Compound having cyclic structure

1. A compound of formula (1) or a pharmacologically acceptable salt thereof:

wherein the symbols in the formula are defined below:

A: a 5- to 6-membered aromatic heterocycle, a 4- to 7-membered saturated heterocycle, benzene, cyclohexane or a ring having the following structure, wherein each of the rings has at least one bond;

E: —O—;

G-R 4 :

X: any ring selected from the following rings, wherein the any ring includes a ring condensed with additional atoms to form a bicyclic ring, and wherein the any ring has at least two bonds:

wherein

A 4 , A 5 : each independently, —CH═ or —N═,

A 6 , A 7 : each independently, —CH 2 —, —O—, or —NH—,

m 1 , m 2 , m 3 : each independently, 0, 1, 2, or 3;

J: a 5-membered aromatic heterocycle wherein J is optionally condensed with X to have a bicyclic structure, or a 5-membered unsaturated heterocycle, wherein the ring has at least two bonds;

Y:

an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y 1 ,

a phenyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 ,

a C3-C8 cycloalkyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 , wherein the C3-C8 cycloalkyl group optionally has the following bridged structures:

a C3-C8 cycloalkenyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 ,

a 4- to 7-membered saturated heterocyclic group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 ,

a 4- to 7-membered unsaturated heterocyclic group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 , or

a group formed by attachment to R 7 , optionally substituted with 1-3 groups independently selected from Substituent group Y 1 , selected from the following:

Substituent group Y 1 :

a hydroxyl group,

an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y 2 ,

a cyano group,

a halogen atom,

a C1-C6 alkyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 2 ,

a C1-C6 alkoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y 2 ,

a 4- to 7-membered saturated heterocyclic group optionally substituted with 1-3 groups independently selected from Substituent group Y 2 , and

any group optionally substituted with 1-3 groups independently selected from Substituent group Y 2 , selected from the following:

Substituent group Y 2 :

a hydroxyl group,

a halogen atom,

a C1-C6 alkyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 3 ,

a C1-C6 alkoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y 3 ,

an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y 3 ,

a 4- to 7-membered saturated heterocyclic group optionally substituted with 1-3 groups independently selected from Substituent group Y 3 , and

any group optionally substituted with 1-3 groups independently selected from Substituent group Y 3 , selected from the following:

Substituent group Y 3 :

a hydroxyl group,

a halogen atom,

a cyano group,

a C1-C6 alkyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 4 ,

a C1-C6 alkoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y 4 , and

any group optionally substituted with 1-3 groups independently selected from Substituent group Y 4 , selected from the following:

Substituent group Y 4 :

a fluorine atom;

R 1 , R 2 , R 3 : each independently, a hydrogen atom, a carboxyl group, a cyano group, a halogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group, a C3-C8 cycloalkyl group, a C3-C8 cycloalkoxy group, a hydroxy C1-C6 alkyl group, a halo C1-C6 alkyl group, a halo C1-C6 alkoxy group, a C1-C6 alkoxycarbonyl group, a C1-C6 alkyl C3-C8 cycloalkyl group, a C3-C8 cycloalkyl C1-C6 alkoxy group, a 4- to 7-membered unsaturated heterocyclic group, a C1-C6 alkyl 4- to 7-membered unsaturated heterocyclic group, a di(C1-C6 alkyl)amino 4- to 7-membered unsaturated heterocyclic group, a 4- to 7-membered unsaturated heterocyclic carbonyl group, or a C3-C8 cycloalkylcarbonyl group;

R 5 : a hydrogen atom, a halogen atom, or a C1-C6 alkyl group;

R 6a , R 6b , and R 6c : each a hydrogen atom;

R 6d : a hydrogen atom or a methyl group;

R 7 : a single bond, a hydrogen atom, or a methyl group;

R 8 : a hydrogen atom or a methyl group;

n 1 is 0;

n 2 is 1; and

n 3 is 0, 1, or 2.

2. A compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein A is a 6-membered aromatic heterocycle or benzene, each of which has at least one substituent.

3. A compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein A is pyridine or benzene, each of which has at least one substituent.

4. A compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein X is benzene, pyridine or cyclohexane, each of which has at least two bonds.

5. A compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein J is a ring selected from the following ring group:

and R 7 is a hydrogen atom, or a single bond.

6. A compound or a pharmacologically acceptable salt thereof according to claim 1 , wherein R 1 , R 2 , and R 3 are, each independently, a hydrogen atom, a carboxyl group, a cyano group, a fluorine atom, a chlorine atom, a methyl group, an isopropyl group, a t-butyl group, a trifluoromethyl group, a trifluoromethoxy group, a cyclopropylmethoxy group, a 1,1-difluoro-2-methylpropyl group, a 1,1-difluoro-2,2-dimethylpropyl group, a 1-methyl-1-cyclobutyl group, a methoxycarbonyl group, an ethoxycarbonyl group, an isopropoxycarbonyl group, a 1-hydroxy-1-methylethyl group, an azetidine-1-carbonyl group, a 3-methyloxetan-3-yl group, a 4,5-dihydrooxazol-2-yl group, or a cyclopropylcarbonyl group.

7. A compound or a pharmacologically acceptable salt thereof according to claim 1 having formula (1′) or a pharmacologically acceptable salt thereof:

wherein the symbols in the formula are defined below:

R 1 : a hydrogen atom, a carboxyl group, a cyano group, a fluorine atom, a chlorine atom, a methyl group, an isopropyl group, a t-butyl group, a trifluoromethyl group, a trifluoromethoxy group, a cyclopropylmethoxy group, a 1,1-difluoro-2-methylpropyl group, a 1,1-difluoro-2,2-dimethylpropyl group, a 1-methyl-1-cyclobutyl group, a methoxycarbonyl group, an ethoxycarbonyl group, an isopropoxycarbonyl group, a 1-hydroxy-1-methylethyl group, an azetidine-1-carbonyl group, a 3-methyloxetan-3-yl group, a 4,5-dihydrooxazol-2-yl group, or a cyclopropylcarbonyl group;

A 1 : ═N—, or ═CH—;

X: benzene, pyridine or cyclohexane, each of which has two substituents;

J: any ring selected from the following ring group:

Y:

an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y 1 ,

a phenyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 ,

any group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 , selected from the following:

a cyclobutyl group, a cyclopentyl group, a cyclohexyl group,

a cyclohexenyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 ,

any group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 , selected from the following:

a piperidinyl group, an azetidinyl group, a tetrahydropyranyl group, a morpholinyl group, or

a tetrahydropyridinyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 1 ;

Substituent group Y 1 :

a hydroxyl group,

an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y 2 ,

a cyano group,

a fluorine atom,

a methyl group, an ethyl group or an isopropyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 2 ,

a methoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y2,

an azetidinyl group, a pyrrolidinyl group or a morpholinyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 2 , and

any group optionally substituted with 1-3 groups independently selected from Substituent group Y 2 , selected from the following:

Substituent group Y 2 :

a hydroxyl group,

a fluorine atom,

a methyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 3 ,

a methoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y 3 ,

an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y 3 ,

an azetidinyl group, a pyrrolidinyl group or a morpholinyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 3 , and

any group optionally substituted with 1-3 groups independently selected from Substituent group Y 3 , selected from the following:

Substituent group Y 3 :

a hydroxyl group,

a fluorine atom,

a cyano group,

a methyl group optionally substituted with 1-3 groups independently selected from Substituent group Y 4 , and

a methoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y 4 ;

Substituent group Y 4 :

a fluorine atom.

8. A compound selected from the group consisting of:

4-Fluoro-1-methyl-4-{1-[trans-4-(4-methyl-5-{(1R)-1-[3-(propan-2-yl)phenoxy]ethyl}-4H-1,2,4-triazol-3-yl)cyclohexyl]-1H-1,2,3-triazol-4-yl}piperidine,

4{-4-[(1R)-1-(Azetidin-1-yl)ethyl]phenyl}-1-[trans-4-(4-methyl-5-{[3-(propan-2-yl)phenoxy[methyl}-4H-1,2,4-triazol-3-yl)cyclohexyl}-1H-1,2,3-triazole,

(3R,6S)-N,N-Dimethyl-6-{1-[trans-4-(4-methyl-5-{(1R)-1-[3-(propan-2-yl)phenoxy]ethyl}-4H-1,2,4-triazol-3-yl)cyclohexyl]-1H-1,2,3-triazol-4-yl}tetrahydro-2H-pyran-3-amine,

4-Fluoro-1-methyl-4-{1-[(3R,6S)-6-(4-methyl-5-{[3-(propan-2-yl)phenoxy]methyl}-4H-1,2,4-triazol-3-yl)tetrahydro-2H-pyran-3-yl]-1H-1,2,3-triazol-4-yl}piperidine,

3-{trans-4-[4-(4-Fluoro-1-methylpiperidin-4-yl)-1H-1,2,3-triazol-1-yl]cyclohexyl}-8-[3-(trifluoromethyl)phenoxy]-5,6,7,8-tetrahydro[1,2,4]triazolo [4,3-a]pyridine,

1,5-Anhydro-6-azetidin-1-yl-2,3,4,6-tetradeoxy-2-{4-[trans-4-(4-methyl-5-{[3-(trifluoromethyl)phenoxy]methyl}-4H-1,2,4-triazol-3-yl)cyclohexyl]-1H-1,2,3-triazol-1-yl}-D-erythro-hexitol,

2-({5-[trans-4-(1-{trans-4-[3-(Fluoromethyl)azetidin-1-yl]cyclohexyl}-1H-1,2,3-triazol-4-yl)cyclohexyl]-4-methyl-4H-1,2,4-triazol-3-yl}methoxy)-4-(trifluoromethyl)pyridine,

3-(trans-4-{1-[trans-4-(Azetidin-1-yl)cyclohexyl]-1H-pyrazol-4-yl}cyclohexyl)-4-methyl-5-{[3-(trifluoromethyl)phenoxy]methyl}-4H-1,2,4-triazole,

4-[trans-4-(4-{trans-4-[4-Methyl-5-({[4-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}-1H-pyrazol-1-yl)cyclohexyl]morpholine,

6-[trans-4-(4-{trans-4-[4-Methyl-5-({[4-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}-1H-pyrazol-1-yl)cyclohexyl]-2-oxa-6-azaspiro[3.3]heptane,

6-[trans-4-(4-{trans-4-[4-Methyl-5-({[4-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}-1H-pyrazol-1-yl)cyclohexyl]-1-oxa-6-azaspiro[3.3]heptane,

2-[trans-4-(4-{trans-4-[4-Methyl-5-({[4-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}-1H-pyrazol-1-yl)cyclohexyl]-6-oxa-2-azaspiro[3.4]octane,

{1-[trans-4-(4-{trans-4-[4-Methyl-5-({[4-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}-1H-pyrazol-1-yl)cyclohexyl]azetidine-3,3-diyl}dimethanol,

Methyl 3-{[4-methyl-5-(trans-4-{1-[trans-4-(2-oxa-6-azaspiro[3.3]hept-6-yl)cyclohexyl]-1H-pyrazol-4-yl}cyclohexyl)-4H-1,2,4-triazol-3-yl]methoxy}benzoate,

8-Methyl-3-[trans-4-(4-methyl-5-{(1R)-1-[3-(propan-2-yl)phenoxy]ethyl}-4H-1,2,4-triazol-3-yl)cyclohexyl]-1-oxa-2,8-diazaspiro [4.5]dec-2-ene, and

pharmacologically acceptable salts thereof.

9. The compound according to claim 1 , wherein the compound is 4-Fluoro-1-methyl-4-{1-[trans-4-(4-methyl-5-{(1R)-1-[3-(propan-2-yl)phenoxy]ethyl}-4H-1,2,4-triazol-3-yl)cyclohexyl]-1H-1,2,3-triazol-4-yl}piperidine.

