Tetrahydronaphthalene derivative

Patent metadata

Field	Value
Publication number	US-10730830-B2
Application number	US-201716073620-A
Country	US
Kind code	B2
Filing date	Jan 27, 2017
Priority date	Jan 29, 2016
Publication date	Aug 4, 2020
Grant date	Aug 4, 2020

Abstract

A compound of general formula (I-1):

wherein the symbols are defined in the specification, has a selective S1P 5 receptor binding activity and modulates the function of an S1P 5 receptor, and can therefore be a therapeutic agent for a S1P 5 -mediated disease, for example, neurodegenerative diseases such as schizophrenia, Binswanger's disease and the like.

First claim

The invention claimed is:

1. A compound represented by general formula (I-1):

wherein, X 1 and X 2 each represent independently a CH 2 or an NH, provided that X 1 and X 2 are not represent NH at the same time,
Y represents (1) —CH 2 —, (2) —NH—, (3) —S— or (4) —O—,
W A represents (1) a C1-12 alkylene group, (2) a C2-12 alkenylene group, (3) a C2-12 alkynylene group, (4) —C1-12 alkylene-O—, (5) —C2-12 alkenylene-O—, (6) —C2-12 alkynylene-O—, (7) —C1-12 alkylene-ring2-, (8) —C2-12 alkenylene-ring2- or (9) —C2-12 alkynylene-ring2-, wherein, an alkylene group, an alkenylene group and an alkynylene group may be substituted with one to five halogen atoms,
R 1 represents (1) -L-, (2) -L-ring3- or (3) -L-NR 13— ,
R 2 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, or (4) a C1-4 haloalkoxy group,
R 3-1 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkoxy group, (6) a nitrile group, (7) —S—C1-4 alkyl group, (8) —S—C1-4 haloalkyl group or (9) an oxo group, provided that the C1-4 alkyl group or the C1-4 haloalkyl group represented by R 3-1 is branched chain, C1-2 alkyl groups branched from the same carbon atom may be taken together with a carbon atom to which they are bound, to form a C3-4 saturated carbocyclic ring,
R 13 represents (1) a hydrogen atom or (2) a C1-4 alkyl group,
L represents a group represented by general formula

wherein, R 11 and R 12 each represent independently a hydrogen atom or a C1-4 alkyl group, or R 11 and R 12 may be taken together with a carbon atom to which they are bound, to form a C3-7 carbocyclic ring, and t represents an integer of 1 to 6,
Z represents (1) a carboxyl group which may be substituted with a C1-8 alkyl group, (2) a hydroxamic acid group which may be substituted with a C1-8 alkyl group, (3) a sulfonic acid group which may be substituted with a C1-8 alkyl group, (4) a boronic acid group which may be substituted with a C1-8 alkyl group, (5) a carbamoyl group which may be substituted with a C1-8 alkyl group, (6) a sulfamoyl group which may be substituted with a C1-8 alkyl group, (7) a sulfoximine group which may be substituted with a C1-8 alkyl group or (8) a tetrazolyl group,
ring 1 represents a C3-10 carbocyclic ring,
ring 2 represents (1) a C3-7 carbocyclic ring or (2) a 3- to 7-membered heterocyclic ring,
ring 3 represents (1) a C3-7 carbocyclic ring which may be substituted with a C1-4 alkyl group or (2) a 3- to 7-membered heterocyclic ring which may be substituted with a C1-4 alkyl group,
m represents an integer of 0 to 2,
n represents an integer of 0 to 2,
p represents an integer of 0 to 3,
q represents an integer of 0 to 5,
v represents an integer of 0 to 1,
when p is 2 or more, a plurality of R 2 s may be the same or different,
when q is 2 or more, a plurality of R 3-1 s may be the same or different,
when t is 2 or more, a plurality of R 11 s may be the same or different, and
when t is 2 or more, a plurality of R 12 s may be the same or different, or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , which is represented by the following general formula (I):

