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US 6,747,048 B2Granted
Pyridine-based thyroid receptor ligands
AssigneeBristol-Myers Squibb Company
InventorsMinsheng Zhang, Jon Hangeland, Yolanda Caringal, Todd Friends
Life of this patent
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Abstract
Novel pyridine-based thyroid receptor ligands are provided which have the general formula I wherein: X is oxygen (—O—), sulfur (—S—), sulfoxide (—S(O)—), sulfonyl (—SO2—), CR8R8 or NR8; Y is —NR8, oxygen (—O—), —CH2— or sulfur (—S—); Z is a bond or substituted or unsubstituted C1-4 alkyl; and wherein the substituents are as described herein. In addition, a method is provided for preventing, inhibiting or treating diseases or disorders associated with metabolism dysfunction or which are dependent upon the expression of a T3 regulated gene, wherein a compound as described above is administered in a therapeutically effective amount.
Claims25
A compound of the formula
- wherein
- X is selected from the group consisting of oxygen, sulfur, sulfoxide, sulfonyl, —CR8R8′ and —NR8;
- Y is selected from the group consisting of —NR8, oxygen, —CH2— and sulfur;
- Z is a bond or substituted or unsubstituted C1-4 alkyl;
- R1 is selected from the group consisting of halogen, trifluoromethyl, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, aryloxy, substituted amide, sulfone, sulfonamide and C3-7 cycloalkyl, wherein said aryl, heteroaryl or cycloalkyl ring(s) are attached or fused to the aromatic ring;
- R1a is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
- R2 and R3 are each independently selected from the group consisting of hydrogen, halogen, unsubstituted or substituted C1-4 alkyl and unsubstituted or substituted C3-5 cycloalkyl, wherein at least one of R2 and R3 being other than hydrogen;
- R4 is selected from the group consisting of hydrogen, halogen, amino, O—R7 and S—R7;
- R5 is selected from the group consisting of hydroxyl, carboxylic acid, sulfonic acid and phosphonic acid;
- R6 is selected from the group consisting of hydrogen, alkyl, alkanoyl and aroyl;
- R7 is hydrogen or C1-4 alkyl;
- R8 for each occurrence is independently selected from the group consisting of hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, aryl or substituted aryl, arylalkyl or substituted arylalkyl, alkoxy and hydroxyl;
- and
- R8′ is selected from the group consisting of hydrogen, a bond, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, aryl or substituted aryl, arylalkyl or substituted arylalkyl, alkoxy and hydroxyl, or R8 and R8′ together form a carbonyl,
- including all prodrug, stereoisomers and pharmaceutically acceptable salts thereof.
12 more elements
A compound of the formula
- wherein
- X is selected from the group consisting of oxygen, sulfur, sulfoxide, sulfonyl, —CR8R8′ and —NR8;
- Y is selected from the group consisting of —NR8, oxygen, —CH2— and sulfur;
- Z is a bond or substituted or unsubstituted C1-4 alkyl;
- R1 is selected from the group consisting of halogen, trifluoromethyl, substituted or unsubstituted C1-6alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, aryloxy, substituted amide, sulfone, sulfonamide and C3-7 cycloalkyl;
- R1a is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
- R2 and R3 are each independently selected from the group consisting of hydrogen, halogen, unsubstituted or substituted C1-4 alkyl and unsubstituted or substituted Cog cycloalkyl, wherein at least one of R2 and R3 being other than hydrogen;
- R4 is selected from the group consisting of hydrogen, halogen, amino, O—R7, S—R7 and unsubstituted or substituted C1-4 alkyl;
- R5 is selected from the group consisting of hydroxyl, carboxylic acid, sulfonic acid and phosphonic acid;
- R6 is selected from the group consisting of hydrogen, alkyl, alkanoyl and aroyl;
- R7 is hydrogen or C1-4 alkyl;
- R8 for each occurrence is independently selected from the group consisting of hydrogen, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, aryl or substituted aryl, arylalkyl or substituted arylalkyl, alkoxy and hydroxyl;
- and
- R8′ is selected from the group consisting of hydrogen, a bond, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, aryl or substituted aryl, arylalkyl or substituted arylalkyl, alkoxy and hydroxyl, or R8 and R8′ together form a carbonyl,
- including all prodrug, stereoisomers and pharmaceutically acceptable salts thereof.
12 more elements
Dependencies are inferred from the claim text.