Category: 20744-39-2

Venkatesan, Aranapakam M.; Chen, Zecheng; Dos Santos, Osvaldo; Dehnhardt, Christoph; Santos, Efren Delos; Ayral-Kaloustian, Semiramis; Mallon, Robert; Hollander, Irwin; Feldberg, Larry; Lucas, Judy; Yu, Ker; Chaudhary, Inder; Mansour, Tarek S. published the artcile< PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor>, Electric Literature of 20744-39-2, the main research area is substituted triazine derivative preparation PI3K mTOR inhibitor.

A series of mono-morpholino 1,3,5-triazine derivatives bearing a 3-oxa-8-azabicyclo[3.2.1]octane were prepared and evaluated for PI3-kinase/mTOR activity. Replacing one of the bis-morpholines in lead compound I (PKI-587) with 3-oxa-8-azabicyclo[3.2.1]octane and reducing the mol. weight led to compound II (PKI-179), an orally efficacious dual PI3-kinase/mTOR inhibitor. The in vitro activity, in vivo efficacy, and PK properties of II are discussed.

Bioorganic & Medicinal Chemistry Letters published new progress about Enzyme inhibitors. 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

Yuan, Xinrui; Wu, Hanshu; Bu, Hong; Zheng, Peiyuan; Zhou, Jinpei; Zhang, Huibin published the artcile< Design, synthesis and biological evaluation of pyridone-aminal derivatives as MNK1/2 inhibitors>, Recommanded Product: Pyridazin-4-amine, the main research area is pyridone aminal derivative preparation MNK1 MNK2 inhibitor colon cancer; MNK1/2; Pyridone–aminal; eFT508; eIF4E.

Excessive phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) plays a major role in the dysregulation of mRNA translation and the activation of tumor cell signaling. eIF4E is exclusively phosphorylated by mitogen-activated protein kinase interacting kinases 1 and 2 (MNK1/2) on Ser209. So, MNK1/2 inhibitors could decrease the level of p-eIF4E and regulate tumor-associated signaling pathways. A series of pyridone-aminal derivatives were synthesized and evaluated as MNK1/2 inhibitors. Several compounds exhibited great inhibitory activity against MNK1/2 and selected compounds showed moderate to excellent anti-proliferative potency against hematol. cancer cell lines. In particular, compound 42i (MNK1 IC50 = 7.0 nM; MNK2 IC50 = 6.1 nM) proved to be the most potent compound against TMD-8 cell line with IC50 value of 0.91 μM. Furthermore, 42i could block the phosphorylation level of eIF4E in CT-26 cell line, and 42i inhibited the tumor growth of CT-26 allograft model significantly. These results indicated that compound 42i was a promising MNK1/2 inhibitor for the potent treatment of colon cancer.

Bioorganic & Medicinal Chemistry published new progress about Antiproliferative agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Recommanded Product: Pyridazin-4-amine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Tolmachova, Kateryna A.; Moroz, Yurii S.; Konovets, Angelika; Platonov, Maxim O.; Vasylchenko, Oleksandr V.; Borysko, Petro; Zozulya, Sergey; Gryniukova, Anastasia; Bogolubsky, Andrey V.; Pipko, Sergey; Mykhailiuk, Pavel K.; Brovarets, Volodymyr S.; Grygorenko, Oleksandr O. published the artcile< (Chlorosulfonyl)benzenesulfonyl Fluorides-Versatile Building Blocks for Combinatorial Chemistry: Design, Synthesis and Evaluation of a Covalent Inhibitor Library>, Product Details of C4H5N3, the main research area is chlorosulfonylbenzenesulfonyl fluoride preparation building block combinatorial chem; parallel synthesis trypsin inhibitor library preparation bioactivity evaluation; chemoselectivity; covalent fragments; parallel synthesis; serine protease inhibitors; sulfonamides; sulfonyl halides.

Multigram synthesis of (chlorosulfonyl)benzenesulfonyl fluorides is described. Selective modification of these building blocks at the sulfonyl chloride function under parallel synthesis conditions is achieved. It is shown that the reaction scope includes the use of (hetero)aromatic and electron-poor aliphatic amines (e.g., amino nitriles). Utility of the method is demonstrated by preparation of the sulfonyl fluoride library for potential use as covalent fragments, which is demonstrated by a combination of in silico and in vitro screening against trypsin as a model enzyme. As a result, several inhibitors were identified with activity on par with that of the known inhibitor.

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

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>, Application of C4H5N3, 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 Letters published new progress about Buchwald-Hartwig reaction. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Application of C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Plate, A. F.; Belikova, N. A.; Egorov, Yu. P. published the artcile< Reaction of five- and six-membered silicohydrocarbons with an atom of silicon in the ring with concentrated sulfuric acid>, SDS of cas: 20744-39-2, the main research area is .

Concentrated H2SO4 caused a rupture of the C-Si bond in cyclic 5-6 membered silanes; the 5-membered ring was somewhat more stable. The method of West (C.A. 49, 14767b) gave 26.6% Si[(CH2)4]2, b750 173-4°, nD20 1.4863, d20 0.9043, m. -52°. This (4.3 g.) shaken 6 hrs. at room temperature with 11.7 g. concentrated H2SO4 gave 4 g. [Bu(CH2)4Si]2O, 90%, b751 293.5-94°, nD20 1.4670, d20 0.9125. Similarly [Et(CH2)4Si]2O in 10 hrs. gave 60% sym-tetraethyltetrabutylcyclotetrasiloxane, b10 194-6°, nD20 1.4422, d20 0.9286. To the Grignard reagent from 37 g. Mg and 161 g. (CH2)5Br2 was added at once at 5° 90 g. Me2SiCl2 in 1 l. Et2O and, after refluxing 15 hrs. and treatment with H2O, there was obtained after distillation and chromatographic purification on silica, 26.7% Me2Si(CH2)5, b740 131.2-1.3°, nD20 1.4428, d20 0.8111, Raman spectrum (cm.-1) 105(15), 146(30), 203(70), 238(18), 253(15), 334(25), 371(10), 482(10), 585(200), 632(5), 663(2), 694(15), 724(15), 741(5), 794(40), 833(3), 908(30), 950(3), 990(8), 1006(40), 1037(2), 1080(12), 1098(10), 1134(15), 1180(19), 1193(15), 1251(15), 1268(12), 1291(15), 1333(7), 1408(15), 1445(25), 1460(10), 2846(75), 2874(20), 2900(125), 2928(15), 2965(50). This shaken with H2SO4 13.5 hrs. gave some CH4 and 85% mixed disiloxanes (I), presumably sym-diamyltetramethyldisiloxane, sym-dimethylbispentamethylenedisiloxane, and AmMe2SiOSiMe(CH2)5. Presumably the cleavage of the rings took place through formation of intermediate sulfate ester of the resulting silanol, and with a 6-membered ring it could take place in 2 possible directions as shown. Si[(CH2)4]2 had Raman spectrum: 242(15), 305(60), 591(25), 618(55), 668(15), 726(10), 757(5), 782(5), 854(60), 946(30), 1026(35), 1068 (12), 1156(20), 1200(7), 1254(25), 1340(5), 1414(25), 1457(35), 2854(120), 2870(35). 2895(135), 2945(275). sym-Tetramethyldiamyldisiloxane has Raman spectrum: 170 (2) 200(4), 479(1), 540(6), 652(5), 682(5), 705(3), 763(1), 767(1), 838(0), 895(4), 922(1), 956(4), 1026(3), 1070(3), 1102(43), 1135(4), 1186(6), 1245(4), 1262(1), 1304(6), 1336(1), 1380(1), 1410(5), 1443(7), 1456(5), 2858(5), 2882(5), 2904(10), 2965(10). I, b. 245-52°, nD20 1.4430, d20 0.8681, was presumed to have the above indicated composition on the basis of elemental analysis and Raman spectrum.

Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya published new progress about Bond. 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

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