Biologically active oreido derivatives useful in the treatment o

Details Biologically active oreido derivatives useful in the treatment o Biologically active oreido derivatives useful in the treatment o

1997-10-09

1999-01-12

Reamer, James H.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

A61K 31395

Patent

active

058590463

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to the use of ureido derivatives of substituted pyrroles in the treatment of multiple sclerosis in mammals, including humans.


DESCRIPTION OF THE BACKGROUND

Multiple sclerosis is a demyelinating disease of the central nervous system the onset of which generally occurs within the age range from about 15 to 45. Myelin is a fatty substance which forms a sheath around certain nerve fibers and which conducts nervous impulse at a rate which enables muscles to make precise and delicate movements. The disease is characterized by induration of the sheath substance leading to the formation of plaques of varying size and location which interfere with the impulses normally conducted by the sheath.
The course of the disease can be highly variable in individual patients. Early stages of the disease in general are characterized by relapsing and remitting phase, subsequently the disease follows a chronic progressive course. However, the disease generally results in progressive deterioration of the control of muscle function with ultimate paralysis in many cases. The precise cause of multiple sclerosis is unknown and it may result from a complex interaction of a number of different factors.
Accordingly, there is a need in therapy for drugs which are active in treating the acute relapse and the progression of multiple sclerosis and/or able to ameliorate clinical symptoms or causes of multiple sclerosis.
PCT/EP94/00268 and PCT/EP94/00984 describe the use of a selected class of poly-4-amino-2-carbonyl-1-methyl pyrrole compounds, which were disclosed in PCT/EP91/00014, in preventing and/or treating the metastatic spread of tumors and the use in the treatment of lentivirus infection, respectively.


SUMMARY OF THE INVENTION

The present invention provides the use of a compound which is a ureido derivative of formula (I) ##STR2## wherein each of m and n, which are the same, is an integer of 1 to 3; and each of the R groups, which are the same, is a naphthyl group substituted by 1 to 3 sulfonic groups, or a pharmaceutically acceptable salt thereof; in the manufacture of a medicament for use in the treatment of multiple sclerosis.
Accordingly, the present invention provides a use as defined above, wherein the medicament is for use in treating relapse, in particular acute relapse, and the progression of multiple sclerosis and in ameliorating clinical symptoms and causes of multiple sclerosis.
The present invention also provides a method of treating a mammal, including a human subject, suffering from multiple sclerosis which comprises administering to the said mammal an effective amount of a compound as defined above.


DETAILED DESCRIPTION OF THE INVENTION

The substituted naphthyl group is preferably a 5-, 6-, 7- or 8-naphthyl group, typically a 7- or 8-naphthyl group. When the naphthyl group is substituted by three sulfonic acid groups, the sulfonic acid substituents are preferably in the 1-, 3- and 5- or 1,3- and 6-positions. When it is substituted by 2 acid groups the sulfonic acid substituents are preferably in the 1- and 3-, 1- and 5-, 3- and 5- or 3- and 6-positions. When it is substituted by one acid group the sulfonic acid substituent is preferably in the 1-, 3- or 5-position.
The invention also includes within its scope all the possible isomers, stereoisomers and their mixtures and the metabolites and the metabolic precursors or bio-precursors of the compounds as defined above.
As already said, the invention includes within its scope also the pharmaceutically acceptable salts of the ureido derivatives of formula (I).
Examples of pharmaceutically acceptable salts are either those with inorganic bases, such as sodium, potassium, calcium and aluminum hydroxides, or with organic bases, such as lysine, arginine, N-methyl-glucamine, triethylamine, triethanolamine, dibenzylamine, methylbenzylamine, di-(2-ethyl-hexyl)-amine, piperidine, N-ethylpiperidine, N,N-diethylaminoethylamine, N-ethylmorpholine, .beta.-phenethyl-amine, N-benzyl-.beta.-phenethylamine, N-benzyl-N,N-dimet

REFERENCES:
patent: 5534539 (1996-07-01), Mongelli et al.

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