- Infrared matrix isolation and ab initio studies of 3(2H)-pyridazinone and photoproduced 3-hydroxypyridazine
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The infrared spectra of 3(2H)-pyridazinone and its rare tautomeric form, 3-hydroxypyridazine, isolated in an argon matrix are reported and discussed.Only the first tautomer was observed after deposition of the matrix.The second form was photochemically pr
- Lapinski, Leszek,Fulara, Jan,Czerminski, Ryszard,Nowak, Maciej J.
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Read Online
- Oxidative addition of haloheteroarenes to palladium(0): Concerted versus SNAr-type mechanism
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The kinetics of the oxidative additions of haloheteroarenes HetX (X=I, Br, Cl) to [Pd0(PPh3)2] (generated from [Pd0(PPh3)4]) have been investigated in THF and DMF and the rate constants have been determined. In contrast to the generally accepted concerted mechanism, Hammett plots obtained for substituted 2-halopyridines and solvent effects reveal a reaction mechanism dependent on the halide X of HetX: an unprecedented SNAr-type mechanism for X=Br or Cl and a classical concerted mechanism for X=I. These results are supported by DFT studies.
- Maes, Bert U. W.,Verbeeck, Stefan,Verhelst, Tom,Ekomié, Audrey,Von Wolff, Niklas,Lefèvre, Guillaume,Mitchell, Emily A.,Jutand, Anny
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Read Online
- Synthetic method of pyridazinone
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The invention relates to a new process for synthesizing pyridazinone, which is characterized in that C-TiO2 solid acid with a core-shell structure is used as a catalyst to replace traditional glacialacetic acid, tetramethyl ammonium bromide serves as a phase transfer catalyst, tert-butylhydrazine and furochloric acid are adopted to synthesize pyridazinone under certain conditions, the reaction efficiency is improved by adding the catalyst, and alkali washing and water washing processes are omitted, so that the yield and the quality of the product are improved, and the generation of three wastes is greatly reduced.
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Paragraph 0022-0031
(2021/03/30)
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- PROTEIN KINASE INHIBITORS (VARIANTS), USE THEREOF IN TREATING ONCOLOGICAL DISEASES AND A PHARMACEUTICAL COMPOSITION BASED THEREON
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The present invention relates to the treatment of oncological, chronic inflammatory and similar diseases with the aid of new families of chemical compounds having improved efficiency with regard to the inhibition of Abl kinase and mutant forms thereof, as well as other therapeutically significant kinases. It describes protein kinase inhibitors in the form of compounds of general formula (I) and compounds of general formula (II), or a tautomer, an individual isomer, a mixture of isomers, a pharmaceutically acceptable salt, a solvate or a hydrate thereof.
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Page/Page column
(2014/07/07)
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- Synthesis of substituted pyridines and pyridazines via ring closing metathesis
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RCM can be used to make aromatic heterocycles, namely pyridines and, for the first time, pyridazines; the key step after RCM involves elimination of sulfinate to provide the aromatic system. The Royal Society of Chemistry 2009.
- Donohoe, Timothy J.,Fishlock, Lisa P.,Basutto, Jose A.,Bower, John F.,Procopiou, Panayiotis A.,Thompson, Amber L.
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supporting information; experimental part
p. 3008 - 3010
(2009/12/01)
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- Ring-closing metathesis for the synthesis of heteroaromatics: evaluating routes to pyridines and pyridazines
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Ring-closing olefin metathesis (RCM) has been applied to the efficient synthesis of densely and diversely substituted pyridine and pyridazine frameworks. Routes to suitable metathesis precursors have been investigated and the scope of the metathesis step has been probed. The metathesis products function as precursors to the target heteroaromatic structures via elimination of a suitable leaving group, which also facilitates earlier steps by serving as a protecting group at nitrogen. Further functionalisation of the metathesis products is possible both prior to and after aromatisation. The net result is a powerful strategy for the de novo synthesis of highly substituted heteroaromatic scaffolds.
- Donohoe, Timothy J.,Bower, John F.,Basutto, José A.,Fishlock, Lisa P.,Procopiou, Panayiotis A.,Callens, Cedric K.A.
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experimental part
p. 8969 - 8980
(2009/12/26)
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- N-phenyl-4-pyrazolo[1,5-6]pyridazin-3-ylpyrimidin-2-amines as potent and selective inhibitors of glycogen synthase kinase 3 with good cellular efficacy
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Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Molecular modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b] pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes.
