Category: pyridazine

Tsujimoto, Toshio; Kobayashi, Chizuko; Nomura, Toshiro; Iifuru, Makiko; Sasaki, Yoshio published the artcile< Studies on carbon-13 magnetic resonance spectroscopy. XV. Correlation between carbon-13 NMR chemical shifts and charge densities of diaza-benzenes>, Application In Synthesis of 20744-39-2, the main research area is LFER diazabenzene carbon NMR; MO electron density pyrazine; substituent effect carbon NMR; pyrimidine carbon NMR MO; pyridazine carbon NMR MO.

Charge d. of 2-substituted pyrazines, 5-substituted pyrimidines, or 4-substituted pyridazines were calculated by MINDO/2. The correlations of the substituent-induced 13C chem. shifts (13C SCS) values of these compounds with total charge d. were determined, and LFER between the 2 parameters were found even at the ipso position; the correlations of the ipso SCS with a linear combination of substituent constants were poor.

Chemical & Pharmaceutical Bulletin published new progress about Bond order. 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

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< Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation>, Safety of Pyridazin-4-amine, the main research area is anilinoquinazoline trypanosome inhibitor antimalarial malaria trypanosomiasis trypanosomicide; Human African trypanosomiasis; Leishmania major; Neglected tropical disease; Plasmodium falciparum; Target class repurposing; Trypanosoma brucei; Trypanosoma cruzi.

Human African trypanosomiasis (HAT) is a deadly disease in need of new chemotherapeutics that can cross into the central nervous system. The authors previously reported the discovery of (NEU-617), a small mol. with activity against T. brucei bloodstream proliferation. Further optimization of NEU-617 to improve the physicochem. properties (LogP, LLE, [1], and MPO score) [2] have led us to twelve sub-micromolar compounds, most importantly the headgroup variants I and II, and the linker variant III. Although these 3 compounds had reduced potency compared to NEU-617, they all had improved LogP, LLE and MPO scores. Cross-screening these analogs against other protozoan parasites uncovered IV with potent activity towards T. brucei, T. cruzi and L. major, while four others compounds showed activity towards P. falciparum D6. This reinforces the effectiveness of lead repurposing for the discovery of new protozoan disease therapeutics.

European Journal of Medicinal Chemistry published new progress about Antimalarials. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Safety of Pyridazin-4-amine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Nitta, Yoshihiro; Tomii, Reiko; Yoneda, Fumio published the artcile< Pyridazine derivatives. IV. The structures of aminopyridazines>, Computed Properties of 20744-39-2, the main research area is CHEMISTRY, PHARMACEUTICAL; EXPERIMENTAL LAB STUDY; PYRIDAZINES; SPECTRUM ANALYSIS.

The infrared spectra of 3(I) and 4-aminopyridazine (II) and their N-deuterated derivatives (III) were examined with KBr discs and in CHCl3 solution, and compared with those of 2- (IV), 3- (V), and 4-aminopyridine (VI), and PhNH2 (VII). III were prepared by adding excess D2O to I and II, evaporating the excess D2O, and repeating the procedure 4 times. The amino form of I and II was confirmed. The structural similarity of II to VI, and that of I to IV were clearly indicated. Curves were shown in the region 800-3500 cm.-1 for I-III in KBr disc, and in the 3000 cm-.1 and 700-1800 cm. -1 regions for I, II, and IV-VII in 0.016M CHCl3 solution, and the assignment of bands made and discussed. Furthermore, the correlation between the position and the nature of the substituent was discussed. Thus, the structures of I and II involve resonance with the excited states VIII and IX, resp., with a greater contribution from the p-quinoid type IX than from VIII, resulting in slight differences in the nature of the NH2 groups in I and II and, therefore, differences in their infrared absorptions.

Chemical & Pharmaceutical Bulletin published new progress about IR spectra. 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

Terekhova, M. I.; Petrov, E. S.; Mikhaleva, M. A.; Shkurko, O. P.; Mamaev, V. P.; Shatenshtein, A. I. published the artcile< Effects of aza groups on the NH acidity of aminoazines and CH acidity of acetylazines>, Related Products of 20744-39-2, the main research area is acidity aminoazine acetylazine aza effect; solvent effect acidity aminoazine.

The NH and CH acidities (pKNH and pKCH, resp.) of RNH2 (I; R = Ph; 2-, 3-, 4-pyridyl; 3-, 4-pyridazinyl; 2-, 4-, 5-pyrimidinyl; 2-pyrazinyl; s-triazin-2-yl) and RCOMe (II, same R) were analyzed. A N atom in position 2, 3, or 4 relative to the NH2 group of I lowered the pKNH value by 3.1, 2.4, and 4.5, resp.; similarly, the pKCH value of II was lowered by 3.5, 2.9, and 4.8, resp. The effects were additive in most cases. The relation pKNH = 0.89 pKCH + 8.7 was found. The differentiating effect of H2O, compared to Me2SO, on the pKNH values of I was attributed to H bonding with the ring N atoms.

Zhurnal Organicheskoi Khimii published new progress about Acidity. 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

Zhou, Shiyang; Chen, Guangying published the artcile< Design, synthesis, and bioactivity evaluation of antitumor sorafenib analogues>, Quality Control of 20744-39-2, the main research area is lung cervical cancer sorafenib antitumor cell growth.

Malignant tumors are a serious threat to human health and are generally treated with chem. therapy. This chem. therapy uses agents that act on signal transduction pathway mechanism of tumor with good selectivity and low toxicity. Sorafenib is a multikinase target inhibitor with good tumor inhibitory activity and a protein kinase inhibitor. In this research, a novel series of sorafenib analogs and derivatives were designed, synthesized, and evaluated as tumor inhibitors. These compounds used sorafenib as the lead compound and achieved modifications using bioisosteres and the alkyl principle. The in vitro the results showed that compounds 3c, 3d, 3h, 3n, 3r, and 3z had good inhibitory effects on human cervical cancer cells (Hela), while compounds 3t and 3v had good inhibitory effects on human lung cancer cells (H1975 and A549). Among these, compound 3d had an inhibitory activity (IC50) of 0.56 ± 0.04 μmol L-1 against Hela cells (human cervical cancer), the compound 3t had an IC50 of 2.34 ± 0.07 μmol L-1 against H1975 cells (human lung cancer), and compound 3v had an IC50 of 1.35 ± 0.03 μmol L-1 against A549 cells (human lung cancer). The in vivo results showed that these compounds had good antitumor effects and low acute toxicity.

RSC Advances published 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

Venkatesan, Aranapakam M.; Dehnhardt, Christoph M.; Delos Santos, Efren; Chen, Zecheng; Dos Santos, Osvaldo; Ayral-Kaloustian, Semiramis; Khafizova, Gulnaz; Brooijmans, Natasja; Mallon, Robert; Hollander, Irwin; Feldberg, Larry; Lucas, Judy; Yu, Ker; Gibbons, James; Abraham, Robert T.; Chaudhary, Inder; Mansour, Tarek S. published the artcile< Bis(morpholino-1,3,5-triazine) Derivatives: Potent Adenosine 5'-Triphosphate Competitive Phosphatidylinositol-3-kinase/Mammalian Target of Rapamycin Inhibitors: Discovery of Compound 26 (PKI-587), a Highly Efficacious Dual Inhibitor>, Synthetic Route of 20744-39-2, the main research area is PI3K mTOR inhibitor dimorpholinotriazine preparation; triazine dimorpholino preparation PI3K mTOR inhibitor.

The PI3K/Akt signaling pathway is a key pathway in cell proliferation, growth, survival, protein synthesis, and glucose metabolism It has been recognized recently that inhibiting this pathway might provide a viable therapy for cancer. A series of bis(morpholino-1,3,5-triazine) derivatives were prepared and optimized to provide the highly efficacious PI3K/mTOR inhibitor 1-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyl)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea (PKI-587). This compound has shown excellent activity in vitro and in vivo, with antitumor efficacy in both s.c. and orthotopic xenograft tumor models when administered i.v. The structure-activity relationships and the in vitro and in vivo activity of analogs in this series are described.

Journal of Medicinal Chemistry published new progress about Antitumor 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

Abdelaziz, Ahmed M.; Basnet, Sunita K. C.; Islam, Saiful; Li, Manjun; Tadesse, Solomon; Albrecht, Hugo; Gerber, Cobus; Yu, Mingfeng; Wang, Shudong published the artcile< Synthesis and evaluation of 2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione derivatives as Mnk inhibitors>, Electric Literature of 20744-39-2, the main research area is spiro cyclohexane imidazopyridine dione preparation chemoselective antitumor Mnk inhibitor; Anti-cancer; Inhibitor; Mnk; eFT508; eIF4E.

A series of 2’H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione derivatives I (R = pyridin-4-yl, pyrimidin-4-yl, oxazol-2-yl, etc.) is presented as Mnk inhibitors. Some of them showed sub-micromolar to low nanomolar inhibitory activities against Mnk1/2 with a high level of selectivity for both kinases over CDKs. Biochem. assays revealed that compounds I (R = pyridin-4-yl, pyrimidin-4-yl) are non-ATP-competitive inhibitors of Mnks. Lead compound I (R = pyrimidin-4-yl) demonstrated a high selectivity for Mnk1/2 over a selection of 51 kinases, and displayed anti-proliferative activities against a panel of cancer cell lines. However, this compound in combination with our inhouse CDK4/6 inhibitor 83 did not show a synergistic effect in A2780 ovarian cancer cells, suggesting that caution be exercised in the selection of an agent to be combined with an Mnk inhibitor.

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

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Yu, Jianjun; Xu, Lei; Hong, Duidui; Zhang, Xiaotuan; Liu, Jieyu; Li, Daqiang; Li, Jia; Zhou, Yubo; Liu, Tao published the artcile< Design, synthesis, and biological evaluation of novel phenol ether derivatives as non-covalent proteasome inhibitors>, Related Products of 20744-39-2, the main research area is phenol ether preparation proteasome inhibitor antitumor SAR mol docking; Non-covalent; Non-peptide; Phenol ether; Proteasome inhibitor; Solid cancers.

A series of novel phenol ether derivatives I (n = 1, 2; R1 = Me, methoxy, n-Pr, etc.; R2 = 4-FC6H4, 2-naphthyl, 3-pyridinyl, etc.) were designed, synthesized, and evaluated as non-covalent proteasome inhibitors. Most compounds exhibited moderate to excellent proteasome inhibitory activity. In particular, compound I (n = 1; R1 = n-Bu; R2 = pyridazine-4-yl) proved to be the most potent compound (chymotrypsin-like: IC50 = 49 nM), exhibiting a 2-fold higher potency compared to the reported PI-1840. Besides, compound I (n = 1; R1 = n-Bu; R2 = pyridazine-4-yl) exhibited excellent metabolic stability and selective anti-proliferative activity against solid cancer cell lines including HepG2 and HGC27, providing incentive for the further development as a potential anticancer agent against solid cancers.

European Journal of Medicinal Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 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