Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-02-20
2004-09-07
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S247000, C514S255060, C514S269000, C544S219000, C544S229000, C544S315000, C544S318000, C544S408000
Reexamination Certificate
active
06787544
ABSTRACT:
TECHNICAL FIELD
The present invention relates to antiviral agents comprising a nitrogen-containing heterocyclic carboxamide derivative or a salt thereof.
BACKGROUND ART
Nowadays, antiviral agents are selected and put to use in accordance with the objective viruses. For instance, Acyclovir and Vidarabine are used against herpes viruses; Gancicrovir and Foscarnet are used against cytomegalo virus; and interferon is used against hepatitis viruses.
Influenza virus is a central virus of the cold syndrome, which has attacked human being periodically to cause many deaths amounting to tens millions. Although the number of deaths shows a tendency of decrease in the recent years owing to the improvement in hygienic and nutritive conditions, the prevalence of influenza is repeated every year, and it is apprehended that a new virus may appear to cause a wider prevalence.
For prevention of influenza virus, vaccine is used widely, in addition to which low molecular weight substances such as Amantadine and Ribavirin are also used.
Amantadine is used for prevention and treatment of influenza. Its function mechanism is said to consist in inhibiting the fusion between influenza virus and cell membrane, and it is effective against A-type influenza virus. Its problems are, however, that it is ineffective against B type influenza virus, its resistant virus appears, and it causes side effects such as nerve disturbance. Although Rimantadine which is a derivative of Amantadine has a more improved antiviral activity, the problem of side effect is not overcome by it. Ribavirin which is a guanosine derivative shows a viral RNA polymerase-inhibitory activity and is effective upon A type and B type influenza viruses. Its internal use, however, brings about no sufficient clinical effect.
The present invention provides an antiviral agent exhibiting a preventive effect and a therapeutic effect against various viruses, especially influenza viruses.
DISCLOSURE OF THE INVENTION
The present inventors have conducted researches and studies on compounds showing an antiviral activity against various viruses, especially influenza viruses. As a result, it has been found that pyrazine carboxamide derivatives have an anti-influenza virus activity. The inventors conducted further studies to find that nitrogen-containing heterocyclic carboxamide derivatives represented by the following general formula [1]:
wherein ring A represents a substituted or unsubstituted pyrazine, pyrimidine, pyridazine or triazine ring; R
1
represents O or OH; R
2
represents a hydrogen atom, an acyl group or a substituted or unsubstituted carbamoylalkyl or carboxyalkyl group; and the broken line represents a single bond or a double bond; or salts thereof exhibit an excellent antiviral activity against A-, B- and C-type of influenza viruses and other various viruses, these compounds have low cytotoxicity and are useful as an antiviral agents of high safety, as well as that novel N-containing heterocyclic carboxamide derivatives represented by the following general formula [1a]:
wherein ring A′ represents a pyrazine ring substituted with a halogen atom, a hydroxyl group or an oxide group; R
1
represents O or OH; R
2
represents a hydrogen atom, an acyl group or a substituted or unsubstituted carbamoylalkyl or carboxyalkyl group; and the broken line represents a single bond or a double bond; or salts thereof exhibit an excellent antiviral activity. Based on these findings, the present invention has been accomplished.
The present invention will be described in detail below.
Unless otherwise indicated, the term “halogen atom” used in this specification means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom; the term “alkyl group” means a straight or branched chain C
1-6
alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl and the like; the term “alkenyl group” means a straight or branched chain C
2-6
alkenyl group such as vinyl, allyl and the like; the term “cycloalkyl group” means a C
3-6
cycloalkyl group such as cyclopropyl, cyclopentyl, cyclohexyl and the like; the term “alkoxy group” means a straight or branched chain C
1-6
alkyl-O— group such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy and the like; the term “cycloalkyloxy group” means a C
3-6
cycloalkyl-O— group such as cyclopropyloxy, cyclopentyloxy, cyclohexyloxy and the like; the term “alkylthio group” means a straight or branched chain C
1-6
alkyl-S— group such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio, pentylthio and the like; the term “alkylamino group” means an amino group substituted with one or more straight or branched chain C
1-6
alkyl groups such as methylamino, ethylamino, propylamino, butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, methylethylamino, dipropylamino, dibutylamino, dipentylamino and the like; the term “cycloalkylamino group” means a C
3-6
cycloalkyl-NH— group such as cyclopropylamino, cyclopentylamino, cyclohexylamino and the like; the term “halogenoalkyl group” means a halogen-substituted C
1-6
alkyl group such as trifluoromethyl, trichloro-methyl, chloromethyl and the like; the term “aryl group” means a phenyl group, a naphthyl group and the like; the term “aryloxy group” means an aryl-O— group such as phenyloxy, naphthyloxy and the like; the term “arylthio group” means an aryl-S— group such as phenylthio, naphthylthio and the like; the term “arylamino group” means an aryl-NH— group such as phenylamino, naphthylamino and the like; the term “acyl group” means a C
2-5
alkanoyl group such as formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl and the like and an aroyl group such as benzoyl, naphthoyl and the like; the term “alkoxycarbonyl group” means a straight or branched chain C
1-6
alkoxycarbonyl group such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl and the like; the term “alkylcarbamoyl group” means a carbamoyl group substituted with one or more straight or branched chain C
1-6
alkyl groups such as methylcarbamoyl, dimethylcarbamoyl and the like; the term “carbamoylalkyl group” means a straight or branched chain C
1-6
alkyl group substituted with a carbamoyl group such as carbamoylmethyl, carbamoylethyl, carbamoylisopropyl and the like; the term “carboxyalkyl group” means a straight or branched chain C
1-6
alkyl group substituted with a carboxyl group such as carboxymethyl, carboxylethyl, carboxyisopropyl and the like; the term “heterocyclic group” means a 4-, 5- or 6-membered ring or a fused ring thereof having, as the hetero atoms constituting said ring, at least one heteroatoms selected from the group consisting of oxygen atom, nitrogen atom and sulfur atom, such as oxetanyl, thietanyl, azetidinyl, furyl, pyrrolyl, thienyl, oxazolyl, isoxazolyl, imidazolyl, thiazolyl, isothiazolyl, pyrrolidinyl, benzofuranyl, benzothiazolyl, pyridyl, quinolyl, pyrimidinyl and morpholinyl; and the term “oxide group” means an oxygen atom linked to a nitrogen atom in a ring. The term “lower” means that the number of carbon atoms is 1 to 6.
The protecting group for carboxyl group includes any groups which can conventionally be used as a protecting group for carboxyl group. The examples thereof include alkyl groups such as methyl, ethyl, n-propyl, isopropyl, 1,1-dimethylpropyl, n-butyl, tert-butyl and the like; aryl groups such as phenyl, naphthyl and the like; aralkyl groups such as benzyl, diphenylmethyl, trityl, p-nitrobenzyl, p-methoxybenzyl, bis(p-methoxyphenyl)methyl and the like; acylalkyl groups such as acetylmethyl, benzoylmethyl, p-nitro-benzoylmethyl, p-bromobenzoylmethyl, p-methanesulfonylbenzoylmethyl and the like; oxygen-containing heterocyclic groups such as 2-tetrahydropyranyl, 2-tetrahydrofuranyl and the like; halogeno-alkyl groups such as 2,2,2-trichloroethyl and the like; alkylsily
Egawa Hiroyuki
Furuta Yousuke
Nomura Nobuhiko
Balasubramanian Venkataraman
Darby & Darby
Raymond Richard L.
Toyama Chemical Co., Ltd.
LandOfFree
Nitrogen-containing heterocyclic carboxamide derivatives or... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Nitrogen-containing heterocyclic carboxamide derivatives or..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nitrogen-containing heterocyclic carboxamide derivatives or... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3258404