- Tavares, Francis X.,Boucheron, Joyce A.,Dickerson, Scott H.,Griffin, Robert J.,Preugschat, Frank,Thomso, Stephen A.,Wang, Tony Y.,Zhouf, Hui-Qiang
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p. 4716 - 4730
(2007/10/03)
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- Endothelin receptor antagonists
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This invention relates to pyridizinone derivatives of formula I STR1 wherein the various substituents are defined in the specification, and salts thereof, which have useful pharmacological properties, in particular endothelin receptor-antagonistic properties. The compounds are thus useful for the treatment of illnesses associated with endothelin activities, such as hypertension, cardiac insufficiency, coronary heart disease, renal, cerebral and myocardial ischaemia, renal insufficiency, cerebral infarct, subarachnoid haemorrhage, arteriosclerosis pulmonary high blood pressure, inflammations, asthma, prostate hyperplasia, endotoxic shock and in complications after the administration of immunosuppressants which produce renal vasoconstriction.
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- Cycloaddition of benzonitrile oxide to pyridazine, pyrimidine and pyrazine
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Cycloaddition of benzonitrile oxide to pyridazine affords an isolable mono-cycloadduct. In cycloadditions to pyrimidine and pyrazine the primary mono-cycloadducts are labile intermediates which undergo further cycloaddition affording isolable bis- and tris-cycloadducts.
- Corsaro, Antonino,Perrini, Giancarlo,Pistara, Venerando,Quadrelli, Paolo,Gamba Invernizzi, Anna,Caramella, Pierluigi
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p. 6421 - 6436
(2007/10/03)
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- Reaction of Diazines and their Benzo derivatives with Benzonitrile oxide
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The reaction of diazines 1 and benzodiazines 2 with benzonitrile oxide in refluxing benzene affords regio, site and stereospecific cycloadducts to the diazine ring and/i43or products derived from them.
- Grassi, Giovanni,Risitano, Francesco,Foti, Francesco
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p. 11855 - 11862
(2007/10/02)
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- Phenyl pyrazolidinones as bronchodilators and anti-inflammatory agents
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There are disclosed compounds of the formula STR1 wherein R1 is hydrogen or lower alkyl; R2 is C3-7 alkyl or C3-7 cycloalkyl; R3 is hydrogen, lower alkyl, carboxyloweralkyl, lower alkoxycarbonyl, lower alkoxycarbonyl loweralkyl, aryl or aralkyl; R4 is hydrogen, C1-8 alkyl, STR2 B is a bond, NH or O; Y is O or S; A is a bond or --C=C--; n is 0-5; R5 is hydrogen when B is NH, or R5 is lower alkyl, C3-8 cycloalkyl; aryl, substituted aryl, aralkyl, substituted aralkyl, aralkenyl, aralkenylalkyl or STR3 R6 is hydrogen or halo; the dotted line represents an optional double bond; and the pharmacologically acceptable salts thereof, which by virtue of their ability to selectively inhibit PDE IV, are bronchodilatory and anti-inflammatory and so are useful in the treatment of acute and chronic bronchial asthma and associated pathologies.
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- Quinazoline-substituted pyridazinone derivatives having cardiotonic activity
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Compounds of the formula STR1 wherein R3 is H or alkyl, Q1 and Q2 are independently hydrogen, alkyl, hydroxyl, alkoxyl, amino, mono or di alkylamino, nitro or halo or pharmaceutically acceptable salts are useful as cardiotonics.
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- 2-alkyl thieno(triazolo)diazepine compounds and pharmaceutical uses thereof
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A thienotriazolodiazepine compound of the formula: STR1 wherein Ar is phenyl, pyridyl, substituted phenyl or substituted pyridyl; R1 and R3 are the same or different and each is hydrogen, alkyl having 1 to 4 carbon atoms; R2 is hydrogen, alkyl having 1 to 4 carbon atoms or trifluoromethyl; R4 is straight or branched chain alkyl, alkenyl or alkynyl having 6 to 18 carbon atoms, or a thienodiazepine compound of the formula: STR2 wherein Ar, R1, R2 and R4 are as defined above, and pharmaceutically acceptable acid addition salt thereof. These compounds are useful as drugs for the treatment of circulatory diseases and various PAF-induced diseases. The compound (II) is also useful as an intermediate for preparing the compound (I).
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- The Mechanism of Thermal Eliminations. Part 18. Relative Rates of Pyrolysis of 2-Ethoxypyrazine, 3-Ethoxypyridazine, 2-and 4-Ethoxypyrimidine, 3-Chloro-6-ethoxypyridazine, and 2-Chloro-4-ethoxypyrimidine : the Effect of the Aza 'Substituent' and ?-Bond Order on the Elimination Rate
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A kinetic study has been made of the first-order thermal decomposition of the title compounds into ethylene and the corresponding aza-substituted pyridines, between 650 and 713 K.The relative elimination rates at 650 K are (2-ethoxypyridine = 1): 0.545, 10.0, 1.03, 1.12, 9.68, and 3.28, respectively.The electronic effects of the aza 'substituent' are small, and a more important factor appears to be the C-N ?-bond order; this latter accounts for the high reactivity of the pyridazines.The effects of the chloro substituent and of the aza 'substituent' are explicable in terms of a balance between electron withdrawal from the C-O bond (producing deactivation) and from the nitrogen involved in the cyclic transition state (producing deactivation).The effects of the chloro substituents confirm that the most important step of the reaction is breaking of the C-O bond.The statistically corrected rate (per ring nitrogen) of 2-ethoxypyrimidine is unexpectedly low.This may reflect difficulty in achieving the coplanar transition state in which the lone pairs in the s-orbitals of oxygen and the nitrogen not involved in the elimination are brought into close proximity.
