US 12,759,996 B2Granted

Glutarimide skeleton-based compounds and use thereof

AssigneeShanghaitech University

InventorsXiaobao Yang, Biao Jiang, Xing Qiu, Ning Sun, Renhong Sun, Chaowei Ren

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Abstract

The present disclosure relates to glutarimide skeleton-based compounds of Formula (I) or a salt, an enantiomer, a stereoisomer, a solvate, or a polymorph thereof, and uses thereof. The present disclosure further relates to a pharmaceutical composition comprising, as an active ingredient, the glutarimide skeleton-based compounds of Formula (I), or a salt, an enantiomer, a stereoisomer, a solvate, or a polymorph thereof, and uses thereof. The series of compounds designed and synthesized in the present disclosure can effectively prevent and/or treat a tumor.

Claims31

Dependent claims

A compound of Formula (I)

or a salt, or an enantiomer thereof, wherein
Y represents H, D, C1-3 alkyl, or deuterated C1-3 alkyl;
R1, R2, R3, R4, and R5 are the same or different and each independently represent H or D;
A represents CH2, CD2, or C(O);
B, U, V, W are the same or different and independently represent CH, CD, or N, wherein B, U, V, and W are not N at the same time, and when any of B, U, V, and W is attached to R, it is not N;
and
(1) when R is O or NH, or R represents a bond,
L represents a linear or branched C5-40 alkylene group, wherein a hydrogen atom of one or more CH2 of the linear or branched C5-40 alkylene group is optionally replaced with a substituent selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, C3-6 cycloalkyl, halogen, halogenated C1-3 alkyl, hydroxyl, and cyano, or any combination thereof;
and
X1 represents the Formula —Xa—Xb, wherein
Xa represents O, N(R6), C(O)N(R6), N(R6)C(O), alkynylene, or alkenylene, wherein R6 represents H, C1-3 alkyl, or deuterated C1-3 alkyl, or Xa represents a bond, and
Xb represents C3-6 cycloalkyl or C7-11 spiro-cycloalkyl, wherein said C3-6 cycloalkyl and said C7-11 spiro-cycloalkyl are each independently optionally substituted with one or more substituents selected from the group consisting of:
D, C1-3 alkyl, C1-3 alkylamino, amino, deuterated C1-3 alkyl, halogenated C1-3 alkyl, C1-3 alkoxy, deuterated C1-3 alkoxy, oxo, halogen, hydroxyl, and cyano, or any combination thereof;
or
(2) when R is O or NH, or R represents a bond,
L represents a linear or branched C1-40 alkylene group, wherein the linear or branched C1-40 alkylene group is optionally interrupted one or more times by a group selected from the group consisting of:
N(R7), phenylene, and combinations thereof, wherein R7 represents H, C1-3 alkyl or deuterated C1-3 alkyl, and a hydrogen atom of one or more CH2 of the linear or branched C1-40 alkylene group and the phenylene are each independently optionally substituted with a substituent selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, C3-6 cycloalkyl, halogen, halogenated C1-3 alkyl, hydroxyl, and cyano;
and
X1 represents the Formula —Xc—Xa, wherein
Xc represents O, N(R8), C(O)N(R8), N(R8)C(O), alkynylene, or alkenylene, wherein R8 represents H, C1-3 alkyl, or deuterated C1-3 alkyl, or Xc represents a bond, and
Xd represents C7-15 bridged cycloalkyl optionally substituted with from 1 to 10 substituents selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, deuterated C1-3 alkoxy, halogen, halogenated C1-3 alkyl, C1-3 alkylamino, amino, hydroxyl, cyano, and oxo;
or
(3) when R is alkynylene or alkenylene,
L represents a linear or branched C1-40 alkylene group, wherein the linear or branched C1-40 alkylene group is optionally interrupted one or more times by a group selected from the group consisting of:
N(R9), phenylene and combinations thereof, wherein R9 represents H, C1-3 alkyl or deuterated C1-3 alkyl, and a hydrogen atom of one or more CH2 of the linear or branched C1-40 alkylene group and the phenylene are each independently optionally substituted with a substituent selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, C3-6 cycloalkyl, halogen, halogenated C1-3 alkyl, hydroxyl, and cyano;
and
X1 represents the Formula —Xe—Xf, wherein
Xe represents —N(R10), C(O)N(R10), N(R10)C(O), alkynylene, or alkenylene, wherein R10 represents H, C1-3 alkyl or deuterated C1-3 alkyl, and
Xf represents C3-15 cycloalkyl, wherein said C3-15 cycloalkyl is bicyclic, tricyclic or polycyclic cycloalkyl and is optionally substituted with a substituent selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, deuterated C1-3 alkoxy, halogen, halogenated C1-3 alkyl, hydroxyl, cyano, oxo, optionally substituted phenyl, C1-3 alkylamino, and amino, and wherein the optionally substituted phenyl is optionally substituted with a substituent selected from the group consisting of:
cyano, halogen, C1-3 alkoxy, halogenated C1-3 alkyl, C1-3 alkyl, hydroxyl, amino, and C1-3 alkylamino.

32 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of Formula (I)

or a salt, or an enantiomer thereof, wherein
Y represents H, D, C1-3 alkyl, or deuterated C1-3 alkyl;
R1, R2, R3, R4, and R5 are the same or different and each independently represent H or D;
A represents CH2, CD2, or C(O);
B, U, V, W are the same or different and independently represent CH, CD, or N, wherein B, U, V, and W are not N at the same time, and when any of B, U, V, and W is attached to R, it is not N;
and
(1) when R is O or NH, or R represents a bond,
L represents a linear or branched C5-40 alkylene group, wherein a hydrogen atom of one or more CH2 of the linear or branched C5-40 alkylene group is optionally replaced with a substituent selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, C3-6 cycloalkyl, halogen, halogenated C1-3 alkyl, hydroxyl, and cyano, or any combination thereof;
and
X1 represents the Formula —Xa—Xb, wherein
Xa represents O, N(R6), C(O)N(R6), N(R6)C(O), alkynylene, or alkenylene, wherein R6 represents H, C1-3 alkyl, or deuterated C1-3 alkyl, or Xa represents a bond, and
Xb represents C3-6 cycloalkyl or C7-11 spiro-cycloalkyl, wherein said C3-6 cycloalkyl and said C7-11 spiro-cycloalkyl are each independently optionally substituted with one or more substituents selected from the group consisting of:
D, C1-3 alkyl, C1-3 alkylamino, amino, deuterated C1-3 alkyl, halogenated C1-3 alkyl, C1-3 alkoxy, deuterated C1-3 alkoxy, oxo, halogen, hydroxyl, and cyano, or any combination thereof;
or
(2) when R is O or NH, or R represents a bond,
L represents a linear or branched C1-40 alkylene group, wherein the linear or branched C1-40 alkylene group is optionally interrupted one or more times by a group selected from the group consisting of:
N(R7), phenylene, and combinations thereof, wherein R7 represents H, C1-3 alkyl or deuterated C1-3 alkyl, and a hydrogen atom of one or more CH2 of the linear or branched C1-40 alkylene group and the phenylene are each independently optionally substituted with a substituent selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, C3-6 cycloalkyl, halogen, halogenated C1-3 alkyl, hydroxyl, and cyano;
and
X1 represents the Formula —Xc—Xa, wherein
Xc represents O, N(R8), C(O)N(R8), N(R8)C(O), alkynylene, or alkenylene, wherein R8 represents H, C1-3 alkyl, or deuterated C1-3 alkyl, or Xc represents a bond, and
Xd represents C7-15 bridged cycloalkyl optionally substituted with from 1 to 10 substituents selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, deuterated C1-3 alkoxy, halogen, halogenated C1-3 alkyl, C1-3 alkylamino, amino, hydroxyl, cyano, and oxo;
or
(3) when R is alkynylene or alkenylene,
L represents a linear or branched C1-40 alkylene group, wherein the linear or branched C1-40 alkylene group is optionally interrupted one or more times by a group selected from the group consisting of:
N(R9), phenylene and combinations thereof, wherein R9 represents H, C1-3 alkyl or deuterated C1-3 alkyl, and a hydrogen atom of one or more CH2 of the linear or branched C1-40 alkylene group and the phenylene are each independently optionally substituted with a substituent selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, C3-6 cycloalkyl, halogen, halogenated C1-3 alkyl, hydroxyl, and cyano;
and
X1 represents the Formula —Xe—Xf, wherein
Xe represents —N(R10), C(O)N(R10), N(R10)C(O), alkynylene, or alkenylene, wherein R10 represents H, C1-3 alkyl or deuterated C1-3 alkyl, and
Xf represents C3-15 cycloalkyl, wherein said C3-15 cycloalkyl is bicyclic, tricyclic or polycyclic cycloalkyl and is optionally substituted with a substituent selected from the group consisting of:
D, C1-3 alkyl, deuterated C1-3 alkyl, C1-3 alkoxy, deuterated C1-3 alkoxy, halogen, halogenated C1-3 alkyl, hydroxyl, cyano, oxo, optionally substituted phenyl, C1-3 alkylamino, and amino, and wherein the optionally substituted phenyl is optionally substituted with a substituent selected from the group consisting of:
cyano, halogen, C1-3 alkoxy, halogenated C1-3 alkyl, C1-3 alkyl, hydroxyl, amino, and C1-3 alkylamino.

32 more elements