US 2022/0017486 A1 · DOCK1-INHIBITING COMPOUND AND USE THEREOF

Abstract

Provided is a compound that is usable as an active ingredient of an anticancer agent. Preferably provided is a compound that has DOCK1-inhibiting activity and exerts an anticancer effect based on the activity. A compound represented by the following formula (A) or a salt thereof: wherein X represents a carbon atom or a nitrogen atom; Y represents an oxygen atom, a hydroxy group, or a hydrocarbon group; R1 and R2 are different, and each represents a hydrogen atom or a group represented by the following formula (A-1): (wherein R6 represents a pyrrolidino group or a phenyl group, and n2 is 0 or 1); R3 represents —CO—R7 (wherein R7 is an alkoxy group, an alkyl group, or an alkylamino group), a 1,3-oxazole group, an alkylhydroxy group, a hydrogen atom, or an oxygen atom; R4 represents a hydrogen atom, an oxygen atom, or a hydrocarbon group in which one or more hydrogen atoms may be replaced by one or more substituents; R5 represents a halogen atom, a halogenated alkyl group, or a halogenated alkylthio group; and n1 is an integer of 0 to 5; and in the skeleton of the compound of formula (A), each single solid line represents a single bond; each double line consisting of a solid line and a dotted line represents a single bond or a double bond; and two dotted lines represent no bond or a double bond.

Claims13

Dependent claims

A compound represented by the following formula (A):

wherein
X represents a carbon atom or a nitrogen atom;
Y represents an oxygen atom, a hydroxy group, or a hydrocarbon group;
R1 and R2 are different, and each represents a hydrogen atom or a group represented by the following formula (A-1):
wherein R6 represents a pyrrolidine group or a phenyl group, and n2 is 0 or 1;
R3 represents —CO—R7, wherein R7 is an alkoxy group, an alkyl group, or an alkylamino group, a 1,3-oxazole group, an alkylhydroxy group, a hydrogen atom, or an oxygen atom;
R4 represents a hydrogen atom, an oxygen atom, or a hydrocarbon group in which one or more hydrogen atoms may be replaced by one or more substituents;
R5 represents a halogen atom, a halogenated alkyl group, or a halogenated alkylthio group;
and
n1 is an integer of 0 to 5;
and
in the skeleton of the compound of formula (A),
each single solid line represents a single bond;
each double line, which consists of a solid line and a dotted line, represents a single bond or a double bond;
and
two dotted lines represent no bond or a double bond;
or
a salt thereof.

15 more elements

A compound represented by the following formula (B):

wherein
Ra is one of the groups represented by the following formulas (B-1) to (B-4):
wherein Re is the same or different, and each represents a halogen atom, a trihaloalkyl group, or a trihaloalkylthio group;
m3 is an integer of 0 to 2;
and m4 is an integer of 0 to 5,
Rb is a hydrogen atom or an amino group;
Rc is a hydrogen atom or an alkyl group;
Rd is
a group represented by the following formula (B-5):
wherein Rf is a hydrogen atom, a hydroxy group, an alkyl group, an acyloxy group, or an alkoxy group, wherein the alkoxy group may be linked to Y to form a ring;
and Rg is a group represented by the following formula (B-6), or a quinolyl group:
wherein Z is a carbon atom or a nitrogen atom;
Rh is the same or different, and each represents a halogen atom, a halogenated alkyl group, a halogenated alkylthio group, an alkyl group, an alkenyl group, or an alkylamino group;
and m5 is an integer of 1 to 3, or
a group represented by formula (B-7):
Y is an oxygen atom, a hydroxy group, or an alkoxy group, wherein when Rd is a group represented by formula (B-5), the alkoxy group may be linked to an alkoxy group represented by Rf to form a ring;
m1 is 0 or 1;
m2 is 0 or 1;
and
the double line, which consists of a dotted line and a solid line, represents a double bond when Y is an oxygen atom, and the double line represents a single bond when Y is a hydroxy group or an alkoxy group;
or
a salt thereof.

19 more elements

A compound selected from the group consisting of the following compounds:

(B8) 1-(2hydroxy-2-(3-hydroxy-3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B9) 1-((2,2-dimethyl-7-(3-(trifluoromethyl)phenyl)-4H-benzo[d][1,3 ]dioxin-4-yl)methyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B10) 1-(2-oxo-2-(3′-((trifluoromethyl)thio)-[1,1′-biphenyl]-4-yl)ethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B11) 3-amino-1-(2-oxo-2-(3′-trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B12) 2-bromo-1-(3-methyl-3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethan-1-one,
(B13) 1-(2-(3-hydroxy-3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-2-oxoethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B14) 1-(2-(3-methoxy-3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-2-oxoethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B15) 4-(2-(2-oxo-5-(pyrrolidin-1-yl-sulfonyl)pyridin-1(2H-yl)acetyl)-3′-(trifluoromethyl)-[1,1′-biphenyl]-3-yl-acetate,
(B16) 1-(2-(3-isobutoxy-3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-2-oxoethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B17) 1-(1-(3-(hexyloxy)-3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl -1-oxooctan-2-yl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B18)-(2-oxo-2-(3-phenethoxy-3′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)ethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B19) 1-(2-oxo-2-(3′-vinyl-[1,1′-biphenyl]-4-yl)ethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B20) 1-(2-(4′-(dimethylamino)-3′-methyl-[1,1′-biphenyl]-4-yl)-2-oxoethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B21) 1-(2-oxo-2-(4-(6-(trifluoromethyl)pyridin-2-y)phenyl)ethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B22) 1-(2-oxo-2-(4-(quinolin-7-yl)phenyl)ethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one,
(B23) 1-(2-oxo-2-(4-(quinolin-6-yl)phenyl)ethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one, and
(B24) 1-(2-((3S,10R,13S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-5-(pyrrolidin-1-yl-sulfonyl)pyridin-2(1H)-one;
or a salt thereof.

15 more elements

Dependencies are inferred from the claim text.

Dock1-inhibiting compound and use thereof

Life of this patent

Dock1-inhibiting compound and use thereof

Life of this patent

Abstract

Claims13