- Al-Awadi, Nouria,Taylor, Roger
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p. 1255 - 1258
(2007/10/02)
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- The Reaction of Meldrum's Acid with α-Dicarbonyl Monohydrazones: A New Synthesis of Pyridazin-3-ones
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Treatment of the monohydrazones of α-dicarbonyl compounds with Meldrum's acid gives the condensation products (13)-(19) under standard conditions.Reaction of pyruvaldehyde 2-phenylhydrazone or 2-t-butylhydrazone with Meldrum's acid at 80 deg C gives the corresponding 2-substituted-2,3-dihydro-6-methyl-3-oxo-pyridazine-4-carboxylic acids (29) and (30).Cyclisation of the other N-monosubstituted condensation products (13), (14), (16), (18), and (19) to 3-oxopyridazine-4-carboxylic acids (31)-(35) can be effected under basic conditions.Gas-phase pyrolysis of the N-aryl derivatives (13)-(16) at 550 deg C and 10E-2 Torr gives N-arylpyridazin-3-ones (38)-(41) while the N-t-butyl derivatives (18) and (19) at 750 deg C and 10E-2 Torr give N-unsubstituted pyridazin-3-ones (44) and (45) by additional loss of 2-methylpropene. 2-t-Butylpyridazin-3-ones (42) and (43) can be isolated from the same precursors under milder conditions (500 deg C and 10E-2 Torr).Pyrolysis of the N,N-dimethyl derivative (17) gave only polymeric material.
- McNab, Hamish,Stobie, Ian
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p. 1845 - 1854
(2007/10/02)
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- Intermediates for preparing hydroxyphenylpyridazinones
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5-(5'-Halo-2'-methoxyphenyl)-3,4-dihalo-2(5H)-furanones are prepared by a Friedel-Crafts reaction using a p-haloanisole and a mucohalic acid in the presence of aluminum chloride. They are used as chemical intermediates for preparing hydroxyphenylpyridazinones.
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- Catalytic dehydrogenation preparation of 3-pyridazones
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Pyridazones are prepared by heating 4,5-dihydro-3-pyridazones in the liquid phase in the presence of a dehydrogenation catalyst. The reaction temperature is in the range of from 150° to 350° C. The dehydrogenation catalyst contains a noble metal of subgroup 8 of the periodic table, which is generally supported on a carrier. The reaction is preferably carried out in the presence of a solvent.
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- 6-(3-SUBSTITUTED AMINO-2-HYDROXYPROPOXYARYL)-4,5-DIHYDRO-3(2H)-PYRIDAZINONES
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The compounds are 6-(3-substituted amino-2-hydroxypropoxyaryl)-4,5-dihydro-3(2H)-pyridazinones which are β-adrenergic blocking agents.
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- Pyridazinones
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Compounds of the general formula: SPC1 In which X represents a straight or branched chain alkyl or alkoxy group, a hydroxymethyl group, a cycloalkyl group, a cycloalkoxy group, an aryloxy group, a hydroxyl group, a fluorine atom, a chlorine atom, an amino or substituted amino group, a piperidino group, a morpholino group, a pyrrolidino group, a 1,2,3,6-tetrahydropyridino group, a 4-[3-azabicyclo(3,2,2)-nonyl] group, or a 4-(piperazin-1-yl) or 4-(4-substituted-piperazin-1-yl) group of the formula SPC2 In which R=H, lower alkyl or 1-5 carbon atoms, aryl, substituted aryl, aralkyl, cinnamyl, acyl, ethoxy-carbonyl, aroyl or substituted aroyl and n is an integer from 1 to 5 except that when n is 1 X is not an alkyl group of 1 to 3 carbon atoms or an alkoxy group of 1 or 2 carbon atoms or a chlorine atom in the 4'-position, or an amino or acylated amino group in positions 2', 3' or 4'; and when n = 2 the groups X cannot both be methyl or both be methoxy in the 2' and 5' positions, nor can X be a chlorine atom in both the 2' and 4' positions or the 3' and 4' positions, and when n = 3, X cannot all three be methoxy. These compounds have anti-hypertensive activity.
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