Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-12-16
1999-11-30
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514252, 544238, 544240, A01N 4358, C07D40100
Patent
active
059943530
DESCRIPTION:
BRIEF SUMMARY
Aromatic compounds and pharmaceutical compositions containing them 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 undesirable 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 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.
The compound 2-[2-methoxybenzylamino]pyridine-5-carboxylic acid is disclosed in European Patent Application No. 0000816 (as example number 28 therein) and stated to be of value in the treatment of diabetes. The compound 4-[2-methoxybenzylamino]-benzoic acid is disclosed in U.S. Pat. No. 4,362,892 (as example number 8 therein) and stated to possess hypolipidaemic activity. The compounds 3-[2-methoxybenzylamino]-4-chloro-5-sulphamoylbenzoic acid and 3-[2,3-dimethoxybenzylamino]-4-chloro-5-sulphamoylbenzoic acid are disclosed by P. Feit et al., J. Med. Chem., 1970, 13, 1071, as diuretics. The compound 5-[2,5-dimethoxybenzylamino]-2-hydroxybenzoic acid is disclosed by P. Nussbaumer et al., J. Med. Chem. 1994, 37, 4079, as an antiproliferative agent.
According to the invention there is provided a compound of the formula 1: ##STR2## wherein: A is an optionally substituted: thiazolyl, oxazolyl or thiadiazolyl having at least two adjacent ring carbon atoms; are positioned in a 1,2 relationship to one another on ring carbon atoms and the ring atom positioned ortho to the OR.sup.4 linking group (and therefore in the 3-position relative to the --CHR.sup.3 NR.sup.2- linking group) is not substituted; pyrazinyl, pyridazinyl or pyrimidyl; --CH(R.sup.3)N(R.sup.2)-- linking group and is carboxy, carboxyC.sub.1-3 alkyl, tetrazolyl, tetrazolylC.sub.1-3 alkyl, tetronic acid, hydroxamic acid, sulphonic acid, or R.sup.1 is of the formula --CONR.sup.a R.sup.a1 wherein R.sup.a is hydrogen or C.sub.1-6 alkyl and R.sup.a1 is hydrogen, C.sub.1-6 alkyl (optionally substituted by halo, amino, C.sub.1-4 alkylamino, di-C.sub.1-4 alkylamino. hydroxy, nitro, cyano, trifluoromethyl, C.sub.1-4 alkoxy or C.sub.1-4 alkoxycarbonyl), C.sub.2-6 alkenyl (provided the double bond in not in the 1-position), C.sub.2-6 alkynyl (provided the triple bond is not in the 1-position), carboxyphenyl, 5- or 6-membered heterocyclylC.sub.1-3 alkyl, 5- or 6-membered heteroarylC.sub.1-3 alkyl, 5- or 6-membered heterocyclyl, or 5- or 6-membered heteroaryl or R.sup.a and R.sup.a1 together with the amide nitrogen to which they are attached (NR.sup.a R.sup.a1) form an amino acid residue or ester thereof, or R.sup.1 is of the formula --CONHSO.sub.2 R.sup.b wherein Rb is C.sub.1-6 alkyl (optionally substituted by halo,
REFERENCES:
patent: 3632760 (1972-01-01), Shen et al.
patent: 3657430 (1972-04-01), Shen et al.
patent: 4152452 (1979-05-01), Douglas et al.
patent: 4206145 (1980-06-01), Hindley et al.
patent: 4277496 (1981-07-01), Los
patent: 4350822 (1982-09-01), Albright et al.
patent: 4362892 (1982-12-01), Hindley et al.
patent: 4555516 (1985-11-01), Cross et al.
patent: 4559336 (1985-12-01), Mueller
patent: 4578390 (1986-03-01), Jensen et al.
patent: 4590199 (1986-05-01), Coker et al.
patent: 4614617 (1986-09-01), Mueller
patent: 4704386 (1987-11-01), Mueller
patent: 4767767 (1988-08-01), Foguet et al.
patent: 4839369 (1989-06-01), Youssefyeh et al.
patent: 4937373 (1990-06-01), Carson et al.
patent: 5087743 (1992-02-01), Jansen et al.
patent: 5105017 (1992-04-01), Diuard
patent: 5189033 (1993-02-01), Tucker
patent: 5210206 (1993-05-01), Morton et al.
patent: 5250548 (1993-10-01), Winn et al.
patent: 5284954 (1994-02-01), Wittenberger et al.
patent: 5314883 (1994-05-01), Tanikawa et al.
patent: 5317101 (1994-05-01), Tucker et al.
patent: 5324743 (1994-06-01), Dillard et al.
patent: 5393768 (1995-02-01), 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: 5530157 (1996-06-01), Mewshaw et al.
Chem. Abstracts, vol. 91, No. 27, 1979, abstract 56831t, p. 691.
Albright et al., J. Med. Chem. 1983, 26, 1378-1393, Potential Antiatherosclerotic Agents. 2..sup.1 (Aralkylamino)- and (Alkylamino) benzoic Acid Analogues of Cetaben.
Brown et al., J. Med. Chem., 1989, 32, 807-825, Hydroxyacetophenone-Derived Antagonists of the Peptidoleukotrienes.
P. Feit et al., J. Med. Chem., 1970, 13, 1071-1075, Aminobenzoic Acid Diuretics. 1. 4-Halogeno-5-sulfamylmetanilic Acid Derivatives.
P. Nussbaumer et al., J Med. Chem., 1994, 37, 4079-4084, Novel Antiproliferative Agents Derived from Lavendustin A.
Mitchell Kenneth F.
Shah Mukund J.
Truong Tamthom N.
Zeneca Limited
LandOfFree
Aromatic compounds and pharmaceutical compositions containing 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 Aromatic compounds and pharmaceutical compositions containing th, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Aromatic compounds and pharmaceutical compositions containing th will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1672912