Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-03-03
2000-02-22
Berch, Mark L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544265, 544276, 544277, A61K 3152, C07D47334, C07D47330, C07D47300, C07D47338
Patent
active
06028076&
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a purine derivative or pharmaceutically acceptable salts thereof which are useful for treatment of cancer or viral diseases such as type B hepatitis, type C hepatitis or AIDS; and to an interferon inducer, an anti-virus agent and an anti-cancer agent which comprise said purine derivative as an active ingredient.
BACKGROUND ART
Interferon is one of the most important factors in defense against infections and regulation of immunity, and it has been used for treatment of type B and type C hepatitis and for immunotherapy of cancer. Interferon is actually the sole drug against type C hepatitis. Because interferon is a polypeptide having a molecular weight of about 20,000, it can be applied only by injection and its neutralizing antibody may arise. Since main object of interferon therapy is chronic diseases, there are clinical problems such as restriction of quality of life by long-period going to hospital and decrease of the effect caused by the generation of neutralizing antibody for interferon. Accordingly, orally applicable interferon inducers are desired.
Double-strand nucleic acids originating from virus or other organisms and high molecular polymers such as poly(I):poly(C) and polycarboxylates have been known as interferon inducers. However, their antigenicity, pollution by pathogens, and biological instability are worried, it is therefore difficult to develop high molecular polymers as oral drugs. Fluorenones, pyrimidinones, and anthraquinones have been studied as low-molecular interferon inducers [Mayer, G. D., et al.: Science, 1970, 169, 1214; Nichol, F. R., et al.: Antimicrob. Agents Chemother., 1976, 9, 433; Stringfellow, D. A., et al.: Antimicrob. Agents Chemother., 1991, 15, 111]. However, their development was abandoned because of their insufficient effect or their toxicity [Reiter, M. A., et al.: J. Leukocyte Biol., 1994, 55, 234]. Although imidazoquinolines are known as low-molecular interferon inducers [EP 145,340], they have a low selectivity to interferon and also induce other cytokines, especially TNF-.alpha. and IL-6.
DISCLOSURE OF INVENTION
The object of the present invention is to provide an interferon inducer, an anti-virus agent, and an anti-cancer agent comprising, as an active ingredient, a low-molecular compound without antigenicity which is orally applicable for treatment of cancer and viral diseases, such as type B and type C hepatitis and AIDS.
The inventors now found that purine derivatives having a specific structure show selective and potent activity of interferon induction, and completed the present invention.
The present invention is a purine derivative represented by the following general formula (I): ##STR2## wherein R.sup.2 is a hydrogen atom or a hydrocarbon group containing at most 14 carbon atoms; any --CH.sub.2 -- group in said hydrocarbon group may be replaced with a carbonyl group, a sulfonyl group, --O-- or --S-- when said --CH.sub.2 -- group is not directly attached to the purine ring or is in --CH.sub.3 group not directly attached to the purine ring; any .dbd.CH.sub.2 group may be replaced with .dbd.O or .dbd.S; C--H group in said hydrocarbon group may be replaced with N, a C-halogen group or a C--CN group when said C--H group is in --CH.sub.2 -- group not directly attached to the purine ring, in --CH.sub.3 group not directly attached to the purine ring, in >CH-- group not directly attached to the purine ring, in .dbd.CH-- group not directly attached to the purine ring or in .dbd.CH.sub.2 group; di-substituted with a hydrocarbon group containing at most 10 carbon atoms; at most 18 carbon atoms or an oxycarbonyloxy group substituted with a hydrocarbon group containing at most 19 carbon atoms; --CH.sub.2 -- group in said R.sup.9 may be replaced with a carbonyl group, a sulfonyl group, --O-- or --S-- when said --CH.sub.2 -- group is not directly attached to the purine ring or is in --CH.sub.3 group not directly attached to the purine ring; any .dbd.CH.sub.2 group may be replaced with .dbd.O or .dbd.S; C--H gr
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Chiba Nobuyoshi
Hirota Kohsaku
Isobe Yoshiaki
Matsui Hiroyuki
Ogita Haruhisa
Berch Mark L.
Japan Energy Corporation
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