Heterocyclic Building Blocks-Pyridazine

Reactions of N-heteroarylformamide oximes and N-heteroarylacetamide oximes with N,N-dimethylformamide dimethyl acetal. Synthesis of 2-methyl-s-triazolo[1,5-x]azines and N-methylcyanoaminoazines was written by Stanovnik, Branko;Stimac, Anton;Tisler, Miha;Vercek, Bojan. And the article was included in Journal of Heterocyclic Chemistry in 1982.Category: pyridazine This article mentions the following:

N-Heteroarylformamide oximes RNHCH:NOH (R = diazinyl, triazinyl) were converted with Me₂NCH(OMe)₂ into MeNRCN, as the main products. In some instances, RNHCN and some other products were also formed. On the other hand, RNMeCH:NOH were cyclized under the same reaction conditions into 2-methyl-s-triazolo[1,5-x]azines. RNHCMe:NOMe and RNMeCMe:NOMe were prepared from RN:CHNMe₂ or RN:CMeNMe₂ and MeONH₂. In the experiment, the researchers used many compounds, for example, 3-Aminopyridazine (cas: 5469-70-5Category: pyridazine).

3-Aminopyridazine (cas: 5469-70-5) 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.Category: pyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthesis and biological activity of 2-cyanoacrylamide derivatives tethered to imidazopyridine as TAK1 inhibitors was written by Kang, Seok Jong;Lee, Jung Wuk;Song, Jiho;Park, Jiwon;Choi, Jaeyul;Suh, Kwee Hyun;Min, Kyung Hoon. And the article was included in Journal of Enzyme Inhibition and Medicinal Chemistry in 2020.Reference of 766-55-2 This article mentions the following:

The importance of transforming growth factor beta-activated kinase 1 (TAK1) to cell survival has been demonstrated in many studies. TAK1 regulates signaling cascades, the NF-魏B pathway and the mitogen-activated protein kinase (MAPK) pathway. TAK1 inhibitors can induce the apoptosis of cancerous cells, and irreversible inhibitors such as (5Z)-7-oxozeaenol are highly potent. However, they can react non-specifically with cysteine residues in proteins, which may have serious adverse effects. Reversible covalent inhibitors have been suggested as alternatives. We synthesized imidazopyridine derivatives as novel TAK1 inhibitors, which have 2-cyanoacrylamide moiety that can form reversible covalent bonding. A derivative with 2-cyano-3-(6-methylpyridin-2-yl)acrylamide exhibited potent TAK1 inhibitory activity with an IC₅₀ of 27 nM. It showed a reversible reaction with 尾-mercaptoethanol, which supports its potential as a reversible covalent inhibitor. In the experiment, the researchers used many compounds, for example, Imidazo[1,2-b]pyridazine (cas: 766-55-2Reference of 766-55-2).

Imidazo[1,2-b]pyridazine (cas: 766-55-2) belongs to pyridazine derivatives. The pyridazine structure is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, and hydralazine. 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.Reference of 766-55-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4- triazol-3-ylmethoxy)-3-(2-fluorophenyl)- 1,2,4-triazolo[4,3-b]pyridazine: A Functionally Selective 纬-Aminobutyric Acid_A (GABA_A) 伪2/伪3-Subtype Selective Agonist That Exhibits Potent Anxiolytic Activity but Is Not Sedating in Animal Models was written by Carling, Robert W.;Madin, Andrew;Guiblin, Alec;Russell, Michael G. N.;Moore, Kevin W.;Mitchinson, Andrew;Sohal, Bindi;Pike, Andrew;Cook, Susan M.;Ragan, Ian C.;McKernan, Ruth M.;Quirk, Kathleen;Ferris, Pushpinder;Marshall, George;Thompson, Sally Ann;Wafford, Keith A.;Dawson, Gerard R.;Atack, John R.;Harrison, Timothy;Castro, Jose L.;Street, Leslie J.. And the article was included in Journal of Medicinal Chemistry in 2005.Safety of 4-tert-Butyl-3,6-dichloropyridazine This article mentions the following:

There is increasing evidence that compounds with selectivity for 纬-aminobutyric acid_A (GABA_A) 伪2- and/or 伪3-subtypes may retain the desirable anxiolytic activity of nonselective benzodiazepines but possess an improved side effect profile. Herein we describe a novel series of GABA_A 伪2/伪3 subtype-selective agonists leading to the identification of the development candidate 17, a nonsedating anxiolytic in preclin. animal assays. In the experiment, the researchers used many compounds, for example, 4-tert-Butyl-3,6-dichloropyridazine (cas: 22808-29-3Safety of 4-tert-Butyl-3,6-dichloropyridazine).

