Urea derivative or pharmacologically acceptable salt thereof

Patent metadata

Field	Value
Publication number	US-9822069-B2
Application number	US-201415039964-A
Country	US
Kind code	B2
Filing date	Nov 27, 2014
Priority date	Nov 28, 2013
Publication date	Nov 21, 2017
Grant date	Nov 21, 2017

Abstract

Provided is a compound having a formyl peptide receptor like 1 (FPRL1) agonist effect.
The present invention relates to a compound represented by the general formula (I) or a pharmacologically acceptable salt thereof. The present invention also relates to a pharmaceutical composition containing the compound represented by the general formula (I) or a pharmacologically acceptable salt thereof.

First claim

The invention claimed is:

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

wherein Ar 1 is a phenyl group optionally having substituent(s), a 5-membered aromatic heterocyclic group optionally having substituent(s), a 6-membered aromatic heterocyclic group optionally having substituent(s), or a bicyclic aromatic heterocyclic group having 8 or 9 atoms and optionally having substituent(s);
Ar 2 is a phenyl group optionally having substituent(s) (except for a phenyl group substituted only with halogen atom(s)), a 5-membered aromatic heterocyclic group optionally having substituent(s), a 6-membered aromatic heterocyclic group optionally having substituent(s), or a bicyclic aromatic heterocyclic group having 8 or 9 atoms and optionally having substituent(s);
X is a group selected from the group consisting of the following a), b), and c),
a) an oxygen atom or a sulfur atom,
b) NR 4 , and
c) NOR 4 , wherein,

when X is b) or c), R 4 is a hydrogen atom, a phenyl group optionally having substituent(s), a heterocyclic group optionally having substituent(s), or a C 1 to C 6 alkyl group optionally having substituent(s);
R 1 is a hydrogen atom, a hydroxy group, a C 1 to C 6 alkoxy group optionally having substituent(s), or a C 1 to C 6 alkyl group optionally having substituent(s);
R 2 and R 3 are each independently a hydrogen atom or a C 1 to C 6 alkyl group optionally having substituent(s) or R 2 and R 3 together form a C 2 to C 6 alkylene group; and
each carbon atom marked with an asterisk is an asymmetric carbon atom.

2. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein
Ar 2 is a group selected from the group consisting of the following A1), A2), A3), A4), A5), A6), A7), A8), A9), and A10):

wherein, when Ar 2 is A2), W 1 is a nitrogen atom or CH optionally substituted with a hydrogen atom, with a halogen atom, or with a C 1 to C 6 alkyl group optionally having substituent(s);
when Ar 2 is A2), W 2 is CH or a nitrogen atom;
when Ar 2 is A3), A4), A5), or A6), W 3 is an oxygen atom, a sulfur atom, or NH optionally substituted with a C 1 to C 6 alkyl group;
when Ar 2 is A3), A4), or A6), W 4 is CH or a nitrogen atom;
when Ar 2 is A7), W 5 is CH 2 , an oxygen atom, or a sulfur atom;
when Ar 2 is A7), W 6 is C═O, CH 2 , CF 2 , CHOH, NH optionally substituted with a C 1 to C 6 alkyl group, SO, SO 2 , an oxygen atom, or a sulfur atom;
when Ar 2 is A8), W 7 is NH optionally substituted with a C 1 to C 6 alkyl group or C═O;
when Ar 2 is A8), W 8 is C═O with W 7 being NH optionally substituted with a C 1 to C 6 alkyl group and W 8 is NH optionally substituted with a C 1 to C 6 alkyl group with W 7 being C═O;
when Ar 2 is A10), W 9 is a nitrogen atom or N═O;
when Ar 2 is A1), A2), A3), A4), or A5), R 6 is a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a C 1 to C 6 alkyl group optionally having substituent(s), a C 1 to C 6 alkoxy group optionally having substituent(s), a C 1 to C 6 acyl group optionally having substituent(s), a C 1 to C 6 alkylsulfanyl group optionally having substituent(s), a C 1 to C 6 alkylsulfinyl group optionally having substituent(s), a C 1 to C 6 alkylsulfonyl group optionally having substituent(s), a heterocyclic group optionally having substituent(s), —CONR 10 R 11 , or —NR 10 R 11 , wherein, when R 6 is —CONR 10 R 11 or —NR 10 R 11 , R 10 is a hydrogen atom, a C 1 to C 6 alkyl group optionally having substituent(s), a C 1 to C 6 acyl group optionally having substituent(s), or a C 1 to C 6 alkylsulfonyl group optionally having substituent(s) and R 11 is a hydrogen atom or a C 1 to C 6 alkyl group optionally having substituent(s), or R 10 and R 11 together form a C 3 to C 10 heterocycloalkyl group;
when Ar 2 is A1), A2), A3), A4), A5), A6), A7), A8), A9), or A10), R 7 is a hydrogen atom, a halogen atom, a C 1 to C 6 alkyl group optionally having substituent(s), or a C 1 to C 6 alkoxy group optionally having substituent(s);
when Ar 2 is A1), A7), A8), or A10), R 8 is a hydrogen atom, a halogen atom, or a C 1 to C 6 alkyl group optionally having substituent(s);
when Ar 2 is A9), R 9 is a hydrogen atom or a C 1 to C 6 alkyl group;
when Ar 2 is A7), m is 0 or 1; and
when Ar 2 is A8), n is 0 or 1;
provided that, when Ar 2 is A1), combinations of the substituents R 6 , R 7 and R 8 exclude a combination of a hydrogen atom and a halogen atom.

