Heterocyclic Building Blocks-Pyridazine

New inhibitors for the BPTF bromodomain enabled by structural biology and biophysical assay development was written by Ycas, Peter D.;Zahid, Huda;Chan, Alice;Olson, Noelle M.;Johnson, Jorden A.;Talluri, Siva K.;Schonbrunn, Ernst;Pomerantz, William C. K.. And the article was included in Organic & Biomolecular Chemistry in 2020.Product Details of 1619994-69-2 This article mentions the following:

Bromodomain-containing proteins regulate transcription through protein-protein interactions with chromatin and serve as scaffolding proteins for recruiting essential members of the transcriptional machinery. One such protein is the bromodomain and PHD-containing transcription factor (BPTF), the largest member of the nucleosome remodeling complex, NURF. Despite an emerging role for BPTF in regulating a diverse set of cancers, small mol. development for inhibiting the BPTF bromodomain has been lacking. Here we cross-validate three complementary biophys. assays to further the discovery of BPTF bromodomain inhibitors for chem. probe development: two direct binding assays (protein-observed ¹⁹F (PrOF) NMR and surface plasmon resonance (SPR)) and a competitive inhibition assay (AlphaScreen). We first compare the assays using three small mols. and acetylated histone peptides with reported affinity for the BPTF bromodomain. Using SPR with both unlabeled and fluorinated BPTF, we further determine that there is a minimal effect of ¹⁹F incorporation on ligand binding for future PrOF NMR experiments To guide medicinal chem. efforts towards chem. probe development, we subsequently evaluate two new BPTF inhibitor scaffolds with our suite of biophys. assays and rank-order compound affinities which could not otherwise be determined by PrOF NMR. Finally, we cocrystallize a subset of small mol. inhibitors and present the first published small mol.-protein structures with the BPTF bromodomain. We envision the biophys. assays described here and the structural insights from the crystallog. will guide researchers towards developing selective and potent BPTF 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: 1619994-69-2Product Details of 1619994-69-2).

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. 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.Product Details of 1619994-69-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Discovery of ARD-2585 as an Exceptionally Potent and Orally Active PROTAC Degrader of Androgen Receptor for the Treatment of Advanced Prostate Cancer was written by Xiang, Weiguo;Zhao, Lijie;Han, Xin;Qin, Chong;Miao, Bukeyan;McEachern, Donna;Wang, Yu;Metwally, Hoda;Kirchhoff, Paul D.;Wang, Lu;Matvekas, Aleksas;He, Miao;Wen, Bo;Sun, Duxin;Wang, Shaomeng. And the article was included in Journal of Medicinal Chemistry in 2021.Name: 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 This article mentions the following:

We report herein the discovery of exceptionally potent and orally bioavailable PROTAC AR degraders with ARD-2585 being the most promising compound ARD-2585 achieves DC₅₀ values of 鈮?.1 nM in the VCaP cell line with AR gene amplification and in the LNCaP cell line carrying an AR mutation. It potently inhibits cell growth with IC₅₀ values of 1.5 and 16.2 nM in the VCaP and LNCaP cell lines, resp., and achieves excellent pharmacokinetics and 51% of oral bioavailability in mice. It is more efficacious than enzalutamide in inhibition of VCaP tumor growth and does not cause any sign of toxicity in mice. ARD-2585 is a promising AR degrader for extensive investigations for the treatment of advanced prostate cancer. 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: 2222112-77-6Name: 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).

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. 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 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: 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

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthesis of glucosides. XXI. Synthesis of 2-N-(尾-D-glucopyranos-1-yl)-6-(4-halophenyl)-3-pyridazinones was written by Xin, Bing-Wei;Sun, Chang-Jun;Qu, Li-Qiang;Cao, Xiao-Ran. And the article was included in Yingyong Huaxue in 2003.Computed Properties of C10H7ClN2O This article mentions the following:

Four pyridazinone glucosides I (X = F, Cl, Br, I) were synthesized by reaction of 2,3,4,6-tetra-O-acetyl-1-bromo-1-deoxy-伪-D-glucopyranose with 6-(4-halophenyl)-3(2H)-pyridazinones under phase transfer catalysis conditions, followed by treatment with dry ammonia at 0 鈭?-5掳C. Their structures were characterized by IR, ¹H NMR, ¹³C NMR and elemental anal. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4Computed Properties of 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. 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.Computed Properties of C10H7ClN2O

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Benzohydrazide incorporated imidazo[1,2-b]pyridazine: synthesis, characterization and in vitro anti-tubercular activity was written by Paidi, K. R.;Tatipamula, V. B.;Kolli, M. K.;Pedakotla, V. T.. And the article was included in International Journal of Chemical Sciences in 2017.Application In Synthesis of 3,6-Dichloropyridazine This article mentions the following:

A novel series of imidazo[1,2-b]pyridazine comprising benzohydrazide derivatives I (R = 4-OMe, 3-NO₂, 4-Cl, etc.) have been synthesized, characterized by using spectral data and screened for anti-tuberculosis activity. The anti-tubercular activity of the synthesized compounds I was determined by microplate alamar blue assay and the outcomes were screened in vitro against Mycobacterium tuberculosis H37Rv strain. All synthesized compounds exhibited good to potent anti-tubercular activity when compared with the standard first line anti-tuberculosis drugs (ciprofloxacin, pyrazinamide and streptomycin). Some of the tested compounds exhibited highest inhibitory activity at 1.6 渭g/mL minimal inhibitory concentration In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Application In Synthesis 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 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.Application In Synthesis of 3,6-Dichloropyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthesis and structure-activity relationship of a series of analgesic imidazo[1,2-b]pyridazine acidic derivatives was written by Luraschi, Elena;Arena, Francesca;Sacchi, Antonia;Laneri, Sonia;Abignente, Enrico. And the article was included in Trends in Heterocyclic Chemistry in 1995.Formula: C6H5N3 This article mentions the following:

Four series of imidazo[1,2-b]pyridazine acidic derivatives, namely 2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acids, 2-methylimidazo[1,2-b]pyridazine-3-carboxylic acids, imidazo[1,2-b]pyridazine-2-acetic acids and imidazo[1,2-b]pyridazine-2-carboxylic acids, were synthesized via a common synthetic method. Their antiinflammatory, analgesic and ulcerogenic activities were evaluated. Pharmacol. results were examined and discussed in order to find structure-activity relationships. A review with 10 references In the experiment, the researchers used many compounds, for example, Imidazo[1,2-b]pyridazine (cas: 766-55-2Formula: C6H5N3).

Imidazo[1,2-b]pyridazine (cas: 766-55-2) belongs to pyridazine derivatives. Pyridazine and phthalazine have quite different spectroscopic properties compared with their isomers, pyrazine and quinoxaline. Pyridazine and derivatives coordinate readily with transition metals to form complexes and catalysts with synthetic utility.Formula: C6H5N3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Production of hydrocarbons from a green algae (Oscillatoria) with exploration of its fuel characteristics over different reaction atmospheres was written by Kawale, Harshal D.;Kishore, Nanda. And the article was included in Energy (Oxford, United Kingdom) in 2019.HPLC of Formula: 5754-18-7 This article mentions the following:

Authors conducted non-catalytic, catalytic, and hydropyrolysis at 550掳C temperature and 1 bar pressure to produce biofuels from an ignored algal biomass of Oscillatoria by thermo-chem. degradation study in a tubular reactor having an internal diameter of 25 mm and 300 mm of active length covered by a furnace of a single heating zone. The catalysts used for the catalytic pyrolysis and hydropyrolysis study are TiO₂:ZnO on 1:1 basis. Characterization of bio-oils by Fourier Transform IR Spectroscopy (FTIR) shows substantial variation in functional groups of all three types of bio-oils. Gas Chromatog.-Mass Spectroscopy (GCMS) gives a detailed list of available hydrocarbons in bio-oil samples and proton NMR confirms the functionality of bio-oil by available proton assignments. Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD) shows morphol. and the structural analogy of biochars with respect to biomass. Calorific values of three types of bio-oils ranges from 16.597 to 16.664 MJ/kg; and revealed that this particular biomass has potential as a resource of feedstock with an approx. yield of one-third of biomass on the dry weight basis. The pH of these bio-oils obtained from green algae varies in the range of 8.25 to 6.07 that indicates the less number of oxygenated compounds unlike very low pH bio-oils obtained from other types of biomass feedstock. Addnl., present results revealed that these bio-oils include formative compounds of most popular hydrocarbons, i.e., benzene, toluene and xylene (BTX). Further, they also include furans, phenols, benzaldehyde, guaiacol, caprolactam, styrene, oximes, etc. which can be used as green chems. In the experiment, the researchers used many compounds, for example, 1,2-Dihydro-4-methyl-3,6-pyridazinedione (cas: 5754-18-7HPLC of Formula: 5754-18-7).

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. 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.HPLC of Formula: 5754-18-7

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Promiscuous targeting of bromodomains by bromosporine identifies BET proteins as master regulators of primary transcription response in leukemia was written by Picaud, Sarah;Leonards, Katharina;Lambert, Jean-Philippe;Dovey, Oliver;Wells, Christopher;Fedorov, Oleg;Monteiro, Octovia;Fujisawa, Takao;Wang, Chen-Yi;Lingard, Hannah;Tallant, Cynthia;Nikbin, Nikzad;Guetzoyan, Lucie;Ingham, Richard;Ley, Steven V.;Brennan, Paul;Muller, Susanne;Samsonova, Anastasia;Gingras, Anne-Claude;Schwaller, Juerg;Vassiliou, George;Knapp, Stefan;Filippakopoulos, Panagis. And the article was included in Science Advances in 2016.Recommanded Product: 1619994-69-2 This article mentions the following:

Bromodomains (BRDs) have emerged as compelling targets for cancer therapy. The development of selective and potent BET (bromo and extra-terminal) inhibitors and their significant activity in diverse tumor models have rapidly translated into clin. studies and have motivated drug development efforts targeting non-BET BRDs. However, the complexmultidomain/subunit architecture of BRD protein complexes complicates predictions of the consequences of their pharmacol. targeting. To address this issue, we developed a promiscuous BRD inhibitor [bromosporine (BSP)] that broadly targets BRDs (including BETs) with nanomolar affinity, creating a tool for the identification of cellular processes and diseases where BRDs have a regulatory function. As a proof of principle, we studied the effects of BSP on leukemic cell lines known to be sensitive to BET inhibition and found, as expected, strong antiproliferative activity. Comparison of the modulation of transcriptional profiles by BSP after a short exposure to the inhibitor resulted in a BET inhibitor signature but no significant addnl. changes in transcription that could account for inhibition of other BRDs. Thus, nonselective targeting of BRDs identified BETs, but not other BRDs, as master regulators of contextdependent primary transcription response. 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: 1619994-69-2Recommanded Product: 1619994-69-2).

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. The pyridazine structure is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, and hydralazine. Pyridazine and derivatives coordinate readily with transition metals to form complexes and catalysts with synthetic utility.Recommanded Product: 1619994-69-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Chromium(III) complex thiocyanates with pyridazone derivatives was written by Guran, Cornelia Jitaru Ioana;Jitaru, Ioana;Ciocoiu, Ioana. And the article was included in Revue Roumaine de Chimie in 1994.Recommanded Product: 6-(4-Chlorophenyl)pyridazin-3(2H)-one This article mentions the following:

K[CrL₂(NCS)₄] (L = p-chlorophenylpyridazone, p-bromophenylpyridazone and p-tolylpyridazone) were prepared and characterized. The compounds are characterized by elemental chem. anal., measurements of elec. conductivity and electronic, IR and x-ray spectra. In the experiment, the researchers used many compounds, for example, 6-(4-Chlorophenyl)pyridazin-3(2H)-one (cas: 2166-13-4Recommanded Product: 6-(4-Chlorophenyl)pyridazin-3(2H)-one).

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. 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.Recommanded Product: 6-(4-Chlorophenyl)pyridazin-3(2H)-one

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Scalable Photoelectrochemical Dehydrogenative Cross-Coupling of Heteroarenes with Aliphatic C-H Bonds was written by Xu, Pin;Chen, Peng-Yu;Xu, Hai-Chao. And the article was included in Angewandte Chemie, International Edition in 2020.Formula: C6H5N3 This article mentions the following:

Heteroarenes are structural motifs found in many bioactive compounds and functional materials. Dehydrogenative cross-coupling of heteroarenes with aliphatic C-H bonds provides straightforward access to functionalized heteroarenes from readily available materials. Established methods employ stoichiometric chem. oxidants under conditions of heating or light irradiation By merging electrochem. and photochem., we have achieved efficient photoelectrochem. dehydrogenative cross-coupling of heteroarenes and C(sp³)-H donors through H₂ evolution, without the addition of metal catalysts or chem. oxidants. Mechanistically, the C(sp³)-H donor is converted to a nucleophilic carbon radical through H-atom transfer with chlorine atom, which is produced by light irradiation of anodically generated Cl₂ from Cl^–. The carbon radical then undergoes radical substitution to the heteroarene to afford alkylated heteroarene products. In the experiment, the researchers used many compounds, for example, Imidazo[1,2-b]pyridazine (cas: 766-55-2Formula: C6H5N3).

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. 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.Formula: C6H5N3

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