PREPARATION AND UTILITY OF SUBSTITUTED CARBOXYLIC ACID COMPOUNDS
First Claim
1. A compound selected from the group consisting of:
- or a single enantiomer, a mixture of a (+)-enantiomer and a (−
)-enantiomer, a mixture of about 90% or more by weight of the (−
)-enantiomer and about 10% or less by weight of the (+)-enantiomer, a mixture of about 90% or more by weight of the (+)-enantiomer and about 10% or less by weight of the (−
)-enantiomer, an individual diastereomer, or a mixture of diastereomers thereof;
or a pharmaceutically acceptable salt, solvate, or prodrug.
1 Assignment
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Accused Products
Abstract
The present disclosure is directed to modulators of cyclooxygenase (COX) enzymes and pharmaceutically acceptable salts and prodrugs thereof, the chemical synthesis thereof, and the medical use of such compounds for the treatment and/or management of the severity and duration of non-specific pain, tension-type pain, headache, migraine, lower back pain, sciatica, dental pain, muscular pain, pain associated with acute soft tissue injuries, bursitis, tendonitis, lumbago, periarthritis, tennis elbow, sprains, strains, muscular problems associated with sports injuries, muscular problems associated with accidents, period pain, primary dysmenorrhoea, acute sore throat pain, osteoarthritis, rheumatoid arthritis, cancer, any disorder requiring analgesic response, any disorder requiring anti-inflammatory response, any disorder requiring antipyretic response, any conditions mediated by cyclooxygenase, cystic fibrosis, dementia, Alzheimer'"'"'s disease, and/or conditions mediated by levels of β-amyloid are described.
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Citations
23 Claims
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1. A compound selected from the group consisting of:
-
or a single enantiomer, a mixture of a (+)-enantiomer and a (−
)-enantiomer, a mixture of about 90% or more by weight of the (−
)-enantiomer and about 10% or less by weight of the (+)-enantiomer, a mixture of about 90% or more by weight of the (+)-enantiomer and about 10% or less by weight of the (−
)-enantiomer, an individual diastereomer, or a mixture of diastereomers thereof;
or a pharmaceutically acceptable salt, solvate, or prodrug.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 18, 19)
or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
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13. The compound of claim 1 selected from the group consisting of:
or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
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14. The compound of claim 1 selected from the group consisting of:
or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
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17. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1, or the (−
- )-enantiomer of a compound according to claim 1, or the (+)-enantiomer of a compound according to claim 1, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and a pharmaceutically acceptable carrier.
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18. The pharmaceutical composition of claim 17, wherein said composition is suitable oral, parenteral, or intravenous infusion administration.
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19. The pharmaceutical composition of claim 17, wherein said oral administration comprises administering a tablet or a capsule.
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15. A method of treating a mammal suffering from a disease or condition involving cyclooxygenase enzymes comprising administering to said mammal a therapeutically effective amount of a compound selected from the group consisting of:
-
or a single enantiomer, a mixture of a (+)-enantiomer and a (−
)-enantiomer, a mixture of about 90% or more by weight of the (−
)-enantiomer and about 10% or less by weight of the (+)-enantiomer, a mixture of about 90% or more by weight of the (+)-enantiomer and about 10% or less by weight of the (−
)-enantiomer, an individual diastereomer, or a mixture of diastereomers thereof;
or a pharmaceutically acceptable salt, solvate, or prodrug.- View Dependent Claims (16)
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20. A process for deuterating a compound by exchanging at least one hydrogen atom of said compound with a deuterium atom, wherein said hydrogen atom is bonded to a carbon atom of an alkyl group directly bonded to an optionally substituted aromatic ring, where the reaction is carried out in a solvent or a mixture of solvents selected from the group consisting of deuterium oxide (D2O), benzene, d6-benzene, ethanol, CH3OD, CH3CH2OD, i-PrOD, octane, heptane, hexane, and pentane, in the presence of a transition metal-containing catalyst selected from the group consisting of palladium-on-alumina, palladium-on-carbon, platinum-on-carbon, PtO2, and rhodium-on-carbon, and an additive selected from the group consisting of cyclohexene, cyclohexadiene, formic acid, hydrazine, isopropanol, d-limonene, 1-methyl-4-t-butylcyclohene, 1-methylcyclohexene, 1-methyl-4-isopropylcyclohexene, β
- -phellandrene, and sodium formate, and at a temperature in the range of about 0°
C. up to about 500°
C., for about 0.01 to about 240 hours, at a pH in the range of about 1 up to about 14, and at a pressure in the range of about 1 mBar up to about 350 Bar. - View Dependent Claims (21)
- -phellandrene, and sodium formate, and at a temperature in the range of about 0°
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22. A process for preparing a compound of Formula 3 comprising contacting a compound of Formula 2 with deuterium oxide under conditions to produce the compound of Formula 3,
wherein, R1 is selected from the group consisting of hydrogen, deuterium, and glucuronide; -
R2 is selected from the group consisting of —
CH3, —
CH2D, —
CHD2, and —
CD3;R6 is selected from the group consisting of optionally deuterated C1-C6 alkyl, optionally deuterated methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, C5-C6 branched alkyl, optionally deuterated C1-C6 substituted alkyl; where the reaction is carried out in a solvent or a mixture of solvents selected from the group consisting of deuterium oxide (D2O), benzene, d6-benzene, ethanol, CH3OD, CH3CH2OD, i-PrOD, octane, heptane, hexane, and pentane, in the presence of a transition metal-containing catalyst selected from the group consisting of palladium-on-alumina, palladium-on-carbon, platinum-on-carbon, PtO2, and rhodium-on-carbon, and an additive selected from the group consisting of cyclohexene, cyclohexadiene, formic acid, hydrazine, isopropanol, d-limonene, 1-methyl-4-t-butylcyclohene, 1-methylcyclohexene, 1-methyl-4-isopropylcyclohexene, α
-phellandrene, and sodium formate, and at a temperature in the range of about 0°
C. up to about 500°
C., for about 0.01 to about 240 hours, at a pH in the range of about 1 up to about 14, and at pressure in the range of about 1 mBar up to about 350 Bar. - View Dependent Claims (23)
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Specification