Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1998-09-10
2000-06-27
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514258, A61K 3154, A61K 31505
Patent
active
060807377
DESCRIPTION:
BRIEF SUMMARY
This is a 371 of PCT/JP97/00854 filed Mar. 18, 1997.
TECHNICAL FIELD
This invention relates to drugs containing methotrexate derivatives. More particularly, it relates to drugs containing methotrexate derivatives which are efficacious against uveitis.
BACKGROUND ART
Although uveitis sometimes occurs in association with Behcet's disease, sarcoidosis, Harada's disease, etc., its pathogenesis is obscure in 50 to 70% of the patients. There are a number of findings on uveitis which can be classified into, for example, iridocyclitis (anterior uveitis), retinochoroiditis (posterior uveitis), panuveitis, intermediary uveitis, etc. depending on the inflammation site. To treat uveitis, steroids are commonly used, however, steroids produce undesirable side effects. Therefore, it has been urgently required to develop drugs efficacious against uveitis.
On the other hand, methotrexate (MTX), which is a folic acid metabolism antagonist, has been employed as a carcinostatic agent in treating acute leukemia, malignant lymphoma, etc. Also, MTX is known as an immunosuppressive agent and used mainly for preventing acute graft-versus-host reactions in bone marrow transplantation. Moreover, it is known that administration of MTX in a small dose is efficacious in treating rheumatoid arthritis.
DISCLOSURE OF THE INVENTION
uveitis.
The present inventors have conducted extensive studies and consequently found that compounds represented by the following general formula (I) or salts thereof are useful as remedies for uveitis, thus completing the present invention: ##STR2##
wherein R.sub.1 represents a member selected from the group consisting of CH.sub.2, CH.sub.2 CH.sub.2, CH.sub.2 O, CH.sub.2 S and CH.sub.2 SO; R.sub.2 represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms or a benzyl group; R.sub.3 represents a group of the general formula COOR.sub.4 (wherein R.sub.4 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms), a group of the general formula NHCOR.sub.5 (wherein R.sub.5 represents an optionally substituted phenyl group), a group of the general formula CONR.sub.6 R.sub.7 (wherein R.sub.6 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms; and R.sub.7 represents a lower alkyl group having 1 to 4 carbon atoms, an optionally substituted phenyl group, a carboxyalkyl group or a lower alkylsulfonyl group), a PO.sub.3 H.sub.2 group or an SO.sub.3 H group; and n is an integer of from 1 to 4.
Accordingly, the present invention relates to remedies for uveitis which contain, as the active ingredient, one or more compounds represented by the following general formula (I) or salts thereof: ##STR3##
wherein R.sub.1 represents a member selected from the group consisting of CH.sub.2, CH.sub.2 CH.sub.2, CH.sub.2 O, CH.sub.2 S and CH.sub.2 SO; R.sub.2 represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms or a benzyl group; R.sub.3 represents a group of the general formula COOR.sub.4 (wherein R.sub.4 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms), a group of the general formula NHCOR.sub.5 (wherein R.sub.4 represents an optionally substituted phenyl group), a group of the general formula CONR.sub.6 R.sub.7 (wherein R.sub.6 represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms; and R.sub.7 represents a lower alkyl group having 1 to 4 carbon atoms, an optionally substituted phenyl group, a carboxyalkyl group or a lower alkylsulfonyl group), a PO.sub.3 H.sub.2 group or an SO.sub.3 H group; and n is an integer of from 1 to 4.
The present invention further relates to remedies for uveitis which contain, as the active ingredient, one or more compounds represented by the following general formula (II) or salts thereof: ##STR4##
wherein R.sub.8 and R.sub.9 are the same or different and each represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a graph which illustrates the effect of the drugs of the present invention on uveal ret
REFERENCES:
patent: 5354753 (1994-10-01), Ohi et al.
patent: 5728692 (1998-03-01), Ohi et al.
McMaster et al., "Prevention of Experimental Allergic .sub.Uve itis", Arch Ophthamol, 93:835-837, (1975).
Lazar et al., "Treatment of Uveitis with Methotrexate", American Journal of Opthalm.sub.o logy, vol. 67, .sub.n o. 3, 383-387, (1969).
Wong, "Immunosuppressive Therapy of Ocular Inflammatory Disease", Arch Ophthalmol, 81:628-637, (1969).
Hemady, "Immunosuppressive Drugs in Immune and Inflammatory Ocular Disease", Survey of Ophthalmology, vol. 35, No. 5, 369-385, (1991).
Hiraoka Miki
Miyasaka Nobuyuki
Chugai Seiyaku Kabushiki Kaisha
Henley III Raymond
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