US 2020/0347030 A1 · COMPOUND HAVING CYCLIC STRUCTURE

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:
—CH2—, —O—, or a single bond;
G:
a 5-membered aromatic heterocycle, wherein the ring has at least two bonds;
if the ring has a nitrogen atom(s), then at least one of the nitrogen atom(s) is next to an atom that is attached to a right-hand portion, wherein the right-hand portion refers to the following portion in the compound of formula (1):
wherein the symbols indicating the respective substituents are the same as defined above;
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
A4, A5:
each independently, —CH═ or —N═,
A6, A7:
each independently, —CH2—, —O—, or —NH—,
m1, m2, m3:
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 Y1,
a phenyl group optionally substituted with 1-3 groups independently selected from Substituent group Y1,
a C3-C8 cycloalkyl group optionally substituted with 1-3 groups independently selected from Substituent group Y1, 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 Y1,
a 4-to 7-membered saturated heterocyclic group optionally substituted with 1-3 groups independently selected from Substituent group Y1,
a 4- to 7-membered unsaturated heterocyclic group optionally substituted with 1-3 groups independently selected from Substituent group Y1, or
a group formed by attachment to R7, optionally substituted with 1-3 groups independently selected from Substituent group Y1, selected from the following:
Substituent group Y1:
a hydroxyl group,
an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y2,
a cyano group,
a halogen atom,
a C1-C6 alkyl group optionally substituted with 1-3 groups independently selected from Substituent group Y2,
a C1-C6 alkoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y2,
a 4- to 7-membered saturated heterocyclic group optionally substituted with 1-3 groups independently selected from Substituent group Y2, and
any group optionally substituted with 1-3 groups independently selected from Substituent group Y2, selected from the following:
Substituent group Y2:
a hydroxyl group,
a halogen atom,
a C1-C6 alkyl group optionally substituted with 1-3 groups independently selected from Substituent group Y3,
a C1-C6 alkoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y3,
an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y3,
a 4- to 7-membered saturated heterocyclic group optionally substituted with 1-3 groups independently selected from Substituent group Y3, and
any group optionally substituted with 1-3 groups independently selected from Substituent group Y3, selected from the following:
Substituent group Y3:
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 Y4,
a C1-C6 alkoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y4, and
any group optionally substituted with 1-3 groups independently selected from Substituent group Y4, selected from the following:
Substituent group Y4:
a fluorine atom;
R1, R2, R3:
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 C-C6 alkyl group, a halo C1-C6 alkyl group, a halo C-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 C-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;
R4:
a hydrogen atom, a C1-C6 alkyl group, a halo C1-C6 alkyl group, or a group formed by attachment to R6c or R6d, selected from the following:
wherein m4 is 0, 1, or 2, and Rm4 is a hydrogen atom or a methyl group,
R5:
a hydrogen atom, a halogen atom, or a C1-C6 alkyl group;
R6a, R6b, R6c, R6d:
each independently, a hydrogen atom or a C1-C6 alkyl group;
R7:
a single bond, a hydrogen atom, or a methyl group;
R8:
a hydrogen atom or a methyl group;
and
n1, n2, n3:
each independently, 0, 1, or 2.

67 more elements

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

wherein the symbols in the formula are defined below:
R1:
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;
R6d:
a hydrogen atom or a methyl group;
A1:
═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 Y1,
a phenyl group optionally substituted with 1-3 groups independently selected from Substituent group Y1,
any group optionally substituted with 1-3 groups independently selected from Substituent group Y1, 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 Y1,
any group optionally substituted with 1-3 groups independently selected from Substituent group Y1, 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 Y1;
Substituent group Y1:
a hydroxyl group,
an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y2,
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 Y2,
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 Y2, and
any group optionally substituted with 1-3 groups independently selected from Substituent group Y2, selected from the following:
Substituent group Y2:
a hydroxyl group,
a fluorine atom,
a methyl group optionally substituted with 1-3 groups independently selected from Substituent group Y3,
a methoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y3,
an amino group optionally substituted with 1-2 groups independently selected from Substituent group Y3,
an azetidinyl group, a pyrrolidinyl group or a morpholinyl group optionally substituted with 1-3 groups independently selected from Substituent group Y3, and
any group optionally substituted with 1-3 groups independently selected from Substituent group Y3, selected from the following:
Substituent group Y3:
a hydroxyl group,
a fluorine atom,
a cyano group,
a methyl group optionally substituted with 1-3 groups independently selected from Substituent group Y4, and
a methoxy group optionally substituted with 1-3 groups independently selected from Substituent group Y4;
Substituent group Y4:
a fluorine atom.

42 more elements

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.

13 more elements

A method according to claim 30, wherein the inflammatory disease is a peripheral inflammatory disease.

A method according to claim 30, wherein the inflammatory disease is a central inflammatory disease.

Compound having cyclic structure

Life of this patent

Compound having cyclic structure

Life of this patent

Abstract

Claims44