Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1992-12-11
1995-04-04
Daus, Donald G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548235, 548236, A61K 3142
Patent
active
054038529
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new oxazole derivatives of general formula: ##STR2## in which: R and R' are identical or different and represent a hydrogen atom or an alkyl radical containing 1 or 2 carbon atoms, halogen atoms or alkyloxy radicals in which the alkyl portion contains 1 to 4 carbon atoms in a straight or branched chain, and pharmaceutical compositions containing them.
In British Patent GB 1,381,860, tetrazole derivatives of structure: ##STR3## have been described, in which structure [Het] is a 5-member heterocycle of general formula: ##STR4## it being possible for to be O or S and R.sup.1 and R.sup.2 being substituted or unsubstituted aryl groups, and n equals 0, 1 or 2.
These derivatives manifest anti-inflammatory activity.
In Patent Application FR 1,584,222, oxazole derivatives of general formula: ##STR5## have been described, in which formula R.sub.1 and R.sub.2 are identical or different and represent phenyl radicals optionally substituted with halogen, alkyl, alkyloxy, nitro or amino, X is an oxygen or sulphur atom and R.sub.3 is an aliphatic acid radical containing 2 to 6 carbon atoms.
These products display anti-inflammatory activity.
In Patent Application DE 2,129,012, -azole derivatives of general formula: ##STR6## have been described, in which formula R.sub.1 is a carboxyl group, R.sub.2 and R.sub.3 are optionally substituted aryl groups, A is C.sub.n H.sub.2n and Z is a sulphur or oxygen atom.
These products are useful as anti-inflammatories.
It has now been found that the oxazole derivatives according to the invention, which possess long chains separating the heterocycles, manifest an antagonist action on the effects of leukotriene B.sub.4 which was not possessed or was barely possessed by the products of the prior art.
Leukotriene B.sub.4 is a potent mediator of inflammation which is formed following the bioconversion of arachidonic acid by means of 5-lipoxygenase. It contributes, in particular, to phenomena such as chemotaxis, cell activation and exocytosis of enzymes, and also participates in immunological and tissue disturbances. The products according to the invention are hence especially advantageous in the treatment of diseases in which this mediator plays a part, in particular in the treatment of inflammatory diseases, for which the products of the prior art were ineffective.
In the general formula (I), when the radicals R.sub.1 and/or R.sub.2 represent halogen atoms, they may be chosen from fluorine, chlorine or bromine atoms. Preferably, they represent a chlorine atom. The symbol n is between 3 and 6, but the chosen value of n will preferably be 4 or 5.
According to the invention, the new oxazole derivatives may be prepared by the action of an alkali metal azide or tri-n-butyltin azide on a nitrile of general formula: ##STR7## in which R, R', R.sub.1, R.sub.2 and n are defined as above.
When an alkali metal azide is reacted, the action of sodium azide is advantageously employed. The reaction is performed in the presence of ammonium chloride or the hydrochloride of a nitrogenous organic base (for example triethylamine, di-n-butylamine), in an organic solvent such as an amide (for example dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone), at a temperature of between 80.degree. and 150.degree. C., and preferably between 80.degree. and 110.degree. C. When the action of tri-n-butyltin azide is employed, the reaction is performed in 1,2-dimethoxyethane at the temperature defined hereinbefore.
The nitrile of general formula (II) for which R or R' is a hydrogen atom may be prepared by hydrolysis of the cyano ester of general formula: ##STR8## in which R, R.sub.1, R.sub.2 and n are defined as above and Alk represents a linear or branched alkyl radical containing 1 to 4 carbon atoms, followed by decarboxylation of the acid obtained.
The hydrolysis of the ester may be carried out in an acidic or basic medium. When the hydrolysis is carried out in acidic medium, the reaction is performed, for example, by the action of p-toluenesulphonic acid or formic acid at a temper
REFERENCES:
patent: 3546342 (1970-12-01), Brown
patent: 3574228 (1971-04-01), Brown
patent: 3586679 (1971-06-01), Tandon et al.
patent: 3933840 (1976-01-01), Dahm et al.
patent: 4051250 (1977-09-01), Dahm et al.
patent: 5262540 (1993-11-01), Meanwell
Barreau Michel
Kryvenko Michel
Lavergne Marc-Pierre
Techer Auguste
Daus Donald G.
Laboratoire Roger Bellon
Nicholson James A.
Parker III Raymond S.
Savitzky Martin F.
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