wherein, W represents (1) a C1-6 alkylene group, (2) a C2-6 alkenylene group, (3) a C2-6 alkynylene group, (4) a —C1-6 alkylene-O—, (5) a —C2-6 alkenylene-O—, (6) a —C2-6 alkynylene-O— or (7) a —C1-6 alkylene-ring2-,
R 3 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkoxy group, (6) a nitrile group, (7) a —S—C1-4 alkyl group, or (8) a —S—C1-4 haloalkyl group, provided that the C1-4 alkyl group or the C1-4 haloalkyl group represented by R 3 is branched chain, C1-2 alkyl groups branched from the same carbon atom may be taken together with a carbon atom to which they are bound, to form a C3-4 saturated carbocyclic ring,
when q is 2 or more, a plurality of R 3 s may be the same or different and other symbols have the same meanings as described in claim 1 , or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein Y is —CH 2 — or —O—, or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein ring 3 is a C3-7 saturated carbocyclic ring which may be substituted with a C1-4 alkyl group, or a 3- to 7-membered saturated heterocyclic ring which may be substituted with a C1-4 alkyl group, or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 1 , wherein Z is a carboxyl group which may be substituted with a C1-8 alkyl group, or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising
the compound represented by general formula (I-1) according to claim 1 , or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.

7. A method for treating a S1P 5 -mediated disease, comprising administering to a mammal in need thereof an effective amount of a compound represented by general formula (I-1), or a pharmaceutically acceptable salt thereof:

wherein, X 1 and X 2 each represent independently a CH 2 or an NH, provided that X 1 and X 2 are not represent NH at the same time,
Y represents (1) —CH 2 — (2) —NH—, (3) —S— or (4) —O—,
W A represents (1) a C1-12 alkylene group, (2) a C2-12 alkenylene group, (3) a C2-12 alkynylene group, (4) —C1-12 alkylene-O—, (5) —C2-12 alkenylene-O—, (6) —C2-12 alkynylene-O—, (7) —C1-12 alkylene-ring2-, (8) —C2-12 alkenylene-ring2-, or (9) —C2-12 alkynylene-ring2-, wherein, an alkylene group, an alkenylene group and an alkynylene group may be substituted with one to five halogen atoms,
R 1 represents (1) -L-, (2) -L-ring3- or (3) -L-NR 13- ,
R 2 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, or (4) a C1-4 haloalkoxy group,
R 3-1 represents (1) a halogen atom, (2) a C1-4 alkyl group, (3) a C1-4 haloalkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkoxy group, (6) a nitrile group, (7) —S—C1-4 alkyl group, (8) —S—C1-4 haloalkyl group or (9) an oxo group, provided that the C1-4 alkyl group or the C1-4 haloalkyl group represented by R 3-1 is branched chain, C1-2 alkyl groups branched from the same carbon atom may be taken together with a carbon atom to which they are bound, to form a C3-4 saturated carbocyclic ring,
R 13 represents (1) a hydrogen atom or (2) a C1-4 alkyl group,
L represents (1) a bond or (2) a group represented by general formula

wherein, R 11 and R 12 each represent independently a hydrogen atom or a C1-4 alkyl group, or R 11 and R 12 may be taken together with a carbon atom to which they are bound, to form a C3-7 carbocyclic ring, and t represents an integer of 1 to 6,
Z represents (1) a carboxyl group which may be substituted with a C1-8 alkyl group, (2) a hydroxy group which may be substituted with a C1-8 alkyl group, (3) a hydroxamic acid group which may be substituted with a C1-8 alkyl group, (4) a sul

Assignees

• Ono Pharmaceutical Co

Inventors

• Watanabe Toshihide
• Kusumi Kensuke
• Inagaki Yuichi

Classifications

• C07D223/06

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms (halogen atoms C07D223/04) · CPC title

• C07C229/46

  having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton · CPC title

• A61K31/402

  1-aryl substituted, e.g. piretanide · CPC title

• C07D217/16

  substituted by oxygen atoms · CPC title

• C07D217/04

  with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom · CPC title