- 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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- 3(2H)-pyridazinone derivatives: Synthesis, in-silico studies, structure-activity relationship and in-vitro evaluation for acetylcholinesterase enzyme inhibition
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New ten compounds bearing pyridazinone ring (5a–j) were designed and synthesized as acetylcholinesterase inhibitors. The new derivatives were acquired via the reaction of propionohydrazides with substituted/nonsubstituted sulphonylchlorides. The structures of the synthesized compounds were explained using FT-IR, 1H-NMR, 13C-NMR, elemental analysis and HRMS spectra. The inhibition profiles of the synthesized compounds on AChE were researched by comparing their IC50 and KI values. According to the activity studies, all the compounds showed significant inhibitory activity against AChE relative to the reference compound Tacrine. The compound 5g showed the best acetylcholinesterase inhibitory effect with a KI value of 11.61 ± 0.77 nM. For all compounds, the parameters of the interaction points on the receptor side were determined on the ligand basis with the 4D-QSAR model. The synthesized pyridazinone derivatives, 5(a-j), were screened for their acetylcholinesterase inhibitory potential, and the results determined that among the series, compounds 5g, 5f and 5j showed the best inhibition, respectively. For anti-Alzheimer activities, 5g, 5f and 5j compounds were performed in silico studies to understand the binding site, binding energy properties in molecular docking.
- ??l, ?mer Faruk,Bozbey, ?rem,Türkmeno?lu, Bur?in,Uysal, Mehtap
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- A new series of pyridazinone derivatives as cholinesterases inhibitors: Synthesis, in vitro activity and molecular modeling studies
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Background: The pyridazinone nucleus has been incorporated into a wide variety of therapeutically interesting molecules to transform them into better drugs. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Inhibition of cholinesterases is an effective method to curb Alzheimer's disease. Here, we prepared 12 new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(nonsubstituted/4-substituted benzenesulfonohydrazide) derivatives and evaluated their inhibitory effects on AChE/BChE in pursuit of potent dual inhibitors for Alzheirmer's Disease. We also tried to get insights into binding interactions of the synthesized compounds in the active site of both enzymes by using molecular docking approach. Method: We obtained our compounds by the reaction of various substituted/nonsubstituted benzenesulfonic acid derivatives with 6-substitutedphenyl-3(2H)-pyridazinone-2-yl acetohydrazide and determined their anticholinesterase activities according to the Ellman's method. Molecular docking studies were done using Glide and the results were evaluated on Maestro (Schr?dinger, LLC, New York, NY, 2019). Results: The title compounds showed moderate inhibition at 100 μg/ml against both enzymes, yet with better activity against BChE. Compound VI2a emerged as a dual inhibitor with 25.02% and 51.70% inhibition against AChE and BChE, respectively. Conclusion: This study supports that novel pyridazinone derivates may be used for the development of new BChE inhibitory agents. It was less potent than the reference drugs, yet promising for further modifications as a lead. The ability of the compounds to adopt energetically more favourable conformations and to engage in more key interactions in the ECBChE active gorge explains their better activity profile against ECBChE.
- ?z?elik, Azime Berna,?zdemir, Zeynep,Sari, Suat,Utku, Semra,Uysal, Mehtap
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p. 1253 - 1263
(2019/11/03)
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- Synthesis and Bioevaluation of 3,6-Diaryl-[1,2,4]triazolo[4,3-b] Pyridazines as Antitubulin Agents
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A series of 3,6-diaryl-[1,2,4]triazolo[4,3-b]pyridazines were designed as a class of vinylogous CA-4 analogues. The easily isomerized (Z,E)-butadiene linker of vinylogous CA-4 was replaced by a rigid [1,2,4]triazolo[4,3-b]pyridazine scaffold. Twenty-one target compounds were synthesized and exhibited moderate to potent antiproliferative activity. The compound 4q with a 3-amino-4-methoxyphenyl moiety as the B-ring, comparable to CA-4 (IC50 = 0.009-0.012 μM), displayed the highly active antiproliferative activity against SGC-7901, A549, and HT-1080 cell lines with IC50 values of 0.014, 0.008, and 0.012 μM, respectively. Tubulin polymerization experiments indicated that 4q effectively inhibited tubulin polymerization, and immunostaining assay revealed that 4q significantly disrupted tubulin microtubule dynamics. Moreover, cell cycle studies revealed that compound 4q dramatically arrested cell cycle progression at G2/M phase in A549 cells. Molecular modeling studies showed that 4q could bind to the colchicine binding site on microtubules.
- Xu, Qile,Wang, Yueting,Xu, Jingwen,Sun, Maolin,Tian, Haiqiu,Zuo, Daiying,Guan, Qi,Bao, Kai,Wu, Yingliang,Zhang, Weige
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supporting information
p. 1202 - 1206
(2016/12/18)
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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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- Reactions of 3-aroylacrylates with α-aminoazoles
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Dihydro derivatives of pyrazolo[3,4-b]pyridine-, pyrazolo[1,5-a]pyrimidine- , and [1,2,4]triazolo-[1,5-a]pyrimidinecarboxylates have been prepared by cyclocondensation of β-aroylacrylates with 5-aminopyrazoles and 3-amino-1,2,4-triazole. Heating dihydro[1,2,4]triazolo[1,5-a]pyrimidine-7- carboxylates with hydrazine hydrate led to recyclization of the pyrimidine ring to form 6-arylpyridazin-3(2H)-ones.
- Kolos,Kovalenko,Borovskoy
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experimental part
p. 983 - 988
(2012/02/16)
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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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- 1-arylsulphonyl, arylcarbonyl and 1-arylphosphonyl-3-phenyl-1,4,5,6-tetrahydropyridazines
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Disclosed are progestin agonists having the following formula: STR1 W is absent or --CH=CH--; R1 are independently selected from the group consisting of halogen, --CF3, and NO2, or both R1 may be joined to form a bi-radical which is --CH=CHCH=CH--; R3 are independently selected from the group consisting of hydrogen, C1-6 branched or linear alkyl, halogen and --CF3, with the proviso that R3 at the 3-position must be H where R3 at the 4-position is H, or both R3 may be joined to form a bi-radical selected from the group consisting of --CH=CHCH=CH--, --C(NC1-4 alkyl2)=CHCH=CH-- and --(CH2)4 --; R5 is selected from the group consisting of H and Me; with the proviso that only one of R1 and R3 forms the fused bi-radical; and the stereoisomers.
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- Dihydropyridazinones, pyridazinones and related compounds as fungicides
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This invention relates to substituted dihydropyridazinones, pyridazinones and related compounds, of the formula STR1 wherein A, Q, D and R1 are as defined within, compositions containing these compounds and methods of controlling agricultural and mammalian fungal diseases.
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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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- 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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- 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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- Method for treating anxiety in mammals
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This disclosure describes compositions of matter useful as anxiolytic agents and the method of meliorating anxiety in mammals therewith; the active ingredients of said compositions of matter being certain substituted 6-phenyl-1,2,4-triazolo[4,3-b]pyridazines or the pharmacologically acceptable acid-addition salts thereof.
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- 6-Phenyl-1,2,4-triazolo[4,3-b]pyridazine hypotensive agents
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This disclosure describes novel substituted 6-phenyl-1,2,4-triazolo[4,3-b]pyridazines useful as hypotensive agents.
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- Hypotensive alkyl-3-[6-(aryl)-3-pyridazinyl]-carbazates
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This disclosure describes novel alkyl 3-[6-(aryl)-3-pyridazinyl]-carbazates useful as hypotensive agents in mammals. SP CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of our copending application Ser. No. 692,254, filed June 3, 1976 now abandoned, which in turn is a continuation-in-part of our abandoned application Ser. No. 552,024, filed Feb. 24, 1975 now abandoned.
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