Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1996-06-04
1998-09-22
Gupta, Yogendra N.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
5142372, 514262, 514252, 514340, 514345, 514568, 514617, 544174, 544329, 544332, 546256, 5462684, 546290, 546298, 546334, 5483381, 564471, 564472, A61K 3119, A61K 31505, C07C 6304, C07C23942
Patent
active
058114599
DESCRIPTION:
BRIEF SUMMARY
This invention relates to novel, aromatic compounds and pharmaceutically-acceptable salts thereof which possess useful pharmacological properties. More particularly the compounds of the invention are antagonists of the pain enhancing effects of E-type prostaglandins. The invention also relates to processes for the manufacture of the aromatic compounds and pharmaceutically-acceptable salts thereof; to novel pharmaceutical compositions containing them; and to use of the compounds in pain relief.
The compounds of the invention are useful in the treatment of pain such as the pain associated with joint conditions (such as rheumatoid arthritis and osteoarthritis), postoperative pain, post-partum pain, the pain associated with dental conditions (such as dental caries and gingivitis), the pain associated with burns (including sunburn), the treatment of bone disorders (such as osteoporosis, hypercalcaemia of malignancy and Paget's disease), the pain associated with sports injuries and sprains and all other painful conditions in which E-type prostaglandins wholly or in part play a pathophysiological role.
Non-steroidal anti-inflammatory drugs (NSAIDS) and opiates are the main classes of drugs in pain relief. However both possess undesireable side effects. NSAIDS are known to cause gastrointestinal irritation and opiates are known to be addictive.
We have now found a class of compounds structurally different to NSAIDS and opiates, and useful in the relief of pain.
The compounds of the invention may also possess anti-inflammatory, anti-pyretic and anti-diarrhoeal properties and be effective in other conditions in which prostaglandin E.sub.2 (PGE.sub.2) wholly or in part plays a pathophysiological role.
According to the invention there is provided a compound of the formula I; ##STR2## wherein: A is optionally substituted: phenyl, naphthyl or a 5- or 6-membered heteroaryl ring system containing no more than two ring nitrogen atoms or thiadiazolyl or a bicyclic ring system of the formula: ##STR3## wherein E is nitrogen or CH, F is nitrogen or CH, G is sulphur or oxygen and H is nitrogen or CH; relationship to one another on ring carbon atoms; carbon atom bearing the --OCH(R.sup.3)-- group and in the 3-position relative to the ring carbon atom bearing the --Z--B--R.sup.1 group is unsubstituted and, when A is naphthyl, either the --Z--B--R.sup.1 group is in the 1-position and the --OCH(R.sup.3)-- group is in the 2-position of the naphthyl group and the ring atom in the 3-position is not substituted, or the --Z--B--R.sup.1 -- group is in the 2-position and the --OCH(R.sup.3)-- group is in the 3-position of the naphthyl group and the ring atom in the 4-position is not substituted (according to the IUPAC system);
B is an optionally substituted 5- or 6-membered heteroaryl ring system, optionally substituted phenyl or an optionally substituted ring system of the formula: ##STR4## wherein 0 or 1 of J and K are ring nitrogen atoms and the remainder are ring carbon atoms and R.sup.4 is C.sub.1-6 alkyl; relationship to one another on ring carbon atoms in B in 6 membered rings and in a 1,3 relationship to one another in ring carbon atoms in B in 5-membered rings;
D is optionally substituted: phenyl or a 5- or 6- membered heteroaryl ring system;
R.sup.1 is carboxy, optionally substituted tetrazolyl, carboxyC.sub.1-4 alkyl, optionally substituted tetrazolylC.sub.1-4 alkyl, hydroxamic acid, sulphonic acid, tetronic acid or a pharmaceutically acceptable amide (--CONR--), reverse amide (--NRCC--), acylsulphonamide (--CONRSO.sub.2 --), acylhydrazide (--CON(R)N ) or C.sub.1-4 alkyl substituted by a pharmaceutically-acceptable amide, reverse amide, acylsulphonamide or acylhydrazide or R.sup.1 is of the formula (IIA), (IIB) or (IIC): ##STR5## wherein X is CH or nitrogen, Y is oxygen or NH, Z is CH.sub.2, NH or oxygen and Y.sup.1 is oxygen or sulphur provided that there is no more than one ring oxygen and there are at least two ring heteroatoms;
R.sup.3 is hydrogen or C.sub.1-4 alkyl;
Z is of the formula --(CH(R.sup.5)).sub.m --, --(CHR.sup.5
REFERENCES:
patent: 3632760 (1972-01-01), Shen et al.
patent: 3657430 (1972-04-01), Shen et al.
patent: 4350822 (1982-09-01), Albright et al.
patent: 4578390 (1986-03-01), Jenson et al.
patent: 4937373 (1990-06-01), Carson et al.
patent: 5087743 (1992-02-01), Janssen et al.
patent: 5189033 (1993-02-01), Tucker
patent: 5317101 (1994-05-01), Oldfield et al.
patent: 5324743 (1994-06-01), Dillard et al.
patent: 5409930 (1995-04-01), Spada et al.
patent: 5420270 (1995-05-01), Chandrakumar et al.
patent: 5441950 (1995-08-01), Collins et al.
patent: 5480883 (1996-01-01), Spada et al.
patent: 5530157 (1996-06-01), Mewshaw et al.
patent: 5552441 (1996-09-01), Dillard et al.
Derwent Patent Abstract of DE 2,701,854 (Abstract No. 52629Y/30).
Albright et al., J. Med. Chem. 1983, 26, 1378-1393.
Brown et al., J. Med. Chem. 1989, 32, 807-826.
Breault Gloria Ann
Oldfield John
Tucker Howard
Warner Peter
Darkes Paul R.
Gupta Yogendra N.
Zeneca Limited
LandOfFree
Ortho substituted aromatic compounds useful as antagonists of th does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Ortho substituted aromatic compounds useful as antagonists of th, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Ortho substituted aromatic compounds useful as antagonists of th will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1622189