Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1988-11-18
1991-09-10
Wax, Robert A.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 27, A01N 4304, A61K 3170, C07H 1702, C07H 1512
Patent
active
050475207
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel compounds, 2'-alkylidenepyrimidine nucleoside derivatives, a process for the production thereof, and antiviral agents comprising the compounds as active ingredients.
BACKGROUND ART
In recent years, the development of preventives and remedies for various viral infections has attracted particular attention with the advance of researches into pathogenic viruses.
Antiviral agents for use in chemotherapy heretofore proposed for clinical purposes are idoxuridine, cytarabine, vidarabine, acyclovir and the like. (See, for example, Yutaka Mizushima and Terumasa Miyamoto, The Edition of 1986, "Konnichi no Chiryo-yaku (Present-Day Remedies), Kaisetsu to Binran (Explanation and Manual)", Nanko-do, pp. 47-50 (Mar. 10, 1986).)
Most of the above-mentioned drugs, however, have been accompanied by problems including limited clinical applicability due, for instance, to antiviral activity spectra, low absorption, poor solubility, easy decomposition, the advent of drug-fast virus strains, and various side effects. Accordingly, there has been an urgent demand for the development of novel antiviral agents.
A primary object of the present invention is to provide novel compounds having remarkable antiviral activities.
DISCLOSURE OF INVENTION
As a result of extensive research efforts for the development of novel compounds useful as antiviral agents, we have found that 2'-alkylidenepyrimidine nucleoside derivatives represented by the following formula [I] have excellent antiviral activities. On the basis of this finding, we have arrived at the present invention.
More particularly, the present invention relates to 2'-alkylidenepyrimidine nucleoside derivatives represented by formula [I]: ##STR2## Wherein R.sup.1 is an amino or hydroxy group, R.sup.2 is a hydrogen or halogen atom or a lower alkyl group, R.sup.3 is a hydrogen atom or a lower alkyl group, and R.sup.4 is a hydrogen atom or a phosphate residue, and salts thereof.
This invention also relates to- a process for producing 2'-alkylidenepyrimidine nucleoside derivatives represented by the above formula [I], which process comprises Steps (1), (2) and (3) set forth below (hereinafter referred to as "the first process"). The first process illustrates inclusively the second, third and fourth processes described hereinlater. ##STR3## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined previously, R.sup.5 is alkoxy, hydroxy, amino or acylamino (-NHR.sup.6, R.sup.6 being an acyl group), and Z is a hydroxy protecting group in the sugar moiety.
In the process shown above, Step (1) involves the alkylidenation of the 2'-position in the sugar moiety of a compound of formula [II] with Wittig's reagent, Step (2) involves the removal of the hydroxy protecting groups in the sugar moiety of a compound of formula [III] thus obtained, and Step (3) involves the hydrolysis or amination of the 4-position in the base moiety of a compound of formula [IV] resulting from Step (2) when R.sup.5 is an alkoxy group, or the removal of the acyl protecting group when R.sup.5 is an acylamino group, and the subsequent optional phosphorylation at the 5'-position in the sugar moiety irrespective of whether R.sup.5 is an alkoxy, hydroxy, amino or acylamino group to obtain a compound of formula [I].
The present invention further relates to a process for producing 2'-alkylidenepyrimidine nucleoside derivatives represented by formula [I] shown earlier, which process comprises the following Steps (1), (2) and (3) (hereinafter referred to as "the second process"). ##STR4## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and Z are as defined previously, and R.sup.5' is an alkoxy group.
In this process, Steps (1) and (2) are the same reaction steps as those in the aforementioned first process, and Step (3) involves the hydrolysis or amination of the 4-position in the base moiety and the subsequent optional phosphorylation at the 5'-position in the sugar moiety to obtain a compound of formula [I].
The present invention still further relates to a process for
REFERENCES:
Beres et al., J. Med. Chem., 1986, 29, 1243-1249.
Machida Haruhiko
Matsuda Akira
Takenuki Kenji
Ueda Tohru
Tsung F.
Wax Robert A.
Yamasa Shoyu Kabushiki Kaisha
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