US 10,689,354 B2 · Aminoazole derivative

Abstract

A compound, represented by the following formula or a medically acceptable salt thereof, having an effect of regulating the activity of an androgen receptor. In the formula, X represents S, O; Z represents (Ra)n-A-(CR13R14)0-1—(CR11R12)0-1; A represents aryl, heteroaryl; R1 represents alkyl, cycloalkyl, alkenyl, alkynyl, alkoxyalkyl, aryl, arylalkyl, heterocycle, heterocyclic alkyl; R2 represents hydrogen, halogen, alkyl, cycloalkyl, phenyl; R3 represents hydrogen, halogen, alkyl, cycloalkyl, alkoxyalkyl, alkenyl, alkynyl, cycloalkenyl, aryl, arylalkyl, heterocycle, heterocyclic alkyl, acyl, cycloalkylcarbonyl, benzoyl, spiroalkyl, adamantyl, silyl, R31R32NCO—; R4 and R5 represent hydrogen, halogen, alkyl, phenyl, and cycloalkyl.

A compound represented by the following formula (I) or a medically acceptable salt thereof,

wherein,
X represents a sulfur atom or an oxygen atom,
Z represents a group selected among the following Z1 to Z3,
A represents a C6-C12 aryl or a 5-12 membered heteroaryl group,
R11 to R14 represent each independently a hydrogen atom;
a halogen;
a hydroxyl group;
a C1-C3 alkyl group optionally substituted with a halogen or a hydroxyl group;
a C1-C3 alkoxy group optionally substituted with a halogen or a hydroxyl group;
also, two selected from R11 to R14 may form a ring,
n is an integer of 0 or more and 3 or less,
Ra's are the same or different, and represent a halogen;
a hydroxyl group;
a C1-C6 alkyl group optionally substituted with a halogen, a hydroxyl group, a phenoxy group or a benzyloxy group;
a C3-C8 cycloalkyl group optionally substituted with a halogen;
a C1-C6 alkoxy group optionally substituted with a halogen, a hydroxyl group, a carboxyl group, a carbamoyl group optionally substituted with a C1-C4 alkyl group, a C1-C4 alkoxy group or a benzyloxy group;
a C3-C8 cycloalkoxy group optionally substituted with a halogen;
a C1-C4 alkoxy C1-C4 alkyl group optionally substituted with a halogen, a hydroxyl group, a cyano group, a C1-C4 alkoxy group or a benzyloxy group;
a phenoxy group;
a benzyloxy group;
a cyano group;
a nitro group;
a carboxyl group;
a C1-C6 acyl group;
a C1-C4 alkoxycarbonyl group;
an amino group;
a C1-C6 monoalkylamino group;
a C1-C6 dialkylamino group;
a carbamoyl group optionally substituted with a C1-C4 alkyl group;
a C6-C12 aryl group optionally substituted with a halogen, a cyano group, a C1-C4 alkyl group optionally substituted with a halogen, or a hydroxyl group;
a 3-12 membered heterocyclic group optionally substituted with a halogen;
a sulfanyl group optionally substituted with a C1-C6 alkyl group optionally substituted with a halogen;
a C1-C6 alkylsulfinyl group optionally substituted with a halogen;
a C1-C6 alkylsulfonyl group optionally substituted with a halogen;
or a pentafluorosulfanyl group,
R1 represents a C1-C9 alkyl group optionally substituted with a halogen, a hydroxyl group, a cyano group, a carboxyl group, a C1-C4 alkoxycarbonyl group, an amino group, a C1-C6 monoalkylamino group, a C1-C6 dialkylamino group or a C1-C6 alkylsulfonyl group;
a C3-C8 cycloalkyl group optionally substituted with a halogen, a hydroxyl group or a cyano group;
a C2-C6 alkenyl group optionally substituted with a halogen or a phenyl group;
a C2-C6 alkynyl group optionally substituted with a halogen or a phenyl group;
a C1-C6 alkoxy C1-C6 alkyl group optionally substituted with a halogen, a hydroxyl group, a cyano group or a C1-C4 alkoxy group;
a C6-C12 aryl group optionally substituted with 1 to 3 moieties of Rc;
a C6-C12 aryl C1-C6 alkyl group optionally substituted with 1 to 3 moieties of Rd;
a 3-12 membered heterocyclic group optionally substituted with 1 to 3 moieties of Re;
or a 3-12 membered heterocyclic C1-C6 alkyl group optionally substituted with 1 to 3 moieties of Rf,
R2 represents a hydrogen atom;
a halogen;
a C1-C6 alkyl group optionally substituted with a halogen, a hydroxyl group or a cyano group;
a C3-C8 cycloalkyl group optionally substituted with a halogen, a hydroxyl group or a cyano group;
or a phenyl group optionally substituted with a halogen, a hydroxyl group or a cyano group,
R3 represents a hydrogen atom;
a halogen;
a C1-C12 alkyl group optionally substituted with a halogen, a hydroxyl group, a cyano group, a carboxyl group, a C3-C8 cycloalkyl group optionally substituted with a halogen or a hydroxyl group, a C3-C8 cycloalkoxy group optionally substituted with a halogen or a hydroxyl group, a C1-C4 alkoxy group optionally substituted with a phenyl group, a C1-C4 alkoxycarbonyl group, an amino group, a C1-C6 monoalkylamino group, a C1-C6 dialkylamino group, a C1-C6 alkylsulfonyl group, a phenoxy group or a silyl group substituted with a C1-C4 alkyl group or a phenyl group;
a C3-C8 cycloalkyl group optionally substituted with a halogen, a hydroxyl group, a cyano group, a carboxyl group, a C1-C4 alkyl group optionally substituted with a halogen or a hydroxyl group, a C1-C4 alkoxy group optionally substituted with a halogen or a hydroxyl group, a C1-C4 alkoxycarbonyl group, an amino group, a C1-C6 monoalkylamino group, a C1-C6 dialkylamino group or a C1-C6 alkylsulfonyl group;
a C1-C6 alkoxy C1-C6 alkyl group optionally substituted with a halogen, a hydroxyl group, a cyano group or a C1-C4 alkoxy group;
a C2-C9 alkenyl group optionally substituted with a halogen, a hydroxyl group or a cyano group;
a C2-C9 alkynyl group optionally substituted with a halogen or a cyano group;
a C3-C8 cycloalkenyl group optionally substituted with halogen, a hydroxyl group or a cyano group;
a C6-C12 aryl group optionally substituted with 1 to 5 moieties of Rg;
a C6-C12 aryl C1-C6 alkyl group optionally substituted with 1 to 5 moieties of Rh;
a 3-12 membered heterocyclic group optionally substituted with 1 to 5 moieties of Ri;
a 3-12 membered heterocyclic C1-C6 alkyl group optionally substituted with 1 to 5 moieties of Rj;
a C1-C9 acyl group optionally substituted with a halogen, a hydroxyl group or a cyano group;
a C3-C8 cycloalkylcarbonyl group;
a benzoyl group;
a C5-C12 spiroalkyl group;
an adamantyl group;
a silyl group substituted with 1 to 3 moieties of C1-C4 alkyl group or a phenyl group;
or R30,
wherein,
R30 is a substituent represented by the above-mentioned formula,
R31 and R32 represent each independently a hydrogen atom;
a C1-C6 alkyl group optionally substituted with a halogen;
a C3-C8 cycloalkyl group optionally substituted with a halogen;
or a phenyl group optionally substituted with a halogen;
and R31 and R32 may form a ring by connecting directly with each other or via an oxygen atom, a nitrogen atom or a sulfur atom,
R4 and R5 represent each independently a hydrogen atom;
a halogen;
a C1-C6 alkyl group optionally substituted with a halogen, a hydroxyl group or a cyano group;
a phenyl group or a C3-C8 cycloalkyl group optionally substituted with a halogen, a hydroxyl group or a cyano group;
and R3 and R4 may form a ring,
Rc, Rd, Re and Rf represent a halogen;
a hydroxyl group;
a C1-C6 alkyl group optionally substituted with a halogen;
a C3-C8 cycloalkyl group optionally substituted with a halogen;
a C1-C6 alkoxy group optionally substituted with a halogen;
a C3-C8 cycloalkoxy group optionally substituted with a halogen;
a C1-C4 alkoxy C1-C4 alkyl group optionally substituted with a halogen, a hydroxyl group, a phenyl group or a C1-C4 alkoxy group;
a cyano group;
a nitro group;
an oxo group;
a carboxyl group;
a C1-C6 acyl group;
a C1-C4 alkoxycarbonyl group;
an amino group;
a C1-C6 monoalkylamino group;
a C1-C6 dialkylamino group;
a sulfanyl group;
a C1-C6 alkylsulfanyl group optionally substituted with a halogen;
a C1-C6 alkylsulfinyl group optionally substituted with a halogen;
or a C1-C6 alkylsulfonyl group optionally substituted with a halogen,
Rg, Rh, Ri and Rj represent a halogen;
a hydroxyl group;
an amino group;
a C1-C6 monoalkylamino group;
a C1-C6 dialkylamino group;
an acetamido group;
a C1-C6 alkyl group optionally substituted with a halogen, a hydroxyl group, a phenoxy group or a benzyloxy group;
a C3-C8 cycloalkyl group;
a C2-C6 alkenyl group optionally substituted with a halogen, a hydroxyl group or a cyano group;
a C2-C6 alkynyl group optionally substituted with a halogen or a cyano group;
a C1-C6 alkoxy group optionally substituted with a halogen, a hydroxyl group, a C1-C4 alkoxy group, an amino group, a C1-C6 monoalkylamino group, a C1-C6 dialkylamino group, a C6-C10 aryl group or a 3-10 membered heterocyclic group optionally substituted with an oxo group;
a C1-C6 alkoxy C1-C6 alkyl group optionally substituted with a halogen, a phenyl group, a phenoxy group or a benzyloxy group;
a C3-C8 cycloalkoxy group;
a cyano group;
a nitro group;
an oxo group;
a carboxyl group;
a sulfanyl group;
a C1-C6 alkylsulfanyl group optionally substituted with a halogen;
a C1-C6 alkylsulfinyl group optionally substituted with a halogen;
a phenylsulfonyl group optionally substituted with a C1-C4 alkyl group;
a C1-C6 alkylsulfonyl group optionally substituted with a halogen;
a C1-C6 acyl group;
a C1-C4 alkoxycarbonyl group;
a phenyl group optionally substituted with a halogen, a cyano group, a trifluoromethyl group or a hydroxyl group;
a 3-12 membered heterocyclic group optionally substituted with a halogen or an oxo group;
a phenoxy group;
a C6-C12 aryl C1-C6 alkoxy group;
a 3-12 membered heterocyclic C1-C6 alkoxy group or a group represented by the formula R30—CH2—O—.

126 more elements

Aminoazole derivative

Life of this patent

Aminoazole derivative

Life of this patent

Abstract

Claims14