Bicyclic or tricyclic heterocyclic compound

Patent metadata

Field	Value
Publication number	US-10065972-B2
Application number	US-201514891845-A
Country	US
Kind code	B2
Filing date	Apr 22, 2015
Priority date	Apr 23, 2014
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

Abstract

The present invention provides a novel bicyclic or tricyclic heterocyclic compound represented by the formula (I)

wherein ring A is an optionally substituted aromatic group,
one of X 1 and X 2 is a carbon atom, and the other is a nitrogen atom, X 3 is a nitrogen atom, or CR 2 , X 4 is a nitrogen atom, or CR 3 , X 5 is a sulfur atom, or —CH═CH—, Z 1 is an oxygen atom, —C(R 6 )(R 7 )—, —NH—, —C(R 6 )(R 7 )—NH—, —NH—C(R 6 )(R 7 )—, —C(R 6 )(R 7 )—O—, —O—C(R 6 )(R 7 )—, or a single bond, one of Z 2 and Z 3 is CH and the other is a nitrogen atom, or both are nitrogen atoms, and other symbols are as defined in the DESCRIPTION, or a pharmacologically acceptable salt thereof.

First claim

The invention claimed is:

1. A compound represented by the formula (I):

wherein ring A is an optionally substituted aromatic group,
one of X 1 and X 2 is a carbon atom, and the other is a nitrogen atom,
X 3 is a nitrogen atom, or CR 2 ,
X 4 is a nitrogen atom, or CR 3 ,
X 5 is a sulfur atom, or —CH═CH—,
Z 1 is an oxygen atom, —C(R 6 )(R 7 )—, —NH—, —C(R 6 )(R 7 )—NH—, —NH—C(R 6 )(R 7 )—, —C(R 6 )(R 7 )—O—, or —O—C(R 6 )(R 7 )—, or is a single bond directly linking the adjacent carbonyl group to ring A
one of Z 2 and Z 3 is CH and the other is a nitrogen atom, or both are nitrogen atoms,
R 1 is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl, an optionally substituted nonaromatic heterocyclic group, or a halogen atom,
R 2 is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted amino, optionally substituted aryl, an optionally substituted nonaromatic heterocyclic group, optionally substituted heteroaryl, optionally substituted alkoxy, or optionally substituted cycloalkoxy,
or, R 1 and R 2 are bonded to each other to form, together with the adjacent X 2 and carbon atom, an optionally substituted ring,
R 3 is a hydrogen atom, optionally substituted alkyl, optionally substituted cycloalkyl, or a halogen atom,
R 4 and R 5 are each independently a hydrogen atom, or optionally substituted alkyl,
or, R 4 and R 5 are bonded to each other to form, together with the adjacent Z 2 and Z 3 , an optionally substituted nitrogen-containing non-aromatic heterocycle,
R 6 and R 7 are each independently a hydrogen atom, optionally substituted alkyl, or optionally substituted cycloalkyl,
or, R 6 and R 7 are bonded to each other to form, together with the adjacent carbon atom, an optionally substituted cycloalkane,
a part represented by the following formula in the aforementioned formula (I):

is
(A) when X 1 is a carbon atom and X 2 is a nitrogen atom, a group represented by the following formula (i-a):

 and
(B) when X 1 is a nitrogen atom and X 2 is a carbon atom, a group represented by the following formula (i-b):

provided (a) when a part represented by the following formula in the aforementioned formula (I):

is a group represented by the formula (ii-a):

(a-1) Z 2 is a nitrogen atom, and Z 3 is CH or a nitrogen atom;
(a-2) Z 2 is CH, and Z 3 is a nitrogen atom, and a part represented by the following formula in the formula (I):

is a group represented by the formula (v-x):

 or
(a-3) Z 2 is CH, and Z 3 is a nitrogen atom, and a part represented by the following formula in the formula (I):

is a group represented by the formula (v-y):

and a part represented by the following formula in the formula (I):

is a group represented by the formula (iii-a), (iii-b), or (iii-c):

wherein R 6x and R 7x are each optionally substituted alkyl or R 6x and R 7x are bonded to each other to form, together with the adjacent carbon atom, an optionally substituted cycloalkane, R 8x is halogenoalkyl, or a fluorine atom, and
(b) when a part represented by the following formula in the aforementioned formula (I):

is a group represented by the formula (ii-b):

(b-1) Z 2 is a nitrogen atom, and Z 3 is CH or a nitrogen atom; or
(b-2) Z 2 is CH, and Z 3 is a nitrogen atom,
R 4 and R 5 are bonded to each other to form, together with the adjacent Z 2 and Z 3 , an optionally substituted nitrogen-containing non-aromatic heterocycle, and a part represented by the following formula in the formula (I):

is a group represented by the formula (iii-d):

or a pharmacologically acceptable salt thereof.

2. The compound according to claim 1 , wherein, in the formula (I), the part represented by the following formula:

is a group represented by the formula (iv-a), (iv-b), (iv-c), (iv-d), (iv-e), (iv-f), or (iv-g):

or a pharmacologically acceptable salt thereof.

3. The compound according to claim 2 , wherein
ring A is a 5- to 11-membered monocyclic or bicyclic aromatic group optionally containing, besides carbon atom, 1-4 hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, wherein said aromatic group is optionally substituted by the same or different 1, 2 or 3 groups selected from the group consisting of (1) alkyl optionally substituted by the same or different 1-7 groups selected from the group consisting of amino optionally substituted by 1 or 2 alkyls, alkoxy, and a halogen atom; (2) cyano; (3) amino optionally substituted by 1 or 2 alkyls; (4) alkoxy optionally substituted by 1-7 halogen atoms; and (5) a halogen atom,
R 1 is (a) a hydrogen atom; (b) alkyl optionally substituted by the same or different 1-7 groups selected from the group consisting of amino (wherein said amino is optionally substituted by the same or different 1 or 2 groups selected from the group consisting of alkyl, halogenoalkyl, and alkoxycarbonyl), hydroxy, alkoxy, a halogen atom, phenyl, alkoxyphenyl, and a 4- to 7-membered monocyclic nonaromatic heterocyclic group containing, besides carbon atom, 1 or 2 hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, wherein said nonaromatic heterocyclic group is optionally substituted by the same or different 1, 2 or 3 groups selected from the group consisting of alkyl, and alkoxycarbonyl; (c) cycloalkyl optionally substituted by 1, 2 or 3 alkoxyalkyls; (d) a halogen atom; (e) phenyl; or (f) a 4- to 7-membered monocyclic nonaromatic heterocyclic group containing, besides carbon atom, 1 or 2 hetero atoms selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, wherein said nonaromatic heterocyclic group is optionally substituted by the same or different 1, 2

Assignees

• Mitsubishi Tanabe Pharma Corp

Inventors

• Okuyama Masahiro
• Fukunaga Kenji
• Usui Kenji
• Hayashi Norimitsu
• Iijima Daisuke
• Horiuchi Hideki
• Itagaki Noriaki

Classifications

• A61P43/00

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• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title