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US 7,378,530 B2Granted
Anti-cancer and anti-microbial 5-membered heterocyclic compounds
AssigneeNereus Pharmaceuticals, Inc.
InventorsVenkata Rami Reddy Macherla, Benjamin Nicholson, Kin Sing Lam
Life of this patent
Estimating the term…
Abstract
Disclosed herein are various novel oxazolidinone, imidazolidinone, and thiazolidinone analogs and methods of treating cancer and/or microbial infection using these analogs. Particular 4-oxazolidinone compounds are shown to have anti-cancer and anti-microbial activity.
Claims35
A compound having the structure of formula I:
- and pharmaceutically acceptable salts or prodrugs thereof, wherein:
- R1 is a molecular fragment having the structure of formula (II),
- Z is selected from the group consisting of O, S, and NR5;
- R6 and R7 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- alkoxy carbonylacyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- R8 and R9 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- alkoxy carbonylacyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- and halogenated alkyl including polyhalogenated alkyl;
- or are separately absent;
- R10 and R11 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- alkoxy carbonylacyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- or are separately absent;
- R2 is selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- heteroaryl;
- ester;
- arylalkoxy carbonyl;
- alkoxy carbonylacyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- R3 is ═O;
- R1′ is selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- alkoxy carbonylacyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- or are separately absent;
- R2′ is selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- heteroaryl;
- ester;
- arylalkoxy carbonyl;
- alkoxy carbonylacyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- or are separately absent;
- Y is separately selected from the group consisting of O, S, and NR5;
- R4 and each R5 are separately selected from the group consisting of hydrogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 heteroalkyl, C2-6 aminoalkyl, C2-6 haloalkyl, C1-6 alkoxycarbonyl, and C2-6 hydroxyalkyl;
- C3-8 cycloalkyl;
- —C(O)—C5-6 aryl substituted with C1-3 alkyl or halo;
- C5-6 aryl;
- C5-6 heteroaryl;
- C5-6 cycloalkyl;
- and C5-6 heterocycloalkyl, or are separately absent;
- any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;
- any bond represented by a single dashed line is a single bond or is absent;
- and
- any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.
204 more elements
A compound having the structure of formula III:
- and pharmaceutically acceptable salts or prodrugs thereof, wherein:
- Y is selected from the group consisting of O, S, and NR5;
- R2, R6, and R7 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- alkoxy carbonylacyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- R2′ is selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- alkoxy carbonylacyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- or is absent;
- R4 and R5 are separately selected from the group consisting of hydrogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 heteroalkyl, C2-6 aminoalkyl, C2-6 haloalkyl, C1-6 alkoxycarbonyl, and C2-6 hydroxyalkyl;
- C3-8 cycloalkyl;
- —C(O)—C5-6 aryl substituted with C1-3 alkyl or halo;
- C5-6 aryl;
- C5-6 heteroaryl;
- C5-6 cycloalkyl;
- and C5-6 heterocycloalkyl or are separately absent;
- R8, R9, R10, and R11 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- alkoxy carbonylacyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- or are separately absent;
- any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;
- any bond represented by a single dashed line is a single bond or is absent;
- and
- any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.
110 more elements
A compound having the structure of formula IV:
- and pharmaceutically acceptable salts or prodrugs thereof, wherein:
- R2, R6, and R7 are separately selected from the group consisting of mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- R2′ is selected from the group consisting of hydrogen and mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- R4 is selected from the group consisting of hydrogen, straight- or branched-chain C1-6 alkyl, straight- or branched-chain C2-6 alkenyl, and straight- or branched-chain C2-6 alkynyl, or is absent;
- any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond with the proviso that such bonds in the compound of formula IV may not both be double bonds;
- and
- any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.
6 more elements
A compound having the structure of formula V:
- and pharmaceutically acceptable salts or prodrugs thereof, wherein:
- Y is selected from the group consisting of O and NR5;
- Z is selected from the group consisting of O, S, and NR5;
- R2, R6, and R7 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- R2′ is selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- or is absent;
- R4 and each R5 are separately selected from the group consisting of hydrogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 heteroalkyl, C2-6 aminoalkyl, C2-6 haloalkyl, C1-6 alkoxycarbonyl, and C2-6 hydroxyalkyl;
- C3-8 cycloalkyl;
- —C(O)—C5-6 aryl substituted with C1-3 alkyl or halo;
- C5-6 aryl;
- C5-6 heteroaryl;
- C5-6 cycloalkyl;
- and C5-6 heterocycloalkyl or are separately absent;
- R8 and R9 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- and halogenated alkyl including polyhalogenated alkyl;
- or are separately absent;
- R10 and R11 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C1-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- or are separately absent;
- any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;
- any bond represented by a single dashed line is a single bond or is absent;
- and any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.
138 more elements
A compound having the structure of formula V:
- and pharmaceutically acceptable salts or prodrugs thereof, wherein:
- Y is selected from the group consisting of O, S, and NR5;
- Z is selected from the group consisting of O, S, and NR5;
- R2, R6, and R7 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- R2′ is selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- or is absent;
- R4 and each R5 are separately selected from the group consisting of hydrogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following groups:
- C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 heteroalkyl, C2-6 aminoalkyl, C2-6 haloalkyl, C1-6 alkoxycarbonyl, and C2-6 hydroxyalkyl;
- C3-8 cycloalkyl;
- —C(O)—C5-6 aryl substituted with C1-3 alkyl or halo;
- C5-6 aryl;
- C5-6 heteroaryl;
- C5-6 cycloalkyl;
- and C5-6 heterocycloalkyl or are separately absent;
- R8 and R9 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl;
- cycloalkenyl;
- alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- and halogenated alkyl including polyhalogenated alkyl;
- or are separately absent;
- R10 and R11 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, or C2-C24 alkynyl;
- acyl;
- acyloxy;
- alkyloxycarbonyloxy;
- aryloxycarbonyloxy;
- cycloalkyl cycloalkenyl alkoxy;
- cycloalkoxy;
- aryl;
- heteroaryl;
- heterocycloalkyl;
- ester;
- arylalkoxy carbonyl;
- amino;
- aminocarbonyl;
- amide;
- aminocarbonyloxy;
- nitro;
- azido;
- phenyl;
- hydroxy;
- alkylthio;
- arylthio;
- oxysulfonyl;
- carboxy;
- cyano;
- and halogenated alkyl including polyhalogenated alkyl;
- or are separately absent;
- any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;
- any bond represented by a single dashed line is a single bond or is absent;
- and any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.
136 more elements
Dependencies are inferred from the claim text.