US 2021/0246122 A1Published application

Triazine Compounds and Uses Thereof

AssigneeAduro Biotech, Inc.

InventorsGeorge Edwin Katibah, Jung Yun Kim, Chudi Obioma Ndubaku, Meiliana Tjandra, Tucker Curran Roberts

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Abstract

The present invention relates to triazine compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating autoimmune, inflammatory, and neurodegenerative diseases by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

Claims83

Dependent claims

A compound of Formula (I) or a pharmaceutically acceptable salt thereof:

wherein
each of Ra and Rb independently is H or C1-C6 alkyl, wherein C1-C6 alkyl is optionally substituted with one or more substituents selected from the group consisting of cyano, halo, —OR, —S(═O)xR, and —NRR′;
each of Rc and Rd independently is, at each occurrence, H, halo, —C(═O)R2, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, —OR, —S(═O)xR, —NRR′;
or
Rc and Rd attached to the same carbon is oxo;
or Rc and Rd attached to the same carbon forms a C3-C3 cycloalkyl, or a 3- to 8-membered heterocycloalkyl, wherein the C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, C1-C3 alkyl and C1-C3 haloalkyl;
and wherein at least one occurrence of Rc is —C(═O)R2;
R2 is —ORg or —NRgRh;
each of Rg and Rh is independently H, C1-C6 alkyl, (CH2CH2O)u—H, or (CH2CH2O)u—C1-C6 alkyl;
each of Re and Rf independently is H, halo, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, —OR, —S(═O)xR, and —NRR′;
or Re and Rf attached to the same carbon is oxo;
or Re and Rf attached to the same carbon forms a C3-C8 cycloalkyl, or a 3- to 8-membered heterocycloalkyl, wherein the C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, C1-C3 alkyl and C1-C3 haloalkyl;
R1 is H, halo, cyano, —OR1, —NRiRj, or C1-C6 alkyl, wherein C1-C6 alkyl is optionally substituted with one or more RS1;
each RS1 is independently halo, cyano, oxo, —OR1, —NRiRj, C3-C8 cycloalkyl, C6-C10 aryl, 3- to 8-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C3-C8 cycloalkyl, C6-C10 aryl, 3- to 8-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, C1-C6 alkyl and C1-C6 haloalkyl;
each of Ri and Rj independently is H, C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl wherein the C1-C6 alkyl is optionally substituted with one or more RS2, and the C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, C1-C6 alkyl and C1-C6 haloalkyl;
each RS2 is independently halo, cyano, —OR, —NRR, C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl, wherein the C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, and —NRR′;
each of R and R′ independently is, at each occurrence, H, C1-C6 alkyl, C1-C6 haloalkyl, C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl, wherein the C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —ORp, —S(═O)xRp, —NRpRq, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —ORp, —S(═O)xRp, and —NRpRq;
A is a 3- to 14-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S and optionally substituted with one or more RS3;
B is a 3- to 14-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S and optionally substituted with one or more RS4;
C is a 3- to 14-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S and optionally substituted with one or more RS5;
each of RS3, and RS4 is independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, and —NRR′;
each RS5 independently is halo, cyano, —C(═O)Rk, —S(═O)xRk, a nitrogen protecting group bound to a suitable nitrogen of ring C, or C1-C6 alkyl, wherein the alkyl is optionally substituted with one or more RS6;
Rk is H, C1-C6 alkyl, C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl, wherein C1-C6 alkyl is optionally substituted with one or more RS6, and wherein C0-3alkylene-C3-C5 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of RS6, C1-C6 alkyl, and C1-C6 alkyl substituted with one or more RS6;
each RS6 independently is halo, cyano, oxo, —ORm, —OC(═O)Rm, —C(═O)Rm, —C(═O)ORm, —S(═O)xRm, —S(═O)2ORm, —OS(═O)2Rm, —NRmRn, —C(═O)NRmRn, —C(═NRm)NRmRn, —S(═O)2NRmRn, —NRmC(═O)Rm, —NRmC(═NRm)Rm, —NRmS(═O)2Rm, —NRmC(═O)NRmRn, —NRmC(═NRm)NRmRn, —NRmS(═O)2NRmRn, —NRmC(═O)ORm, —OC(═O)NRmRn, C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl, wherein the C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, ORm, OC(═O)Rm, C(═O)Rm, C(═O)ORm, S(═O)xRm, S(═O)2ORm, OS(═O)2Rm, NRmRn, C(═O)NRmRn, C(═NRm)NRmRn, S(═O)2NRmRn, NRmC(═O)Rm, NRmC(═NRm)Rm, NRmS(═O)2Rm, NRmC(═O)NRmRn, NRmC(═NRm)NRmRn, NRmS(═O)2NRmRn, NRmC(═O)ORm, OC(═O)NRmRn, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, ORm, OC(═O)Rm, C(═O)Rm, C(═O)ORm, S(═O)xRm, S(═O)2ORm, OS(═O)2Rm, NRmRn, C(═O)NRmRn, C(═NRm)NRmRn, S(═O)2NRmRn, NRmC(═O)Rm, NRmC(═NRm)Rm, NRmS(═O)2Rm, NRmC(═O)NRmRn, NRmC(═NRm)NRmRn, NRmS(═O)2NRmRn, NRmC(═O)ORm, OC(═O)NRmRn;
each of Rm and Rn independently is, at each occurrence, H, C1-C6 alkyl, C1-C6 haloalkyl, C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl, wherein the C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —ORp, —OC(═O)Rp, —C(═O)Rp, —C(═O)ORp, —S(═O)xRp, —S(═O)2ORp, —OS(═O)2Rp, —NRpRq, —C(═O)NRpRq, —C(═NRp)NRpRq, —S(═O)2NRpRq, —NRpC(═O)Rp, —NRpC(═NRp)Rp, —NRpS(═O)2Rp, —NRpC(═O)NRpRq, —NRpC(═NRp)NRpRq, —NRpS(═O)2NRpRq, —NRpC(═O)ORp, —OC(═O)NRpRq, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —ORp, —OC(═O)Rp, —C(═O)Rp, —C(═O)ORp, —S(═O)xRp, —S(═O)2ORp, —OS(═O)2Rp, —NRpRq, —C(═O)NRpRq, —C(═NRp)NRpRq, —S(═O)2NRpRq, —NRpC(═O)Rp, —NRpC(═NRp)Rp, —NRpS(═O)2Rp, —NRpC(═O)NRpRq, —NRpC(═NRp)NRpRq, —NRpS(═O)2NRpRq, —NRpC(═O)ORp, —OC(═O)NRpRq;
each Rp and Rq are independently H or C1-C6 alkyl;
m is 0, 1, 2, or 3;
n is 1, 2, 3, or 4;
each occurrence of x is independently 0, 1, or 2;
and
each u independently is 1, 2, or 3.

28 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/734,293Filed 14 Jun 2019
Priority: 22 Jun 2018
Published: 12 Aug 2021
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 251/50
Two nitrogen atoms: with a halogen atom attached to the third ring carbon atom
C07D 403/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group…
A61P 19/00
Drugs for skeletal disorders
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…

Family

Application62/688,543Us provisional application · filed 22 Jun 2018
US 2021/0246122 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula (I) or a pharmaceutically acceptable salt thereof:

wherein
each of Ra and Rb independently is H or C1-C6 alkyl, wherein C1-C6 alkyl is optionally substituted with one or more substituents selected from the group consisting of cyano, halo, —OR, —S(═O)xR, and —NRR′;
each of Rc and Rd independently is, at each occurrence, H, halo, —C(═O)R2, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, —OR, —S(═O)xR, —NRR′;
or
Rc and Rd attached to the same carbon is oxo;
or Rc and Rd attached to the same carbon forms a C3-C3 cycloalkyl, or a 3- to 8-membered heterocycloalkyl, wherein the C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, C1-C3 alkyl and C1-C3 haloalkyl;
and wherein at least one occurrence of Rc is —C(═O)R2;
R2 is —ORg or —NRgRh;
each of Rg and Rh is independently H, C1-C6 alkyl, (CH2CH2O)u—H, or (CH2CH2O)u—C1-C6 alkyl;
each of Re and Rf independently is H, halo, or C1-C3 alkyl, wherein the C1-C3 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, —OR, —S(═O)xR, and —NRR′;
or Re and Rf attached to the same carbon is oxo;
or Re and Rf attached to the same carbon forms a C3-C8 cycloalkyl, or a 3- to 8-membered heterocycloalkyl, wherein the C3-C8 cycloalkyl, or 3- to 8-membered heterocycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, C1-C3 alkyl and C1-C3 haloalkyl;
R1 is H, halo, cyano, —OR1, —NRiRj, or C1-C6 alkyl, wherein C1-C6 alkyl is optionally substituted with one or more RS1;
each RS1 is independently halo, cyano, oxo, —OR1, —NRiRj, C3-C8 cycloalkyl, C6-C10 aryl, 3- to 8-membered heterocycloalkyl, or 5- to 10-membered heteroaryl, wherein the C3-C8 cycloalkyl, C6-C10 aryl, 3- to 8-membered heterocycloalkyl, or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, C1-C6 alkyl and C1-C6 haloalkyl;
each of Ri and Rj independently is H, C1-C6 alkyl, C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl wherein the C1-C6 alkyl is optionally substituted with one or more RS2, and the C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, C1-C6 alkyl and C1-C6 haloalkyl;
each RS2 is independently halo, cyano, —OR, —NRR, C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl, wherein the C3-C8 cycloalkyl, 3- to 10-membered heterocycloalkyl, C6-C10 aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, and —NRR′;
each of R and R′ independently is, at each occurrence, H, C1-C6 alkyl, C1-C6 haloalkyl, C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl, wherein the C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —ORp, —S(═O)xRp, —NRpRq, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —ORp, —S(═O)xRp, and —NRpRq;
A is a 3- to 14-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S and optionally substituted with one or more RS3;
B is a 3- to 14-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S and optionally substituted with one or more RS4;
C is a 3- to 14-membered ring optionally containing 1-4 heteroatoms selected from N, O, and S and optionally substituted with one or more RS5;
each of RS3, and RS4 is independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, —NRR′, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —OR, —S(═O)xR, and —NRR′;
each RS5 independently is halo, cyano, —C(═O)Rk, —S(═O)xRk, a nitrogen protecting group bound to a suitable nitrogen of ring C, or C1-C6 alkyl, wherein the alkyl is optionally substituted with one or more RS6;
Rk is H, C1-C6 alkyl, C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl, wherein C1-C6 alkyl is optionally substituted with one or more RS6, and wherein C0-3alkylene-C3-C5 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of RS6, C1-C6 alkyl, and C1-C6 alkyl substituted with one or more RS6;
each RS6 independently is halo, cyano, oxo, —ORm, —OC(═O)Rm, —C(═O)Rm, —C(═O)ORm, —S(═O)xRm, —S(═O)2ORm, —OS(═O)2Rm, —NRmRn, —C(═O)NRmRn, —C(═NRm)NRmRn, —S(═O)2NRmRn, —NRmC(═O)Rm, —NRmC(═NRm)Rm, —NRmS(═O)2Rm, —NRmC(═O)NRmRn, —NRmC(═NRm)NRmRn, —NRmS(═O)2NRmRn, —NRmC(═O)ORm, —OC(═O)NRmRn, C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl, wherein the C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, ORm, OC(═O)Rm, C(═O)Rm, C(═O)ORm, S(═O)xRm, S(═O)2ORm, OS(═O)2Rm, NRmRn, C(═O)NRmRn, C(═NRm)NRmRn, S(═O)2NRmRn, NRmC(═O)Rm, NRmC(═NRm)Rm, NRmS(═O)2Rm, NRmC(═O)NRmRn, NRmC(═NRm)NRmRn, NRmS(═O)2NRmRn, NRmC(═O)ORm, OC(═O)NRmRn, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, ORm, OC(═O)Rm, C(═O)Rm, C(═O)ORm, S(═O)xRm, S(═O)2ORm, OS(═O)2Rm, NRmRn, C(═O)NRmRn, C(═NRm)NRmRn, S(═O)2NRmRn, NRmC(═O)Rm, NRmC(═NRm)Rm, NRmS(═O)2Rm, NRmC(═O)NRmRn, NRmC(═NRm)NRmRn, NRmS(═O)2NRmRn, NRmC(═O)ORm, OC(═O)NRmRn;
each of Rm and Rn independently is, at each occurrence, H, C1-C6 alkyl, C1-C6 haloalkyl, C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl, wherein the C0-3alkylene-C3-C8 cycloalkyl, C0-3alkylene-C6-C10 aryl, C0-3alkylene-3- to 8-membered heterocycloalkyl, or C0-3alkylene-5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —ORp, —OC(═O)Rp, —C(═O)Rp, —C(═O)ORp, —S(═O)xRp, —S(═O)2ORp, —OS(═O)2Rp, —NRpRq, —C(═O)NRpRq, —C(═NRp)NRpRq, —S(═O)2NRpRq, —NRpC(═O)Rp, —NRpC(═NRp)Rp, —NRpS(═O)2Rp, —NRpC(═O)NRpRq, —NRpC(═NRp)NRpRq, —NRpS(═O)2NRpRq, —NRpC(═O)ORp, —OC(═O)NRpRq, and C1-C6 alkyl, wherein the C1-C6 alkyl is optionally substituted with one or more substituents independently selected from the group consisting of cyano, halo, oxo, —ORp, —OC(═O)Rp, —C(═O)Rp, —C(═O)ORp, —S(═O)xRp, —S(═O)2ORp, —OS(═O)2Rp, —NRpRq, —C(═O)NRpRq, —C(═NRp)NRpRq, —S(═O)2NRpRq, —NRpC(═O)Rp, —NRpC(═NRp)Rp, —NRpS(═O)2Rp, —NRpC(═O)NRpRq, —NRpC(═NRp)NRpRq, —NRpS(═O)2NRpRq, —NRpC(═O)ORp, —OC(═O)NRpRq;
each Rp and Rq are independently H or C1-C6 alkyl;
m is 0, 1, 2, or 3;
n is 1, 2, 3, or 4;
each occurrence of x is independently 0, 1, or 2;
and
each u independently is 1, 2, or 3.

28 more elements

Facts

Application

15/734,293Filed 14 Jun 2019

Priority

22 Jun 2018

Published

12 Aug 2021

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 251/50
Two nitrogen atoms: with a halogen atom attached to the third ring carbon atom
C07D 403/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group…
A61P 19/00
Drugs for skeletal disorders
A61P 25/28
Drugs for disorders of the nervous system: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents,…