Antiviral 2, 4-pyrimidinedione derivatives

Details Antiviral 2, 4-pyrimidinedione derivatives Antiviral 2, 4-pyrimidinedione derivatives

1996-06-18

1998-05-05

Ford, John M.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

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

514 86, 544300, 544301, 544302, 544303, 544304, 544306, 544243, 544309, 544310, 544311, 544312, 544313, 544314, C07D23954, C07D23956, A61K 31505

Patent

active

057475008

DESCRIPTION:

BRIEF SUMMARY
This is a 371 of PCT/KR94/00178 filed Dec. 20, 1994, published as WO95/18109 Jul. 6, 1995.
1. Field of the Invention
The present invention relates to novel pyrimidinedione derivatives, which are useful as an antiviral agent, particularly as a treating agent for acquired immunodeficiency syndrome (AIDS), and pharmaceutically acceptable salts thereof. The invention also relates to processes for the preparation of such derivatives and to pharmaceutical compositions containing same as active ingredients.
2. Description of the Prior Art
Various compounds such as AZT (3'-azido-3'-deoxythymidine); DDC (2',3'-dideoxycytidine), DDI (2',3'-dideoxyinosine) and D4T (3'-deoxy-2',3'-didehydrothymidine) have been reported to have the ability, albeit limited, to inhibit the reproduction of AIDS virus; and they are also known to produce undesirable side effects due to their toxicity.
In order to minimize such problems, therefore, many attempts have been made. For example, 2,4-pyrimidinedione derivatives substituted with an alkoxymethylene group on the N-1 position thereof have been published in J. Med. Chem., 35, 4713 (1992); J. Med. Chem., 35, 337 (1992); J. Med. Chem., 34, 1508 (1991); J. Med. Chem., 34, 1394 (1991); J. Med. Chem., 34, 349 (1991); Molecular Pharm., 39, 805 (1991); Molecular Pharm., 44, 694 (1993); EP 0,449,726 A1; EP 0,420,763 A2; and U.S. Pat. No. 5,318,972 and reported to have an improved activity against human immunodeficiency virus (HIV), while exhibiting a lower toxicity. However, needs have continued to exist for effective compounds with excellent potency against HIV with a lower toxicity.
The present inventors have studied for a long time in search for 2,4-pyrimidinedione compounds which have a strong activity against HIV as well as a lower toxicity, and, as a result, have discovered that 2,4-pyrimidinedione compounds with an allyl or propargyl group in the N-1 position of the 2,4-pyrimidinedione ring exhibit strong antiviral activities against HIV.


SUMMARY OF THE INVENTION

Accordingly, it is a primary object of the present invention to provide novel compounds having superior antiviral activities against HIV with reduced toxicity.
It is another object of the present invention to provide pharmaceutical compositions containing same.
It is a further object of the present invention to provide processes for the preparation of said novel compounds.
In accordance with one aspect of the present invention, there are provided novel 2,4-pyrimidinedione compounds of formula(I): ##STR2## wherein: R.sup.1 represents an unsubstituted or substituted allyl group represented by CH.sub.2 CH.dbd.CR.sup.5 R.sup.6 or an unsubstituted or substituted propargyl group represented by CH.sub.2 C.tbd.CR.sup.7 wherein R.sup.5, R.sup.6 and R.sup.7 are each independently a hydrogen atom; a methyl group optionally substituted with a halogen atom, or a C.sub.1-10 carbonyloxy, hydroxy, azido, cyano, optionally substituted amino, optionally substituted phosphonyl, optionally substituted phenyl, C.sub.3-10 heteroaryl, C.sub.1-3 alkoxy or benzyloxy radical; a C.sub.2-10 alkyl or alkenyl group; a cyclopropyl group; an optionally substituted phenyl group; a C.sub.3-10 heteroaryl group; a C.sub.1-10 ester group; or an optionally substituted C.sub.1-10 alkylamide group; alkyl, C.sub.3-6 cycloalkyl, C.sub.2-8 alkenyl or C.sub.2-8 alkynyl group, or a benzyl group; a hydroxy, C.sub.1-3 alkyl fluoromethyl, C.sub.1-3 alkoxy, amino, C.sub.2-6 alkylester or C.sub.2-7 alkylamide group; a methylene group optionally substituted with at least one selected from the group consisting of a halogen, and a cyano, hydroxy, azido, amino, C.sub.1-3 alkylamide, C.sub.1-4 ester, and nitro groups.
In accordance with another aspect of the present invention, there are provided pharmaceutically acceptable salts of the compounds of formula(I).
In accordance with a further aspect of the present invention, there are provided pharmaceutical compositions comprising one or more of the 2,4-pyrimidinedione compounds represented by formula(I) and their salts as active i

REFERENCES:
patent: 5162326 (1992-11-01), Naka et al.

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