US 10,858,314 B2 · Urea derivative or pharmacologically acceptable salt thereof

Abstract

The present invention provides a urea compound or a pharmacologically acceptable salt thereof that has a formyl peptide receptor like 1 (hereinafter may be abbreviated as FPRL1) agonist effect, a pharmaceutical composition containing the urea compound or the pharmacologically acceptable salt thereof and a pharmaceutical use thereof. It has been found that a urea derivative represented by the general formula (I) below or a pharmacologically acceptable salt thereof has a superior FPRL1 agonist effect. Compound (I) or a pharmacologically acceptable salt thereof is highly useful for treatment, prevention, or suppression of inflammatory diseases, chronic airway diseases, cancers, septicemia, allergic symptoms, HIV retrovirus infection, circulatory disorders, neuroinflammation, nervous disorders, pains, prion diseases, amyloidosis, immune disorders and the like.

A compound represented by the formula (I) or a pharmacologically acceptable salt thereof:

wherein
in the formula (I), Ar1 is a phenyl group optionally having substituent(s), a monocyclic aromatic heterocyclyl group optionally having substituent(s), or a bicyclic aromatic heterocyclyl group having 9 or 10 atoms and optionally having substituent(s);
Ar2 is a group selected from the group consisting of B1a) and B4a):
wherein when Ar2 is B1a), R8 is a fluorine atom, a chlorine atom, a cyano group, a C1 to C3 alkyl group, a C1 to C3 alkyloxy group, a C1 to C3 acyl group, or a hydroxy C1 to C4 alkyl group;
and
R9 is a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, or a C1 to C3 alkyl group;
R1 is a hydrogen atom, a C1 to C3 alkyl group, or —CONXY;
X and Y are independently a hydrogen atom or a C1 to C3 alkyl group;
A is a group selected from the group consisting of a cyano group, a hydroxy group, or the following A1), A2), A3), A4), A5), A6), A7), A8), A9), and A10):
wherein R2 is a hydrogen atom or a C1 to C6 alkyl group optionally having substituent(s);
R3 is a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a carboxyl group, a C1 to C6 alkyl group optionally having substituent(s), a C1 to C6 alkyloxy group optionally having substituent(s), a C1 to C6 alkyloxycarbonyl group, a C1 to C6 acyl group optionally having substituent(s), a C1 to C6 alkylsulfanyl group optionally having substituent(s), a C1 to C6 alkylsulfinyl group optionally having substituent(s), a C1 to C6 alkylsulfonyl group optionally having substituent(s), a heterocyclyl group optionally having substituent(s), —CONR5R6, or —NR5R6, wherein when R3 is —CONR5R6 or —NR5R6, then R5 is a hydrogen atom, a C1 to C6 alkyl group optionally having substituent(s), a C1 to C6 acyl group optionally having substituent(s), or a C1 to C6 alkylsulfonyl group optionally having substituent(s), and R6 is a hydrogen atom or a C1 to C6 alkyl group optionally having substituent(s), or R5 and R6 may together form a 3- to 10-membered heterocycloalkyl group;
Z is a hydrogen atom, hydroxy group, a C1 to C6 alkyl group optionally having substituent(s), a C1 to C6 acyl group optionally having substituent(s), a C1 to C6 alkyloxy group optionally having substituent(s), a carboxy C1 to C6 alkyl group optionally having substituent(s), or a C1 to C6 alkylsulfonyl group optionally having substituent(s);
R4 is a C1 to C3 alkyl group optionally having substituent(s);
W1 is C—R7 or a nitrogen atom;
R7 is a hydrogen atom or a C1 to C6 alkyl group optionally having substituent(s);
and
W2 is an oxygen atom, a sulfur atom, or N—R2;
wherein said optional substituents are halogen atoms, an amino group, a hydroxy group, a cyano group, a nitro group, a carboxy group, C1 to C6 alkyloxycarbonyl groups, a formyl group, C1 to C6 acyl groups, C1 to C6 alkyl groups, C1 to C6 alkylamino groups, C1 to C6 alkyloxy groups, C1 to C6 alkylsulfanyl groups, C3 to C6 cycloalkyl groups, 3- to 10-membered heterocycloalkyl groups, aromatic hydrocarbon cyclic groups optionally having a halogen atom, heterocyclyl groups, C1 to C6 acylamino groups, C3 to C6 cycloalkylcarbonylamino groups, 3- to 10-membered heterocycloalkylcarbonylamino groups, aromatic hydrocarbon cyclic carbonylamino groups, or heterocyclyl carbonylamino groups;
L is a single bond or a C1 to C3 alkylene;
and
each carbon atom marked with an asterisk is an asymmetric carbon atom when the carbon is a tertiary carbon atom.

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Urea derivative or pharmacologically acceptable salt thereof

Life of this patent

Urea derivative or pharmacologically acceptable salt thereof

Life of this patent

Abstract

Claims10