Tricyclic compound and JAK inhibitor
Novel tricyclic compounds which have JAK inhibitory activities are useful for prevention, treatment or improvement of autoimmune diseases, inflammatory diseases and allergic diseases are provided. Novel tricyclic compound represented by the formula (I), the formula (II) or the formula (III) (wherein: each of A 1 , A 2 and A 3 is a cyclohexane-1,4-diyl group or the like; each of L 1 , L 2 and L 3 is a methylene group or the like; each of X 1 and X 3 is O or NH; each of R 1 and R 3 is a cyano C 1-6 haloalkyl group or the like; and R 2 is an aromatic heterocyclic group), a tautomer or pharmaceutically acceptable salt of the compound or a solvate thereof.
1. A compound represented by the formula (III):
wherein:
A 3 is a C 3-7 cycloalkylene group,
L 3 is a C 1-6 alkylene group,
X 3 is O or NH, and
when X 3 is O, R 3 is a C 1-6 haloalkyl group, a cyano C 1-6 haloalkyl group or a cyano C 1-6 alkyl group, and
when X 3 is NH, R 3 is a cyano C 1-6 haloalkyl group or a cyano C 1-6 alkyl group,
or a tautomer or pharmaceutically acceptable salt of the compound.
2. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , wherein L 3 is a methylene group.
3. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , wherein A 3 is a cyclohexanediyl group.
4. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , wherein X 3 is O.
5. The compound, tautomer, or pharmaceutically acceptable salt according to claim 4 , wherein R 3 is a C 1-4 haloalkyl group or a cyano C 1-4 haloalkyl group.
6. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , wherein X 3 is NH.
7. The compound, tautomer, or pharmaceutically acceptable salt according to claim 6 , wherein R 3 is a cyano C 1-4 haloalkyl group.
8. A composition comprising
the compound, tautomer, or pharmaceutically acceptable salt according to claim 1 as an active ingredient, and
one or more inactive ingredients.
9. The composition according to claim 8 , wherein the one or more inactive ingredients comprise at least one selected from the group consisting of lactose, corn starch, low-viscosity hydroxypropylcellulose, magnesium stearate, microcrystalline cellulose, carboxymethylcellulose sodium salt, and saturated fatty acid glyceride.
10. The compound, tautomer, or pharmaceutically acceptable salt according to claim 4 , wherein R 3 is a 2,2,2-trifluoroethyl group or a 3,3,3-trifluoropropyl group.
11. The compound, tautomer, or pharmaceutically acceptable salt according to claim 4 , wherein R 3 is a 3-cyano-1,1,1-trifluoropropan-2-yl group or a 2-cyano-1,1,1-trifluoropropan-2-yl group.
12. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , which is 1-{trans-4-[(2,2,2-Trifluoroethoxy)methyl]cyclohexyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one, a tautomer or pharmaceutically acceptable salt thereof.
13. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , which is 1-{trans-4-[(3,3,3-Trifluoropropoxy)methyl]cyclohexyl}-1H-pyrrolo[2,3-h][1,6]naphthyridin-4(7H)-one, a tautomer or pharmaceutically acceptable salt thereof.
14. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , which is 4,4,4-Trifluoro-3-{[trans-4-(4-oxo-4,7-dihydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclohexyl]methoxy}butanenitrile, a tautomer or pharmaceutically acceptable salt thereof.
15. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , which is (R)-4,4,4-Trifluoro-3-{[trans-4-(4-oxo-4,7-dihydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclohexyl]methoxy}butanenitrile, a tautomer or pharmaceutically acceptable salt thereof.
16. The compound, tautomer, or pharmaceutically acceptable salt according to claim 6 , wherein R 3 is a 3-cyano-1,1,1-trifluoropropan-2-yl group.
17. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , which is 4,4,4-Trifluoro-3-({[trans-4-(4-oxo-4,7-dihydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclohexyl]methyl}amino)butanenitrile, a tautomer or pharmaceutically acceptable salt thereof.
18. The compound, tautomer, or pharmaceutically acceptable salt according to claim 1 , which is (R)-4,4,4-Trifluoro-3-({[trans-4-(4-oxo-4,7-dihydro-1H-pyrrolo[2,3-h][1,6]naphthyridin-1-yl)cyclohexyl]methyl}amino)butanenitrile, a tautomer or pharmaceutically acceptable salt thereof.