Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Patent
1989-11-21
1992-05-12
Shen, Cecilia
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
544301, 544303, 544304, 544305, 544306, 544309, 544310, 544313, 544314, 544317, C07D23946, C07D23947, C07D23954, C07D23960
Patent
active
051128357
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel 6-substituted acyclopyrimidine derivatives, antiviral agents containing the derivatives as the active ingredients and a process for preparation of the derivatives.
BACKGROUND ART
Infectious diseases caused by human acquired immunodeficiency virus (HIV), which is a type of retrovirus, have recently become a serious social problem. A compound of 3'-deoxy-3'-azidothymidine is known as a nucleoside compound used in the clinical treatment of HIV-infection. However, this compound has side-effects since it also exhibits considerable toxicity in the host cell.
Although some 2',3'-dideoxyribonucleosides are known as nucleoside compounds exhibiting an anti-retroviral activity, it is still necessary to develop a substance possessing a higher activity and lower toxicity to the host cell (Hiroaki Mitsuya, Bodily Defense, Vol. 4, pp. 213 to 223 (1987)).
On the other hand, various acyclonucleoside compounds have been synthesized since Acyclovir (acycloguanosine) was developed as an antiviral substance effective against herpes virus (C. K. Chu and S. J. Culter, J. Heterocyclic Chem., 23, p. 289 (1986)). However, no acyclonucleoside compound having a sufficient activity especially against retroviruses has yet been discovered.
We have focussed our attention on 6-substituted acyclopyrimidine nucleoside compounds and have synthesized various novel 6-substituted acyclopyrimidine nucleoside derivatives and screened those compounds to detect an effective antiviral agent, especially to the retrovirus. Some 6-substituted acyclopyrimidine nucleoside compounds such as 6-fluoro substituted derivatives, 6-alkylamino substituted derivatives (DD-232492-A) and 6-methyl substituted derivatives (C.A. 107, 129717w (1987)), are known; however, the anti-retroviral activity of these compounds has not been described. As a result of our investigation, it was found that specific 6-substituted pyrimidine nucleoside compounds according to the invention satisfy the above demand which enables one to provide effective anti-retroviral agents.
SUMMARY OF THE INVENTION
The present invention concerns a 6-substituted acyclopyrimidine nucleoside derivative represented by the following general formula I: ##STR2## wherein R.sup.1 represents a hydrogen or halogen atom or a group of alkyl, alkenyl, alkynyl, alkylcarbonyl, arylcarbonyl, arylcarbonylalkyl, arylthio or aralkyl; R.sup.2 represents a group of arylthio, alkylthio, cycloalkylthio, aryl sulfoxide, alkyl sulfoxide, cycloalkyl sulfoxide, alkenyl, alkynyl, aralkyl, arylcarbonyl, arylcarbonylalkyl or aryloxy; R.sup.3 represents a hydroxyalkyl group of which alkyl portion may contain an oxygen atom; X represents an oxygen or sulfur atom or an amino group; Y represents an oxygen or sulfur atom; and A represents .dbd.N-- or --NH--, or a pharmaceutically acceptable salt thereof.
The present invention also concerns a process for the preparation of the 6-substituted acyclopyrimidine nucleoside derivative of formula I.
The present invention further concerns an antiviral agent containing as the active ingredient a 6-substituted acyclopyrimidine nucleoside derivative of formula I or a pharmaceutically acceptable salt thereof.
DETAILED DESCRIPTION OF THE INVENTION
The 6-substituted acyclopyrimidine derivative according to the invention is represented by the general formula I. In the general formula I, the groups of R.sup.1, R.sup.2 and R.sup.3 may be optionally substituted with one or more suitable substituents.
The group of R.sup.1 represents a hydrogen atom; a halogen atom such as a chlorine, iodine, bromine and fluorine atom; an alkyl group such as a methyl, ethyl, n-propyl, i-propyl and n-butyl group; an alkenyl group such as vinyl, propenyl, butenyl, phenylvinyl, bromovinyl, cyanovinyl, alkoxycarbonylvinyl and carbamoylvinyl group; an alkynyl group such as an ethynyl, propynyl and phenylethynyl group; an alkylcarbonyl group such as an acetyl, propionyl and i-butyryl group; an arylcarbonyl group such as benzoyl and naphthoyl group; an arylcarbonyla
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Drabikowska et al., CA107-129717w(1987).
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Baba Masanori
De Clercq Erik D. A.
Miyasaka Tadashi
Tanaka Hiromichi
Ubasawa Masaru
Laughlin, Jr. James H.
Mitsubishi Kasei Corporation
Shen Cecilia
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