Tag: M.W:0-100

Mason, S. F. published the artcile< The electronic spectra of N-heteroaromatic systems. VI. The π → π transitions of monocyclic amino- and mercaptoazines>, Category: pyridazine, the main research area is .

Ultraviolet absorption spectra are reported for 2-(I), 3-, and 4-aminopyridine (II), 2-(III), 4-(IV), and 5-aminopyrimidine, 4-aminopyridazine, 2-aminopyrazine, and 3-amino-6-methylpyridazone (V), in approx. neutral solution (pH about 7-9.5) and in acid (pH 1), and the 1-methochlorides of I, II, III, and IV, and the 2-methochloride of V, at pH 12-14. Most of the neutral spectra are repeated in EtOH and cyclohexane, and spectra of 1-methyl-2-, and -4-pyridone imine, 1-methyl-2-, and -4-pyrimidone imine and 2,6-dimethyl-3-pyridazone imine are reported in H2O and cyclohexane. Spectra are also reported for 2-, 3-, and 4-methylthiopyridine and for 4-methyl-2-methylthio-, 2-mercapto-4-methyl-, 6-methyl-4-methylthio-, and 4-mercapto-6-methylthiopyrimidine in neutral, acidic, and basic solution The spectra are discussed in relation to a benzyl anion model (loc. cit.) and a substituted benzene charge transfer model (Murrell, C.A. 53, 6749b). The latter model is more consistent with the exptl. data.

Journal of the Chemical Society published new progress about Azines. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Category: pyridazine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Devine, William; Thomas, Sarah M.; Erath, Jessey; Bachovchin, Kelly A.; Lee, Patricia J.; Leed, Susan E.; Rodriguez, Ana; Sciotti, Richard J.; Mensa-Wilmot, Kojo; Pollastri, Michael P. published the artcile< Antiparasitic Lead Discovery: Toward Optimization of a Chemotype with Activity Against Multiple Protozoan Parasites>, Application of C4H5N3, the main research area is trypanosomicide leishmanicide antimalarial development NEU1045 analog preparation pharmacokinetics; Antiparasitic agents; Chagas disease; Leishmania major; Plasmodium falciparum; Trypanosoma brucei; Trypanosoma cruzi; human African trypanosomiasis; leishmaniasis.

Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis present a significant burden across the developing world. Existing therapeutics for these protozoal neglected tropical diseases suffer from severe side effects and toxicity. Previously, NEU-1045 was identified as a promising lead with cross-pathogen activity, though it possessed poor physicochem. properties. The authors have designed a library of analogs with improved calculated physicochem. properties built on the quinoline scaffold of 3 incorporating small, polar aminoheterocycles in place of the 4-(3-fluorobenzyloxy)aniline substituent. The authors report the biol. activity of these inhibitors against Trypanosoma brucei (HAT), T. cruzi (Chagas disease), and Leishmania major (cutaneous leishmaniasis), and describe the identification of N-(5-chloropyrimidin-2-yl)-6-(4-(morpholinosulfonyl)phenyl)quinolin-4-amine (13t) as a promising inhibitor of L. major proliferation and 6-(4-(morpholinosulfonyl)phenyl)-N-(pyrimidin-4-yl)quinolin-4-amine (13j), a potent inhibitor of T. brucei proliferation with improved drug-like properties.

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

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Tsujimoto, Toshio; Nomura, Toshiro; Iifuru, Makiko; Sasaki, Yoshio published the artcile< Studies on carbon-13 magnetic resonance spectroscopy. XIII. Carbon-13 and proton NMR of 4-substituted pyridazine and 2-substituted pyrazine derivatives>, Product Details of C4H5N3, the main research area is NMR carbon pyridazine pyrazine derivative; substituent constant pyridazine pyrazine derivative.

13C NMR chem. shifts of 4-substituted pyridazines and 2-substituted pyrazines, together with 1H chem. shifts of the former compounds were measured. Linear correlations of the 13C and 1H chem. shifts of 4-substituted pyridazines with those of monosubstituted benzenes and monosubstituted pyridines and with substituent constants σπ were found. In addition, similar trends were noted for 2-substituted pyrazines. Chem. shifts of pyridazines and pyrazines can be predicted on the basis of these relationships.

Chemical & Pharmaceutical Bulletin published new progress about NMR (nuclear magnetic resonance). 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Product Details of C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Kwiatkowski, J. S. published the artcile< Electronic structure and spectra of organic molecules. XVI. Amine-imine tautomerism in azines substituted by amino groups>, COA of Formula: C4H5N3, the main research area is tautomerism aminoazine electronic structure; azine tautomerism electronic structure; iminoazine electronic transition energy; pyridine tautomerism electronic structure; diazine tautomerism electronic structure.

For both amine and imine tautomers of amine-substituted pyridines and diazines, Pariser-Parr-Pople type calculations (K., 1970) gave singlet-singlet transition energies which agreed with exptl. data. In all cases, the singlet-singlet transitions of the imine forms red shifted relative to the corresponding transitions of the amine forms.

Acta Physica Polonica, A published new progress about Tautomers. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, COA of Formula: C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

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>, Synthetic Route 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, Synthetic Route 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>, SDS of cas: 20744-39-2, 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, SDS of cas: 20744-39-2.

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>, Formula: C4H5N3, 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, Formula: 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>, Safety of Pyridazin-4-amine, 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, Safety of Pyridazin-4-amine.

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>, Application 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, Application of C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Haider, N.; Holzer, W. published the artcile< Product class 8: pyridazines>, Safety of Pyridazin-4-amine, 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, Safety of Pyridazin-4-amine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem