Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-06-03
1995-11-07
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544127, 546122, A61K 31435, C07D 4704
Patent
active
054647819
DESCRIPTION:
BRIEF SUMMARY
This application is the national phase of PCT/EP92/02901 filed Dec. 12, 1992.
The present invention relates to therapeutic agents, and in particular to substituted 4(5)-amino-1,8-naphthyridines, to processes for their preparation, to pharmaceutical compositions containing them and to their therapeutic activity as anti-rheumatic agents.
Rheumatoid arthritis is currently treated with anti-inflammatory agents, which alleviate the symptoms but do not affect the progression of the condition, or with disease-modifying antirheumatic drugs e.g. gold compounds, D-penicillamine, sulphasalazine, azathioprine and methotrexate. However, most disease-modifying antirheumatic drugs are associated with side-effects, often of a serious nature. This means that such drugs are often only used as a last resort in the most serious cases. Consequently a need exists for a less toxic, disease-modifying, antirheumatic drug which may be administered orally.
EP 0,361,177 discloses compounds of formula A ##STR2## in which R represents alkyl, cyclopropyl, methylamino and p-fluorophenyl; R.sub.1 represents hydrogen or a C.sub.1-2 alkyl group; R.sub.2 represents halo and A represents --CH-- or a nitrogen atom. It is disclosed that these compounds may be used to treat rheumatoid arthritis by intraarticular administration.
Japanese patent application number 38774/69, publication number J47-29519 (1972) discloses ethyl 4-anilino-7-methyl-1,8-naphthyridine-3-carboxylate amongst a number of compounds which are prepared as intermediates for use in the preparation of anti-bacterial agents. It is suggested that these intermediates possess anti-bacterial and antiprotozoal activity but no results are given.
2-Diethylaminomethyl-4-(7'-methyl-1',8'-naphthyridin-4'-ylamino)phenol and 2-diethylaminomethyl-4-(1',8'-naphthyridin-4-ylamino)phenol are disclosed in the Australian Journal of Chemistry, 1984, 37, 1065 as having minimal anti-malarial activity.
The present invention relates to compounds of formula I ##STR3## and pharmaceutically acceptable salts thereof in which R.sub.1 represents hydrogen, a C.sub.1-6 alkyl group, hydroxy, a carboxy C.sub.2-4 alkenyl group, a C.sub.2-6 alkoxycarbonyl C.sub.2-4 alkenyl group, a hydroxy C.sub.1-6 alkyl group, a carboxy C.sub.1-4 alkyl group, a C.sub.2-6 alkoxycarbonyl C.sub.1-4 alkyl group, a C.sub.1-6 alkoxy group, a halogenated C.sub.1-6 alkyl group, a carboxy group, a C.sub.2-6 alkoxycarbonyl group or a C.sub.1-6 alkanoylamino group; C.sub.1-6 alkanoyloxy group, or a phenoxy group (which may be optionally substituted by a C.sub.1-4 alkyl group, halo or a C.sub.1-4 alkoxy group); benzyloxycarbonyl group (which may be optionally substituted by a C.sub.1-4 alkyl group, halo or a C.sub.1-4 alkoxy group), a C.sub.1-6 alkanoyl group, a benzoyl group (which may be optionally substituted by a C.sub.1-4 alkyl group, halo or a C.sub.1-4 alkoxy group), carbamoyl, a C.sub.1-6 alkyl group, a carboxy group, a C.sub.1-6 hydroxyalkyl group or a C.sub.1-6 alkylthio group; substituted by one or more of the following: hydroxy, halo or an amino group of formula --NR.sub.12 R.sub.13 (in which R.sub.12 and R.sub.13 independently represent hydrogen or a C.sub.1-4 alkyl group or R.sub.12 and R.sub.13 together with the nitrogen atom to which they are attached represent a pyrrolidine ring, a morpholine ring or a piperidine ring)], a C.sub.3-12 alicyclic hydrocarbon group, a phenyl group (which may be optionally substituted by a C.sub.1-4 alkyl group, halo or a C.sub.1-4 alkoxy group), a C.sub.3-6 cycloalkyl C.sub.1-4 alkyl group or a benzyl group (which may be optionally substituted by a C.sub.1-4 alkyl group, halo or a C.sub.1-4 alkoxy group); C.sub.1-6 alkyl group, a carboxy group, or a C.sub.1-6 alkoxy group; C.sub.1-6 alkyl group or a C.sub.1-6 alkoxy group; and
It will be understood that a group containing a chain of 3 or more carbon atoms may be straight or branched, for example, propyl includes n-propyl and isopropyl and butyl includes n-butyl, sec-butyl, isobutyl and tert-butyl. Alicyclic groups may be bridged.
A preferred gro
REFERENCES:
patent: 4801592 (1989-01-01), Graf
patent: 5143920 (1992-09-01), Ite
Weinblatt M. E. Maier Al. Disease-Modifying agents and experimental treatments of rhematoid arthritis Clin. Orthop (1991 Apr.) 265 103-15.
Sofia et al., Comparative Effects of Anti-Arthritic and Other Pharmacological Agents in the 18-hour Arthritis and Carrageenan Edema Tests in Rats. Pharm. Res. Comm. 11, No. 2, 179-193 (1979).
Barlin et al., Potential Antimalarials. 1. 1,8-Naphthyridines. Aust. J. Chem. 37, 1065-1173 (1984).
Kuroda et al., A Novel Synthesis and Potent Antiinflammatory Activity of 4-Hydroxy-2(1H)-oxo-1-phenyl-1,8-naphthyridine-3-carboxamides. J. Med. Chem. 35, 1130-1136 (1992).
Heber et al., Synthesis of 2- and 4-alkylamino-1,8-naphthyridine Derivatives as Potential Positive Inotropic Agents. Arch. Pharm. 324, No. 9, p600 (1991).
Crossley et al., Studies on the Effects of Pharmacological Agents on Antigen-Induced Arthritis in BALB/c Mice. Drugs Exptl. Clin. Res. XIII (5) 273-277 (1987).
Hunneyball et al., Pharmacological Studies of Antigen-Induced Arthritis in BALB/c Mice I. Characterization of the Arthritis and the Effects of Steroidal and Non-Steroidal Anti-Inflammatory Agents. Agents and Actions 18, 3/4 384-393 (1986).
Hunneyball et al., Pharmacological Studies of Antigen-Induced Arthritis in BALB/c Mice II. The effects of second-line antirheumatic drugs and cytotoxic agents on the histopathological changes. Agents and Actions 18, 3/4 394-400 (1986).
Armitage Bernard J.
Bowen John G.
Crossley Malcolm J.
Hunneyball Ian M.
Leslie Bruce W.
Huang Evelyn
Ivy C. Warren
The Boots Company PLC
LandOfFree
Amino naphthyridine compounds as anti-rhoumatic agents does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Amino naphthyridine compounds as anti-rhoumatic agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Amino naphthyridine compounds as anti-rhoumatic agents will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-196946