Category: 20744-39-2

Woodring, Jennifer L.; Lu, Shao-Hung; Krasnova, Larissa; Wang, Shih-Chi; Chen, Jhih-Bin; Chou, Chiu-Chun; Huang, Yi-Chou; Cheng, Ting-Jen Rachel; Wu, Ying-Ta; Chen, Yu-Hou; Fang, Jim-Min; Tsai, Ming-Daw; Wong, Chi-Huey published the artcile< Disrupting the Conserved Salt Bridge in the Trimerization of Influenza A Nucleoprotein>, Computed Properties of 20744-39-2, the main research area is antiviral drug influenza infections neuraminidase inhibitors SAR mol docking.

Antiviral drug resistance in influenza infections has been a major threat to public health. To develop a broad-spectrum inhibitor of influenza to combat the problem of drug resistance, we previously identified the highly conserved E339…R416 salt bridge of the nucleoprotein trimer as a target and compound 1 as an inhibitor disrupting the salt bridge with an EC50 = 2.7μM against influenza A (A/WSN/1933). We have further modified this compound via a structure-based approach and performed antiviral activity screening to identify compounds 29 and 30 with EC50 values of 110 and 120 nM, resp., and without measurable host cell cytotoxicity. Compared to the clin. used neuraminidase inhibitors, these two compounds showed better activity profiles against drug-resistant influenza A strains, as well as influenza B, and improved survival of influenza-infected mice.

Journal of Medicinal Chemistry published new progress about Antiviral 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

Sakai, Taki; Matsumoto, Yotaro; Ishikawa, Minoru; Sugita, Kazuyuki; Hashimoto, Yuichi; Wakai, Nobuhiko; Kitao, Akio; Morishita, Era; Toyoshima, Chikashi; Hayashi, Tomoatsu; Akiyama, Tetsu published the artcile< Design, synthesis and structure-activity relationship studies of novel sirtuin 2 (SIRT2) inhibitors with a benzamide skeleton>, Formula: C4H5N3, the main research area is benzamide derivative preparation SAR sirtuin 2 inhibitor; SIRT2; Sirtuin.

Human sirtuin 2 (SIRT2) is an attractive target mol. for development of drugs to treat neurodegenerative diseases and cancer, because SIRT2 inhibitors have a protective effect against neurodegeneration and an anti-proliferative effect on cancer stem cells. We designed and synthesized a series of benzamide derivatives as SIRT2 inhibitor candidates. Among them, compound (I) showed the most potent SIRT2-inhibitory activity (IC50 = 0.60 μM), with more than 150-fold selectivity over SIRT1 and SIRT3 isoforms (IC50 >100 μM).

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

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Demange, Luc; Abdellah, Fatma Nait; Lozach, Olivier; Ferandin, Yoan; Gresh, Nohad; Meijer, Laurent; Galons, Herve published the artcile< Potent inhibitors of CDK5 derived from roscovitine: Synthesis, biological evaluation and molecular modelling>, Related Products of 20744-39-2, the main research area is isopropyl hydroxyalkylamino arylamino purine preparation roscovitine analog CDK5 inhibitor; structure isopropyl hydroxyalkylamino arylamino purine inhibition CDK5 DYRK1A kinase; mol docking energetics isopropyl hydroxyalkylamino arylamino purine binding CDK5; cell death induction CDK5 inhibiting isopropyl hydroxyalkylamino arylamino purine.

9-Isopropyl-2-(hydroxyalkylamino)-6-(arylamino)purines I [R = 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 4-pyridazinyl; R1 = Cl, (R)-Et(HOCH2)CHNH, (S)-Et(HOCH2)CHNH, (R)-Me2CH(HOCH2)CHNH, (S)-Me2CH(HOCH2)CHNH, (HOCH2)2CH, HOCH2CMe2NH, 5-pyrimidinylamino, 2-pyrazinylamino] were prepared as analogs of the CDK inhibitor roscovitine for potential use as selective inhibitors of cyclin-dependent kinase 5 (CDK5) over CDK2, glycogen synthase kinase-3 (GSK3αβ), and casein kinase 1 (CK1). Regioselective alkylation of 2,6-dichloropurine, regioselective Buchwald-Hartwig amination with arylamines, and reaction with amino alcs. yielded I, with chlorides generated by omission of the reaction with amino alcs., and I (R = R1 = 5-pyrimidinylamino, 2-pyrazinylamino) generated as diamination byproducts from Buchwald-Hartwig amination. I [R = 3-pyridinyl, 4-pyridinyl, 5-pyrimidinyl, 4-pyridazinyl; R1 = (R)-Et(HOCH2)CHNH, (S)-Et(HOCH2)CHNH, (R)-Me2CH(HOCH2)CHNH] inhibited CDK5 with IC50 values ranging from 17 to 50 nM and induced cell death in human neuroblastoma cells with IC50 values ranging from 2 to 9 μM in SH-SY5Y cells. Mol. docking of I [R = 4-pyrimidinyl; R1 = (R)-Et(HOCH2)CHNH] and I [R = 4-pyridazinyl; R1 = (R)-Et(HOCH2)CHNH] into the ATP binding domain of the CDK5 catalytic site highlighted the importance of a hydrogen bond between the arylamino ring nitrogen atoms and residue Lys-89 of CDK5 for enzyme inhibition. The calculated final energy balances for complexation measured for several inhibitors is consistent with the ranking of the IC50 values. I [R = 3-pyridinyl, 5-pyrimidinyl; R1 = (R)-Me2CH(HOCH2)CHNH, (S)-Me2CH(HOCH2)CHNH] inhibited dual specificity, tyrosine phosphorylation regulated kinase 1A (DYRK1A), a kinase involved in Down’s syndrome and Alzheimer’s disease, with IC50 values ranging from 300 to 400 nM.

Bioorganic & Medicinal Chemistry Letters published new progress about Cell death. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Related Products of 20744-39-2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Harcken, Christian; Riether, Doris; Kuzmich, Daniel; Liu, Pingrong; Betageri, Raj; Ralph, Mark; Emmanuel, Michel; Reeves, Jonathan T.; Berry, Angela; Souza, Donald; Nelson, Richard M.; Kukulka, Alison; Fadra, Tazmeen N.; Zuvela-Jelaska, Ljiljana; Dinallo, Roger; Bentzien, Jorg; Nabozny, Gerald H.; Thomson, David S. published the artcile< Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects>, Application In Synthesis of 20744-39-2, the main research area is nonsteroidal glucocorticoid receptor agonist antiinflammatory reduced bone side effect.

Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain “”diazaindole”” moieties and display different transcriptional regulatory profiles in vitro and are considered “”dissociated”” between gene transrepression and transactivation. The lead optimization effort described in this article focused in particular on limiting the transactivation of genes which result in bone side effects and these were assessed in vitro in MG-63 osteosarcoma cells, leading to the identification of the R enantiomers of I and II. These compounds maintained anti-inflammatory activity in vivo in collagen induced arthritis studies in mouse but had reduced effects on bone relevant parameters compared to the widely used synthetic glucocorticoid prednisolone in vivo. To our knowledge, we are the first to report on selective glucocorticoid ligands with reduced bone loss in a preclin. in vivo model.

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Application In Synthesis of 20744-39-2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Itai, Takanobu; Kamiya, Shozo published the artcile< Potential anticancer agents. XI. Synthesis of 4- and 5-azidopyridazine 1-oxide>, Product Details of C4H5N3, the main research area is .

The reaction of NaOMe with 3,4,5-trichloropyridazine (I) was studied. 4-Azidopyridazine 1-oxide (II) and 5-azidopyridazine 1-oxide (III) were synthesized from the corresponding hydrazino compounds 4-hydrazinopyridazine 1-oxide (IV) and 5-hydrazinopyridazine 1-oxide (V) with HNO2; II was also derived from 4-chloropyridazine 1-oxide (VI). I (4.88 g.) kept 1 hr. at 0-5° with 0.61 g. Na in 50 ml. MeOH, then 3 hrs. at room temperature, refluxed 1 hr., the filtrate evaporated, and the product crystallized gave 1.6 g. 5-methoxy-3,4-dichloropyridazine (VII), m. 101-2°. VII (1 g.) in 20 ml. MeOH treated with H and Pd-C gave quant. 4-methoxypyridazine, m. 143-4°. VII (1.4 g.) refluxed 3 hrs. with 0.18 g. Na in 20 ml. MeOH gave 0.57 g. 4-chloro-3,5-dimethoxypyridazine (VIII), m. 161-2°. The mother liquors afforded 0.36 g. 3-chloro-4,5-dimethoxypyridazine (IX), m. 91-2°. VIII was dehalogenated by catalytic hydrogenation in the presence of concentrated NH4OH to give 74% 3,5-dimethoxypyridazine, m. 73-5°. Similarly, IX gave 4,5-dimethoxypyridazine, m. 98-100°; picrate m. 165°. I (5.22 g.) similarly treated with 2 equimolar amounts of MeONa gave 25% VIII and 41% IX. VI (1.042 g.) heated 2 hrs. with 0.19 g. Na in 40 ml. MeOH gave 0.97 g. 4-methoxypyridazine 1-oxide (X), m. 124-5°. X (0.97 g.), 5 ml. 80% N2H4.H2O, and 5 ml. alc. refluxed 3 hrs. gave 0.42 g. IV, m. 192-3° (decomposition); benzylidene derivative m. 252° (decomposition); isopropylidene derivative m. 218°; cyclohexylidene derivative m. 196-9°. IV (0.1 g.) in 5 ml. 5% HCl treated dropwise with 55 mg. NaNO2 in 2 ml. H2O, kept 20 min., and basified gave 52 mg. II, m. 123° (decomposition). VI (0.6 g.), 0.6 g. NaN3, 2 ml. H2O, and 8 ml. alc. heated 5 hrs. in a sealed tube gave 51% II. The aqueous layer afforded 4% 4-aminopyridazine 1-oxide. II (0.25 g.) in 10 ml. CHCl3, refluxed 2 hrs. with 0.7 g. PCl3, evaporated, the residue left with 5 ml. ice-H2O, basified, and extracted with CHCl3 gave 0.16 g. 4-azidopyridazine (XI), m. 62-4°. XI (30 mg.) in 5 ml. MeOH shaken 5 min. with Pd-C and H gave 4-aminopyridazine, m. 129-30°. IV (0.2 g.), 0.24 g. acetylacetone, and 30 ml. alc. refluxed 3 hrs. gave 0.23 g. 4-(3,5-dimethyl-1-pyrazolyl)pyridazine 1-oxide (XIa), m. 155-6°. 5-Methoxypyridazine 1-oxide (0.55 g.), 5 ml. alc., and 2.5 ml. 80% N2H4.H2O refluxed 1 hr. gave 0.3 g. V, m. 188° (decomposition); benzylidene derivative m. 280° (decomposition). V (0.2 g.) in 5 ml. 5% HCl treated 20 min. with 0.12 g. NaNO2 in H2O gave 0.16 g. III, m. 100-2° (decomposition). 3-Azidopyridine (3.1 g.), 40 ml. AcOH, and 7 ml. 30% H2O2 heated 3 hrs. at 75°, then 3 hrs. with 4 ml. more 30% H2O2, and the product separated gave 2.25 g. 3-azidopyridine 1-oxide (XII) m. 99-103°. XII refluxed 2 hrs. with Na in MeOH gave 90% starting material. II (0.1 g.) refluxed 1 hr. with 17 mg. Na in 10 ml. MeOH, evaporated, the residue extracted with hot CHCl3, evaporated, and crystallized gave 74% X. II similarly treated with PhCH2ONa gave 71% 4-benzyloxypyridazine 1-oxide, m. 140-1°. III (0.12 g.) heated 1 hr. with Na in anhydrous PhCH2OH gave 51% 5-benzyloxypyridazine 1-oxide, m. 100-2°. Similar treatment of XIa with MeONa gave 63% 5-methoxypyridazine 1-oxide, m. 106-9°.

Chemical & Pharmaceutical Bulletin published new progress about Neoplasm. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Product Details of C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Haider, N.; Holzer, W. published the artcile< Product class 8: pyridazines>, Product Details of C4H5N3, the main research area is review pyridazine preparation cyclization; ring transformation pyridazine preparation review; aromatization pyridazine preparation review.

A review. Methods of preparing pyridazines are reviewed including cyclization, ring transformation, aromatization, and substituent modification.

Science of Synthesis published new progress about Aromatization. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Product Details of C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Harcken, Christian; Riether, Doris; Kuzmich, Daniel; Liu, Pingrong; Betageri, Raj; Ralph, Mark; Emmanuel, Michel; Reeves, Jonathan T.; Berry, Angela; Souza, Donald; Nelson, Richard M.; Kukulka, Alison; Fadra, Tazmeen N.; Zuvela-Jelaska, Ljiljana; Dinallo, Roger; Bentzien, Jorg; Nabozny, Gerald H.; Thomson, David S. published the artcile< Identification of Highly Efficacious Glucocorticoid Receptor Agonists with a Potential for Reduced Clinical Bone Side Effects>, Formula: C4H5N3, the main research area is nonsteroidal glucocorticoid receptor agonist antiinflammatory reduced bone side effect.

Synthesis and structure-activity relationship (SAR) of a series of nonsteroidal glucocorticoid receptor (GR) agonists are described. These compounds contain “”diazaindole”” moieties and display different transcriptional regulatory profiles in vitro and are considered “”dissociated”” between gene transrepression and transactivation. The lead optimization effort described in this article focused in particular on limiting the transactivation of genes which result in bone side effects and these were assessed in vitro in MG-63 osteosarcoma cells, leading to the identification of the R enantiomers of I and II. These compounds maintained anti-inflammatory activity in vivo in collagen induced arthritis studies in mouse but had reduced effects on bone relevant parameters compared to the widely used synthetic glucocorticoid prednisolone in vivo. To our knowledge, we are the first to report on selective glucocorticoid ligands with reduced bone loss in a preclin. in vivo model.

Journal of Medicinal Chemistrypublished new progress about Anti-inflammatory agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Formula: C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Liu, Bin; Xu, Xiaona; Tong, Hongjuan; Zhu, Zhoujing; Tang, Wenqiang; Tang, Chu published the artcile< Synthesis and Antiproliferative Evaluation of Novel 5-Substituted Pyridazin-4-Amine Derivatives>, Quality Control of 20744-39-2, the main research area is aminopyridazine preparation antitumor SAR.

A series of 5-substituted pyridazin-4-amine derivatives were synthesized, characterized and evaluated for antitumor activities. The target compounds exhibited moderate to high anti-proliferative activities depending on the type of substituents of the pyridazine skeleton. Preliminary data on their biol. activity against several cancer cell lines of A549, PC3, MCF-7 and HeLa cells was further reported. Specifically, introduction of bulky aromatic substituents onto the pyridazine skeleton have potential benefit against liver cancer cells.

Organic Preparations and Procedures Internationalpublished new progress about Antitumor agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Quality Control of 20744-39-2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Burton, Rebecca J.; Crowther, Mandy L.; Fazakerley, Neal J.; Fillery, Shaun M.; Hayter, Barry M.; Kettle, Jason G.; McMillan, Caroline A.; Perkins, Paula; Robins, Peter; Smith, Peter M.; Williams, Emma J.; Wrigley, Gail L. published the artcile< Highly regioselective Buchwald-Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries>, Reference of 20744-39-2, the main research area is Buchwald Hartwig amination dichloropyridine bisanilinopyridine library.

The highly regioselective Buchwald-Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodol. is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald-Hartwig amination at higher temperature to enable rapid exploration of the chem. space at C-4 and to provide a library of 2,4-bisaminopyridines.

Tetrahedron Letterspublished new progress about Buchwald-Hartwig reaction. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Reference of 20744-39-2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Tear, Westley F.; Bag, Seema; Diaz-Gonzalez, Rosario; Ceballos-Perez, Gloria; Rojas-Barros, Domingo I.; Cordon-Obras, Carlos; Perez-Moreno, Guiomar; Garcia-Hernandez, Raquel; Martinez-Martinez, Maria Santos; Ruiz-Perez, Luis Miguel; Gamarro, Francisco; Gonzalez Pacanowska, Dolores; Caffrey, Conor R.; Ferrins, Lori; Manzano, Pilar; Navarro, Miguel; Pollastri, Michael P. published the artcile< Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis>, Product Details of C4H5N3, the main research area is human african trypanosomiasis Trypanosoma brucei antiparasitic activity trypanosome infection.

From a high-throughput screen of 42 444 known human kinases inhibitors, a pyrazolo[1,5-b]pyridazine scaffold was identified to begin optimization for the treatment of human African trypanosomiasis. Previously reported data for analogous compounds against human kinases GSK-3β, CDK-2, and CDK-4 were leveraged to try to improve the selectivity of the series, resulting in 23a which showed selectivity for T. b. brucei over these three human enzymes. In parallel, properties known to influence the absorption, distribution, metabolism, and excretion (ADME) profile of the series were optimized resulting in 20g being progressed into an efficacy study in mice. Though 20g showed toxicity in mice, it also demonstrated CNS penetration in a PK study and significant reduction of parasitemia in four out of the six mice.

Journal of Medicinal Chemistrypublished new progress about Central nervous system (CNS penetration). 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Product Details of C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem