Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-01-04
1999-03-30
Clardy, S. Mark
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514279, 514270, 514274, 544300, 544301, 544302, 544303, 544310, 544311, 544314, A61K 31505, C07D23902
Patent
active
058890130
DESCRIPTION:
BRIEF SUMMARY
This application has been filed under 35 USC 371 as a national Stage application of PCT/KR94/00102 filed on Jul. 29, 1994.
FIELD OF THE INVENTION
The present invention relates to novel pyrimidine acyclonucleoside derivatives, antiviral agents containing the derivative as the active ingredients and processes of preparation therefor.
BACKGROUND OF THE INVENTION
AIDS (Acquired immunodeficiency syndrome), caused by human immunodeficiency virus (HIV), is one of the world's most serious health problems. 3'-Deoxy-3'-azidothymidine (AZT), which is available in the clinic, has been proven to improve the clinical and immunological status of patients with AIDS and AIDS-related complex. However, serious side effects such as anemia and leukopenia strongly limit its clinical usefulness. Although 2',3'-dideoxyinosine (DDI) and 2',3'-dideoxycytidine (DDC) have more recently been approved for the patients who do not tolerate AZT, they are also suffering from side effects such as peripheral neuropathy and pancreatitis. Therfore, there is an urgent need to develop a substance possessing higher antiviral activity and lower toxicity to the host cells. Various pyrimidine acyclonucleoside derivatives having (substituted) phenylthio group or (substituted) benzyl group at the 6-position of the pyrimidine ring have been disclosed and found to have effective antiviral activity against retrovirus (WO 89/09213, EP 420,763 A2, EP 449,726 A1). A few 6-phenylselenenyl substituted pyrimidine acyclonucleoside derivatives (J. Med. Chem. 1991, 34, 3305-3309, Antiviral Chem. & Chemother. 1992, 3(5), 263-266 and J. Heterocyclic Chem. 1194, 31, 177-185) have been synthesized, however, the antiviral activity against retrovirus is only marginal. The present inventors have synthesized a wide variety of novel pyrimidine acyclonucleoside derivatives having ethyl group or isopropyl group at the 5-position and having (substituted) phenylselenenyl group at the 6-position of the pyrimidine ring, and found that most of these pyrimidine acyclonucleoside derivatives possessed excellent antiretroviral activity to satisfy the above demand(KR Application No. 94-3794, 94-18324 and 94-18325). The present invention has been accomplishied based on this finding.
SUMMARY OF THE INVENTION
A primary objective of the present invention is to provide novel pyrimidine acyclonucleoside derivatives represented by the following general formula (I): ##STR2## wherein R.sup.1 represents ethyl group or isopropyl grop; R.sup.2 represents phenylselenenyl group, optionally substituted with one or more suitable substituents selected from C.sub.1 -C.sub.3 alkyl group or halogen atom; R.sup.3 represents hydrogen atom, C.sub.1 -C.sub.3 alkyl group, C.sub.1 -C.sub.3 hydroxyalkyl group, acyloxyalkyl group, or phenyl group that is optionally substituted with one or more suitable substituents selected from C.sub.1 -C.sub.3 alkyl group, C.sub.1 -C.sub.3 alkoxy group or halogen atom; X represents oxygen atom or sulfur atom; and Y represents oxygen atom or methylene; with the proviso that R.sup.1 does not represent ethyl group when R.sup.2 represents phenylselenenyl group, R.sup.3 represents methyl group or phenyl group, and X and Y represent oxygen atom.
Another objective of the present invention is to provide an antiviral agent containing pyrimidine acyclonucleoside derivative of general formula (I) or pharmaceutically acceptable salt thereof as active ingredient.
And another objective of the present invention is to provide processes of preparation for the pyrimidine acyclonucleoside derivative of general formula (I).
DETAILED DESCRIPTION OF THE INVENTION
The pyrimidine acyclonucleoside derivatives according to the invention are represented by the general formula (I). In the general formula(I), the group of R.sup.1 represents ethyl group or isopropyl group. The group of R.sup.2 represents phenylselenenyl group, and this group may be optionally substituted with one or more suitable substituents selected from C.sub.1 -C.sub.3 alkyl group such as methyl, ethyl, propyl and isopropy
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H. Tanaka, et al., "Synthesis and Antiviral Activity of Selective Anti-HIV-1 Agents" J. Med. Chem. 35, 4713-17 (1992).
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Gam Jongsik
Kim Dae-Kee
Kim Ganghyeok
Kim Hun-Taek
Kim Key Hyup
Clardy S. Mark
Qazi Sabiha N.
Sunkyong Industries Co., Inc.
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