteroaryl containing one or two nitrogen atoms, pyrazolyl or imidazolyl, R a1 and R a2 independently represent H, C 1-6 alkyl, -OC 1-6 alkyl, -OC 1-6 alkylene-C 2-6 alkenyl, -OC 1-6 alkylene-C 2-6 alkynyl, halogen, halogen-C 1-6 alkyl, -O-halogen-C 1-6 alkyl or -OH, R b1 and R b2 independently represent H, C 1-6 alkyl, -O 1-6 alkyl, halogen-C 1-6 alkyl, -O-halo-C 1-6 alkyl, halogen, -C 1-6 alkylene-OH, -C 1-6 alkylene-NR c R d , -C(=O)-NR c R d , -NR c R d , -CN or -OH, R c and R d independently represent H, C 1-6 alkyl, C3-8 cycloalkyl, -C(=O)-C 1-6 alkyl or -S(=O)2-C 1-6 alkyl, or R c and R d may be optionally linked together to form a 4- to 7-membered saturated heterocyclyl together with the nitrogen atom to which R is attached c and R d , wherein heterocyclyl may be optionally substituted with one or two R e , R e represents C 1-6 alkyl, -OC 1-6 alkyl or halogen, R 1 represents H, optionally substituted with C 1-6 alkyl optionally substituted with C 3-8 cycloalkyl, optionally substituted 4-7-membered saturated heterocyclyl, optionally substituted phenyl or optionally substituted heteroaryl, R 2 represents C 1-6 alkyl that is substituted by one or two R 3 , C 3-8 cycloalkyl which is substituted by one or two R 4, 4-7-membered saturated heterocyclyl, which is substituted with one or two R 5 , or phenyl, which is substituted by one or two R 6 , or R 1 and R 2 are linked together to form a 4-7 membered saturated heterocyclyl with the nitrogen atom to which R is attached 1 and R 2 , wherein the heterocyclyl may be optionally fused with phenyl, and the heterocyclyl and / or fused phenyl may be optionally substituted with one to three R 7 , each R 3 independently represents -OH, -OC 1-6 alkyl, -C(=O)-NH2, -C(=O)-NH-C 1-6 alkyl, -C(=O)-N(C 1-6 alkyl)2, -NH2, -NH-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH-C(=O)-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkylene-OH, -NH-S(=O)2-C 1-6 alkylene-C(=O)-OH, -S(=O)2-NH2, -S(=O)2-C 1-6 alkyl or -S(=O)(=NH)-C 1-6 alkyl, each R 4independently represents -OH, -OC 1-6 alkyl, -C(=O)-NH2, -C(=O)-NH-C 1-6 alkyl, -C(=O)-N(C 1-6 alkyl)2, -NH2, -NH-C 1-6 alkyl, -N(C 1-6 alkyl)2, -NH-C(=O)-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkyl, -S(=O)2-NH2, -S(=O)2-C 1-6 alkyl or -S(=O)(=NH)-C 1-6 alkyl, each R 5 independently represents -OH, oxo, or imino, each R 6 independently represents -C(=O)-OH, -S(=O)2-NH2, -S(=O)2-C 1-6 alkyl, -S(=O)(=NH)-C 1-6 alkyl or -NH-S(=O)2-C 1-6 alkyl, and each R 7 independently represents C 1-6 alkyl, -C 1-6 alkylene-OH, -C 1-6 alkylene-C(=O)-OH, C 3-8 cycloalkyl, -OH, -OC 1-6 alkyl, -NH2, -NH-C 1-6 alkyl -N(C 1-6 alkyl)2, -NH-C(=O)-C 1-6 alkyl, -NH-S(=O)2-C 1-6 alkyl, -S(=O)2-C 1-6 alkyl, -S(=O)(=NH)-C 1-6alkyl, -C(=O)-OH, -C(=O)-NH2, -C(=O)-NH-C 1-6 alkyl, -C(=O)-N(C 1-6 alkyl)2, oxo, imino or 4-7 membered saturated heterocyclyl, which may be optionally substituted with one or two oxo.