3. The compound according to claim 2 or a pharmacologically acceptable salt thereof, wherein
Ar 1 is a group selected from the group consisting of the following B1), B2), B3), B4), B5), B6), B7), B8), B9), B10), B11), and B12):

wherein, when Ar 1 is B2), B3), B7), B8), B10), B11), or B12), R 12 is a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a C 1 to C 6 alkyl group optionally having substituent(s), a C 1 to C 6 alkoxy group optionally having substituent(s), a C 3 to C 6 cycloalkyl group optionally having substituent(s), a C 3 to C 6 cycloalkoxy group optionally having substituent(s), a C 1 to C 6 acyl group optionally having substituent(s), a C 2 to C 6 alkenyl group optionally having substituent(s), a C 2 to C 6 alkynyl group optionally having substituent(s), a C 1 to C 6 alkoxycarbonyl group, a C 1 to C 6 alkylsulfanyl group optionally having substituent(s), a C 1 to C 6 alkylsulfinyl group optionally having substituent(s), a C 1 to C 6 alkylsulfonyl group optionally having substituent(s), —CONR 10 R 11 , —NR 10 R 11 , an aryloxy group, or a heterocyclic group optionally having substituent(s), wherein, when R 12 is —CONR 10 R 11 or —NR 10 R 11 , R 10 is a hydrogen atom, a C 1 to C 6 alkyl group optionally having substituent(s), a C 1 to C 6 acyl group optionally having substituent(s), or a C 1 to C 6 alkylsulfonyl group optionally having substituent(s) and R 11 is a hydrogen atom or a C 1 to C 6 alkyl group optionally having substituent(s), or R 10 and R 11 together form a C 3 to C 10 heterocycloalkyl group;
when Ar 1 is B1), R 12 is a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a C 1 to C 6 alkyl group optionally having substituent(s), a C 1 to C 6 alkoxy group optionally having substituent(s), a C 3 to C 6 cycloalkyl group optionally having substituent(s), a C 3 to C 6 cycloalkoxy group optionally having substituent(s), a C 1 to C 6 acyl group optionally having substituent(s), a C 2 to C 6 alkenyl group optionally having substituent(s), a C 2 to C 6 alkynyl group optionally having substituent(s), a C 1 to C 6 alkoxycarbonyl group, a C 1 to C 6 alkylsulfanyl group optionally having substituent(s), a C 1 to C 6 alkylsulfinyl group optionally having substituent(s), a C 1 to C 6 alkylsulfonyl group optionally having substituent(s), —CONR 10 R 11 , —NR 10 R 11 , an aryloxy group, or a heterocyclic group optionally having substituent(s), wherein, when R 12 is —CONR 10 R 11 or —NR 10 R 11 , R 10 is a hydrogen atom, a C 1 to C 6 alkyl group optionally having substituent(s), a C 1 to C 6 acyl group optionally having substituent(s), or a C 1 to C 6 alkylsulfonyl group optionally having substituent(s) and R 11 is a hydrogen atom or a C 1 to C 6 alkyl group optionally h

Assignees

• Kyorin Seiyaku Kk
• Kyorin Seiyaku Kk

Inventors

• Takahashi Hiroyasu
• Saito Yoshifumi
• Tsuda Kosuke
• Shibasaki Mitsuhito
• Ohata Kohei

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title