Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1997-08-14
1999-11-09
Ford, John M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
544 582, 544 584, 544 6, A61K 3154
Patent
active
059815230
DESCRIPTION:
BRIEF SUMMARY
This invention relates to novel thiomorpholinone compounds useful for treating multiple sclerosis.
Multiple Sclerosis was first described as a clinical entity in 1868. Clinically, it is a highly variable disease, which usually begins between the second and fifth decades of life. The most common signs of multiple sclerosis are sensory and visual motor dysfunction. In the chronic form the patient has periods of remission, but with each remission there is greater neurological dysfunction.
Macroscopically, multiple sclerosis involves lesions of 1 to 4 cm called plaques scattered throughout the white matter of the central nervous system. Microscopically, the disease is characterized by a break down of the nervous systems myelin sheath. There is also a loss of myelin basic protein in the area of the lesions.
The etiology and pathogenesis of multiple sclerosis remains obscure. Both chronic infectious agents and autoimmunity have been involved and, in fact, both might be important.
Meanwhile, the need continues for safer, better calibrated drugs which will either slow the process of neurodegeneration associated with multiple sclerosis or even prevent such neurodegeneration altogether. The present invention provides new thiomorpholinone compounds useful for treating multiple sclerosis. These compounds provide for safe and efficacious treatment of multiple sclerosis by slowing the process of neurodegeneration associated with such disease.
This invention provides compounds of the formula (I) ##STR2## wherein:
R.sup.1 and R.sup.2 are each independently selected from C.sub.1 -C.sub.8 alkyl; C.sub.2 -C.sub.8 alkenyl; C.sub.2 -C.sub.8 alkynyl; C.sub.1 -C.sub.8 alkyloxy; C.sub.1 -C.sub.8 alkylthio; trifluoromethyl; C.sub.1 -C.sub.4 alkyl substituted with phenyl; phenyl; F; Cl; NO.sub.2 ; phenoxy; C.sub.1 -C.sub.4 alkyl substituted with phenoxy; thiophenyl; C.sub.1 -C.sub.4 alkylthiophenyl; --COOR.sup.7 ; --N(R.sup.7).sub.2 or --N(R.sup.7)SO.sub.2 R.sup.7 where each R.sup.7 is independently hydrogen or C.sub.1 -C.sub.6 alkyl;
R.sup.3 is H or C.sub.1 -C.sub.4 alkyl;
R.sup.4 and R.sup.5 are each individually H, or when taken together form a bond;
R.sup.6 is H; C.sub.1 -C.sub.8 alkyl; C.sub.2 -C.sub.8 alkenyl; C.sub.2 -C.sub.8 alkynyl; --SO.sub.2 CH.sub.3 ; --(CH.sub.2).sub.n NR.sup.8 R.sup.9 ; --(CH.sub.2).sub.n CO.sub.2 R.sup.8 ; --(CH.sub.2).sub.n OR.sup.8 where n is an integer from 1 to 6, both inclusive, and R.sup.8 and R.sup.9 are each independently hydrogen; C.sub.1 -C.sub.6 alkyl; C.sub.2 -C.sub.6 alkenyl; C.sub.2 -C.sub.6 alkynyl; phenyl; C.sub.1 -C.sub.4 alkyl substituted with phenyl; --(CH.sub.2).sub.q OH; or (CH.sub.2).sub.q S(C.sub.1 -C.sub.4 alkyl) where q is an integer from 2 to 6, both inclusive; and ##STR3## where m is 0 or 1;
or a pharmaceutically acceptable salt or optical isomer thereof.
According to a further aspect of the present invention there are provided pharmaceutical compositions comprising as active ingredient a compound of Formula I or a pharmaceutically acceptable salt thereof, in association with one or more pharmaceutically acceptable diluents, carriers and excipients thereof.
The present invention also provides a method for treating multiple sclerosis in a mammal in need of such treatment, which comprises administering to said mammal a therapeutically effective amount of a compound, or pharmaceutically acceptable salt or isomer thereof, of the formula I.
Other objects, features and advantages of the present invention will become apparent from the subsequent description and the appended claims.
As used herein, the term "C.sub.1 -C.sub.8 alkyl" represents a straight or branched alkyl chain having from one to eight carbon atoms. Typical C.sub.1 -C.sub.8 alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, neopentyl, heptyl, hexyl, octyl and the like. The term "C.sub.1 -C.sub.8 alkyl" includes within its definition the terms "C.sub.1 -C.sub.4 alkyl" and "C.sub.1 -C.sub.6 alkyl".
"C.sub.1 -C.sub.4 alkyl substituted with phenyl" repres
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Panetta Jill A
Phillips Michael L
Eli Lilly and Company
Ford John M.
Lentz Nelsen L.
Palmberg Arleen
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