- CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS
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The present invention is directed to compounds of the formula (I) wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.
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Page/Page column 83; 84
(2019/03/17)
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- CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS
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The present invention is directed to compounds of the formula (I), wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.
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Page/Page column 160
(2019/05/02)
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- Facile alkylation of 4-nitrobenzotriazole and its platelet aggregation inhibitory activity
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We explored the facile alkylation of 4-nitrobenzotriazole under basic conditions and the synthesized derivatives were tested for their potential ADP induced platelet aggregation inhibition activity in comparison with standard drug ticagrelor (selective P2Y12 inhibitor). The nitro group at 4-position is highly activating toward alkylation reactions (under strong basic conditions) and resulted in formation of degradation product like 3-nitrobenzene-1,2-diamine which make isolation of alkyl products very difficult. We optimized the reaction under mild basic condition (potassium carbonate and DMF) which is devoid of any degradation product. This is perhaps the first report of 4-nitrobenzotriazole derivatives possessing platelet aggregation inhibitory activity. Generally activity increases with increase in length of alkyl chain and 1-alkyl positional isomers were found to be more potent than 2-alkyl isomers. The benzoyl derivative was found to be the most potent [compound 22; (4-Nitro-1H-benzotriazol-1-yl)(phenyl)methanone; IC50 = 0.65 ± 0.10 mM] which may be attributed to electronegative oxygen atom and aromatic ring. Benzyl derivatives [compound 20; 1-Benzyl-4-nitro-1H-benzotriazole; IC50 = 0.81 ± 0.08 mM, compound 21; 2-Benzyl-4-nitro-2H-benzotriazole; IC50 = 0.82 ± 0.19 mM] and sulfonyl derivative [compound 23; 1-[(4-Methylphenyl)sulfonyl]-4-nitro-1H-benzotriazole; IC50 = 0.82 ± 0.19 mM] are also found to be highly active. Furthermore, all compounds possess P2Y12 binding affinity as confirmed by VASP/P2Y12 phosphorylation assay.
- Singh, Dhandeep,Silakari, Om
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p. 5260 - 5267
(2017/10/05)
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- Facile synthesis of benzotriazole derivatives using nanoparticles of organosilane-based nitrite ionic liquid immobilized on silica and two room-temperature nitrite ionic liquids
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Nanoparticles of organosilane-based nitrite ionic liquid immobilized on silica, 1-butyl-3-methylimidazolium nitrite, and 1-(3-trimethoxysilylpropyl)-3- methylimidazolium nitrite were used as effective reagents for the preparation of benzotriazole derivatives from 1,2-diaminobenzenes at room temperature under mild solvent-free conditions. These ionic liquids play as nitrosonium sources in this procedure.1,2-Diaminobenzene derivatives have been treated with ionic liquids to give the related diaminobenzenes in very good to excellent yields in short reaction times. Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the full experimental and spectral details.
- Valizadeh, Hassan,Gholipour, Hamid,Mahmoodian, Manzar
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p. 2801 - 2808
(2013/08/15)
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- INDAZOLE DERIVATIVES AS ADENOSINE MONOPHOSPHATE DEAMINASE (AMPD) INHIBITORS FOR USE IN DIABETES AND RELATED DISEASES OF METABOLIC SYNDROME
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Herein, we describe a method for treatment of diabetes and other disorders classified as Metabolic Syndrome. The invention provides novel AMP Deaminase (AMPD) inhibitors comprising novel indazole and benzotriazole derivatives including a phosphorous containing derivative, a carboxylic acid, or an amino acid ester prodrug. The invention also provides support for a novel mechanism of action for the existing drug metformin: direct inhibition of the enzyme AMPD. The inhibition of AMPD in turn activates AMP Kinase, known to be linked to the action of metformin. The invention also makes novel use of a double inhibitor assay allowing identification of selective AMPD inhibitors over ADA inhibitors. The new inhibitors, structurally distinct from metformin, offer selectivity that may obviate side effects known for metformin itself, providing new benefits for diabetes and Metabolic Syndrome.
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Page/Page column 5
(2012/06/01)
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- JNK MODULATORS
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Compounds of formula I modulate JNK: wherein X1 and X2 are each simultaneously N or CH;X3 is CH—R2 or N—SO2R, where R is lower alkyl;R1 is aryl or heteroaryl, substituted with 0-3 lower alkyl radicals;R2 is where R3 is H, lower acyl, or an amino acid, or a pharmaceutically acceptable salt thereof.
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Page/Page column 14
(2010/07/04)
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- 1H, 13C and 15N NMR spectroscopy and tautomerism of nitrobenzotriazoles
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Benzotriazole nitro derivatives were prepared by nitration of the corresponding benzotriazoles and by methylation or cyclization of appropriate nitro-1,2-phenylenediamines. Structures and tautomerism of the nitrobenzotriazoles were studied by multinuclear 1H, 13C, 15N, and 2D NMR spectroscopy and quantum chemistry. Copyright
- Larina, Lyudmila I.,Milata, Viktor
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experimental part
p. 142 - 148
(2009/12/26)
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- [1,2,3]Triazolo[4,5-h]quinolones. A new class of potent antitubercular agents against multidrug resistant Mycobacterium tuberculosis strains
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In this preliminary study we report the activity of 3-methyl-9-substituted-6-oxo-6,9-dihydro-3H-[1,2,3]-triazolo[4,5-h]quinolone-carboxylic acids and their esters as a new class of antiinfective agents against MDR Mycobacterium tuberculosis. In antitubercular screening against H37Rv and 11 clinically isolated strains of M. tuberculosis several derivatives (1o,3a,c,i,j,p) showed MIC90 in the range 0.5-3.2 μg/mL. 3c showed no cytotoxicity and proved to be the most potent derivative exhibiting MIC90 = 0.5 μg/mL against all M. tuberculosis strains and infected human macrophages (J774-A1) tested.
- Carta, Antonio,Palomba, Michele,Paglietti, Giuseppe,Molicotti, Paola,Paglietti, Bianca,Cannas, Sara,Zanetti, Stefania
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p. 4791 - 4794
(2008/09/19)
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- Electron-deficient benzotriazoles for the selective N-acetylation of nucleosides
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The use of an acetylated benzotriazole for the selective protection of the amino groups of cytidine and 2′-deoxycytidine is reported. The use of the acetyl group is of considerable interest industrially in this role, and a single-step protection strategy advantageous in bulk production. 1-Acetyl-4-nitrobenzotriazole was found to readily acetylate the amine of cytidine preferentially over the exposed alcohol functionalities. With adaptation of the protocol, 2′-deoxycytidine was protected using the same reagent. A similar approach was attempted for the benzoylation of adenosine but was found to be unsuitable.
- Reid, Andrew K.,McHugh, Callum J.,Richie, Graham,Graham, Duncan
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p. 4201 - 4203
(2007/10/03)
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- THIADIAZOLES AS CXC- AND CC- CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of Formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and ischemia reperfusion injury, pain (e.g., acute pain, acute and chronic inflammatory pain, and neuropathic pain) using a compound of Formula (IA).
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Page/Page column 182
(2010/02/12)
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- ISOTHIAZOLE DIOXIDES AS CXC- AND CC- CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of the formula (IA): and the pharmaceutically acceptable salts and solvates thereof. D and E are different groups wherein one is N and the other is CR50. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and cardiac reperfusion injury, pain (e.g., acute pain, acute and chronic inflammatory pain, and neuropathic pain) using a compound of formula IA.
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Page/Page column 185
(2010/02/13)
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- NOVEL ALKYNYL DERIVATIVES AS MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
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The present invention relates to novel compounds of formula (I) wherein W, n, X and W’ are defined in the description; invention compounds are modulators of metabotropic glutamate receptors - subtype 5 (“mGluR5”) which are useful for the treatment of central nervous system disorders as well as other disorders modulated by mGluR5 receptors.
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Page/Page column 180
(2008/06/13)
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- 1H,6H-Triazolo[4,5-e]benzotriazole-3-oxides and 5,5′-(Z)-diazene-1,2-diylbis(2-methyl-2H-1,2,3-benzotriazole) derived from chloronitrobenzotriazoles and hydrazine
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Nitration of 5-chlorobenzotriazole (1) and its N1-methyl derivatives (2 and 3) produced 5-chloro-4-nitrobenzotriazole (5), 5-chloro-1-methyl-4-nitrobenzotriazole (6) and 6-chloro-1-methyl-7-nitrobenzotriazole (7) respectively. Nitration of 5-chloro-2-methylbenzotriazole (4) gave either 5-chloro-2-methyl-4-nitrobenzotriazole (8) or 5-chloro-2-methyl-4,6-dinitrobenzotriazole (9). Introduction of the nitro group activated chlorine atom that underwent nucleophilic displacement by hydrazine to give rise to a new tricyclic system 1H,6H-triazolo[4,5-e]benzotriazole-3-oxide compounds (10 and 11) in the case of 5 and 6. From 9 no linear or angular tricyclic triazolobenzotriazole was obtained but instead the 5,5′-(Z)-diazene-1,2-diylbis(2-methyl-2H-1,2,3-benzotriazole) (18).{A figure is presented}.
- Carta, Antonio,Piras, Sandra,Boatto, Gianpiero,Paglietti, Giuseppe
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p. 2471 - 2481
(2007/10/03)
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- THIADIAZOLEDIOXIDES AND THIADIAZOLEOXIDES AS CXC- AND CC-CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of the formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and cardiac reperfusion injury, acute pain, acute and chronic inflammatory pain, and neuropathic pain using a compound of formula (IA).
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- 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
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There are disclosed compounds of the formula or a pharmaceutically acceptable salt or solvate thereof which are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.
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- 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
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There are disclosed compounds of the formula or a pharmaceutically acceptable salt or solvate thereof which are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.
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Page 105-106
(2008/06/13)
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- Controlled synthesis of electron deficient nitro-1H-benzotriazoles
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Nitro-1H-benzotriazole derivatives containing electron withdrawing substitutents in the ortho and meta positions to the nitro group have been synthesized by the simple and direct nitration of the parent 1H-benzotriazoles. The route of nitration and assignment of isomerism in these compounds is proposed based upon high level density functional theory (DFT) calculations.
- McHugh, Callum J.,Tackley, Daniel R.,Graham, Duncan
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p. 1461 - 1470
(2007/10/03)
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- IL-8 receptor antagonists
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This invention relates to novel benzo-2-triazole substituted compounds, pharmaceutical compositions, processes for their preparation, and use thereof in treating IL-8, GROα, GROβ, GROγ and NAP-2 mediated diseases.
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- Nitration of nitrogen heterocycles using microwaves
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A comparative study of reaction time and yields for nitration of nitrogeneous heterocyclic compounds using Cu(NO3)2, KNO3 and NaNO3 under microwave irradiation as well as by conventional heating is reported.
- Kidwai, Mazaahir,Kohli, Seema
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p. 1071 - 1073
(2007/10/03)
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- Novel Dimroth Rearrangements of the Benzotriazole System: 4-Amino-1-(arylsulfonyl)benzotriazoles to 4-benzotriazoles
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A variety of mono- and diarylsulfonyl-substituted 4-aminobenzotriazoles were prepared.Thermal rearrangements of 4-amino-1-(arylsulfonyl)benzotriazoles to 4-benzotriazoles were observed and confirmed by separation of the rearrangement products.Their structures were characterized by spectral methods and by X-ray crystallography.The rearrangement rates were studied by variable-temperature NMR experiments.Crossover experiments support an intramolecular mechanism involving a heterolytic benzotriazole ring cleavage to form a diazo intermediate followed by recyclization to the 4-amino group.
- Katritzky, Alan R.,Ji, Fu-Bao,Fan, Wei-Qiang,Gallos, John K.,Greenhill, John V.,et al.
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p. 190 - 195
(2007/10/02)
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- SYNTHESE ET REACTIONS DE DEPLACEMENT NUCLEOPHILE DE DERIVES NITRES ET HALOGENES DU PYRIDINO BENZO-1,3a,6,6a-TETRAAZAPENTALENE.
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The reactions of pyridino benzo-1,3a,6,6a-tetraazapentalene and its nitro- or halogeno-derivatives with some electrophiles and nucleophiles are described.The directive influence of the tetraazapentalene nucleus on electrophilic and nucleophilic substitution reactions at the pyridine and the benzene rings is discussed.
- Maquestiau, A.,Flammang-Barbieux, M.,Vilain, E.
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p. 973 - 982
(2007/10/02)
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- Method for controlling undesirable plants using 1H-benzotriazole and 2H-benzotriazole compounds
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The invention is a method for the control of undesirable broadleaf weeds and grass weeds. More particularly, the invention relates to a method for controlling undesirable weeds by applying to the foliage thereof or to soil containing seeds of the undesirable weeds, a herbicidally effective amount of a 1H-benzotriazole or 2H-benzotriazole compound.
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- 1H- and 2H-Benzotriazoles
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This invention relates to novel 1H- and 2H-benzotriazoles. These benzotriazoles are useful as herbicidal agents for the control of undesirable broadleaf weeds and grass weeds and may be applied to the foliage of undesirable plants or to soil containing seeds of said undesirable plants in order to obtain the control thereof.
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