Heterocyclic Building Blocks-Pyridazine

An expeditious one-pot multicomponent synthesis of sterically hindered bis-1,2,4-triazolopyridazines under solvent-free conditions was written by Aggarwal, Ranjana;Mamta;Sumranb, Garima. And the article was included in ARKIVOC (Gainesville, FL, United States) in 2019.Reference of 141-30-0 This article mentions the following:

A simple and ecol. facile synthesis of sterically hindered 3,6-disubstituted-bis-1,2,4-triazolo-[4,3-b:3′,4′-f]pyridazines was accomplished via a three-component reaction sequence between 3,6-dihydrazinopyridazine, an aromatic or heteroaromatic aldehydes and iodobenzene diacetate (IBD) on grinding at room temperature The 3,6-bis-arylidenehydrazinopyridazine intermediates, generated in-situ, undergo oxidative cyclization to afford the title compounds The present protocol was excellent yields, short reaction times, broad substrate scope, solvent-free greener synthesis and was an easy purification of product. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Reference of 141-30-0).

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. 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.Reference of 141-30-0

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Proton NMR studies of protonation in pyridazin-3(2H)-one and 6-hydroxypyridazin-3(2H)-one was written by Barlin, Gordon B.;Fenn, M. David. And the article was included in Australian Journal of Chemistry in 1979.Quality Control of 4-Hydroxypyridazine This article mentions the following:

A ¹H NMR study of protonation in pyridazin-3-ol and pyridazine-3,6-diol revealed that the processes are not simple and suggests that a mobile tautomeric equilibrium may be involved. In the experiment, the researchers used many compounds, for example, 4-Hydroxypyridazine (cas: 20733-10-2Quality Control of 4-Hydroxypyridazine).

4-Hydroxypyridazine (cas: 20733-10-2) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. 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 4-Hydroxypyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Reaction of 6-aryl-4,5-dihydro-3-(2H)-pyridazinones with molecular bromine. Reaction features and mechanism was written by Ovchinnikov, K. L.;Cherkalin, M. S.;Kurmanov, A. M.;Sadovnikova, Ya. V.;Kolobov, A. V.;Kofanov, E. R.. And the article was included in Izvestiya Vysshikh Uchebnykh Zavedenii, Khimiya i Khimicheskaya Tekhnologiya in 2011.Category: pyridazine This article mentions the following:

Dehydration of 6-aryl-4,5-dihydropyridazin-3(2H)-ones by Br₂ was studied. The reaction was shown to proceed through the formation of the enamine form of the substrate. The reaction mechanism was proposed. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4Category: pyridazine).

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.Category: pyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Piperazinyl oxazolidinone antibacterial agents containing a pyridine, diazene, or triazene heteroaromatic ring was written by Tucker, John A.;Allwine, Debra A.;Grega, Kevin C.;Barbachyn, Michael R.;Klock, Jennifer L.;Adamski, Jenifer L.;Brickner, Steven J.;Hutchinson, Douglas K.;Ford, Charles W.;Zurenko, Gary E.;Conradi, Robert A.;Burton, Phillip S.;Jensen, Randy M.. And the article was included in Journal of Medicinal Chemistry in 1998.Formula: C6H5Cl2N3O This article mentions the following:

Oxazolidinones are a novel class of synthetic antibacterial agents active against gram-pos. organisms including methicillin-resistant Staphylococcus aureus as well as selected anaerobic organisms. Important representatives of this class include the morpholine derivative linezolid, which is currently in phase III clin. trials, and the piperazine derivative eperezolid. As part of an investigation of the structure-activity relationships of structurally related oxazolidinones, we have prepared and evaluated the antibacterial properties of a series of piperazinyl oxazolidinones in which the distal nitrogen of the piperazinyl ring is substituted with a six-membered heteroaromatic ring. Compounds having MIC values ≤ 2 μg/mL vs. selected gram-pos. pathogens were discovered among each of the pyridine, pyridazine, and pyrimidine structural classes. Among these the cyanopyridine I, the pyridazines II and III, and the pyrimidine IV exhibited in vivo potency vs. Staphylococcus aureus comparable to that of linezolid. In the experiment, the researchers used many compounds, for example, N-(3,6-Dichloropyridazin-4-yl)acetamide (cas: 121163-50-6Formula: C6H5Cl2N3O).

N-(3,6-Dichloropyridazin-4-yl)acetamide (cas: 121163-50-6) 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. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.Formula: C6H5Cl2N3O

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthesis of N,N-Dioxopyridazines was written by Rozen, Shlomo;Shaffer, Avshalom. And the article was included in Organic Letters in 2017.Reference of 141-30-0 This article mentions the following:

1,2-Pyridazine dioxides were prepared chemoselectively by treatment of pyridazines with HOF·MeCN (generated in situ from N₂-diluted fluorine, water, and acetonitrile) at 0°. Oxidation of 3,6-dihalopyridazines and 3-chloropyridazine with HOF·MeCN yielded only pyridazine mono-N-oxides under similar conditions. The structure of pyridazine-N,N’-dioxide was determined by X-ray crystallog. The fluorine used to prepare HOF·MeCN should be handled with appropriate precautions. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Reference of 141-30-0).

3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. Pyridazine and phthalazine have quite different spectroscopic properties compared with their isomers, pyrazine and quinoxaline. 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.Reference of 141-30-0

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Insight into the key interactions of bromodomain inhibitors based on molecular docking, interaction fingerprinting, molecular dynamics and binding free energy calculation was written by Ran, Ting;Zhang, Zhimin;Liu, Kejun;Lu, Yi;Li, Huifang;Xu, Jinxing;Xiong, Xiao;Zhang, Yanmin;Xu, Anyang;Lu, Shuai;Liu, Haichun;Lu, Tao;Chen, Yadong. And the article was included in Molecular BioSystems in 2015.Application In Synthesis 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:

The bromodomain is a key protein-protein interaction module that specifically reads the acetylation marks of histones in epigenetic regulation. Currently, lots of inhibitors targeting the bromodomain have been reported as therapeutic agents. To better understand the interaction mechanism of bromodomain inhibitors, 20 diverse bromodomain inhibitors were studied using a combination of computational methods, including mol. docking, interaction fingerprinting, mol. dynamics simulation and binding free energy calculation As a result, interactions important for the activity were critically analyzed, and the energy contribution in terms of individual residues was explored. These integrated results provided insights into two hot spots in the active site of the bromodomain, where the hydrophobic hot spot formed by Trp81, Val87, Leu92 and Ile146 played a central role in the interaction, and the hydrogen-bond hot spot mediated by Asn140 exhibited a moderate contribution to the binding affinity of the bromodomain inhibitors. This interaction mechanism study may facilitate the rational design of novel small-mol. bromodomain inhibitors. 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: 1619994-69-2Application In Synthesis 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 compounds have attracted interest in various fields like medicinal, industrial, and agricultural research as they are used for numerous biological activities and other applications.Application In Synthesis 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

Photochemistry. II. Formation of methyl paraconates and dimethyl succinates from pyridazines was written by Tsuchiya, Takashi;Arai, Heihachiro;Igeta, Hiroshi. And the article was included in Chemical & Pharmaceutical Bulletin in 1971.Name: 1,2-Dihydro-4-methyl-3,6-pyridazinedione This article mentions the following:

Irradiation of 6-chloro-3(2H)-pyridazones, maleic hydrazides, and 3,6-dichloropyridazines in MeOH containing HCl, afforded γ-lactones, Me paraconates (I), and dimethyl succinates MeO2CCH2CH(R)CO2Me (II). A short time irradiation of 3,6-dichloropyridazines resulted in the formation of methylated pyridazines (III and IV), hydroxymethylated pyridazines (V), and methylated pyridazones (VI), along with the γ-lactones (I) and the succinates (II). The mechanism of the formation of the γ-lactones and the succinates was also discussed. In the experiment, the researchers used many compounds, for example, 1,2-Dihydro-4-methyl-3,6-pyridazinedione (cas: 5754-18-7Name: 1,2-Dihydro-4-methyl-3,6-pyridazinedione).

1,2-Dihydro-4-methyl-3,6-pyridazinedione (cas: 5754-18-7) belongs to pyridazine derivatives. Pyridazines are rare in nature, possibly reflecting the scarcity of naturally occurring hydrazines, common building blocks for the synthesis of these heterocycles. 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.Name: 1,2-Dihydro-4-methyl-3,6-pyridazinedione

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

The discovery of a non-competitive GOT1 inhibitor, hydralazine hydrochloride, via a coupling reaction-based high-throughput screening assay was written by Wu, Qiqi;Sun, Zhongya;Chen, Zhifeng;Liu, Jingqiu;Ding, Hong;Luo, Cheng;Wang, Mingliang;Du, Daohai. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2022.Safety of 3-Aminopyridazine This article mentions the following:

Glutamate oxaloacetate transaminase 1 (GOT1) plays a key role in aberrant glutamine metabolism GOT1 suppression can arrest tumor growth and prevent the development of cancer, indicating GOT1 as a potential anticancer target. Reported GOT1 inhibitors, on the other hand, are quite restricted. Here, we developed and optimized a coupling reaction-based high-throughput screening assay for the discovery of GOT1 inhibitors. By using this screening assay, we found that the cardiovascular drug hydralazine hydrochloride inhibited GOT1 catalytic activity, with an IC50 of 26.62 ± 7.45 μM, in a non-competitive and partial-reversible manner. In addition, we determined the binding affinity of hydralazine hydrochloride to GOT1, with a Kd of 16.54 ± 8.59 μM, using a microscale thermophoresis assay. According to structure-activity relationship anal., the inhibitory activity of hydralazine hydrochloride is mainly derived from its hydrazine group. Furthermore, it inhibits the proliferation of cancer cells MCF-7 and MDA-MB-468 with a slight inhibitory effect compared to other tested cancer cells, highlighting GOT1 as a promising therapeutic target for the treatment of breast cancer. In the experiment, the researchers used many compounds, for example, 3-Aminopyridazine (cas: 5469-70-5Safety of 3-Aminopyridazine).

3-Aminopyridazine (cas: 5469-70-5) 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 activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.Safety of 3-Aminopyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

One-pot preparation of 6-substituted 3(2H)-pyridazinones from ketones was written by Coates, W. J.;McKillop, A.. And the article was included in Synthesis in 1993.SDS of cas: 2166-13-4 This article mentions the following:

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 heteroaromatic ketones have been overcome, and the processes described offer the rapid and efficient synthesis of many 6-substituted pyridazinones from readily available ketones. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4SDS of cas: 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. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.SDS of cas: 2166-13-4

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthesis of imidazo[1,2-b]pyridazine was written by Lu, Hongguo;Xu, Yungen;Ren, Dong;Zhou, Bin. And the article was included in Zhongguo Yiyao Gongye Zazhi in 2006.COA of Formula: C6H5N3 This article mentions the following:

A method for the synthesis of the title compound is reported here. This compound is an intermediate for cefozopran [i.e., 1-[[(6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetyl]amino]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]imidazo[1,2-b]pyridazinium inner salt]. Imidazo[1,2-b]pyridazine was synthesized from 3,6-dichloropyridazine by ammonolysis to give 3-amino-6-chloropyridazine, which was subjected to condensation and cyclization followed by catalytic hydrogenolysis (overall yield 85.4%). In the experiment, the researchers used many compounds, for example, Imidazo[1,2-b]pyridazine (cas: 766-55-2COA of Formula: C6H5N3).

Imidazo[1,2-b]pyridazine (cas: 766-55-2) 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. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.COA of Formula: C6H5N3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem