Syntheses of some 4-dialkylaminoalkylamino derivatives of 2,3-dimethyl-2H- and 3,9-dimethyl-9H-pyrazolo[3,4-b]quinoline

Stanislav Rádl; Viktor Zikán

doi:10.1135/cccc19861692

Syntheses of some 4-dialkylaminoalkylamino derivatives of 2,3-dimethyl-2H- and 3,9-dimethyl-9H-pyrazolo[3,4-b]quinoline

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19861692 ◽

1986 ◽

Vol 51 (8) ◽

pp. 1692-1697 ◽

Cited By ~ 5

Author(s):

Stanislav Rádl ◽

Viktor Zikán

Keyword(s):

Influenza Virus ◽

Thionyl Chloride ◽

Encephalomyocarditis Virus ◽

Methoxy Derivative ◽

Derivatives Of

Reactions of 4-chloro-2,3-dimethyl-2H-pyrazolo[3,4-b]quinoline and 4-chloro-6-methoxy-2,3-dimethyl-2H-pyrazolo[3,4-b]quinoline with 3-dimethylaminopropylamine and/or 2-dimethylaminoethylamine afforded 4-(3-dimethylaminopropylamino)-2,3-dimethyl-2H-pyrazolo[3,4-b]quinoline (IIa), its 6-methoxy derivative (IIc), 4-(2-diethylaminoethylamino)-2,3-dimethyl-2H-pyrazolo[3,4-b]quinoline (IIb) and its 6-methoxy derivative (IId). Reaction of 4,9-dihydro-3,9-dimethyl-4-oxo-1H-pyrazolo[3,4-b]quinoline with thionyl chloride gave an intermediate, whose reaction with 3-dimethylaminopropylamine afforded 4-(3-dimethylaminopropylamino)-3,9-dimethyl-9H-pyrazolo[3,4-b]quinoline (III). The compounds were tested in vivo in mice for efficacy against the A2-Hongkong influenza virus and the encephalomyocarditis virus.

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Synthesis of 1,2, and 9-methyl derivatives of 4,9-dihydro-6-methoxy-3-methyl-4-oxo-1H(2H)-pyrazolo[3,4-b]quinoline and 4,9-dihydro-6-hydroxy-3-methyl-4-oxo-1H(2H)-pyrazolo[3,4-b]quinoline and their antiviral activity

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19870788 ◽

1987 ◽

Vol 52 (3) ◽

pp. 788-792 ◽

Cited By ~ 6

Author(s):

Stanislav Rádl ◽

Viktor Zikán

Keyword(s):

Influenza Virus ◽

Antiviral Activity ◽

Hydrobromic Acid ◽

Encephalomyocarditis Virus ◽

Methyl Derivative ◽

Pyridine Hydrochloride ◽

Methyl Derivatives ◽

Derivatives Of

The paper describes syntheses of 4,9-dihydro-6-methoxy-3-methyl-4-oxo-1H(2H)-pyrazolo[3,4-b]quinoline (Ia), its 1-methyl derivative (Ic), 1,9-dimethyl derivative (Ie), 2-methyl derivative (IIa), and 2,9-dimethyl derivative (IIc). Demethylation of these compounds with hydrobromic acid afforded 4,9-dihydro-6-hydroxy-3-methyl-4-oxo-1H(2H)-pyrazolo[3,4-b]quinoline (Ib), its 1-methyl derivative (Id), 1,9-dimethyl derivative (If), 2-methyl derivative (IIb), and 2,9-dimethyl derivative (IId) respectively. 4,9-Dihydro-6-hydroxy-3,9-dimethyl-4-oxo-1H-pyrazolo[3,4-b]quinoline (Ig) was prepared by demethylation of Ie and/or IIc with pyridine hydrochloride. The compounds prepared were tested for antiviral activity in vivo in mice against influenza virus A2-Hongkong and encephalomyocarditis virus.

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Synthesis and biological activity of some basic-substituted 4,9-dihydro-3-methyl-4-oxo-1H(2H)-pyrazolo[3,4-b]quinolines

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19881812 ◽

1988 ◽

Vol 53 (8) ◽

pp. 1812-1819

Author(s):

Stanislav Rádl ◽

Viktor Zikán

Keyword(s):

