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AssigneeRoussel Uclaf
InventorsFrancois Clemence, Odile Le Martret, Francoise Delevallee
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A 4-hydroxy-3-quinoline-carboxamides of the formula ##STR1## wherein X is in the 5,6,7 or 8-position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CH.sub.3, --OCF.sub.3 or --SCF.sub.3, R.sub.1 is selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, R.sub.2 is selected from the group consisting of a heterocycle connected to the nitrogen by a carbon atom selected from thiazolyl, 4,5-dihydro-thiazolyl, pyridinyl, oxazolyl, isoxazolyl, imidazolyl, pyrimidinyl or tetrazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms or phenyl optionally substituted with at least one member of the group consisting of --OH, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CH.sub.3, --NO.sub.2 or halogen, R.sub.3 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms or aryl, R.sub.4 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms or aryl, and their non-toxic, pharmaceutically acceptable acid addition salts and salts with non-toxic, pharmaceutically acceptable bases having very good analgesis activity and a non-negligible anti-inflammatory activity and novel intermediates.
A compound of the formula ##STR21## wherein X is in the 5, 6, 7 or 8-position and is selected from the group consisting of hydrogen, halogen, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 4 carbon atoms, --CF.sub.3, --OCF.sub.3 --SCF.sub.3, R.sub.2 is selected from the group consisting of a heterocycle connected to the nitrogen atom by a carbon atom selected from thiazolyl, 4,5-dihydro-thiazolyl, pyridinyl, oxazolyl, isoxazolyl or imidazolyl, all optionally substituted with alkyl of 1 to 4 carbon atoms and phenyl optionally substituted with one or two members of the group consisting of --OH, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbons, --CF.sub.3, --NO.sub.2 or halogen, R.sub.3 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, phenyl or naphthyl, and R.sub.4 is selected from the group consisting of hydrogen, alkyl of 1 to 4 carbon atoms, phenyl or naphthyl.
Dependencies are inferred from the claim text.
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With hetero atoms directly attached in position 4: oxygen atoms
Drugs for disorders of the nervous system: centrally acting analgesics, e.g. opioids
Non-central analgesic, antipyretic or antiinflammatory agents
Oxygen atoms: in positions 2 and 3, e.g. isatin
Term ended 5 Apr 2005 (estimated)
USPTO file history isn’t available for this patent, so only indexed dates are shown.
Commonly assigned U.S. Pat. Nos. 4,299,831 and 4,107,310 and commonly assigned U.S. patent application Ser. No. 262,952 filed May 12, 1981, now U.S. Pat. No. 4,397,856 described various 3-quinoline-carboxamides of different structure.
It is an object of the invention to provide the novel compounds of formula I and their non-toxic, pharmaceutically acceptable salts and a novel process and intermediates for their preparation.
It is another object of the invention to provide novel analgesic and anti-inflammatory compositions and a novel method of treating pain and inflammation in warm-blooded animals.
In the following examples there are described several preferred embodiments to illustrate the invention. However, it should be understood that the invention is not intended to be limited to the specified embodiments.
A mixture of 4 g of 2-(1-chloroethyl)-4-hydroxy-N-(2-thiazolyl)-8-trifluoromethyl-3-quinoline- carboxamide [described in Examples 5 and 14 of U.S. patent application Ser. No. 262,952 filed May 12, 1981], 40 ml of acetic acid and 1.23 g of anhydrous potassium acetate was stirred at reflux for 90 minutes and was then cooled to room temperature and poured into 200 ml of iced water. The mixture stood overnight and was then vacuum filtered. The product was washed with water and dried under reduced pressure at 90.degree. C. to obtain 3.2 g of product. The latter was taken up in refluxing dioxane and the mixture was filtered hot. The filtrate was iced and the product was washed with water and dried under reduced pressure at 80.degree. C. to obtain 1.3 g of 2-(1-acetyloxy-ethyl)-4-hydroxy-N-(2-thiazolyl)-8-trifluoromethyl-3-quinol ine-carboxamide melting at 262.degree. C.
Analysis: C.sub.18 H.sub.14 N.sub.3 O.sub.4 F.sub.3 S Calculated: %C 50.82, %H 3.32, %N 9.88, %F 13.40, %S 7.54. Found: %C 51.0, %H 3.3, %N 9.7, %F 13.3, %S 7.5.