10. The compound according to claim 1 , wherein the compound is (3R,6S)-N,N-Dimethyl-6-{1-[trans-4-(4-methyl-5-{(1R)-1-[3-(propan-2-yl)phenoxy]ethyl}-4H-1,2,4-triazol-3-yl)cyclohexyl]-1H-1,2,3-triazol-4-yl}tetrahydro-2H-pyran-3-amine.

11. The compound according to claim 1 , wherein the compound is 2-({5-[trans-4(1-{trans-4-[3-(Fluoromethyl)azetidin-1-yl]cyclohexyl}-1H-1,2,3-triazol-4-yl)cyclohexyl]-4-methyl-4H-1,2,4-triazol-3-yl}methoxy)-4-(trifluoromethyl)pyridine.

12. The compound according to claim 1 , wherein the compound is 6-[trans-4-(4-[trans-4[4-Methyl-5-({[4-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}-1H-pyrazol-1-yl)cyclohexyl]-2-oxa-6-azaspiro[3.3]heptane.

13. The compound according to claim 1 , wherein the compound is 6-[trans-4-(4-{trans-4-[4-Methyl-5-({[4-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}-1H-pyrazol-1-yl)cyclohexyl]-1-oxa-6-azaspiro[3.3]heptane.

14. The compound according to claim 1 , wherein the compound is 2-[trans-4-(4-{trans-4-[4-Methyl-5-({[4-(trifluoromethyl)pyridin-2-yl]oxy}methyl)-4H-1,2,4-triazol-3-yl]cyclohexyl}-1H-pyrazol-1-yl)cyclohexyl]-6-oxa-2-azaspiro[3.4]octane.

15. The compound according to claim 1 , wherein the compound is Methyl 3-{[4-methyl-5-(trans-4-{-[trans-4-(2-oxa-6-azaspiro[3.3]hept-6-yl)cyclohexyl]-1H-pyrazol-4-yl}cyclohexyl)-4H-1,2,4-triazol-3-yl]methoxy}benzoate.

16. A pharmaceutical composition comprising a compound or a pharmacologically acceptable salt thereof according to claim 1 as an active ingredient.

17. A crystal of a compound according to claim 9 , having peaks at diffraction angles (2θ(°)) of about 3.9, 4.1, 8.34, 12.6, 16.2, 18.4, 19.5 and 22.3 by powder X-ray diffraction.

18. A crystal of a compound according to claim 10 , having peaks at diffraction angles (2θ(°)) of about 3.8, 16.4, 18.0, 18.6, 19.8, 21.2 and 22.7 by powder X-ray diffraction.

19. A crystal of a compound according to claim 11 , having peaks at diffraction angles (2θ(°)) of about 13.5, 15.7, 17.2, 17.8, 18.2, 19.2, 20.4, 20.8, 22.0 and 27.2 by powder X-ray diffraction.

20. A crystal of a compound according to claim 12 , having peaks at diffraction angles (2θ(°)) of about 3.3, 13.4, 15.5, 16.8, 17.5, 17.9, 18.9, 20.4, 21.8 and 26.9 by powder X-ray diffraction.

21. A crystal of a compound according to claim 13 , having peaks at diffraction angles (2θ(°)) of about 13.2, 15.8, 16.5, 17.8, 18.1, 20.3, 20.8, 21.4 and 27.9 by powder X-ray diffraction.

22. A crystal of a compound according to claim 14 , having peaks at diffraction angles (2θ(°)) of about 14.2, 16.8, 17.4, 18.2, 18.6, 19.5, 20.0, 20.9, 21.6 and 21.8 by powder X-ray diffraction.

23. A crystal of a compound according to claim 15 , having peaks at diffraction angles (2θ(°)) of about 15.4, 17.6, 17.9, 18.4, 18.7, 19.2, 20,2, 20.7, 23.0 and 23.8 by powder X-ray diffraction.