4-tert-Butyl-3,6-dichloropyridazine (cas: 22808-29-3) 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.Safety of 4-tert-Butyl-3,6-dichloropyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Pyridazinones containing the (4-methoxyphenyl)piperazine moiety as AChE/BChE inhibitors: design, synthesis, in silico and biological evaluation was written by Merde, Irem B.;Onel, Gulce T.;Turkmenoglu, Burcin;Gursoy, Sule;Dilek, Esra. And the article was included in Medicinal Chemistry Research in 2022.COA of Formula: C4H2Cl2N2 This article mentions the following:

Alzheimer disease is a progressive and fatal neurodegenerative disease affecting the elderly population accompanied by a decrease in cholinergic transmission, impairing cognitive functions. Acetylcholine deficiency is important in the development of disease symptoms. Inhibition of acetylcholinesterase, an important enzyme in acetylcholine hydrolysis, is one of the important drug targets to increase acetylcholine levels. In this study, we aimed to develop acetylcholinesterase inhibitor compounds For this, we synthesized compounds 6(a-e) bearing 3(2H)-pyridazinone and 1,2,4-triazole ring structures. We determined the IC₅₀, Ki and inhibition types of N-substituted-(p-methoxyphenyl)pyridazin-3(2H)-one derivatives that we synthesized and elucidated their structures. The compound with the best AChE activity was compound 6b (Ki = 3.73 卤 0.9 nM) with the p-methylphenyl group it carried and showed competitive inhibition. Kinetic study was also performed for the compounds with the highest BChE 6a (Ki = 0.95 卤 0.16 nM) inhibitory activities. Mol. docking studies have shown that the p-methylphenyl group is indeed active in the hinge region of the AChE crystal structure as a result of exptl. activity. In addition, the best free binding energy (螖GBind), docking score and Glide score values were determined by examining the interactions with AChE crystal structure for compound 6b and with BChE crystal structure for 6a in silico approaches. Graphical abstract In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0COA of Formula: C4H2Cl2N2).

3,6-Dichloropyridazine (cas: 141-30-0) 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. 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: C4H2Cl2N2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Microwave assisted synthesis, characterization and pharmacological evaluation of pyridazinone derivatives was written by Jha, K. K.;Kumar, Y.;Shaharyar, Mohd.;Sharma, Gajraj. And the article was included in Asian Journal of Chemistry in 2009.Formula: C10H7ClN2O This article mentions the following:

Two series of compounds I (R = H, Me, Cl etc.) and II were synthesized by microwave assisted methods. These compounds were evaluated for their hypotensive and anticonvulsant activities. They showed the hypotensive activity ranging from 17.8 to 27.4% while standard drug minoxidil showed 27% reduction in blood pressure. All these compounds showed significant anticonvulsant activity when compared with phenytoin. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4Formula: C10H7ClN2O).

6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4) 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. 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.Formula: C10H7ClN2O

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Determination of some acids in alkyds and polyesters by classical and oscillographic polarography with a vibrating dropping-mercury electrode was written by Novak, V.. And the article was included in Plaste und Kautschuk in 1965.Electric Literature of C5H6N2O2 This article mentions the following:

An efficient method is described whereby vibrations from a loudspeaker cone are transmitted through a metal rod to a dropping Hg capillary connected by a rubber ring. The method permits simultaneous determination of maleic (I), fumriac (II), and phthalic (III), or of citraconic (IV), mesaconic (V), and III acids in hydrolyzates of polyesters or alkyds. In 0.04M HCl with 0.5M NH₄Cl, I and II are undissociated and have the same half-wave potential (E_0.5), giving their sum, followed at a distance by the cation of III. In the same medium, IV, V, and III show up sep. I and II are separated in buffers of pH 6.8-7.5, where I anion is readily reduced (-1.46 v.). Between 1 and 5 ml. product from resin, hydrolyzed in Me₂CO by aqueous KOH, 12.5 ml. M NH₄Cl, 1 ml. M HCl, and H₂O to fill a 25-ml. flask was polarographed against a S.C.E., starting at -0.4 v.; E_0.5 were -0.65 v. for I and II, -0.53 for IV, -0.65 for V, and -1.05 for III. The oscillographic determination in the presence of vibrations was greatly improved by insertion of a Ge diode in the circuit. I and II were best determined in a 9:1 mixture of M NH₄Cl and M HCl; IV and V by a 3:1 mixture of the same. Accuracy of the methods is discussed. In the experiment, the researchers used many compounds, for example, 1,2-Dihydro-4-methyl-3,6-pyridazinedione (cas: 5754-18-7Electric Literature of C5H6N2O2).

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. 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.Electric Literature of C5H6N2O2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthesis of a novel 6,5-bicyclic hexahydropyridazine derivative was written by Dragovich, Peter S.;Tada, Hiroki;Zhou, Ru. And the article was included in Heterocycles in 1995.Name: (S)-1-((Benzyloxy)carbonyl)hexahydropyridazine-3-carboxylic acid This article mentions the following:

A convergent synthesis of the 6,5-bicyclic hexahydropyridazine derivative I is described in which (3S)-N¹-Cbz-piperazic acid Me ester is coupled with the functionalized carboxylic acid fragment II. The Sharpless asym. dihydroxylation reaction (AD) of the 1,1-disubstituted olefin EtOCOC(CH₂CH₂Me):CH₂ is utilized in the preparation of II and is observed to produce the corresponding diol with 44% enantiomeric excess and R stereochem. In the experiment, the researchers used many compounds, for example, (S)-1-((Benzyloxy)carbonyl)hexahydropyridazine-3-carboxylic acid (cas: 65632-62-4Name: (S)-1-((Benzyloxy)carbonyl)hexahydropyridazine-3-carboxylic acid).

(S)-1-((Benzyloxy)carbonyl)hexahydropyridazine-3-carboxylic acid (cas: 65632-62-4) 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. 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.Name: (S)-1-((Benzyloxy)carbonyl)hexahydropyridazine-3-carboxylic acid

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Syntheses, structures, and properties of dipyridazino-fused 1,3,4,6-tetraazapentalenes was written by Pereira, David E.;Petric, Andrej;Leonard, Nelson J.. And the article was included in Tetrahedron in 1988.Formula: C4H5N3 This article mentions the following:

The fluorescent 2,9-dichloro[2”,3”:1′,2′]imidazo[4′,5′:4,5]imidazo[1,2-b]pyridazine (I, R = Cl) and the unsubstituted parent I (R = H) have been synthesized. The chloro groups of I (R = Cl) were easily displaced by a variety of nucleophiles to provide the 2,9-disubstituted compounds I (R = MeO, N₃, NH₂, NHNH₂, OH). A single crystal x-ray structure determination of the 2,9-dimethoxy compound I (R = MeO) revealed two crystallog. independent structures in the unit cell. I (R = H) forms a 2:1 complex with cobalt(II). In the experiment, the researchers used many compounds, for example, 3-Aminopyridazine (cas: 5469-70-5Formula: C4H5N3).

3-Aminopyridazine (cas: 5469-70-5) 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: C4H5N3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Lead identification of novel and selective TYK2 inhibitors was written by Liang, Jun;Tsui, Vickie;Van Abbema, Anne;Bao, Liang;Barrett, Kathy;Beresini, Maureen;Berezhkovskiy, Leo;Blair, Wade S.;Chang, Christine;Driscoll, James;Eigenbrot, Charles;Ghilardi, Nico;Gibbons, Paul;Halladay, Jason;Johnson, Adam;Kohli, Pawan Bir;Lai, Yingjie;Liimatta, Marya;Mantik, Priscilla;Menghrajani, Kapil;Murray, Jeremy;Sambrone, Amy;Xiao, Yisong;Shia, Steven;Shin, Young;Smith, Jan;Sohn, Sue;Stanley, Mark;Ultsch, Mark;Zhang, Birong;Wu, Lawren C.;Magnuson, Steven. And the article was included in European Journal of Medicinal Chemistry in 2013.Quality Control of 3-Aminopyridazine This article mentions the following:

A therapeutic rationale is proposed for the treatment of inflammatory diseases, such as psoriasis and inflammatory bowel diseases (IBD), by selective targeting of TYK2. Hit triage, following a high-throughput screen for TYK2 inhibitors, revealed pyridine (I) as a promising starting point for lead identification. Initial expansion of 3 sep. regions of the mol. led to eventual identification of cyclopropyl amide (II), a potent lead analog with good kinase selectivity, physicochem. properties, and pharmacokinetic profile. Anal. of the binding modes of the series in TYK2 and JAK2 crystal structures revealed key interactions leading to good TYK2 potency and design options for future optimization of selectivity. In the experiment, the researchers used many compounds, for example, 3-Aminopyridazine (cas: 5469-70-5Quality Control of 3-Aminopyridazine).

3-Aminopyridazine (cas: 5469-70-5) belongs to pyridazine derivatives. The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. 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.Quality Control of 3-Aminopyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthesis of New 6-[4-(2-Fluorophenylpiperazin-1-yl)]-3(2H)-Pyridazinone-2-Acetyl-2- (Substituted benzal)Hydrazone Derivatives and Evaluation of Their Cytotoxic Effects in Liver and Colon Cancer Cell Lines was written by Ozdemir, Zeynep;Basak-Turkmen, Nese;Ayhan, Idris;Ciftci, Osman;Uysal, Mehtap. And the article was included in Pharmaceutical Chemistry Journal in 2019.Application of 141-30-0 This article mentions the following:

In this study, seven new 3(2H)-pyridazinone derivatives I (R = H, 2-Cl, 4-NMe₂, 4-Me, 4-Cl, 4-Br, 2-MeO) expected to show cytotoxic activity in liver and colon cancer cell lines were synthesized. Compounds I were tested on HEP3B (liver cancer) and HTC116 (colon cancer) cell lines for cytotoxicity by using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] proliferation assay. Human fibroblast cells were used as a safety control in these tests. Compound I (R = 2-Cl) was the most active agent with respect to HEP3B and HTC116 cell lines. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Application of 141-30-0).

3,6-Dichloropyridazine (cas: 141-30-0) 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. 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.Application of 141-30-0

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem