Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-08-12
1999-09-21
Ramsuer, Robert W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548151, A61K 31425, C07D51302
Patent
active
059554851
DESCRIPTION:
BRIEF SUMMARY
The present invention is concerned with the use of a a medicament for the therapeutic or prophylactic treatment of humans suffering from ageing of, or degenerative diseases of the nervous and vascular system which are associated with oxidative stress. Pat. No. 4,262,004 as agents inhibiting the enzyme monoamine oxidase (MAO) and having therapeutic potential for treating depression and Parkinsonism. derivatives disclosed therein have potent antioxidant activity both in vitro and in vivo. In view of their antioxidant properties, these derivatives have therapeutical utility in the treatment of degenerative diseases, as well as ageing, of the nervous and vascular system which are associated with oxidative stress.
Consequently, the present invention is concerned with the use of acceptable acid addition salts, the stereochemically isomeric forms, and any mixtures of said derivatives, salts and stereoisomers, for the manufacture of a medicament for the therapeutic or prophylactic treatment of humans suffering from ageing of, or degenerative diseases of the nervous and vascular system which are associated with oxidative stress, said derivatives having the formula (I): ##STR1## wherein R.sup.1 represents C.sub.1-10 alkyl or C.sub.5-12 cycloalkyl, R.sup.2 represents hydrogen or C.sub.1-10 alkyl; and C.sub.1-4 alkyl.
The invention also concerns a method of treating patients suffering from ageing and degenerative diseases of the nervous and vascular system which are associated with oxidative stress, by administering to said patients an (I) effective in improving, halting, retarding or palliating the course and/or effects of said ageing and degenerative diseases.
C.sub.1-4 alkyl defines methyl, ethyl, propyl, butyl and the branched isomers thereof. C.sub.1-10 alkyl defines straight and branched saturated hydrocarbon radicals having from 1 to 10 carbon atoms, e.g. methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl and the branched isomers thereof. C.sub.5-12 cycloalkyl defines monocylic and where possible also bi- and tricyclic saturated hydrocarbon radicals having from 5 to 12 carbon atoms, e.g. cyclopentyl, cyclohexyl, cycloheptyl cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, like cycloalkyl radicals.
Preferred are the compounds wherein R.sup.1 represents C.sub.4-10 alkyl or C.sub.7-10 cycloalkyl; and R.sup.2 represents hydrogen. R.sup.3, R.sup.4 and R.sup.5 preferably represent hydrogen; and R.sup.3 and R.sup.5 also may represent methyl, ethyl, 2-propyl and 2-methyl-2-propyl. Especially preferred are the compounds wherein R.sup.1 represents a straight C.sub.6-10 alkyl group, a C.sub.4-10 alkyl group branched in .alpha.- or .beta.-position or a monocyclic C.sub.7-10 cycloalkyl group.
Specific compounds according to the invention include:
The compounds of formula (I) may be prepared following the procedures described in U.S. Pat. No. 4,262,004. As they have basic properties, these compounds may be converted into their pharmaceutically acceptable acid addition salt forms by treatment with an appropriate acid. Appropriate acids comprise, for example, inorganic acids such as hydrohalic acids, e.g. hydrochloric or hydrobromic acid; sulfuric; nitric; phosphoric and the like acids; or organic acids such as, for example, acetic, propanoic, hydroxyacetic, lactic, pyruvic, oxalic, malonic, succinic, maleic, fumaric, malic, tartaric, citric, methanesulfonic, ethanesulfonic, benzenesulfonic, p-toluenesulfonic, cyclamic, salicylic, p-aminosalicylic, pamoic and the like acids. The term addition salt as used hereinabove also comprises the solvates which the compounds of formula (I) as well as the salts thereof, are able to form. Such solvates are for example hydrates, alcoholates and the like. The preferred acid addition salt of dihydrochloride salt. Salts which are not pharmaceutically acceptable may be useful in the preparation of the compounds of formula (I) and of compositions comprising such compounds.
Oxidative stress refers to phenomena related to the action, in particular the deleterio
REFERENCES:
patent: 4262004 (1981-04-01), Sipido
patent: 4340738 (1982-07-01), Sipido
patent: 4364942 (1982-12-01), Sipido
J. Neural Transm., Suppl., vol. 43, 1994, pp. 183-201, XP000604350 KW. Lange et al. "Neuroprotection by Dopamine Agonists." see pp. 183-189.
Progress Neurobiol., vol. 48, No. 1, 1996, pp. 1-19, XP000604403 M. Ebadi et al.; Oxidative Stress and Antioxidant Therapy in Parkinson's Disease .
Neurobiol. Aging, vol. 16, No. 4, 1995, pp. 661-674, SP000604397 G. Benzi et al: "Are Reactive Oxygen Species Involved in Alzheimer's Disease?".
De Brabander Marc Joris
Lesage Anne Simone Josephine
Leysen Josepha Eduarda Maria Francisca
Ciambrone Coletti Ellen
Janssen Pharmaceutica N.V.
Murray Joseph
Ramsuer Robert W.
LandOfFree
Use of fused benzothiazoles as neuroprotectants does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Use of fused benzothiazoles as neuroprotectants, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Use of fused benzothiazoles as neuroprotectants will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-80646