Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-12-16
2000-08-08
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514252, 514340, 514354, 514355, 514356, 514576, 514620, 544114, 544224, 544238, 546322, 546323, 546326, 5462684, 562451, 564165, A61K 315377, A61K 3150, C07D23724, C07D40304
Patent
active
061002585
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 mild to moderate 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 mild to moderate pain relief. However both classes 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 mild to moderate 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; ##STR1## wherein: A is an optionally substituted: phenyl, naphthyl, pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, thienyl, thiazolyl, oxazolyl or thiadiazolyl having at least two adjacent ring carbon atoms; provided that the --CH(R.sup.3)N(R.sup.2)B--R.sup.1 and --OD groups are positioned in a 1,2 relationship to one another on ring carbon atoms and the ring atom positioned ortho to the --OD linking group (and therefore in the 3-position relative to the --CHR.sup.3 NR.sup.2 -linking group) is not substituted; thienyl, thiadiazolyl, imidazolyl, 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 R.sup.b is C.sub.1-6 alkyl (optionally substituted by halo, hydroxy, nitro, cyano, amino, C.sub.1-4 alkylamino, di-C.sub.1-6 alkylamino, trifluoromethyl, C.sub.1-4 alkoxy or C.sub.1-4 alkoxycarbonyl), C.sub.2-6 alkenyl (provided the double bond is not in the 1-position), C.sub.2-6 alkynyl (provided the triple bond is not in the 1-position), 5- or 6-membered heterocyclylC.sub.1-3 alkyl, 5- or 6-membered heteroarylC.sub.1-3 alkyl phenylC.sub.1-3 alkyl, 5- or 6-membered heterocyclyl, 5- or 6-membered heteroaryl or phenyl; substituted by halo, hydroxy, nitro, cyano, trifluoromethyl, C.sub.1-4 alkoxy or C.sub.1-4 alkoxycarbonyl and any phenyl, hete
REFERENCES:
patent: 3632760 (1972-01-01), Shen et al.
patent: 3657430 (1972-04-01), Shen et al.
patent: 4152452 (1979-05-01), Doulgas 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: 4578390 (1986-03-01), Jensen et al.
patent: 4590199 (1986-05-01), Coker et al.
patent: 4631287 (1986-12-01), Chakraborty et al.
patent: 4725619 (1988-02-01), Chakraborty et al.
patent: 4728668 (1988-03-01), Chakraborty 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: 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: 5480883 (1996-01-01), Spada et al.
patent: 5530157 (1996-06-01), Mewshaw et al.
patent: 5811459 (1998-09-01), Breault et al.
patent: 5834468 (1998-11-01), Breault et al.
patent: 5843942 (1998-12-01), Breault et al.
Derwent Abstract of DE 1,543,519 (Abstract No. 71-26731S/16), 1971.
Derwent Abstract of WO 93/23364 (Abstract No. 93-386430/48), 1993.
Chem. Abstracts, vol. 91, No. 27, 1979, abstract 56831t, p. 691.
Chem. Abstracts, vol. 101, 1984 , abstract 63594w.
Chem. Abstracts, vol. 102, 1985, abstract 1871w.
Albright et al., J. Med. Chem. 1983, 26, 1378-1393, Potential Antiatherosclerotic Agents, 2,' (Aralkylamino)-and (Alkylamino) benzoic Acid Analogues of Cetaben.
Brown et al., J. Med. Chem., 1989, 32, 807-825, Hydroxyacetophenone-Derived Antagonists of the Peptidolekotrienes.
Mazumder et al., Biochemistry, 1995, 34, pp. 15111-15122, Effects of Tyrphostins, Protein kinase Inhibitors, on Human Immunodeficiency Virus Type 1 Integrase.
Chen et al, J. Med. Chem., 1993, 36, 4094-4098, Synthesis and Structure-Activity Studies of a Series of [(Hydroxybenzyl)amino]Salicylates as Inhibitors of EGF Receptor-Associated Tyrosine Kinase Activity.
Hsu et al., J. of Biological Chemistry, 1991, Bol. 266, No. 31, Issue of Nov. 5, pp. 21105-21112, Kinetic Analysis of the Inhibition of the Epidermal Growth Factor Receptor Tyrosine Kinase by Lavendustin-A and its Analogue.
Iskander et al., Eur J. Med Chem, 1991, 26, 129-136, Transition-state analogues as inhibotors for GABA-aminotransferase.
Walker et al., J. Med. Chem., 1966, 9, 624-630, Synthesis of Varied Heterocyclic and Substituted Aryl Alkyl Secondary Amines, Related Schiff, Bases, and Amides.
Bernhardt Emily
Mitchell Kenneth F.
Zeneca Limited
LandOfFree
Aromatic amine compounds that antagonize the pain enhancing effe 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 amine compounds that antagonize the pain enhancing effe, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Aromatic amine compounds that antagonize the pain enhancing effe will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1150344