Influenza Virus ◽

Biological Activity ◽

Antiviral Activity ◽

Encephalomyocarditis Virus ◽

Methoxy Derivative

Compounds Ia, Ib were obtained by an alkylation of 4,9-dihydro-6-hydroxy-1,3,9-trimethyl-4-oxo-1H-pyrazolo[3,4-b]quinoline (VIIb) with the respective dialkylaminoalkyl chloride. The same alkylation of 4,9-dihydro-6-hydroxy-2,3,9-trimethyl-4-oxo-2H-pyrazolo[3,4-b]quinoline (VIIIb) yielded compounds IIa and IIb. Similar alkylation of 4,9-dihydro-6-hydroxy-3,9-dimethyl-4-oxo-1H-pyrazolo[3,4-b]quinoline (IXa) and its 6-methoxy derivative (IXb) afforded IIIa-IIId. Compound IV was prepared from 4-chloro-3-methyl-1H-pyrazolo[3,4-b]quinoline (Xa) via its 1-(3-dimethylaminopropyl)derivative (Xb). Compounds VIa, VIb were prepared from 4,9-dihydro-6-hydroxy-3,9-dimethyl-4-oxo-1H-pyrazolo[3,4-b]quinoline (IXc) and the respective dialkylaminoalkyl chloride. The compounds prepared were tested for antiviral activity in vivo in mice against influenza virus A2-Hongkong and encephalomyocarditis virus.

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Syntheses of 1, 2, and 9-methyl derivatives of 4,9-dihydro-3-methyl-4-oxo-1H(2H)-pyrazolo[3,4-b]quinoline and their antiviral activity

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19851057 ◽

1985 ◽

Vol 50 (5) ◽

pp. 1057-1063 ◽

Cited By ~ 13

Author(s):

Stanislav Rádl ◽

Viktor Zikán ◽

František Šmejkal

Keyword(s):

Influenza Virus ◽

Antiviral Activity ◽

Methyl Iodide ◽

Room Temperature ◽

Encephalomyocarditis Virus ◽

Methyl Derivative ◽

Sodium Salts ◽

Methyl Derivatives ◽

Derivatives Of

The paper describes syntheses of 4,9-dihydro-3-methyl-4-oxo-1H(2H)-pyrazolo[3,4-b]quinoline (Ia), its 1-methyl derivative (Ib), 2-methyl derivative (IIa), 9-methyl derivative (Ic), 1,9-dimethyl derivative (Id) and 2,9-dimethyl derivative (IIb). Sodium salts of compounds Ia, Ib, Ic and IIa were methylated with methyl iodide in dimethylformamide at room temperature, compounds Id and IIb were demethylated with pyridine hydrochloride. The compounds prepared were tested for antiviral activity in vivo in mice against influenza virus A2-Hongkong and the Encephalomyocarditis virus.

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Some 1-substitution derivatives of 4-aryl-2,3-dihalogeno-1-naphthols

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19840110 ◽

1984 ◽

Vol 49 (1) ◽

pp. 110-121 ◽

Cited By ~ 1

Author(s):

Jiří Křepelka ◽

Drahuše Vlčková ◽

Milan Mělka

Keyword(s):

Thionyl Chloride ◽

Oxirane Ring ◽

Secondary Amines ◽

Two Phase ◽

Lytic Effect ◽

Primary And Secondary Amines ◽

Phase Medium ◽

Chloro Derivatives ◽

Derivatives Of

Alkylation of derivatives of 4-aryl-1-naphthols (I-V) by 2,3-epoxypropyl chloride in methanolic sodium hydroxide gave epoxy derivatives VI, VIII, IX, XI and XII, apart from products of cleavage of the oxirane ring, VII and X. Analogous alkylation of compounds I, IV and V by 2-(N,N-diethylamino)ethyl chloride hydrochloride in a two-phase medium afforded basic ethers XIII to XV. The cleavage of the oxirane ring in compound VI by the action of primary and secondary amines, piperidine and substituted piperazines led to compounds XVI-XXIV. Reaction of thionyl chloride with compounds XXI, XXII and XXIV gave chloro derivatives XXV-XXVII.Exposure of compound XXII to 4-methylbenzenesulfonyl chloride produced compound XXVIII, retaining the secondary alcoholic group. In an antineoplastic screening in vivo none of the compounds prepared had an appreciable activity. Compound XVII, being an analogue of propranolol, was used in the test of isoproterenolic tachycardia, and showed a beta-lytic effect comparable with that of propranol.

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Virus-specific interferon action. Protection of newborn Mx carriers against lethal infection with influenza virus.

Journal of Experimental Medicine ◽

10.1084/jem.154.1.199 ◽

1981 ◽

Vol 154 (1) ◽

pp. 199-203 ◽

Cited By ~ 36

Author(s):

O Haller ◽

H Arnheiter ◽

I Gresser ◽

J Lindenmann

Keyword(s):

Influenza Virus ◽

Influenza Virus Infection ◽

Specific Effect ◽

Influenza Viruses ◽

Encephalomyocarditis Virus ◽

Lethal Challenge ◽

Newborn Mice ◽

Adult Mice ◽

High Degree

The efficacy of interferon in antiviral protection of newborn mice differing at the Mx locus was investigated. Adult mice bearing the allele Mx exhibit a high degree of specific resistance toward lethal challenge with influenza viruses. In contrast, newborn Mx carriers are virtually as susceptible to influenza viruses as newborn mice devoid of Mx. Resistance can be abrogated by treating adult animals with anti-interferon serum. Here, we provide direct evidence of a virus-specific effect of interferon in vivo: newborn mice carrying the resistance gene Mx could be protected against lethal influenza virus infection with doses of interferon that were not protective in the absence of Mx. The efficacy of interferon towards a picornavirus (encephalomyocarditis virus) and a rhabdovirus (vesicular stomatitis virus) was independent of Mx.

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Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses

Nature Communications ◽

10.1038/s41467-019-12632-5 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 12

Author(s):

Miyu Moriyama ◽

Takumi Koshiba ◽

Takeshi Ichinohe

Keyword(s):

Mitochondrial Dna ◽

Influenza Virus ◽

Immune Responses ◽

Virus Replication ◽

Influenza A ◽

Nonstructural Protein ◽

Encephalomyocarditis Virus ◽

Dependent Manner ◽

Nonstructural Protein 1

Abstract Cytosolic mitochondrial DNA (mtDNA) activates cGAS-mediated antiviral immune responses, but the mechanism by which RNA viruses stimulate mtDNA release remains unknown. Here we show that viroporin activity of influenza virus M2 or encephalomyocarditis virus (EMCV) 2B protein triggers translocation of mtDNA into the cytosol in a MAVS-dependent manner. Although influenza virus-induced cytosolic mtDNA stimulates cGAS- and DDX41-dependent innate immune responses, the nonstructural protein 1 (NS1) of influenza virus associates with mtDNA to evade the STING-dependent antiviral immunity. The STING-dependent antiviral signaling is amplified in neighboring cells through gap junctions. In addition, we find that STING-dependent recognition of influenza virus is essential for limiting virus replication in vivo. Our results show a mechanism by which influenza virus stimulates mtDNA release and highlight the importance of DNA sensing pathway in limiting influenza virus replication.

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Some Biological Aspects of �Mutilated Virus� Obtained by the Action of Ketoaldehydic Derivatives of Biphenyl in A-PR8 Influenza Virus Infection �in vivo�

Antiviral Chemotherapy ◽

10.1159/000388256 ◽

2015 ◽

pp. 299-307

Author(s):

F. Magrassi ◽

P. Altucci ◽

G. Lorenzutti ◽

U. Sapio

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Virus Infection ◽

Biological Aspects ◽

Derivatives Of

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Syntheses of some N-carboxymethyl derivatives of 4,9-dihydro-3-methyl-4-oxo-1H-(2H)-pyrazolo[3,4-b]quinoline with antiviral effects

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19852010 ◽

1985 ◽

Vol 50 (9) ◽

pp. 2010-2014 ◽

Cited By ~ 2

Author(s):

Stanislav Rádl ◽

Viktor Zikán ◽

František Šmejkal

Keyword(s):

Encephalomyocarditis Virus ◽

Antiviral Effects ◽

Derivatives Of

The paper describes the syntheses of 4,9-dihydro-9-carboxymethyl-1,3-dimethyl-4-oxo-1H-pyrazolo[3,4-b]quinoline (Ic), 4,9-dihydro-9-carboxymethyl-2,3-dimethyl-4-oxo-2H-pyrazolo[3,4-b]quinoline (IIc), 4,9-dihydro-1-carboxymethyl-3-methyl-4-oxo-1H-pyrazolo[3,4-b]quinoline (Id), 4,9-dihydro-1-carboxymethyl-3,9-dimethyl-4-oxo-1H-pyrazolo[3,4-b]quinoline (If) and 4,9-dihydro-2-carboxymethyl-3,9-dimethyl-4-oxo-2H-pyrazolo[3,4-b]quinoline (IIf). The compounds were tested in vivo in mice for their efficacy against the virus A2-Hongkong and the encephalomyocarditis virus.

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Acyl-Enzymes as Thrombolytic Agents in Dog Models of Venous Thrombosis and Pulmonary Embolism

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661069 ◽

1984 ◽

Vol 51 (02) ◽

pp. 248-253 ◽

Cited By ~ 22

Author(s):

R J Dupe ◽

P D English ◽

R A G Smith ◽

J Green

Keyword(s):

Pulmonary Embolism ◽

Side Effects ◽

Venous Thrombosis ◽

Active Site ◽

Acute Pulmonary Embolism ◽

Quantitative Model ◽

Beagle Dog ◽

Thrombosis Model ◽

Derivatives Of

SummaryA quantitative model of venous thrombosis in the beagle dog is described. The model was adapted to permit ageing of isolated experimental clots in vivo. A model of acute pulmonary embolism in this species is also described. In the venous thrombosis model, infusion of streptokinase (SK) or SK-activated human plasmin gave significant lysis but bolus doses of SK. plasmin complex were ineffective. Active site anisoylated derivatives of SK. plasminogen complex, SK-activated plasmin and activator-free plasmin were all active when given as bolus doses in both models. At lytic doses, the acyl-enzymes caused fewer side-effects attributable to plasminaemia than the corresponding unmodified enzymes.

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