Ding, Xiao’s team published research in Bioorganic & Medicinal Chemistry Letters in 2019-01-15 | 20744-39-2

Bioorganic & Medicinal Chemistry Letters published new progress about Central nervous system. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Formula: C4H5N3.

Ding, Xiao; Stasi, Luigi Piero; Dai, Xuedong; Long, Kai; Peng, Cheng; Zhao, Baowei; Wang, Hailong; Sun, Changhui; Hu, Huan; Wan, Zehong; Jandu, Karamjit S.; Philps, Oliver J.; Chen, Yan; Wang, Lizhen; Liu, Qian; Edge, Colin; Li, Yi; Dong, Kelly; Guan, Xiaoming; Tattersall, F. David; Reith, Alastair D.; Ren, Feng published the artcile< 5-Substituted-N-pyridazinylbenzamides as potent and selective LRRK2 inhibitors: Improved brain unbound fraction enables efficacy>, Formula: C4H5N3, the main research area is CNS penetration LRRK2 Parkinson’s disease PFI unbound fraction; CNS penetration; LRRK2; PFI; Parkinson’s disease; Unbound fraction.

We describe the discovery and optimization of 5-substituted-N-pyridazinylbenzamide derivatives as potent and selective LRRK2 inhibitors. Extensive SAR studies led to the identification of compounds 18 and 23, which demonstrated good in vitro pharmacokinetic profile and excellent selectivity over 140 other kinases. Both compounds demonstrated high unbound fractions in both blood and brain. Compound 18, 2-(benzyloxy)-5-morpholino-N-(pyridazin-4-yl)benzamide [2305380-32-7], proved to be brain penetrant, and the high unbound fraction of compound 18 in brain enabled its in vivo efficacy in CNS, wherein a significant inhibition of LRRK2 Ser935 phosphorylation was observed in rat brain following i.v. infusion at 5 mg/kg/h.

Bioorganic & Medicinal Chemistry Letters published new progress about Central nervous system. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Formula: C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Ren, Huiyu’s team published research in Journal of Medicinal Chemistry in 2020-12-10 | 20744-39-2

Journal of Medicinal Chemistry published new progress about Antitumor agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Computed Properties of 20744-39-2.

Ren, Huiyu; Bakas, Nicole A.; Vamos, Mitchell; Chaikuad, Apirat; Limpert, Allison S.; Wimer, Carina D.; Brun, Sonja N.; Lambert, Lester J.; Tautz, Lutz; Celeridad, Maria; Sheffler, Douglas J.; Knapp, Stefan; Shaw, Reuben J.; Cosford, Nicholas D. P. published the artcile< Design, Synthesis, and Characterization of an Orally Active Dual-Specific ULK1/2 Autophagy Inhibitor that Synergizes with the PARP Inhibitor Olaparib for the Treatment of Triple-Negative Breast Cancer>, Computed Properties of 20744-39-2, the main research area is pyrimidine synthesis anticancer ULK1 ULK2 PARP breast cancer autophagy.

Inhibition of autophagy, the major cellular recycling pathway in mammalian cells, is a promising strategy for the treatment of triple-neg. breast cancer (TNBC). We previously reported SBI-0206965, a small mol. inhibitor of unc-51-like autophagy activating kinase 1 (ULK1), which is a key regulator of autophagy initiation. Herein, we describe the design, synthesis, and characterization of new dual inhibitors of ULK1 and ULK2 (ULK1/2). One inhibitor, SBP-7455 (compound 26), displayed improved binding affinity for ULK1/2 compared with SBI-0206965, potently inhibited ULK1/2 enzymic activity in vitro and in cells, reduced the viability of TNBC cells and had oral bioavailability in mice. SBP-7455 inhibited starvation-induced autophagic flux in TNBC cells that were dependent on autophagy for survival and displayed synergistic cytotoxicity with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib against TNBC cells. These data suggest that combining ULK1/2 and PARP inhibition may have clin. utility for the treatment of TNBC.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Computed Properties of 20744-39-2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Gumus, Selcuk’s team published research in Turkish Journal of Chemistry in 2011 | 20744-39-2

Turkish Journal of Chemistry published new progress about Aromaticity. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Reference of 20744-39-2.

Gumus, Selcuk published the artcile< A computational study on substituted diazabenzenes>, Reference of 20744-39-2, the main research area is aromaticity diazabenzene substituent effect.

The results of computational calculations on the aromaticity of the monosubstituted diazabenzenes (pyridazine, pyrimidine, and pyrazine) are reported herein. The aromaticity of the parent heterocycle was enhanced by substitution of strong electron-withdrawing groups. The effects of the position of the substituent on the aromaticity and the stability of the system were also studied by studying all possible derivatives of the systems.

Turkish Journal of Chemistry published new progress about Aromaticity. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Reference of 20744-39-2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

D’Ascenzio, Melissa’s team published research in Angewandte Chemie, International Edition in 2019 | CAS: 53085-52-2

6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine(cas: 53085-52-2) belongs to anime. Large quantities of aliphatic amines are made synthetically. The most widely used industrial method is the reaction of alcohols with ammonia at a high temperature, catalyzed by metals or metal oxide catalysts (e.g., nickel or copper). Mixtures of primary, secondary, and tertiary amines are thereby produced.Product Details of 53085-52-2

《An Activity-Based Probe Targeting Non-Catalytic, Highly Conserved Amino Acid Residues within Bromodomains》 was published in Angewandte Chemie, International Edition in 2019. These research results belong to D’Ascenzio, Melissa; Pugh, Kathryn M.; Konietzny, Rebecca; Berridge, Georgina; Tallant, Cynthia; Hashem, Shaima; Monteiro, Octovia; Thomas, Jason R.; Schirle, Markus; Knapp, Stefan; Marsden, Brian; Fedorov, Oleg; Bountra, Chas; Kessler, Benedikt M.; Brennan, Paul E.. Product Details of 53085-52-2 The article mentions the following:

Bromodomain-containing proteins are epigenetic modulators involved in a wide range of cellular processes, from recruitment of transcription factors to pathol. disruption of gene regulation and cancer development. Since the druggability of these acetyl-lysine reader domains was established, efforts were made to develop potent and selective inhibitors across the entire family. Here we report the development of a small mol.-based approach to covalently modify recombinant and endogenous bromodomain-containing proteins by targeting a conserved lysine and a tyrosine residue in the variable ZA or BC loops. Moreover, the addition of a reporter tag allowed in-gel visualization and pull-down of the desired bromodomains. 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: 53085-52-2Product Details of 53085-52-2)

6-Chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-amine(cas: 53085-52-2) belongs to anime. Large quantities of aliphatic amines are made synthetically. The most widely used industrial method is the reaction of alcohols with ammonia at a high temperature, catalyzed by metals or metal oxide catalysts (e.g., nickel or copper). Mixtures of primary, secondary, and tertiary amines are thereby produced.Product Details of 53085-52-2

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Yamagami, Chisako’s team published research in Quantitative Structure-Activity Relationships in 1990 | CAS: 62567-44-6

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.Quality Control of 3-Ethoxypyridazine

Yamagami, Chisako; Takao, Narao; Fujita, Toshio published their research in Quantitative Structure-Activity Relationships on December 31 ,1990. The article was titled 《Hydrophobicity parameter of diazines. 1. Analysis and prediction of partition coefficients of monosubstituted diazines》.Quality Control of 3-Ethoxypyridazine The article contains the following contents:

The octanol/water partition coefficient (P) of a number of monosubstituted diazines was measured. The composition of the π value of substituents, the increment in the log P value accompanying the introduction of substituents, was examined in terms of physicochem. substituent parameters and correlation anal. The diazine-π value of substituents was generally higher than the pyridine-π value of corresponding substituents, indicating that the intramol. electronic interactions between the ring-N atoms and substituent are more pronounced than those in substituted pyridines in governing the log P value of the mol. Except for 2-substituted pyrimidines, the π value of substituents in each series of monosubstituted diazines was in general nicely correlated with the π value of the corresponding substituents in substituted pyridines along with electronic parameter terms representing bidirectional electronic effects on the relative solvation of the ring-N atom(s) and the hydrogen-bondable substituents with partitioning solvents according to the procedure proposed previously for the anal. of the π value in disubstituted benzenes and monosubstituted pyridines. Keeping in mind that 2-pyrimidines substituted by hydrogen-bondable groups sometimes behave as outliers, the correlations were believed to be usable for prediction of log P values of monosubstituted diazines. In the experiment, the researchers used many compounds, for example, 3-Ethoxypyridazine(cas: 62567-44-6Quality Control of 3-Ethoxypyridazine)

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.Quality Control of 3-Ethoxypyridazine

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Issac, Yvette A.’s team published research in Zeitschrift fuer Naturforschung, B: Chemical Sciences in 1999 | CAS: 40020-05-1

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, vasodilator, antiarrhythmic, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, neuroleptic, sedative-hypnotic, anticonvulsant, immunosuppressant, cardiotonic, and hypocholesterolaemic. Recommanded Product: 40020-05-1

《Synthesis, reactions, and spectroscopy of 3-benzoyl-6-phenylpyridazines of expected biological activity》 was written by Issac, Yvette A.. Recommanded Product: 40020-05-1 And the article was included in Zeitschrift fuer Naturforschung, B: Chemical Sciences on August 31 ,1999. The article conveys some information:

Oxidative decyanation of α,6-diphenyl-3-pyridazineacetonitrile in MeOH yielded 3-benzoyl-6-phenylpyridazine (I). α,6-Diphenyl-3-pyridazinemethanol was obtained via NaBH4 reduction of I. Reaction of I with NH2OH or its O-alkyl derivatives yields 3-benzoyl-6-phenylpyridazine oxime (II) and alkyloximes, resp. Treatment of II with AcOH/H2SO4 afforded I again and not the rearranged products. Beckmann rearrangement was achieved for II and the corresponding ethyloxime giving solely 3-carboxanilide-6-phenylpyridazine. 4-Benzoyl-3-phenyl-6-chloropyridazine oxime was synthesized from the corresponding ketone. The results came from multiple reactions, including the reaction of 4,6-Dichloro-3-phenylpyridazine(cas: 40020-05-1Recommanded Product: 40020-05-1)

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, vasodilator, antiarrhythmic, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, neuroleptic, sedative-hypnotic, anticonvulsant, immunosuppressant, cardiotonic, and hypocholesterolaemic. Recommanded Product: 40020-05-1

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Itoh, Takashi’s team published research in Journal of the Chemical Society, Chemical Communications in 1995 | CAS: 62567-44-6

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.SDS of cas: 62567-44-6

SDS of cas: 62567-44-6On October 21, 1995 ,《A regiospecific reaction of pyridazines with vicarious nucleophilic substitution via their dicyanomethylide derivatives》 was published in Journal of the Chemical Society, Chemical Communications. The article was written by Itoh, Takashi; Matsuya, Yuji; Nagata, Kazuhiro; Okada, Mamiko; Ohsawa, Akio. The article contains the following contents:

The phenyl(or p-tolyl)sulfonylmethyl group is introduced with complete regiospecificity to the C-4 position of 3-substituted pyridazines using vicarious nucleophilic substitution of pyridazinium dicyanomethylides. In the experiment, the researchers used many compounds, for example, 3-Ethoxypyridazine(cas: 62567-44-6SDS of cas: 62567-44-6)

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.SDS of cas: 62567-44-6

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Itoh, Takashi’s team published research in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry in 1998 | CAS: 62567-44-6

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.Recommanded Product: 62567-44-6

Recommanded Product: 62567-44-6On May 21, 1998 ,《Vicarious nucleophilic substitution of pyridazinium N-dicyanomethylides》 appeared in Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry. The author of the article were Itoh, Takashi; Matsuya, Yuji; Nagata, Kazuhiro; Miyazaki, Michiko; Tsutsumi, Nozomi; Ohsawa, Akio. The article conveys some information:

Pyridazines have been allowed to react with tetracyanoethylene oxide to give pyridazinium N-dicyanomethylides, which are subjected to vicarious nucleophilic substitution to afford the corresponding 4-substituted derivatives in moderate to good yields. The dicyanomethylene group is readily eliminated by a radical reaction, and 4-substituted pyridazines are obtained. The results came from multiple reactions, including the reaction of 3-Ethoxypyridazine(cas: 62567-44-6Recommanded Product: 62567-44-6)

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.Recommanded Product: 62567-44-6

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Leivers, Martin’s team published research in Journal of Medicinal Chemistry in 2014-03-13 | 120276-59-7

Journal of Medicinal Chemistry published new progress about Antiviral agents. 120276-59-7 belongs to class pyridazine, and the molecular formula is C5H4Cl2N2, Safety of 3-Chloro-6-(chloromethyl)pyridazine.

Leivers, Martin; Miller, John F.; Chan, Stephanie A.; Lauchli, Ryan; Liehr, Sebastian; Mo, Wenyan; Ton, Tony; Turner, Elizabeth M.; Youngman, Michael; Falls, J. Greg; Long, Susan; Mathis, Amanda; Walker, Jill published the artcile< Imidazopyridazine Hepatitis C Virus Polymerase Inhibitors. Structure-Activity Relationship Studies and the Discovery of a Novel, Traceless Prodrug Mechanism>, Safety of 3-Chloro-6-(chloromethyl)pyridazine, the main research area is imidazopyridazine hepatitis C antiviral polymerase structure activity preparation.

By reducing the basicity of the core heterocycle in a series of HCV NS5B inhibitors, the hERG liability was reduced. The SAR was then systematically explored to increase solubility and enable dose escalation while retaining potency. During this exploration, a facile decarboxylation was noted and was exploited as a novel prodrug mechanism. The synthesis and characterization of these prodrugs and their utilization in chronic toxicity studies are presented.

Journal of Medicinal Chemistry published new progress about Antiviral agents. 120276-59-7 belongs to class pyridazine, and the molecular formula is C5H4Cl2N2, Safety of 3-Chloro-6-(chloromethyl)pyridazine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

 

Woodring, Jennifer L’s team published research in European Journal of Medicinal Chemistry in 2018-05-25 | 20744-39-2

European Journal of Medicinal Chemistry published new progress about Antimalarials. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Reference of 20744-39-2.

Woodring, Jennifer L.; Bachovchin, Kelly A.; Brady, Kimberly G.; Gallerstein, Mitchell F.; Erath, Jessey; Tanghe, Scott; Leed, Susan E.; Rodriguez, Ana; Mensa-Wilmot, Kojo; Sciotti, Richard J.; Pollastri, Michael P. published the artcile< Corrigendum to ""Optimization of physicochemical properties for 4-Anilinoquinazoline inhibitors of trypanosome proliferation"" [Eur. J. Med. Chem. 141 (2017) 446-459] [Erratum to document cited in CA167:595582]>, Reference of 20744-39-2, the main research area is anilinoquinazoline trypanosome inhibitor antimalarial malaria trypanosomiasis trypanosomicide erratum.

In the original publication, the acknowledgments section has information omitted; the correction is provided here.

European Journal of Medicinal Chemistry published new progress about Antimalarials. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Reference of 20744-39-2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem