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US 12,595,250 B2Granted
Substituted pyrimidine compounds as multifunctional radical quenchers and their uses
AssigneeArizona Board of Regents on behalf of Arizona State University
InventorsSidney Hecht, Omar Khdour, Arnaud Chevalier
Life of this patent
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Abstract
The invention provides compounds having the general formula I: and pharmaceutically acceptable salts thereof, wherein the variables R1, R2, R3 and R4 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.
Claims15
A method of treating mitochondrial disease, neurodegenerative disease, cardiovascular disease, cancer or diabetes in an animal comprising administering to the animal an effective amount of compound of formula I:
- wherein R1 is hydrogen or C1-6 alkyl;
- R2 is C1-20 alkyl, C2-20 alkenyl or C2-20 alkynyl, and wherein the C1-20 alkyl, C2-20 alkenyl and C2-20 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —ORa, —SRa, —N(Ra)2, oxo, —NO2 and —CN;
- R3 is —NR6R7;
- R4 is —OR8 or —NR9R10;
- R6 and R7 taken together with the nitrogen to which they are attached form a 3-10 membered heterocycle that is optionally substituted with one or more groups independently selected from C1-4 alkyl, C1-4 haloalkyl, —F, —C, —Br, —I, —ORe, —SRe, —N(Re)2, oxo, —NO2 and —CN;
- R8 is C3-10 cycloalkyl or C1-8 alkyl;
- wherein C3-10 cycloalkyl and C1-8 alkyl are optionally substituted with one or more groups independently selected from C1-4 alkyl, C1-4 haloalkyl, —F, —Cl, —Br, —I, —ORf, —SRf, —N(Rf)2, oxo, —NO2 and —CN;
- R9 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, and wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —ORg, —SRg, —N(Rg)2, oxo, —NO2 and —CN;
- R10 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, and wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —ORh, —SRh, —N(Rh)2, oxo, —NO2 and —CN;
- or R9 and R10 taken together with the nitrogen to which they are attached form a 3-10 membered heterocycle that is optionally substituted with one or more groups independently selected from C1-4 alkyl, C1-4 haloalkyl, —F, —Cl, —Br, —I, —ORi, —SRi, —N(Ri)2, oxo, —NO2 and —CN;
- each Ra is independently hydrogen or C1-4 alkyl;
- or two Ra taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- each Re is independently hydrogen or C1-4 alkyl;
- or two Re taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- each Rf is independently hydrogen or C1-4 alkyl;
- or two Rf taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- each Rg is independently hydrogen or C1-4 alkyl;
- or two Rg taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- each Rh is independently hydrogen or C1-4 alkyl;
- or two Rh taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- and
- each Ri is independently hydrogen or C1-4 alkyl;
- or two Ri taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- or a pharmaceutically acceptable salt thereof.
21 more elements
A method of treating mitochondrial disease, neurodegenerative disease, cardiovascular disease, cancer or diabetes in an animal comprising administering to the animal an effective amount of compound of formula Ib:
- wherein R1 is hydrogen or C1-6 alkyl;
- R2 is C1-20 alkyl, C2-20 alkenyl or C2-20 alkynyl, and wherein the C1-20 alkyl, C2-20 alkenyl and C2-20 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —ORa, —SRa, —N(Ra)2, oxo, —NO2 and —CN;
- R6 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, and wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —ORc, —SRC, —N(Rc)2, oxo, —NO2 and —CN;
- R7 is C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl, and wherein the C1-6 alkyl, C2-6 alkenyl and C2-6 alkynyl are optionally substituted with one or more groups independently selected from —F, —Cl, —Br, —I, —ORd, —SRd, —N(Rc)2, oxo, —NO2 and —CN;
- or R6 and R7 taken together with the nitrogen to which they are attached form a 3-10 membered heterocycle that is optionally substituted with one or more groups independently selected from C1-4 alkyl, C1-4 haloalkyl, —F, —Cl, —Br, —I, —ORe, —SRe, —N(Re)2, oxo, —NO2 and —CN;
- R8 is C3-10 cycloalkyl or C1-8 alkyl;
- wherein C3-10 cycloalkyl and C1-8 alkyl are optionally substituted with one or more groups independently selected from C1-4 alkyl, C1-4 haloalkyl, —F, —Cl, —Br, —I, —ORf, —SRf, —N(Rf)2, oxo, —NO2 and —CN;
- each Ra is independently hydrogen or C1-4 alkyl;
- or two Ra taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- each Rc is independently hydrogen or C1-4 alkyl;
- or two Rc taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- each Rd is independently hydrogen or C1-4 alkyl;
- or two Rd taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- each Re is independently hydrogen or C1-4 alkyl;
- or two Re taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- each Rf is independently hydrogen or C1-4 alkyl;
- or two Rf taken together with the nitrogen to which they are attached form pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl;
- and
- or a pharmaceutically acceptable salt thereof.
16 more elements
A method of treating mitochondrial disease, neurodegenerative disease, cardiovascular disease, cancer or diabetes in an animal comprising administering to the animal an effective amount of compound of formula:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.