Month: February 2023

The effect of solvent on the synthesis of pyridazinones and some reactions of the new compounds was written by Sayed, Galal Hosni;Radwan, Azza;Hamed, Ashraf Ahmed;Boraie, Waleed El Sayed. And the article was included in Bulletin of the Chemical Society of Japan in 1993.Application of 2166-13-4 This article mentions the following:

The reaction of 4-aryl-4-oxo-2-(5-oxo-1,3-diphenyl-2-pyrazolin-4-yl)butanoic acids with hydrazine hydrate in ethanol afforded (oxopyrazolinyl)pyridazinones I (R = p-ClC₆H₄, p-tolyl); in 1-butanol pyrazolo[3,4-c]pyridazino[4,3-e]pyridazine derivative II was obtained, while in acetic acid the 6-aryl-3(2H)-pyridazinone was the product. A probable mechanism has been proposed. The behavior of I toward di-Me sulfate, di-Et sulfate, Et bromoacetate, p-anisaldehyde, phosphoryl chloride and phosphorus pentasulfide has been studied. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4Application of 2166-13-4).

6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. The unsubstituted pyridazines are more resistant to eletrophilic substitution due to the nature of withdrawal of electron density from the ring by two heteroatoms, while the related electron deficiency of the ring makes pyridazine more easily attacked by nucleophiles.Application of 2166-13-4

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Discovery of VU6028418: A Highly Selective and Orally Bioavailable M₄ Muscarinic Acetylcholine Receptor Antagonist was written by Spock, Matthew;Carter, Trever R.;Bollinger, Katrina A.;Han, Changho;Baker, Logan A.;Rodriguez, Alice L.;Peng, Li;Dickerson, Jonathan W.;Qi, Aidong;Rook, Jerri M.;O’Neill, Jordan C.;Watson, Katherine J.;Chang, Sichen;Bridges, Thomas M.;Engers, Julie L.;Engers, Darren W.;Niswender, Colleen M.;Conn, P. Jeffrey;Lindsley, Craig W.;Bender, Aaron M.. And the article was included in ACS Medicinal Chemistry Letters in 2021.Quality Control of 3,6-Dichloropyridazine This article mentions the following:

Herein, we report the SAR leading to the discovery of VU6028418, a potent M₄ mAChR antagonist with high subtype-selectivity and attractive DMPK properties in vitro and in vivo across multiple species. VU6028418 was subsequently evaluated as a preclin. candidate for the treatment of dystonia and other movement disorders. During the characterization of VU6028418, a novel use of deuterium incorporation as a means to modulate CYP inhibition was also discovered. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Quality Control of 3,6-Dichloropyridazine).

3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. The pyridazine structure is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, and hydralazine. Pyridazine can act as a hydrogen bond acceptor to improve the physicochemical properties of drug molecules by increasing their water solubility, and has a high affinity for complexing with targets due to its dipole moment.Quality Control of 3,6-Dichloropyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Production of 6-arylpyridazin-3-ones was written by Anonymous. And the article was included in Research Disclosure in 1990.Reference of 2166-13-4 This article mentions the following:

The cyclization of benzoylacrylic acid derivatives with NH₃ and hydrazine derivatives gave phenylpyridazinone derivatives I (R = H, Me, F, Cl, Br, OMe; R¹ = H, CH₂OH, Ph, CH(OH)Ph, CH(OH)CH₂OBu, CH₂CO₂H). In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4Reference of 2166-13-4).

6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. Pyridazine compounds have attracted interest in various fields like medicinal, industrial, and agricultural research as they are used for numerous biological activities and other applications.Reference of 2166-13-4

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Saturated heterocycles. Part 226. Copper(II) chloride as an efficient reagent for the dehydrogenation of pyridazinone derivatives was written by Csende, Ferenc;Szabo, Zoltan;Bernath, Gabor;Stajer, Geza. And the article was included in Synthesis in 1995.HPLC of Formula: 2166-13-4 This article mentions the following:

A new procedure is described for the preparation of the pyridazinones I [R = H, Me, F, Cl, Br; R¹ = H; R¹₂ = (CH₂)₄] from the corresponding 4,5-dihydropyridazinones under mild conditions with CuCl₂ in MeCN via halogenation and spontaneous HCl elimination. For the trans-phthalazinone I [R = Me; R¹₂ = (CH₂)₄], the HCl elimination is 5 times faster than for its cis isomer. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4HPLC of Formula: 2166-13-4).

6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. The unsubstituted pyridazines are more resistant to eletrophilic substitution due to the nature of withdrawal of electron density from the ring by two heteroatoms, while the related electron deficiency of the ring makes pyridazine more easily attacked by nucleophiles.HPLC of Formula: 2166-13-4

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Relations between structure and activity of maleic hydrazide analogs and related compounds was written by Parups, E.;Hoffman, I.;Morley, H. V.. And the article was included in Canadian Journal of Biochemistry and Physiology in 1962.Formula: C5H6N2O2 This article mentions the following:

The growth- inhibiting activities of a number of compounds structurally related to maleic hydrazide (I) were examined by the technique of bud-growth inhibition. The degree of inhibitory activity of I derivatives depended on tile ease with which the plant can split off substituents. Straight-chain compounds which partially resemble I were not as active as the parent compound, and ring closure was necessary for full activity. Residue data for some of the tested compounds showed that activity failure was not due to lack of uptake and translocation. The anal. procedure for I is shown to be valid for the quant. determination of hydroxymethyl-I and N-benzoyl-I. In the experiment, the researchers used many compounds, for example, 1,2-Dihydro-4-methyl-3,6-pyridazinedione (cas: 5754-18-7Formula: C5H6N2O2).

1,2-Dihydro-4-methyl-3,6-pyridazinedione (cas: 5754-18-7) belongs to pyridazine derivatives. The pyridazine structure is a popular pharmacophore which is found within a number of herbicides such as credazine, pyridafol and pyridate. In the past decade, X-ray data were reported with regard to the characterization and structural elucidation of a number of pyridazine-metal complexes, including pyridazine ligands with zinc, nickel, copper, cadmium and ruthenium.Formula: C5H6N2O2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

3-Bromoimidazo[1,2-b]pyridazine-bromine and 3-bromo-6-chloroimidazo[1,2-b]pyridazine-bromine complexes: new brominating agents for organic compounds was written by Stanovnik, Branko;Tisler, Miha;Drnovsek, Iztok. And the article was included in Synthesis in 1981.Electric Literature of C6H3BrClN3 This article mentions the following:

Title compounds I.HBr.Br₂ (R = H or Cl) were prepared and used to brominate a variety of alkenes, ketones, 3-oxoalkanoic esters, and monocyclic and polycyclic N-heterocyclic compounds at room temperature or on gentle heating, monobrominated compounds are obtained in practically quant. yields. In the experiment, the researchers used many compounds, for example, 3-Bromo-6-chloroimidazo[1,2-b]pyridazine (cas: 13526-66-4Electric Literature of C6H3BrClN3).

3-Bromo-6-chloroimidazo[1,2-b]pyridazine (cas: 13526-66-4) belongs to pyridazine derivatives. The pyridazine structure is a popular pharmacophore which is found within a number of herbicides such as credazine, pyridafol and pyridate. Pyridazine compounds have attracted interest in various fields like medicinal, industrial, and agricultural research as they are used for numerous biological activities and other applications.Electric Literature of C6H3BrClN3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Epigenetic drug screen identifies the histone deacetylase inhibitor NSC3852 as a potential novel drug for the treatment of pediatric acute myeloid leukemia was written by Wiggers, Caroline R. M.;Govers, Anita M. A. P.;Lelieveld, Daphne;Egan, David A.;Zwaan, C. Michel;Sonneveld, Edwin;Coffer, Paul J.;Bartels, Marije. And the article was included in Pediatric Blood & Cancer in 2019.Safety of Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate This article mentions the following:

Acute myeloid leukemia (AML) is a heterogeneous disease regarding morphol., immunophenotyping, genetic abnormalities, and clin. behavior. The overall survival rate of pediatric AML is 60% to 70%, and has not significantly improved over the past two decades. Children with Down syndrome (DS) are at risk of developing acute megakaryoblastic leukemia (AMKL), which can be preceded by a transient myeloproliferative disorder during the neonatal period. Intensification of current treatment protocols is not feasible due to already high treatment-related morbidity and mortality. Instead, more targeted therapies with less severe side effects are highly needed. To identify potential novel therapeutic targets for myeloid disorders in children, including DS-AMKL and non-DS-AML, we performed an unbiased compound screen of 80 small mols. targeting epigenetic regulators in three pediatric AML cell lines that are representative for different subtypes of pediatric AML. Three candidate compounds were validated and further evaluated in normal myeloid precursor cells during neutrophil differentiation and in (pre-)leukemic pediatric patient cells. Candidate drugs LMK235, NSC3852, and bromosporine were effective in all tested pediatric AML cell lines with antiproliferative, proapoptotic, and differentiation effects. Out of these three compounds, the pan-histone deacetylase inhibitor NSC3852 specifically induced growth arrest and apoptosis in pediatric AML cells, without disrupting normal neutrophil differentiation. NSC3852 is a potential candidate drug for further preclin. testing in pediatric AML and DS-AMKL. In the experiment, the researchers used many compounds, for example, Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2Safety of Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate).

Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (cas: 1619994-69-2) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. Pyridazine is bioavailable (especially in the CNS) and can reduce toxicity. Pyridazine is a component of several drug molecules, and the pyridazine pharmacophore has contributed to a variety of pharmacologically active compounds.Safety of Ethyl (3-methyl-6-(4-methyl-3-(methylsulfonamido)phenyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Pyridazines. XXXI. A facile synthesis of 3-pyridazinecarbonitriles via 2-(4-toluenesulfonyl)-2,3-dihydro-3-pyridazinecarbonitriles was written by Dostal, Wolfgang;Heinisch, Gottfried. And the article was included in Heterocycles in 1986.Category: pyridazine This article mentions the following:

Pyridazines I(R = R¹ = R² = H; R = R² = H, R¹ = Me; R = R¹ = H, R² = Me) reacted with Me₃SiCN/4-MeC₆H₄SO₂Cl to give dihydropyridazines II (R³ = tosyl) in 63-84% yields. II were converted to pyridazines I (R = cyano) in 71-99% yields by the action of DBU. In the experiment, the researchers used many compounds, for example, 4-Methylpyridazine-3-carbonitrile (cas: 106861-17-0Category: pyridazine).

4-Methylpyridazine-3-carbonitrile (cas: 106861-17-0) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. In the past decade, X-ray data were reported with regard to the characterization and structural elucidation of a number of pyridazine-metal complexes, including pyridazine ligands with zinc, nickel, copper, cadmium and ruthenium.Category: pyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Development of an LC-MS/MS Method for ARV-110, a PROTAC Molecule, and Applications to Pharmacokinetic Studies was written by Nguyen, Thi-Thao-Linh;Kim, Jin Woo;Choi, Hae-In;Maeng, Han-Joo;Koo, Tae-Sung. And the article was included in Molecules in 2022.Category: pyridazine This article mentions the following:

ARV-110, a novel proteolysis-targeting chimera (PROTAC), has been reported to show satisfactory safety and tolerability for prostate cancer therapy in phase I clin. trials. However, there is a lack of bioanal. assays for ARV-110 determination in biol. samples. In this study, we developed and validated an LC-MS/MS method for the quantitation of ARV-110 in rat and mouse plasma and applied it to pharmacokinetic studies. ARV-110 and pomalidomide (internal standard) were extracted from the plasma samples using the protein precipitation method. Sample separation was performed using a C18 column and a mobile phase of 0.1% formic acid in distilled water-0.1% formic acid in acetonitrile (30:70, volume/volume). Multiple reaction monitoring was used to quantify ARV-110 and pomalidomide with ion transitions at m/z 813.4 → 452.2 and 273.8 → 201.0, resp. The developed method showed good linearity in the concentration range of 2-3000 ng/mL with acceptable accuracy, precision, matrix effect, process efficiency, and recovery. ARV-110 was stable in rat and mouse plasma under long-term storage, three freeze-thaw cycles, and in an autosampler, but unstable at room temperature and 37°C. Furthermore, the elimination of ARV-110 via phase 1 metabolism in rat, mouse, and human hepatic microsomes was shown to be unlikely. Application of the developed method to pharmacokinetic studies revealed that the oral bioavailability of ARV-110 in rats and mice was moderate (23.83% and 37.89%, resp.). These pharmacokinetic findings are beneficial for future preclin. and clin. studies of ARV-110 and/or other PROTACs. In the experiment, the researchers used many compounds, for example, N-(trans-4-(3-Chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide (cas: 2222112-77-6Category: pyridazine).

N-(trans-4-(3-Chloro-4-cyanophenoxy)cyclohexyl)-6-(4-((4-(2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxoisoindolin-5-yl)piperazin-1-yl)methyl)piperidin-1-yl)pyridazine-3-carboxamide (cas: 2222112-77-6) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Specifically, the pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic.Category: pyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem