Heterocyclic Building Blocks-Pyridazine

Li, Xin; Wu, Yizhe; Tian, Gaofei; Jiang, Yixiang; Liu, Zheng; Meng, Xianbin; Bao, Xiucong; Feng, Ling; Sun, Hongyan; Deng, Haiteng; Li, Xiang David published an article in Journal of the American Chemical Society. The title of the article was 《Chemical Proteomic Profiling of Bromodomains Enables the Wide-Spectrum Evaluation of Bromodomain Inhibitors in Living Cells》.Name: 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine The author mentioned the following in the article:

Bromodomains, epigenetic “”readers”” of lysine acetylation marks, exist in different nuclear proteins with diverse biol. functions in chromatin biol. Malfunctions of bromodomains are associated with the pathogenesis of human diseases, such as cancer. Bromodomains have therefore emerged as therapeutic targets for drug discovery. Given the high structural similarity of bromodomains, a critical step in the development of bromodomain inhibitors is the evaluation of their selectivity to avoid off-target effects. While numerous bromodomain inhibitors have been identified, new methods to evaluate the inhibitor selectivity toward endogenous bromodomains in living cells remain needed. Here we report the development of a photoaffinity probe, photo-bromosporine (photo-BS), that enables the wide-spectrum profiling of bromodomain inhibitors in living cells. Photo-BS allowed light-induced crosslinking of recombinant bromodomains and endogenous bromodomain-containing proteins (BCPs) both in vitro and in living cells. The photo-BS-induced labeling of the bromodomains was selectively competed by the corresponding bromodomain inhibitors. Proteomics anal. revealed that photo-BS captured 28 out of the 42 known BCPs from the living cells. Assessment of the two bromodomain inhibitors, bromosporine and GSK6853, resulted in the identification of known as well as previously uncharacterized bromodomain targets. Collectively, we established a chem. proteomics platform to comprehensively evaluate bromodomain inhibitors in terms of their selectivity against endogenous BCPs in living cells. The experimental part of the paper was very detailed, including the reaction process of 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine(cas: 53085-52-2Name: 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine)

6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine(cas: 53085-52-2) belongs to anime. The reaction of alkyl halides, R―X, where X is a halogen, or analogous reagents with ammonia (or amines) is useful with certain compounds. Not all alkyl halides are effective reagents; the reaction is sluggish with secondary alkyl groups and fails with tertiary ones. Its usefulness is largely confined to primary alkyl halides (those having two hydrogen atoms on the reacting site).Name: 6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

The author of 《Mesoionic pyridazine ribonucleosides. A novel biologically active nucleoside metabolite》 were Bambury, Ronald E.; Feeley, Daniel T.; Lawton, Gerald C.; Weaver, John M.; Wemple, James. And the article was published in Journal of Medicinal Chemistry in 1984. Formula: C5H2ClN3 The author mentioned the following in the article:

Ribofuranosylpyridazinium I was prepared from 4-cyano-3(2H)-pyridazinone (II) by using a low-temperature, kinetically controlled, silyl Hilbert-Johnson reaction followed by deblocking of the resulting triacetate derivative with NaHCO3 in MeOH. I is a urine metabolite of II in mice. I possesses Gram-neg. antibacterial activity in vivo against a systemic Escherichia coli infection in mice with an ED50 of 25-50 mg/kg. A series of 4-substituted 3-oxidopyridazinium ribonucleosides were synthesized as analogs of I. 4-Chloro-3-oxido-1-β-D-ribofuranoylpyridazinium was several times more active than I against E. coli in vitro although it showed no in vivo activity.3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3Formula: C5H2ClN3) was used in this study.

3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3) belongs to pyridazine derivatives.The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazines are also important because of their utility in synthetic organic chemistry and in physical organic chemistry.There are reports available for the synthesis of pyridazine and their derivatives by using 2-oxoaldehyes.Formula: C5H2ClN3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

The author of 《The mechanism of thermal eliminations. Part 19. Relative rates of pyrolysis of 2-ethoxypyrazine, 3-ethoxypyridazine, 2- and 4-ethoxypyrimidine, 3-chloro-6-ethoxypyridazine, and 2-chloro-4-ethoxypyrimidine: the effect of the aza ‘substituent’ and π-bond order on the elimination rate》 were Al-Awadi, Nouria; Taylor, Roger. And the article was published in Journal of the Chemical Society in 1986. Formula: C6H8N2O The author mentioned the following in the article:

The kinetics were examined of the 1st-order thermal decomposition of the title compounds into C2H4 and the corresponding aza-substituted pyridines at 650-713 K. The electronic effects of the aza substituent are small; a more important factor appears to be the C-N π-bond order, which accounts for the high reactivity of the pyridazines. The substituent effects of the Cl and aza groups are explicable in terms of the balance between electron withdrawal from the C-O bond, producing activation, and from the N in the cyclic transition state, producing deactivation. The most important reaction step is cleavage of the C-O bond. The statistically corrected rate (per ring N atom) of 2-ethoxypyrimidine is unexpectedly low. This may reflect difficulty in achieving the coplanar transition state in which the lone pairs in the s-orbitals of O and N not involved in the elimination are brought into close proximity. The experimental process involved the reaction of 3-Ethoxypyridazine(cas: 62567-44-6Formula: C6H8N2O)

3-Ethoxypyridazine(cas: 62567-44-6) belongs to pyridazine derivatives.The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazines are also important because of their utility in synthetic organic chemistry and in physical organic chemistry.There are reports available for the synthesis of pyridazine and their derivatives by using 2-oxoaldehyes.Formula: C6H8N2O

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

《Diazine systems. I. Infrared spectra of 3,6-disubstituted pyridazines》 was published in Journal of Heterocyclic Chemistry in 1967. These research results belong to Salisbury, R. G.; Ryan, D. P.; Mason, James W.. HPLC of Formula: 5788-60-3 The article mentions the following:

The ir spectra of 26 3-halo-6-alkoxypyridazines (I) was given. Three bands at 1600-1540, 1325-1295, and 1065-935 cm.-1, found in all spectra gave evidence for the presence of the pyridazine nucleus. The bands at 1450-1400 cm.-1 were subject to many interfering factors. The H in-plane and out-of-plane deformation bands at 1150-1100 and 860-830 cm.-1 were useful in determining the substitution pattern. In the part of experimental materials, we found many familiar compounds, such as 3-Chloro-6-propoxypyridazine(cas: 5788-60-3HPLC of Formula: 5788-60-3)

3-Chloro-6-propoxypyridazine(cas: 5788-60-3) belongs to pyridazine derivatives.The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazines are also important because of their utility in synthetic organic chemistry and in physical organic chemistry.There are reports available for the synthesis of pyridazine and their derivatives by using 2-oxoaldehyes.HPLC of Formula: 5788-60-3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Synthetic Route of C7H9ClN2OOn September 9, 2004 ,《N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as Potent and Selective Inhibitors of Glycogen Synthase Kinase 3 with Good Cellular Efficacy》 was published in Journal of Medicinal Chemistry. The article was written by Tavares, Francis X.; Boucheron, Joyce A.; Dickerson, Scott H.; Griffin, Robert J.; Preugschat, Frank; Thomson, Stephen A.; Wang, Tony Y.; Zhou, Hui-Qiang. The article contains the following contents:

Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Mol. modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b]pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes. In the experimental materials used by the author, we found 3-Chloro-6-propoxypyridazine(cas: 5788-60-3Synthetic Route of C7H9ClN2O)

3-Chloro-6-propoxypyridazine(cas: 5788-60-3) belongs to pyridazine derivatives.The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazines are also important because of their utility in synthetic organic chemistry and in physical organic chemistry.There are reports available for the synthesis of pyridazine and their derivatives by using 2-oxoaldehyes.Synthetic Route of C7H9ClN2O

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Haider, Norbert; Hochholdinger, Iris; Matyus, Peter; Wobus, Andrea published an article in Chemical & Pharmaceutical Bulletin. The title of the article was 《Synthesis of ortho-functionalized 4-aminomethylpyridazines as substrate-like semicarbazide-sensitive amine oxidase inhibitors》.COA of Formula: C5H2ClN3 The author mentioned the following in the article:

A series of 4-aminomethylpyridazines and -pyridazin-3(2H)-ones (diaza-benzylamines), bearing alkylamino side chains in ortho position relative to the CH2NH2 unit, was synthesized by catalytic hydrogenation of nitriles in strongly acidic medium. N-Benzyl protecting groups either at the pyridazinone ring nitrogen or at an exocyclic nitrogen were selectively removed hydrogenolytically or by treatment with a Lewis acid. The new compounds were tested in vitro for semicarbazide-sensitive amine oxidase (SSAO) inhibitory activity and 4-(aminomethyl)-N,N’-diethylpyridazine-3,5-diamine was found to be the most active representative.3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3COA of Formula: C5H2ClN3) was used in this study.

3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3) belongs to pyridazine derivatives.The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazines are also important because of their utility in synthetic organic chemistry and in physical organic chemistry.There are reports available for the synthesis of pyridazine and their derivatives by using 2-oxoaldehyes.COA of Formula: C5H2ClN3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

In 1971,Chemical & Pharmaceutical Bulletin included an article by Yanai, Mitsuji; Kinoshita, Toshio; Watanabe, Hiroshi; Iwasaki, Susumu. Name: 3,6-Dichloropyridazine-4-carboxamide. The article was titled 《Pyridazine derivatives. XIV. Synthesis and reaction of pyrimido-[4,5-c]pyridazines》. The information in the text is summarized as follows:

New pyrimido[4,5-c]pyridazines were prepared by cyclization of 3-amino-4-carbamoylpyridazines (I, R=Cl, R1=NH2; R=NH2, R1=Cl) and 3-chloro-4-(ethoxycarbonyl)pyridazine. When 3-chloro-5-hydroxypyrimido[4,5-c]pyridazine was treated with POCl3 and N,N-dimethylaniline, 1,4-dihydro-3,5-dichloro-4-[4-(N,N-dimethylamino)phenyl]pyrimido[4,5-c]pyridazine (II) was obtained; the structure was established by NMR spectra of the dechlorination and hydrolysis products. Amination of II afforded 3-chloro-5-amino compounds. In the experiment, the researchers used 3,6-Dichloropyridazine-4-carboxamide(cas: 27427-66-3Name: 3,6-Dichloropyridazine-4-carboxamide)

3,6-Dichloropyridazine-4-carboxamide(cas: 27427-66-3) belongs to anime. The methylamines occur in small amounts in some plants. Many polyfunctional amines (i.e., those having other functional groups in the molecule) occur as alkaloids in plants—for example, mescaline, 2-(3,4,5-trimethoxyphenyl)ethylamine; the cyclic amines nicotine, atropine, morphine, and cocaine; and the quaternary salt choline, N-(2-hydroxyethyl)trimethylammonium chloride, which is present in nerve synapses and in plant and animal cells.Name: 3,6-Dichloropyridazine-4-carboxamide

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

In 2019,Angewandte Chemie, International Edition included an article by Wang, Pan; Yang, Zhenlin; Wang, Ziwei; Xu, Chenyang; Huang, Lei; Wang, Shengchun; Zhang, Heng; Lei, Aiwen. Computed Properties of C6H8N2O. The article was titled 《Electrochemical Arylation of Electron-Deficient Arenes through Reductive Activation》. The information in the text is summarized as follows:

An electrochem. method has been developed to achieve arylation of electron-deficient arenes through reductive activation. Various electron-deficient arenes and aryldiazonium tetrafluoroborates are amenable to this transformation within the conditions of an undivided cell, providing the desired products in up to 92 % yield. Instead of preparing diazonium reagents, these reactions can begin from anilines, and they can be carried out in one pot. ESR studies indicate that cathodic reduction of quinoxaline occurs using the transformation. Moreover, cyclic voltammetry indicates that both quinoxaline and aryl diazonium salt have relatively low reduction potentials, which suggests they can be activated through reduction during the reaction. The experimental part of the paper was very detailed, including the reaction process of 3-Ethoxypyridazine(cas: 62567-44-6Computed Properties of C6H8N2O)

3-Ethoxypyridazine(cas: 62567-44-6) belongs to pyridazine derivatives.The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazines are also important because of their utility in synthetic organic chemistry and in physical organic chemistry.There are reports available for the synthesis of pyridazine and their derivatives by using 2-oxoaldehyes.Computed Properties of C6H8N2O

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Klempier, Norbert; De Raadt, Anna; Griengl, Herfried; Heinisch, Gottfried published their research in Journal of Heterocyclic Chemistry on February 29 ,1992. The article was titled 《Enzymic hydrolysis of heterocyclic nitriles》.Computed Properties of C5H2ClN3 The article contains the following contents:

Chemoselective hydrolysis of heterocyclic nitriles can be achieved by an easy to use immobilized biocatalyst prepared from Rhodococcus sp. Pyrimidine-2-carbonitrile and 3-chloropyridazine-4-carbonitrile were converted into the corresponding amides, while 2-ethoxycarbonyl-4-pyridinecarbonitrile, 6-methylpyridazine-3-carbonitrile, 3-chloropyridazine-4-carbonitrile, 3-ethoxycarbonyl-4,5-dihydroisoxazole-5-carbonitrile, indole-3-carbonitrile, and indole-3-acetonitrile were hydrolyzed to the acids. In addition to this study using 3-Chloropyridazine-4-carbonitrile, there are many other studies that have used 3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3Computed Properties of C5H2ClN3) was used in this study.

3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3) belongs to pyridazine derivatives.The pyridazine derivatives are mostly present in biologically active compounds and are also present with different pharmacophores. Pyridazines are also important because of their utility in synthetic organic chemistry and in physical organic chemistry.There are reports available for the synthesis of pyridazine and their derivatives by using 2-oxoaldehyes.Computed Properties of C5H2ClN3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Winter-Holt, Jon J.; Bardelle, Catherine; Chiarparin, Elisabetta; Dale, Ian L.; Davey, Paul R. J.; Davies, Nichola L.; Denz, Christopher; Fillery, Shaun M.; Guerot, Carine M.; Han, Fujin; Hughes, Samantha J.; Kulkarni, Meghana; Liu, Zhaoqun; Milbradt, Alexander; Moss, Thomas A.; Niu, Huijun; Patel, Joe; Rabow, Alfred A.; Schimpl, Marianne; Shi, Junjie; Sun, Dongqing; Yang, Dejian; Guichard, Sylvie published an article on February 24 ,2022. The article was titled 《Discovery of a Potent and Selective ATAD2 Bromodomain Inhibitor with Antiproliferative Activity in Breast Cancer Models》, and you may find the article in Journal of Medicinal Chemistry.Related Products of 53085-52-2 The information in the text is summarized as follows:

ATAD2 is an epigenetic bromodomain-containing target which is overexpressed in many cancers and has been suggested as a potential oncol. target. While several small mol. inhibitors have been described in the literature, their cellular activity has proved to be underwhelming. In this work, we describe the identification of a novel series of ATAD2 inhibitors by high throughput screening, confirmation of the bromodomain region as the site of action, and the optimization campaign undertaken to improve the potency, selectivity, and permeability of the initial hit. The result is compound 5 (AZ13824374)(I), a highly potent and selective ATAD2 inhibitor which shows cellular target engagement and antiproliferative activity in a range of breast cancer models.6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine(cas: 53085-52-2Related Products of 53085-52-2) was used in this study.

6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine(cas: 53085-52-2) belongs to anime. Reduction of nitro compounds, RNO2, by hydrogen or other reducing agents produces primary amines cleanly (i.e., without a mixture of products), but the method is mostly used for aromatic amines because of the limited availability of aliphatic nitro compounds. Reduction of nitriles and oximes (R2C=NOH) also yields primary amines.Related Products of 53085-52-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem