- Synthesis, Characterization and Solubility Determination of 6-Phenyl-pyridazin-3(2H)-one in Different Pharmaceutical Solvents
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The current research work proposed the solubility data and solution thermodynamic properties of the cardiovascular agent 6-phenylpyridazin-3(2H)-one [PPD] in twelve pharmaceutical solvents at “T = 298.2 K to 318.2 K” and “p = 0.1 MPa”. The measured solubilities of PPD were regressed well with “van’t Hoff and Apelblat models”. The solid phases of pure and equilibrated PPD were characterized using differential scanning calorimetry and powder X-ray differactometry, and the results suggested no transformation of PPD into solvates/hydrates/polymorphs after equilibrium. The solubilities of PPD in a mole fraction at “T = 318.2 K” were noted at a maximum in dimethyl sulfoxide (DMSO, 4.73 × 10?1), followed by polyethylene glycol-400 (PEG-400, 4.12 × 10?1), Transcutol (3.46 × 10?1), ethyl acetate (EA, 81 × 10?2), 2-butanol (2.18 × 10?2), 1-butanol (2.11 × 10?2), propylene glycol (PG, 1.50 × 10?2), isopropyl alcohol (IPA, 1.44 × 10?2), ethylene glycol (EG, 1.27 × 10?2), ethanol (8.22 × 10?3), methanol (5.18 × 10?3) and water (1.26 × 10?5). Similar tendencies were also noted at other studied temperatures. The results of the “apparent thermodynamic analysis” showed an endothermic and entropy-driven dissolution of PPD in all pharmaceutical solvents. The results of the activity coefficients suggested a maximum interaction at the molecular level in PPD-DMSO, PPD-PEG-400 and PPD-Transcutol, compared with other combination of the solute and solvents.
- Shakeel, Faiyaz,Imran, Mohd,Haq, Nazrul,Alshehri, Sultan,Khalid Anwer
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- Discovery of novel pyridazine-based cyclooxygenase-2 inhibitors with a promising gastric safety profile
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Cyclooxygenase-2 (COX-2) is implicated in the development of chronic inflammatory diseases. Recently, pyridazine derivatives have emerged as a novel prototype to develop COX-2 inhibitors. Accordingly, some pyridazine-based COX-2 inhibitors are reported herein. The reaction of aldehyde 3 and different hydrazines yielded the corresponding hydrazones. The hydrazones were further derivatized to the title compounds, which were assessed for COX-1 and COX-2 inhibitory action, gastric ulcerogenic effects, and lipid peroxidation properties. Molecular docking studies and determination of the physicochemical parameters were also carried out. The allocated structures of the reported compounds were coherent with their spectroscopic data. The compounds 9a (IC50 = 15.50 nM, 114.77%), 9b (IC50 = 17.50 nM, 101.65%), 12 (IC50 = 17.10 nM, 104.03%), 16b (IC50 = 16.90 nM, 105.26%), and 17 (IC50 = 17.70 nM, 100.5%) displayed better COX-2 inhibition than celecoxib (IC50 = 17.79 nM, 100%). These outcomes were harmonious with the molecular docking studies of 9a, 9b, 12, 16b, and 17. These compounds also displayed comparable onset and the duration of action concerning celecoxib and indomethacin in the in vivo studies. No ulcerogenic effects were observed for 9a and 12, whereas 9b, 16b, and 17 showed an insignificant ulcerogenic effect compared to celecoxib. The compounds 9a, 9b, 12, 16b, and 17 displayed a better lipid peroxidation profile than celecoxib and indomethacin. The compounds 9a (%ABS = 84.09), 9b (%ABS = 84.09), 12 (%ABS = 66.87), 16b (%ABS = 75.02), and 17 (%ABS = 81.42) also displayed appreciable calculated absorption compared to celecoxib (%ABS = 82.09). The compounds 9a, 9b, 11, 16b, and 17 have been recognized and postulated as non-ulcerogenic COX-2 inhibitors with promising physicochemical parameters and gastric safety profile. These compounds may be useful candidates to combat diseases caused by higher levels of COX-2.
- Afroz Bakht, Md.,Diwan, Anupama,Imran, Mohd,Khan, Abida,Thabet, Hamdy Kh.
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- Development of pyridazine derivatives as potential EGFR inhibitors and apoptosis inducers: Design, synthesis, anticancer evaluation, and molecular modeling studies
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Novel hybrids of pyridazine-pyrazoline were synthesized aiming to develop new antiproliferative candidates. All compounds were submitted to the National Cancer Institute (NCI), USA, and many were proved to have significant antiproliferative activity. In addition, in vitro studies of the epidermal growth factor receptor (EGFR) inhibition showed that compounds IXn, IXg, IXb and IXl exhibited excellent inhibitory effect (IC50 = 0.65, 0.75, 0.82 and 0.84 μM, respectively) compared to Erlotinib (IC50 = 0.95 μM). The mechanistic effectiveness in cell cycle progression, apoptotic induction and gene regulation were assessed for the promising compounds IXg and IXn due to their significant EGFR inhibition. Flow cytometeric analysis indicated that compounds IXg and IXn result in increased cell numbers in phase G2/M, suggesting cell cycle arrest in phase G2/M in UO-31cells. Furthermore, real time PCR assay illustrated that compounds IXg and IXn elevated Bax/Bcl2 ratio which confirmed the mechanistic pathway of them. Moreover, the apoptotic induction of UO-31 renal cancer cells was enhanced effectively through activation of caspase-3 by compounds IXg and IXn. On the other hand, molecular docking study was performed to investigate binding mode of interaction of compounds with EGFR-PK in the active site with the aim of rationalizing its promising inhibitory activity. Finally, based on the aforementioned findings, compounds IXg and IXn could be considered as effective apoptosis modulators and promising leads for future development of new anti-renal cancer agents.
- Ahmed, Marwa F.,Santali, Eman Y.,Mohi El-Deen, Eman M.,Naguib, Ibrahim A.,El-Haggar, Radwan
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- Copper-mediated rapid and facile oxidative dehydrogenation of dihydrobenzocarbazoles
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Rapid method for the oxidative dehydrogenation of dihydrobenzocarbazoles has been introduced by using bench scale and commercially available reagent; copper chloride, in excellent yield with easy workup. The scope of the reaction has been studied with broad range of substitutes.
- Humne, Vivek T.,Ulhe, Avinash G.
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supporting information
(2020/03/16)
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- Synthesis of novel N-substitutedphenyl-6-oxo-3-phenylpyridazine derivatives as cyclooxygenase-2 inhibitors
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Some novel non-ulcerogenic N-substitutedphenyl-6-oxo-3-phenylpyridazines as COX-2 inhibitors have been developed (Supplementary material Appendix 1). The novel aldehyde 3 was prepared by reacting 6-phenylpyridazin-3(2H)-one with 4-fluorobenzaldehyde. The aldehyde 3 was reacted with different hydrazines and thiazolidin-4-ones to obtain the novel N-substitutedphenyl-6-oxo-3-phenylpyridazine derivatives. These were assessed for their anti-inflammatory potential and gastric ulcerogenic effects. The molecular docking investigations were also undertaken. The spectroscopic data were coherent with the allocated structures of the compounds. The compounds 4a (IC50 = 17.45 nm; p 50 = 17.40 nm; p 50 = 16.76 nm; p 50 = 17.15 nm; p 50 = 17.79 nm; p .05). These findings were consistent with the molecular docking investigations of 4a, 4b, 5a, and 10. The in vivo anti-inflammatory profile of 4a, 4b, 5a, and 10 was also superior to celecoxib and indomethacin. The compounds 4b, 5a, and 10 revealed no gastric ulcerogenic effects, wherein the compound 4a produced almost negligible gastric ulcerogenic effects than celecoxib and indomethacin. The compounds 4a, 4b, 5a, and 10 have been postulated as promising non-ulcerogenic COX-2 inhibitors.
- Khan, Abida,Diwan, Anupama,Thabet, Hamdy K,Imran, Mohd
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p. 573 - 584
(2020/03/23)
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- Rhodium(III)-Catalyzed Alkynylation of 4-Arylphthalazin-1(2H)-one Scaffolds via C-H Bond Activation
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Selective C–H bond alkynylation toward modular access to material and pharmaceutical molecules is of great desire in modern organic synthesis. Disclosed herein is rhodium(III)-catalyzed selective C–H bond mono-/bialkynylation of 4-aryl phthalazin-1(2H)-one was developed. The silver salt AgSbF6 are demonstrated to play a vital role in promoting the bialkynylation reactions. The present alkynylation strategy is simple, efficient, and features high functional group tolerance and broad substrate scope under an air atmosphere. Additionally, 6-aryl pyridazin-3(2H)-one scaffold is amenable to the selective monoalkynylation and sequential bialkynylation, respectively.
- Du, Xuxin,Hou, Hongcen,Zhao, Yongli,Sheng, Shouri,Chen, Junmin
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supporting information
p. 1100 - 1107
(2020/02/25)
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- Design and synthesis of 3-aminophthalazine derivatives and structural analogues as PDE5 inhibitors: anti-allodynic effect against neuropathic pain in a mouse model
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Neuropathic pain is a chronic pain caused by a lesion or disease affecting the somatosensory nervous system. To date, no specific treatment has been developed to cure this pain. Antidepressants and anticonvulsant drugs are used, but they do not demonstrate universal efficacy, and they often cause detrimental adverse effects. Some studies highlighted the efficacy of sildenafil, a well-known inhibitor of phosphodiesterase 5 (PDE5, (IC50 = 3.3 nM)), in models of pain. Based on these results, we focused our attention on MY 5445, another known PDE5 inhibitor. Homologues, isosteres and structural analogues of MY 5445 were designed and all synthesized compounds were evaluated for their inhibitory activity toward PDE5. Selectivity profiles towards other PDE1-4 isoenzymes, water solubility and stability in acidic medium of the most potent PDE5 inhibitors were determined and the aminophthalazine 16h and its mimetic 41n (3-aminoindazole)were evaluated in comparison to MY 5445 (4b)in vivo in a model of neuropathic pain induced by sciatic nerve cuffing in mice (3 and 0.5 mg/kg, ip twice a day). Both compounds showed the same efficacy on neuropathic allodynia as MY 5445, and thus produced a significant relief of mechanical hypersensitivity after 12 days of treatment.
- Bollenbach, Maud,Lugnier, Claire,Kremer, Mélanie,Salvat, Eric,Megat, Salim,Bihel, Frédéric,Bourguignon, Jean-Jacques,Barrot, Michel,Schmitt, Martine
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supporting information
p. 269 - 290
(2019/06/05)
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- Scope and limitation of propylene carbonate as a sustainable solvent in the Suzuki-Miyaura reaction
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The Suzuki-Miyaura reaction is one of the most used transformations in drug research. Thus making this reaction more sustainable is of considerable current interest. Here we show that propylene carbonate (PC) can be used as a solvent for the Suzuki-Miyaura reaction. PC is one of the greenest solvents since it is synthesized under green conditions by the use of carbon dioxide in the air. All reactions proceeded well and good or excellent yields were observed for the biaryl products. Nonetheless in the case of pyridazinones, 2-hydroxypropyl- chain containing side-products were observed. Importantly, this fact allowed the isolation of several novel compounds which were generated under prominently green conditions.
- Czompa, Andrea,Pásztor, Balázs László,Sahar, Jennifer Alizadeh,Mucsi, Zoltán,Bogdán, Dóra,Ludányi, Krisztina,Varga, Zoltán,Mándity, István M.
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p. 37818 - 37824
(2019/12/03)
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- AMINE-LINKED C3-GLUTARIMIDE DEGRONIMERS FOR TARGET PROTEIN DEGRADATION
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This invention provides amine-linked C3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.
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Page/Page column 297-298
(2017/12/01)
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- Direct Conversion of Haloarenes to Phenols under Mild, Transition-Metal-Free Conditions
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A high-yielding and practical method for the synthesis of phenols from electron-deficient haloarenes and heteroarenes has been developed. The products are formed from acetohydroxamic acid as the hydroxide source via a novel SNAr reaction/Lossen rearrangement sequence. Notably, these reactions employ inexpensive and air-stable reagents, require no special handling, occur under mildly basic conditions, and form products in high yields in the presence of electrophilic and protic functionality. The utility of this methodology is demonstrated by the high-yielding hydroxylation of two base-sensitive complex substrates.
- Fier, Patrick S.,Maloney, Kevin M.
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supporting information
p. 2244 - 2247
(2016/06/01)
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- Synthesis, vasorelaxant activity and 2D-QSAR study of some novel pyridazine derivatives
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Novel 3,6-disubstituted pyridazines were synthesized by facile method and screened for their vasorelaxant properties utilizing isolated thoracic rat aortic rings. Compounds 8a and 11a exerted potent vasorelaxant activity (IC50 = 198 and 177 μM, respectively) relative to doxazosin mesylate (used reference standard, IC50 = 226 μM), that, they may represent promising hits for treatment of cardiovascular disorders. The observed activity was validated by a statistically significant QSAR model (N = 32, n = 6, R2 = 0.811782, R2cvOO = 0.7153, R2cvMO = 0.7209, F = 17.9708, s2 = 9.65226 × 10-8) that was obtained employing CODESSA-Pro software.
- George, Riham F.,Saleh, Dalia O.
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p. 663 - 673
(2016/01/09)
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- Synthesis and cytotoxic activities of some pyrazoline derivatives bearing phenyl pyridazine core as new apoptosis inducers
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The cyclization of chalcones 3a-3u with 3-hydrazinyl-6-phenylpyridazine 7 under basic condition led to the formation of new pyrazoline derivatives 8a-8u. All final compounds were characterized by spectral and elemental analyses. They were screened for their antiproliferative activities against A549 (lung), HepG-2 (liver), CaCo-2 (intestinal) and MCF-7 (breast) cancer cell lines. Some of the synthesized compounds exhibited promising antiproliferative activities especially compound 8k with IC50values of 8.33, 1.67 and 10?μM against HepG-2, MCF-7 and CaCo-2 cancer cell lines, respectively. Moreover, their antiproliferative activity was due to apoptosis rather than necrosis induction except compound 8h which exhibited equal apoptotic and necrotic properties. Compound 8k showed 5 fold increase in caspase-3 activity indicating that the apoptosis proceeds via caspase-3 activation.
- George, Riham F.,Fouad, Marwa A.,Gomaa, Iman E.O.
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- Synthesis of some new 2,6-disubstituted-3(2H)-pyridazinone derivatives and investigation of their analgesic, anti-inflammatory and antimicrobial activities
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In this study, 12 new 3(2H)-pyridazinone derivatives carrying 4-substituted phenylpiperazinylethyl moiety on lactam nitrogen were synthesized and their chemical structures were confirmed by 1H-NMR, mass, and elemental analysis. Analgesic and anti-inflammatory activities of the synthesized compounds were evaluated in mice. Among the synthesized compounds, compound 9c showed the best analgesic and anti-inflammatory activities without causing any gastric effect in stomachs of tested animals. In addition, the synthesized compounds were screened for their antibacterial and antifungal activities against some pathogenic strains.
- Tiryaki, Didem,Sukuroglu, Murat,Dogruer, Deniz S.,Akkol, Esra,Ozgen, Selda,Sahin, M. Fethi
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p. 2553 - 2560
(2013/07/26)
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- Synthesis of some new 3(2H)-pyridazinone derivatives and evaluation of their analgesic-anti-inflammatory and antimicrobial activities
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In this study, 15 new 3(2H)-pyridazinone derivatives carrying N'-(4-substitutedphenylmethylidene)acetohydrazide moiety on lactam nitrogen were synthesized and their chemical structures were confirmed by 1H-NMR, mass, and elemental analysis. Analgesic and anti-inflammatory activities of the synthesized compounds were evaluated in mice. Among the synthesized compounds, compound 11e exhibited the best analgesic and anti-inflammatory activities, without causing any gastric effect in stomachs of tested animals. Additionally, the synthesized compounds were screened for their antibacterial and antifungal activities against some pathogenic strains.
- Sukuroglu, Murat,Yamali, Cem,Tiryaki, Didem,Onurdag, Fatma Kaynak,Akkol, Esra,Dogruer, Deniz Songuel
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p. 507 - 514
(2013/07/26)
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- Copper-catalyzed aerobic dehydrogenation of C-C to C=C bonds in the synthesis of pyridazinones
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A simple and efficient procedure for the synthesis of pyridazin-3(2H)-ones through copper-catalyzed dehydrogenation of a single C-C bond of 4,5-dihydropyridazin-3(2H)-ones to a C=C bond with oxygen as the terminal oxidant is described. Functional groups including hydroxy, carboxylic, bromo, chloro, cyano, nitro and alkoxy were all tolerated under the reaction conditions. Moreover, this methodology was applied to the preparation of a series of structurally similar N-substituted 6-phenylpyridazinone compounds containing fluorine. The dehydrogenation reactions exhibit good yields and selectivity. Copper-catalyzed dehydrogenation of a C-C bond of 4,5-dihydropyridazinones to a C=C bond with oxygen as the terminal oxidant is described. Various functional groups were tolerated under the reaction conditions. The method was also applied to the preparation of a series of N-substituted 6-phenylpyridazinones containing fluoride. The dehydrogenation reactions exhibit good yields and selectivity.
- Liang, Lei,Yang, Guanyu,Xu, Fengrong,Niu, Yan,Sun, Qi,Xu, Ping
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supporting information
p. 6130 - 6136
(2013/09/24)
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- OXO-HETEROCYCLICALLY SUBSTITUTED ALKYL CARBOXYLIC ACIDS AND USE THEREOF
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The present application relates to novel alkylcarboxylic acids having an oxo-substituted azaheterocyclic partial structure, to processes for their preparation, to their use for the treatment and/or prevention of diseases, and to their use for producing medicaments for the treatment and/or prevention of diseases, especially for the treatment and/or prevention of cardiovascular disorders.
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Page/Page column 24-25
(2012/02/06)
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- Unexpected C-C bond cleavage: A route to 3,6-diarylpyridazines and 6-arylpyridazin-3-ones from 1,3-dicarbonyl compounds and methyl ketones
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An unexpected C-C bond cleavage has been revealed in the absence of metal. This observation has been exploited to develop an efficient approach toward 3,6-diarylpyridazines and 6-arylpyridazin-3-ones from simple and commercially available 1,3-dicarbonyl compounds and methyl ketones.
- Gao, Qinghe,Zhu, Yanping,Lian, Mi,Liu, Meicai,Yuan, Jingjing,Wu, Anxin,Yin, Guodong
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p. 9865 - 9870,6
(2012/12/12)
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- OXO-HETEROCYCLIC SUBSTITUTED CARBOXYLIC ACID DERIVATIVES AND THE USE THEREOF
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The present application relates to novel carboxylic acid derivatives having an oxo-substituted azaheterocyclic partial structure, processes for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for producing medicaments for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prevention of cardiovascular disorders.
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(2011/02/26)
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- Iodine-mediated facile dehydrogenation of dihydropyridazin-3(2H)one
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A new protocol for the dehydrogenation of dihydropyridazin-3(2H)-one has been carried out by catalytic amount of iodine in dimethyl sulphoxide in good yield with easy workup.
- Humne, Vivek T.,Konda, Shankaraiah G.,Hasanzadeh, Kamal,Lokhande, Pradeep D.
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experimental part
p. 1435 - 1438
(2012/06/01)
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- Structure-activity relationship study of pyridazine derivatives as glutamate transporter EAAT2 activators
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Excitatory amino acid transporter 2 (EAAT2) is the major glutamate transporter and functions to remove glutamate from synapses. A thiopyridazine derivative has been found to increase EAAT2 protein levels in astrocytes. A structure-activity relationship study revealed that several components of the molecule were required for activity, such as the thioether and pyridazine. Modification of the benzylthioether resulted in several derivatives (7-13, 7-15 and 7-17) that enhanced EAAT2 levels by >6-fold at concentrations 50 of 0.5 μM.
- Xing, Xuechao,Chang, Ling-Chu,Kong, Qiongman,Colton, Craig K.,Lai, Liching,Glicksman, Marcie A.,Lin, Chien-Liang Glenn,Cuny, Gregory D.
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scheme or table
p. 5774 - 5777
(2011/10/18)
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- Synthesis and analgesic and antiinflammatory activity of 6-phenyl/(4-methylphenyl)-3(2H)-pyridazinon-2-propionamide derivatives
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For reducing gastrointestinal toxicity associated with non-steroidal anti-inflammatory drugs (NSAIDs) a variety of 6-phenyl/(4-methylphenyl)-3(2H)- pyridazinon-2-propionamide were synthesized. The structures of these new pyridazinone derivatives were confirmed by their IR, 1 H-NMR spectra and elementary analysis. All the new compounds were tested in vivo for their analgesic and anti-inflammatory activities. The analgesic activity of the test compounds was determined by phenylbenzoquinone-induced writhing assay and the anti-inflammatory activity was evaluated by the carrageenan-induced rat paw edema model. 6-Phenyl-3(2H)-pyridazinon-2-yl-[4-(4-fluorophenyl) piperazinyl] propanamide IV a-3 was the most active one among the synthesized compounds. Also this compound exhibited most potent anti-inflammatory activity. Acetylsalicylic acid and indometacin were used as reference drugs. Adverse effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with the reference NSAIDs. ECV Editio Cantor Verlag.
- Goekce, Mehtap,Colak, Meral Sirin,Kuepeli, Esra,Sahin, Mustafa Fethi
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experimental part
p. 357 - 363
(2010/03/23)
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- Metalation of bromodiazines. Diazines XL
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The syntheses of 2-bromopyrazine, 2,4-dibromopyrimidines, and 3-bromo-6-phenylpyrazine were improved and their metalation with lithium alkylamides was studied.
- Decrane, Laurence,Pie, Nelly,Turck, Alain
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p. 509 - 513
(2007/10/03)
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- Pyridazines. Part XXIX: Synthesis and platelet aggregation inhibition activity of 5-substituted-6-phenyl-3(2H)-pyridazinones. Novel aspects of their biological actions
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A series of 6-phenyl-3(2H)-pyridazinones with a diverse range of substituents in the 5-position have been prepared and evaluated in the search for new antiplatelet agents. A significant dependence of the substituent on the inhibitory effect has been observed. The pharmacological study of these compounds confirms that modification of the chemical group at position 5 of the 6-phenyl-3(2H)-pyridazinone system influences both variations in the antiplatelet activity and the mechanism of action.
- Sotelo, Eddy,Fraiz, Nuria,Yáez, Matilde,Terrades, Vicente,Laguna, Reyes,Cano, Ernesto,Ravia, Enrique
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p. 2873 - 2882
(2007/10/03)
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- Microwave assisted synthesis of 4,6-diarylpyridazin-3(2H)-ones in solid state
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Microwave assisted synthesis of dihydropyridazin-3(2H)-ones and the subsequent dehydrogenation using selenium dioxide are described.
- Meenakshi,Ramamoorthy,Muthusubramanian,Sivasubramanian
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p. 645 - 651
(2007/10/03)
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- Efficient aromatization of 4,5-dihydro-3(2H)-pyridazinones substituted at 5 position by using anhydrous copper (II) chloride
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An efficient conversion of 5-substituted-4,5-dihydro-3(2H)-pyridazinones into their corresponding dehydrogenated derivatives was achieved by treatment with anhydrous copper(II) chloride in acetonitrile.
- Sotelo, Eddy,Ravina, Enrique
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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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- Copper(II) chloride as an efficient reagent for the dehydrogenation of pyridazinone derivatives
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A new procedure is described for the preparation of pyridazinones from 4,5-dihydropyridazinones under mild conditions with CuCl2 in MeCN via halogenation and spontaneous HCl elimination. For the trans-hexahydrophthalazin-8(1H)-one 1B*, the HCl elimination is five times faster than for the corresponding cis isomer 1B.
- Csende,Szabo,Bernath,Stajer
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p. 1240 - 1242
(2007/10/02)
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- PREPARATION AND REACTIONS OF SOME 2-THIENYL AND 3-THIENYL PYRIDAZINONES AND PYRIDAZINES
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The preparation and reactions of some pyridazinone derivatives with 2- and 3-thienyl substituents are described.Precursor 4-oxobutanoic acids Ar2COCH2CH(Ar1)CO2H (Ar1=Pb, Ar2=2-thienyl and Ar1=2-thienyl, Ar2=Pb) were obtained by addition of HCN to the chalcones Ar1CH=CHCOAr2 followed by acid hydrolysis of the resulting nitrile.Nitriles, ArCOCH(CH3)CH2CN were prepared by the Michael-Stetter reaction and converted via the acids to the 4,5-dihydropyridazin-3(2H)-ones.Two methods wereused to obtain pyridazin-3(2H)-ones viz oxidation of the 4,5-dihydro derivatives with selenium dioxide and base-catalyzed condensation of methanal or aryl aldehydes at the 4-position of the 4,5-dihydro compound.
- Powell, Paul,Sosabowski, Michael H.
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p. 1840 - 1852
(2007/10/03)
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- One-pot preparation of 6-substituted 3(2H)-pyridazinones from ketones
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A one-pot process for the preparation of 6-phenyl-3(2H)-pyridazinone from acetophenone and glyoxylic acid has been investigated and shown to have wide utility in the preparation of 6- and 5,6-substituted 3(2H)-pyridazinones. Limitations to the process encountered with 2'-hydroxyacetophenone and with basic hetero-aromatic ketones have been overcome, and the processes described offer the rapid and efficient synthesis of many 6-substituted pyridazinones from readily available ketones.
- Coates,McKillop
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p. 334 - 342
(2007/10/02)
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- QUANTITATIVE DETERMINATION OF THE ELECTRONIC EFFECTS OF 3- AND 4-PYRIDAZINYL GROUPS FROM NMR SPECTRAL DATA FOR ISOMERIC AMINOPHENYL- AND PHENYLPYRIDAZINES
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The previously unknown aminophenylpyridazines were synthesized.The inductive and resonance constants of 3- and 4-pyridazinyl groups were calculated on the basis of 1H and 13C NMR spectral data for isomeric aminophenyl- and phenylpyridazines in dimethyl sulfoxide (DMSO).
- Shkurko, O. P.,Kuznetsov, S. A.,Denisov, A. Yu.,Mamaev, V. P.
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p. 763 - 770
(2007/10/02)
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- Obtention selective d'hydroxy-4 pyridazinones-3 et de pyridazones-3. Etude des modalites de la cyclocondensation des acides β-acyl lactiques avec l'hydrazine
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The authors reinvestigate the cyclocondensation reaction of β-acyl lactic acids with hydrazine and propose operating conditions allowing a selective and quantitative access either to 4-hydroxypyridazin-3 ones or, directly, to the corresponding pyridazin-3- ones.
- Maghioros, G.,Schlewer, G.,Wermuth, C. G.
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p. 865 - 870
(2007/10/02)
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- PREPARATION AND SOME REACTIONS OF 4- AND 5-ARYL-4,5-DIHYDROPYRIDAZIN-3(2H)-ONES
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Efficient preparations of 4- and 5-phenyl-4,5-dihydropyridazin-3(2H)-ones have been developed, the main reactions of these compounds have been studied, and the synthetic routes have been used to give analogues with substituents in the phenyl rings.In the best synthesis of the 4-phenyldihyropyridazinone (72 percent overall yield) the product was obtained from phenylacetic acid by three simple stages.This approach was applied in preparations of the 2- and 4-hydroxyphenyl compounds and, in conjunction with a recent method for amine protection, the 4-aminophenyl analogue.A four stage synthesis starting from benzaldehyde gave the 5-phenyldihydropyridazinone in 47 percent overall yield; hydroxybenzaldehydes were similarly converted into 5-(allyloxyphenyl)dihydropyridazinones.Oxidation to phenylpyridazinones occured more readily with the 4- and 5-phenyldihydropyridazinones than with the 6-phenyl isomer.The 4- and 5-dihydropyridazinones were smoothly reduced to tetrahydropyridazinones by hydrogenation over platinum but were uneffected by palladium in the presence of hydrazine or cyclohexene.
- Breukelman, Stephen P.,Meakins, G. Denis
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p. 1627 - 1636
(2007/10/02)
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- Substituted 6-phenyl-3(2H)-pyridazinones useful as cardiotonic agents
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Substituted 6-phenyl-3(2H)-pyridazinone compounds are useful as cardiotonic agents. Said compounds cause a significant increase in myocardial contractility in the anesthetized dog. Said compounds are produced by reacting substituted γ-oxobenzenebutanoic acids with suitably substituted hydrazines to provide 6-phenyl-4,5-dihydro-3(2H)-pyridazinones which are dehydrogenated to the desired product. The intermediate 6-phenyl-4,5-dihydro-3(2H)-pyridazinones are themselves useful as cardiotonic agents.
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- Synthesis of 6-(α-Styryl)pyridazin-3(2H)-ones
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6-(α-Styryl)pyridazin-3(2H)-ones (1a-c) have been prepared by the action of SeO2 on 4,5-dihydro derivatives (2) in ethanol.This method has also been applied successfully in the synthesis of 6-arylpyridazin-3(2H)-ones (1d-f). 4-Substituted 6-(α-styryl)pyridazin-3(2H)-ones (6) have been readily obtained by the base-catalysed condensation of 2 with aromatic aldehydes.The reactions of 1 with dimethyl sulphate and POCl3 are also described.
- Ismail, M. Fekry,Shams, Nabil A.,Mostafa, Omnia E.
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p. 371 - 372
(2007/10/02)
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- Method of treating asthma
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A method of treating asthma in a warm-blooded animal using the compound 6-phenyl-1,2,4-triazolo[4,3-b]pyridazin-3(2H)-one.
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- Reactions of 3-Chloropyridazines with Some Nucleophilic Reagents
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3-Chloro-6-phenylpyridazine (1a) and its 4-methyl derivative (1b) react with sodamide, hydrazines, 3-aminopyridazines and phenothiazine in polar and non-polar solvents as well as by fusion to give different products.The structures assigned to the products have been confirmed by their IR spectra.
- Moustafa, A. H.,Kaddah, A. M.,Shams, N. A.
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p. 1084 - 1086
(2007/10/02)
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