Heterocyclic compound
The present invention provides an agent for the prophylaxis or treatment of autoimmune diseases (e.g., psoriasis, rheumatoid arthritis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, multiple sclerosis, systemic lupus erythematosus etc.) and the like, which has a superior Tyk2 inhibitory action. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or a salt thereof.
1. A compound represented by the formula (I):
wherein
R 1 is an optionally substituted C 1-6 alkyl group or an optionally substituted cyclic group;
R 2 is a hydrogen atom or a cyano group; and
R 3 is a halogen atom, a 5-membered aromatic ring group optionally having one substituent, or an optionally substituted 6- to 12-membered aromatic ring group, or a salt thereof.
2. The compound or salt of claim 1 , wherein R 2 is a hydrogen atom.
3. The compound or salt of claim 1 , wherein
R 1 is
(1) a C 1 - 6 alkyl group optionally substituted by 1 to 3 substituents selected from (a) a halogen atom, and (b) a C 3-8 cycloalkyl,
(2) a C 3-10 cycloalkyl group optionally substituted by 1 to 3 substituents selected from (a) a halogen atom, and (b) a C 1-6 alkyl group,
(3) a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from (a) a halogen atom, (b) a C 1-6 alkyl group optionally substituted by 1 to 3 halogen atoms, (c) a cyano group, (d) an amino group optionally mono- or di-substituted by C 1-6 alkyl-carbonyl group(s), and (e) a C 1-6 alkoxy group,
(4) a 3- to 8-membered monocyclic non-aromatic heterocyclic group, or
(5) a 5- or 6-membered monocyclic aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from
(a) a halogen atom, and (b) a cyano group;
R 2 is a hydrogen atom or a cyano group; and
R 3 is
(1) a halogen atom,
(2) a C 6-12 aryl group optionally substituted by 1 to 3 halogen atoms,
(3) a 5-membered monocyclic aromatic heterocyclic group optionally substituted by one substituent selected from the following Substituent Group C,
(4) a 6-membered monocyclic aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from following Substituent Group C, or (5) a 8- to 12-membered fused aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from following Substituent Group C
[Substituent Group C:
(a) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from (i) a hydroxy group, (ii) a C 1-6 alkoxy group, (iii) a C 1-6 alkylsulfonyl group, (iv) an amino group optionally mono- or di-substituted by substituent(s) selected from a C 1-6 alkyl-carbonyl group, a formyl group and a C 1-6 alkyl group, (v) a cyano group, (vi) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 C 1-6 alkyl groups, (vii) a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group optionally substituted by 1 to 3 hydroxy groups, and (viii) a carbamoyl group optionally mono- or di-substituted by substituent(s) selected from a 3- to 8-membered monocyclic non-aromatic heterocyclic group and a C 1-6 alkyl group,
(b) a cyano group,
(c) an amino group optionally mono- or di-substituted by substituent(s) selected from (i) a formyl group, (ii) a C 1-6 alkyl group optionally substituted by 1 to 3 amino groups optionally mono- or di-substituted by C 1-6 alkyl group(s), and (iii) a C 1-6 alkyl-carbonyl group,
(d) a carbamoyl group optionally mono- or di-substituted by substituent(s) selected from (i) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a hydroxy group and a C 1-6 alkoxy group, and (ii) a 3- to 8-membered monocyclic non-aromatic heterocyclic group,
(e) a C 1-6 alkoxy-carbonyl group,
(f) a C 1-6 alkoxy group optionally substituted by 1 to 3 substituents selected from (i) a C 1-6 alkoxy group, (ii) an amino group optionally mono- or di-substituted by substituent(s) selected from a C 1-6 alkyl group and a C 1-6 alkyl-carbonyl group, (iii) a carbamoyl group optionally mono- or di-substituted by C 1-6 alkyl group(s), (iv) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by oxo group(s), (v) a hydroxy group, and (vi) a C 6-14 aryl group optionally substituted by 1 to 3 C 1-6 alkoxy groups,
(g) a 3- to 8-membered monocyclic non-aromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from (i) a C 1-6 alkyl group optionally substituted by 1 to 3 hydroxy groups, (ii) a C 1-6 alkoxy group, (iii) a C 1-6 alkyl-carbonyl group, (iv) an oxo group, (v) a hydroxy group, and (vi) a halogen atom,
(h) a 3- to 8-membered monocyclic non-aromatic heterocyclylcarbonyl group,
(i) a 3- to 8-membered monocyclic non-aromatic heterocyclyloxy group,
(j) a C 3-8 cycloalkyloxy group, and
(k) a hydroxy group].
4. 3 -Amino-5 -(2,6-difluorophenyl)-7(1-methyl-1H-pyrazol-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one or a salt thereof.
5. 2-(3-Amino-7-(1-methyl-1H-pyrazol-3-yl)-4-oxo- 1,4-dihydro-5H-pyrazolo [4,3 -c]pyridin-5-yl)-3-fluorobenzonitrile or a salt thereof.
6. 3-Amino-5-(1-cyclopropylethyl)-7-(1-methyl-1H-pyrazol-3-yl)-1,5-dihydro-4H-pyrazolo[4,3-c]pyridin-4-one or a salt thereof.
7. A pharmaceutical composition comprising the compound or salt of claim 1 and a pharmaceutically acceptable carrier.
8. The pharmaceutical composition of claim 7 , which is a tyrosine kinase 2 inhibitor.