Heterocyclic Building Blocks-Pyridazine

Safety of 3-Chloropyridazine-4-carbonitrileOn May 31, 1991, Czech, Karin; Haider, Norbert; Heinisch, Gottfried published an article in Monatshefte fuer Chemie. The article was 《Pyridazines. LIV. The synthesis of pyridazine-fused S-heterocycles: thieno[2,3-c]pyridazine, pyrimido[4′,5′:4,5]thieno[2,3-c]pyridazine, and pyridazino[3,4-b][1,4]benzothiazine》. The article mentions the following:

Starting from 3-chloro-4-pyridazinecarbonitrile (I), the thienopyridazine derivatives II (R = OMe; R1 = OMe, NH2) were prepared Condensation of II (R = NH2) with (EtO3)CH afforded the novel tricyclic system III. Reaction of I (R = R1 = NH2) with 2-H2NC6H4SH, followed by treatment with NaH/DMSO gave pyridazinobenzothiazine IV instead of the expected condensed thiazepine. In the experiment, the researchers used many compounds, for example, 3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3Safety of 3-Chloropyridazine-4-carbonitrile)

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.Safety of 3-Chloropyridazine-4-carbonitrile

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Dostal, Wolfgang; Heinisch, Gottfried; Loetsch, Gerhard published an article in Monatshefte fuer Chemie. The title of the article was 《Chemistry of pyridazines. XXXVI. Novel diaza-analogs of 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one》.Name: 3-Chloropyridazine-4-carbonitrile The author mentioned the following in the article:

Procedures for the preparation of the novel tricyclic ketones 10,11-dihydro-5H-benzo[4,5]cyclohepta[1,2-d]pyridazin-5-one (I), 5,6-dihydro-11H-benzo[4,5]cyclohepta[2,1-c]pyridazin-11-one, and 10,11-dihydro-5H-benzo[4,5]cyclohepta[1,2-c]pyridazin-5-one starting from a preformed 1,2-diazine system are proposed. The key intermediates, e.g., II (R = CO2Et) are prepared from (2-phenylethyl)pyridazines, e.g., II (R = H) by introduction of a carboxylic functionality via homolytic alkoxycarbonylation or via a sulfonyl Reissert-type reaction. The experimental process involved the reaction of 3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3Name: 3-Chloropyridazine-4-carbonitrile)

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.Name: 3-Chloropyridazine-4-carbonitrile

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

《A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer’s disease mouse model》 was published in Journal of Neuroinflammation in 2007. These research results belong to Munoz, Lenka; Ranaivo, Hantamalala Ralay; Roy, Saktimayee M.; Hu, Wenhui; Craft, Jeffrey M.; McNamara, Laurie K.; Chico, Laura Wing; Van Eldik, Linda J.; Watterson, D. Martin. Quality Control of 4,6-Dichloro-3-phenylpyridazine The article mentions the following:

Background: An accumulating body of evidence is consistent with the hypothesis that excessive or prolonged increases in proinflammatory cytokine production by activated glia is a contributor to the progression of pathophysiol. that is causally linked to synaptic dysfunction and hippocampal behavior deficits in neurodegenerative diseases such as Alzheimer’s disease (AD). This raises the opportunity for the development of new classes of potentially disease-modifying therapeutics. A logical candidate CNS target is p38α MAPK, a well-established drug discovery mol. target for altering proinflammatory cytokine cascades in peripheral tissue disorders. Activated p38 MAPK is seen in human AD brain tissue and in AD-relevant animal models, and cell culture studies strongly implicate p38 MAPK in the increased production of proinflammatory cytokines by glia activated with human amyloid-beta (Aβ) and other disease-relevant stressors. However, the vast majority of small mol. drugs do not have sufficient penetrance of the blood-brain barrier to allow their use as in vivo research tools or as therapeutics for neurodegenerative disorders. The goal of this study was to test the hypothesis that brain p38α MAPK is a potential in vivo target for orally bioavailable, small mols. capable of suppressing excessive cytokine production by activated glia back towards homeostasis, allowing an improvement in neurol. outcomes. Methods: A novel synthetic small mol. based on a mol. scaffold used previously was designed, synthesized, and subjected to analyses to demonstrate its potential in vivo bioavailability, metabolic stability, safety and brain uptake. Testing for in vivo efficacy used an AD-relevant mouse model. Results: A novel, CNS-penetrant, non-toxic, orally bioavailable, small mol. inhibitor of p38α MAPK (MW01-2-069A-SRM) was developed. Oral administration of the compound at a low dose (2.5 mg/kg) resulted in attenuation of excessive proinflammatory cytokine production in the hippocampus back towards normal in the animal model. Animals with attenuated cytokine production had reductions in synaptic dysfunction and hippocampus-dependent behavioral deficits. Conclusion: The p38α MAPK pathway is quant. important in the Aβ-induced production of proinflammatory cytokines in hippocampus, and brain p38α MAPK is a viable mol. target for future development of potential disease-modifying therapeutics in AD and related neurodegenerative disorders.4,6-Dichloro-3-phenylpyridazine(cas: 40020-05-1Quality Control of 4,6-Dichloro-3-phenylpyridazine) was used in this study.

4,6-Dichloro-3-phenylpyridazine(cas: 40020-05-1) belongs to pyridazine. The pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, antiulcer, antidepressant, neuroleptic, sedative-hypnotic, anticonvulsant, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, immunosuppressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic. Quality Control of 4,6-Dichloro-3-phenylpyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Product Details of 5788-60-3On May 31, 2015, Kim, Chaewon; Lee, Jihee; Park, Myung-Sook published an article in Archives of Pharmacal Research. The article was 《Synthesis of new diorganodiselenides from organic halides: their antiproliferative effects against human breast cancer MCF-7 cells》. The article mentions the following:

A new series of bis(aryl or aralkyl) diselenides was synthesized by selenylation from aryl halide (or aralkyl halide) for development of new anticancer agents. The process involves the reaction of aryl halides (or aralkyl halides) with selenium, hydrazine hydrate under atm. pressure in the presence of sodium hydroxide, to afford diorganodiselenides. These new compounds showed antiproliferative activities against breast cancer (MCF-7) cells in CCK-8 assays, and could be promising candidates for chemotherapy of carcinomas. Among 17 synthesized compounds for inhibiting the growth of these cell lines, 1,2-bis(chloropyridazinyl) diselenide I showed the highest potency. This result suggests the potential anticancer activity of compound I. The experimental process involved the reaction of 3-Chloro-6-propoxypyridazine(cas: 5788-60-3Product Details of 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.Product Details of 5788-60-3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Siegrist, Romain; Pozzi, Davide; Jacob, Gael; Torrisi, Caterina; Colas, Kilian; Braibant, Bertrand; Mawet, Jacques; Pfeifer, Thomas; de Kanter, Ruben; Roch, Catherine; Kessler, Melanie; Corminboeuf, Olivier; Bezencon, Olivier published their research in Journal of Medicinal Chemistry on December 8 ,2016. The article was titled 《Structure-Activity Relationship, Drug Metabolism and Pharmacokinetics Properties Optimization, and in Vivo Studies of New Brain Penetrant Triple T-Type Calcium Channel Blockers》.Computed Properties of C5H2ClN3 The article contains the following contents:

Despite the availability of numerous antiepileptic drugs, 20-30% of epileptic patients are pharmacoresistant with seizures not appropriately controlled. Consequently, new strategies to address this unmet medical need are required. T-type calcium channels play a key role in neuronal excitability and burst firing and selective triple T-type calcium channel blockers could offer a new way to treat various CNS disorders, in particular epilepsy. Herein the authors describe the identification of new 1,4-benzodiazepines as brain penetrant and selective triple T-type calcium channel blockers. From racemic hit 4 ((±)-N,1-dibenzyl-3,5-cis-dimethyl-1,2,3,5-tetrahydro-4H-benzo[e][1,4]diazepine-4-carboxamide), optimization work led to the preparation of pyridodiazepine 31c with improved physicochem. properties, solubility and metabolic stability. The racemic mixture was separated by chiral preparative HPLC and the resulting lead compound (3R,5S)-31c ((3R,5S)-N,1-dibenzyld-3,5-dimethyl-1,2,3,5-tetrahydro-4,5-pyrido[3,4-e][1,4]diazepine-4-carboxamide) showed promising efficacy in the WAG/Rij-rat model of generalized non-convulsive absence-like epilepsy. In the experiment, the researchers used many compounds, for example, 3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3Computed Properties of C5H2ClN3)

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

Reference of 5-(Trifluoromethyl)pyridazin-3(2H)-oneOn March 6, 2020, Trofymchuk, Serhii; Bugera, Maksym Ya.; Klipkov, Anton A.; Razhyk, Bohdan; Semenov, Sergey; Tarasenko, Karen; Starova, Viktoriia S.; Zaporozhets, Olga A.; Tananaiko, Oksana Yu.; Alekseenko, Anatoliy N.; Pustovit, Yurii; Kiriakov, Oleksandr; Gerus, Igor I.; Tolmachev, Andrei A.; Mykhailiuk, Pavel K. published an article in Journal of Organic Chemistry. The article was 《Deoxofluorination of (Hetero)aromatic Acids》. The article mentions the following:

Diverse trifluoromethyl-substituted compounds were synthesized by deoxofluorination of cinnamic and (hetero)aromatic carboxylic acids with sulfur tetrafluoride. The obtained products were used as starting materials in the preparation of novel fluorinated amino acids, anilines, and aliphatic amines – valuable building blocks for medicinal chem. and agrochem. Of note, sulfur tetrafluoride (SF4) and hydrogen fluoride (HF) are toxic, therefore, safety and addnl. tech. training must be taken before working with them. The experimental part of the paper was very detailed, including the reaction process of 5-(Trifluoromethyl)pyridazin-3(2H)-one(cas: 244268-34-6Reference of 5-(Trifluoromethyl)pyridazin-3(2H)-one)

5-(Trifluoromethyl)pyridazin-3(2H)-one(cas: 244268-34-6) 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.Reference of 5-(Trifluoromethyl)pyridazin-3(2H)-one

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Haider, Norbert; Heinisch, Gottfried; Lassnigg, Doris published their research in Journal of Heterocyclic Chemistry on February 29 ,1988. The article was titled 《Pyridazines. XXXV. Preparation of some novel pyrimido[4,5-c]pyridazine derivatives from 3-(alkylamino)- and 3-(arylamino)-4-pyridazinecarboxamides》.Product Details of 1445-56-3 The article contains the following contents:

Pyrimido[4,5-c]pyridazinediones I (R = Ph, PhCH2; R1R2 = O), pyrimido[4,5-c]pyridazinones II (R = Ph, PhCH2; R3 = H, Me, Et), and dihydropyrimido[4,5-c]pyridazinones I (R = Ph, PhCH2, Me2CH; R1 = H, R2 = Ph, 3-pyridyl) were prepared from 3-chloro-4-pyridazinecarbonitrile III (R4 = Cl) via amino carbonitriles III (R4 = NHR) and amino carboxamides. In addition, III (R4 = NH2) was prepared from III (R4 = Cl), via the tetrazolo[1,5-b]pyridazine IV as the key intermediate.3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3Product Details of 1445-56-3) 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.Product Details of 1445-56-3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

In 1970,Journal of Heterocyclic Chemistry included an article by Yanai, Mitsuji; Kuraishi, Tsukasa; Kinoshita, Toshio; Nishimura, Masakuni. Formula: C5H3Cl2N3O. The article was titled 《Recyclization of 3-amino-6-chloroimidazo[4,5-c]pyridazine》. The information in the text is summarized as follows:

3-Benzylideneamino-6-chloroimidazo[4,5-c]pyridazine refluxed with HCl or AcOH gave 5-chloro-8-amino-s-triazolo-[4,5-b]pyridazine and 3-benzylid enehydrazino-4-amino-6-chloropyridazine.3,6-Dichloropyridazine-4-carboxamide(cas: 27427-66-3Formula: C5H3Cl2N3O) was used in this study.

3,6-Dichloropyridazine-4-carboxamide(cas: 27427-66-3) belongs to anime. Milder oxidation, using reagents such as NaOCl, can remove four hydrogen atoms from primary amines of the type RCH2NH2 to form nitriles (R―C≡N), and oxidation with reagents such as MnO2 can remove two hydrogen atoms from secondary amines (R2CH―NHR′) to form imines (R2C=NR′). Tertiary amines can be oxidized to enamines (R2C=CHNR2) by a variety of reagents.Formula: C5H3Cl2N3O

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

In 1977,Chemical & Pharmaceutical Bulletin included an article by Yanai, Mitsuji; Takeda, Shigeko; Mitsuoka, Tamao. Category: pyridazine. The article was titled 《Studies on heterocyclic compounds. XX. The reaction of 4-cyano-3,6-dichloropyridazine with amines》. The information in the text is summarized as follows:

4-Cyano-3,6-dichloropyridazine (I) was treated with primary amines in MeOH under mild conditions (stirring at 0-5°) to give the corresponding 5-amino derivatives II (R = NHCH2CH2OH, NH2, PhCH2NH, NHMe, etc.) resulting from nuclear amination. When I was treated with secondary amines, the corresponding 3- or 6-amino derivatives were obtained.3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3Category: pyridazine) 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.Category: pyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

In 1998,Molecules [Electronic Publication] included an article by Fulep, Gunther; Haider, Norbert. Synthetic Route of C5H2ClN3. The article was titled 《Synthesis and intramolecular [4+2] cycloaddition reactions of 4-pyridazinecarbonitriles with alkyne side chains》. The information in the text is summarized as follows:

Title compounds I (X = O, R = H, Me; X = NH, R = H) were prepared I underwent thermally induced intramol. Diels-Alder reactions with inverse electron demand, affording fused benzonitriles (II). Incorporation of a 1,2-phenylene unit into the side chain, as in III (X = O, NAc), resulted in a more favorable conformation of the dienophilic substructure and thus in a pronounced acceleration of the [4+2] cycloaddition reaction. In the experiment, the researchers used 3-Chloropyridazine-4-carbonitrile(cas: 1445-56-3Synthetic Route of C5H2ClN3)

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.Synthetic Route of C5H2ClN3

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem