Category: 20744-39-2

Ribeiro, Juliano S.; Augusto, Fabio; Ferreira, Marcia M. C.; Salva, Terezinha J. G. published the artcile< The use of chromatographic profiles from roasted Arabica coffees to differentiate samples according to cleanliness, flavor and overall quality of the beverage>, Safety of Pyridazin-4-amine, the main research area is roasted coffee beverage flavor taste volatile compound profile.

The volatile compound profiles of roasted Arabica coffee samples previously examined for sensory attributes were analyzed by GC, GC-MS, and principal component data anal. The volatiles were isolated by solid-phase microextraction The correlation optimized warping (COW) algorithm was used to align the GC profiles. Of the >250 compounds found by GC-MS, 54 were related to the studied sensory attributes and important in principal component anal. (of these 36 were identified). The levels of pyrrole, 1-methylpyrrole, cyclopentanone, dihydro-2-methyl-3-furanone, furfural, 2-ethyl-5-methylpyrazine, 2-ethenyl-N-methylpyrazine, and 5-methyl-2-propionylfuran were important for the differentiation of coffee beverage according to flavor, taste, and overall quality. The sensitivity and specificity (or selectivity) of the analytes indicated that ∼30 volatile compounds can be used to interpret the sensory attributes studied.

Quimica Nova published new progress about Coffea arabica. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Safety of Pyridazin-4-amine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Turck, Alain; Ple, Nelly; Mojovic, Ljubica; Ndzi, Bruno; Queguiner, Guy; Haider, Norbert; Schuller, Herbert; Heinisch, Gottfried published the artcile< On the metalation of 4-substituted pyridazines>, Recommanded Product: Pyridazin-4-amine, the main research area is pyridazine metalation lithium methylpiperidide.

A series of new pyridazines bearing ortho-directing groups at C-4 (protected/activated amino or carboxylic acid functionalities) was prepared and their metalation with lithium 2,2,6,6-tetramethylpiperidide was studied. Reactions of the ortho-lithiated species thus obtained with aldehydes as electrophiles opens an access to 4,5-disubstituted pyridazines I (R = NHCOCMe3, CONHCMe3, R1 = Me, Ph).

Journal of Heterocyclic Chemistry published new progress about Metalation. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Recommanded Product: Pyridazin-4-amine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Heinisch, G.; Matuszczak, B.; Pachler, S.; Rakowitz, D. published the artcile< The inhibitory activity of diazinyl-substituted thiourea derivatives on human immunodeficiency virus type 1 reverse transcriptase>, Safety of Pyridazin-4-amine, the main research area is diazinylthiourea preparation HIV1 reverse transcriptase inhibition.

Starting from 2-(2-aminoethyl)pyridine, a series of N-diazinyl-N’-[2-(2-pyridyl)ethyl]thioureas was prepared via the (2-pyridyl)ethylisothiocyanate and was screened as non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors. Derivatives bearing a 3-pyridazinyl or a 4-pyrimidinyl moiety turned out to be the most potent compounds However, they exhibited less activity than nevirapine or trovirdine.

Antiviral Chemistry & Chemotherapy published new progress about Antiviral 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

Ross-MacDonald, Petra; de Silva, Heshani; Patel, Vishal; Truong, Amy; He, Aiqing; Neuhaus, Isaac; Tilford, Charles; Ji, Rui Ru; Siemers, Nathan; Greer, Ann; Carboni, Joan; Gottardis, Marco; Menard, Krista; Lee, Frank; Dodier, Marco; Frennesson, David; Sampognaro, Anthony; Saulnier, Mark; Trainor, George; Vyas, Dolatrai; Zimmermann, Kurt; Wittman, Mark published the artcile< Biochemical and transcriptional profiling to triage additional activities in a series of IGF-1R/IR inhibitors>, Safety of Pyridazin-4-amine, the main research area is preparation IGFR kinase inhibitor cancer.

Therapeutic development of a targeted agent involves a series of decisions over addnl. activities that may be ignored, eliminated or pursued. This paper details the concurrent application of two methods that provide a spectrum of information about the biol. activity of a compound: biochem. profiling on a large panel of kinase assays and transcriptional profiling of mRNA responses. Our mRNA profiling studies used a full dose range, identifying subsets of transcriptional responses with differing EC50s which may reflect distinct targets. Profiling data allowed prioritization for validation in xenograft models, generated testable hypotheses for active compounds, and informed decisions on the general utility of the series.

Bioorganic & Medicinal Chemistry published new progress about Antiproliferative 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

Mehta, Naimee; Ferrins, Lori; Leed, Susan E.; Sciotti, Richard J.; Pollastri, Michael P. published the artcile< Optimization of Physicochemical Properties for 4-Anilinoquinoline Inhibitors of Plasmodium falciparum Proliferation>, Recommanded Product: Pyridazin-4-amine, the main research area is anilinoquinoline NEU1953 preparation antiplasmodial Plasmodium proliferation; drug repurposing; malaria; target class repurposing; tropical diseases.

The authors recently reported the medicinal chem. reoptimization of a known human tyrosine kinase inhibitor, lapatinib, against a variety of parasites responsible for numerous tropical diseases, including human African trypanosomiasis (Trypanosoma brucei), Chagas disease (T. cruzi), Leishmaniasis (Leishmania spp.), and malaria (Plasmodium falciparum). Herein, the authors report the authors’ continuing efforts to optimize this series against P. falciparum. Through the design of a library of compounds focused on reducing the lipophilicity and mol. weight, followed by an SAR exploration, the authors have identified NEU-1953 (40). This compound is a potent inhibitor of P. falciparum with an improved ADME profile over the previously reported compound, NEU-961.

ACS Infectious Diseases published new progress about Antimalarials. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Recommanded Product: Pyridazin-4-amine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Chen, Meijun; Li, Zhong; Shao, Xusheng; Maienfisch, Peter published the artcile< Scaffold-Hopping Approach To Identify New Chemotypes of Dimpropyridaz>, Computed Properties of 20744-39-2, the main research area is dimpropyridaz analog heterocyclic replacement diazine insecticide scaffold hopping; pyrazolecarboxamide preparation insecticide structure activity Myzus; 1,2-diazine; density functional theory (DFT); dimpropyridaz; heterocyclic replacement; pyrazole carboxamide insecticide; scaffold hopping.

Dimpropyridaz is a pyrazole carboxamide insecticide with a novel mode of action, currently under worldwide development by BASF, providing excellent activity against sucking pests. A series of dimpropyridaz analogs were designed to investigate the impact of bioisosteric heterocyclic replacements on the biol. activity and mol. properties. Focus was given to prepare analogs where the 4-pyridazinyl moiety was replaced by 5-pyrimidinyl, 2-pyrimidinyl, 3-pyridazinyl, and 2-pyrazinyl groups. Five different synthetic routes were developed for the preparation of these analogs, delivering the target compounds in moderate to good yields. We explained some aspects of the observed structure-activity relationship by a d. functional theory (DFT) calculation and DFT-derived Multiwfn and VMD program models. These findings provide first insights into the important role of the 4-pyridazinyl heterocyclic moiety in the pyrazole carboxamide insecticide chem. class and the mechanism of action of dimpropyridaz.

Journal of Agricultural and Food Chemistry published new progress about Aphicides. 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

Katritzky, A. R.; Pojarlieff, I. published the artcile< The kinetics and mechanism of electrophilic substitution of heteroaromatic compounds. XVI. Acid-catalyzed hydrogen exchange of some pyridazine derivatives>, Reference of 20744-39-2, the main research area is kinetics substitution heteroaromatics; substitution heteroaromatics kinetics; heteroaromatics kinetics substitution; mechanism substitution heteroaromatics; pyridazine substitution; hydrogen exchange pyridazines.

4-Aminopyridazine exchanges in acid solution as the conjugate acid at the 5-position. In the low acidity region, the conjugate acid exchanges by the ylide mechanism at the 3- and 6-positions. Pyridazin-4-one exchanges by the acid-catalyzed mechanism as the neutral species at the 5-position; ylide-mechanism exchange on the conjugate acid occurs at the 3- and 6-positions. Pyridazin-3-one exchanges in acid solution at the 5-position; the mechanism probably involves a hydrated species. Rate constants are measured and discussed. 19 references.

Journal of the Chemical Society [Section] B: Physical Organic published new progress about Entropy. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Reference 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< 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

Nakagome, Takenari published the artcile< Syntheses of pyridazine derivatives. II. 3-Methoxy-6-pyridazinol 1-oxide>, Recommanded Product: Pyridazin-4-amine, the main research area is HETEROCYCLIC COMPOUNDS/chemistry.

3-Chloro-6-methoxypyridazine (I) (7.3 g.) in 50 mL. AcOH treated with 24 mL. 30% H2O2, kept 5 h. at 70°, the solution concentrated in vacuo, the residue made alk. with Na2CO3 and the product extracted with CHCl3 gave 1.4 g. 3-methoxy-6-chloropyridazine 1-oxide (II), m. 157-8° (C6H6). The mother liquor from washing II with 2N NaOH gave 0.4 g. 3-methoxy-6(1H)-pyridazinone (III), plates, m. 162-3° (AcOEt). A solution of 18 g. BzO2H in 337 mL. CHCI3 treated with 14.5 g. I, kept 3 days at room temperature and the product treated as above gave 14.3 g. II, m. 157-8°. I (3 g.), 20 mL. AcOH, and 3.4 g. AcOK in a sealed tube heated 1.5 h. at 140-50° and the AcOH removed gave 3.6 g. III, m. 162-3°. III (4 g.) and 30 mL. POCl3 heated 30 min. at 100° the product poured into ice-H2O and extracted with Et2O gave 1.5 g. 3,6-dichloropyridazine (IV), m. 68-9°. Catalytic reduction of 0.5 g. II in 3 mL. 28% NH4OH and 30 mL. MeOH with 0.05 g. 10% Pd-C absorbed 77 mL. H and gave 0.35 g. 3-methoxypyridazine 1-oxide (V), m. 79-80°. Catalytic reduction of 0.5 g. II in 3 mL. 28% NH4OH and 30 mL. MeOH with Pd-C (from 10 mL. 1% PdCl2 and 0.5 g. C) absorbed 160 mL. H in 15 min. and gave 0.5 g. 3-methoxypyridazine; picrate m. 111°. II (3.2 g.), 12 mL. AcOH, and 1.64 g. AcONa in a sealed tube heated 1 h. at 150-60° and the product concentrated gave 1.64 g. 1-hydroxy-3-methoxy-5(1H)-pyridazinone (VI), m. 178-9°. A solution of 29.5 g. 3,6-dimethoxypyridazine I-oxide in 400 mL. 2N HCl heated 20 min. at 80-90° and the solution concentrated gave 25.3 g. VI, m. 178-9°. VI (2.8 g.), 2.54 g. BzCl, 0.46 g. Na and 30 mL. MeOH in a sealed tube heated 2 h. at 100° the solution concentrated and the residue extracted with CHCl3 gave 3.1 g. 1-benzoyloxy-3-methoxy-6(1H)pyridazinone (VII), m. 86.5-87°. VI (2 g.), 2.5 g. MeI, Ag2O (from 3 g. AgNO3), and 20 mL. MeOH in a sealed tube heated 2 h. at 100° and the solution concentrated gave 100% 1,3-dimethoxy-6(1H)-pyridazinone, m. 66-7°. A solution of 250 mL. dry C6H6, 20.6 g. PhCH2OH, and 4.4 g. Na, refluxed 1 h., after disappearance of Na, with 20 g. 3-chloropyridazine, and the product distilled gave 18 g. 3-benzyloxypyridazine (VIII), b0.15 120-5°, m. 49-50°. VIII (6 g) and 84.5 mL. CHCl3 containing 4.46 g. BzO2H kept 2 days at room temperature gave 100% VIII I-oxide (VIIIa), m. 118-18.5°. Catalytic reduction of 0.5 g. VIIIa in 30 mL. MeOH with 0.05 g. 10% Pd-C absorbed 64 mL. H in 5 min.and gave 3-pyridazinol 1-oxide, m. 201-2° (decomposition). Catalytic reduction of 0.5 g. VIIIa in 30 mL. MeOH with 0.2 g. 10% Pd-C absorbed 128 mL. H in 15 min. and gave 0.25 g. 3(2H)-pyridazinone-H2O, m. 74°. IV (21 g.) and 240 mL. CHCl3 containing 18.7 g. BzO2H kept 2 days at room temperature and the product concentrated gave 10.4 g. IV 1-oxide, m. 110-12°. IV 1-oxide (1 g.) and 0.33 g. 22.6% MeONa-MeOH heated several min. on a water bath, the solution acidified with AcOH and the product extracted with CHCl3 gave 0.6 g. II, m. 155-7°.

Yakugaku Zasshi published new progress about 20744-39-2. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Recommanded Product: Pyridazin-4-amine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Itai, Takanobu; Natsume, Sachiko published the artcile< Potential anticancer agents. IX. Nitration of pyridazine 1-oxide>, Category: pyridazine, the main research area is .

Preceding abstract To 5 g. pyridazine 1-oxide (I) in 40 cc. cold CHCl3 was added 6 cc. BzCl, followed portionwise by 9.7 g. finely powd. AgNO3 at below – 10° with stirring, the mixture stirred 4 hrs. at below – 10°, kept 4 days at room temperature, the precipitate (II) (mixture of AgCl and a yellow solid) filtered off, washed twice with cold CHCl3 [the combined filtrate and washings (III) were kept], extracted with hot CHCl3, and the extract concentrated to dryness to give 2.15 g. 3-NO2 derivative (IV) of I, m. 166° (MeOH), ν (KBr) 1543, 1523, 1337, 1324 cm.-1, (95% EtOH) 232, 281, and 350 mμ (log ε 4.02, 3.99, and 3.73); the MeOH mother liquor evaporated, the residue chromatographed on SiO2, and the column eluted gave the following fractions: (1) with 9:1 C6H6CHCl3, 50 mg. BzOH; (2) with same solvent mixture, 22 mg. 5-NO2 derivative (V) of I, m. 142-3° (MeOH); (3) with same solvent mixture, 45 mg. IV, m. 167-9° (MeOH); (4) with CHCl3, 100 mg. sirupy mixture; and (5) with CHCl3, 270 mg. unchanged I (perchlorate m. 184°). The residue remaining after extracting II with hot CHCl3 extracted with hot MeOH gave 0.06 g. IV; III evaporated, the residue treated with 30 cc. H2O and 60 cc. Et2O, and the precipitate filtered off [the filtrate (VI) was kept] gave 0.12 g. IV, m. 169° (MeOH); VI extracted with Et2O and the extract dried and evaporated gave 5.9 g. BzOH; the remaining aqueous layer evaporated in vacuo, the residue extracted repeatedly with CHCl3, the combined extracts dried, evaporated, and the residue chromatographed on SiO2 as above gave 40 mg. V, m. 142-3°, 45 mg. IV, m. 169°, and 1.12 g. unchanged I. I (5 g.) in 50 cc. cold CHCl3 treated with 4.1 cc. AcCl followed portionwise by 9.7 g. finely powd. AgNO3 at below -10° with stirring, the mixture stirred 1.5 hrs. at below – 10°, kept 3 days at room temperature, and worked up as above gave 1.26 g. IV, 57 mg. V, and 1.72 g. unchanged I. V (0.042 g.) in 15 cc. 50% MeOH containing 1 cc. concentrated HCl hydrogenated over 20% Pd-C, when 4 equivalents H were absorbed the solution filtered, the filtrate evaporated, the residue dissolved in a little MeOH, and the solution treated with MeOH-Na picrate (VIa) gave 4-aminopyridazine (VII) picrate, m. 226-8° (decomposition) (MeOH), converted by passage in MeOH through Amberlite IRA-410 (OH form) into VII, m. 127-9°. IV (145 mg.) suspended in 30 cc. MeOH and 30 cc. 4% aqueous HCl hydrogenated over 20% Pd-C (prepared from 4.2 cc. 1% aqueous PdCl2 and 0.1 g. C) (the reduction was interrupted after rapid absorption of 4 equivalents H), the product (100 mg.) isolated as usual, and treated with 1 equivalent VIa gave 100 mg. 3-aminopyridazine (VIII) picrate (IX), m. 248-9° (EtOH), converted as above into VIII, m. 170°. IV (1.08 g.) and 20% Pd-C (prepared from 0.2 g. C and 8.4 cc. 1% aqueous PdCl2) in 100 cc. MeOH shaken in a stream of H until 2 equivalents H were absorbed (H was absorbed rapidly), the mixture warmed, the catalyst filtered off hot, washed with hot MeOH, and the combined filtrate and washings evaporated gave 0.74 g. 3-hydroxyaminopyridazine 1-oxide (X), m. 184° (decomposition) (EtOH);λ (95% EtOH) 229,262, and 341 mμ (log ε 4.17, 4.14, and 3.63); ν (KBr) 3160 cm.-1 IV (1.06 g.) and 20% Pd-C (prepared from 0.2 g. C and 8.4 cc. 1% aqueous PdCl2) in 200 cc. MeOH hydrogenated as above until uptake of 3 equivalents H, the mixture worked up as above, and the residue recrystallized from MeOH gave 0.2 g. X, m. 182° (decomposition). The mother liquor evaporated, the residue dissolved in MeOH, the solution treated with MeOH-picric acid, and the precipitate filtered off gave 0.25 g. IX, m. 248-9° (MeOH); the filtrate kept overnight with Amberlite IRA-410 (OH form), the resin filtered off, and the filtrate evaporated gave 0.27 g. VIII 1-oxide (XI), m. 139-41° (EtOAc); λ (95% EtOH) 217, 246-8, and 338-40 mμ (log ε 4.23, 4.13, and 3.74); ν (KBr) 3340, 3300, 3210, 1632 cm.-1 X (0.2 g.) and 0.12 g. 20% Pd-C in 50 cc. MeOH shaken in a stream of H until 1 equivalent H was absorbed and treated as above gave 60 mg. IX, m. 245-9°, and 75 mg. XI, m. 139-41°. IV (0.2 g.) suspended in 70 cc. anhydrous MeOH treated with NaOMe solution (prepared from 40 mg. Na and 7 cc. MeOH), the mixture kept 1.5 hrs. at 30° (IV dissolved slowly), and the precipitate filtered off and washed with C6H6 gave 30 mg. unchanged IV, m. 168-9°; the combined filtrate and washings evaporated in vacuo, the residue treated with a little H2O, and the product isolated with CHCl3 gave 137 mg. 3-OMe derivative (XII) of I, m. 79-80° (C6H6). IV (0.4 g.) in 50 cc. hot MeOH mixed with 10 cc. MeONa solution (prepared from 80 mg. Na) and the solution refluxed 1 hr. and treated as above gave 0.26 g. XII. IV (0.59 g.) suspended in 15 cc. AcCl refluxed until solution occurred (9 hrs.), the AcCl removed in vacuo, and the residue recrystallized from (iso-Pr)2O gave 0.36 g. 3-Cl derivative (XIII) of I, m. 93°, λ (95% EtOH) 266 mμ (log ε 4.00), ν (KBr) 1340 cm.-1 ; the mother liquor evaporated and the residue chromatographed on Al2O3 with CHCl3 gave 80 mg. XIII. IV (0.1 g.) suspended in 1 cc. AcCl kept 3 hrs. at 35°, the mixture evaporated in vacuo, and the residue extracted repeatedly with (iso-Pr)2O gave (as insoluble product) 90 mg. unchanged IV, m. 167-9°; the combined extracts evaporated and the residue chromatographed on Al2O3 with CHCl3 gave 2 mg. XIII. IV (0.15 g.) added to 0.4 g. Na dissolved in 0.7 g. PhOH by warming, the mixture heated 1 hr. at 100°, the PhOH removed in vacuo, the residue treated with H2O, the product isolated with CHCl3, the residue dissolved in CHCl3, the solution passed through Al2O3, and the eluate evaporated gave 100 mg. 3-OPh derivative of I, m. 115-16° (C6H6). HONH2.HCl (0.27 g.) in MeOH (saturated solution) treated with 0.27 g. K2CO3 in a little H2O, the precipitate filtered off, the filtrate treated with 80 mg. XIII in 3 cc. MeOH, refluxed 5.5 hrs., evaporated to dryness, the residue treated with a little H2O, the mixture extracted with CHCl3, and the extract evaporated gave 22 mg. unchanged XIII, m. 90-2° (iso-Pr)2O; the product insoluble in CHCl3 and H2O filtered off and recrystallized from EtOH gave 6 mg. X, m. 182-3° (decomposition). XIII (0.2 g.), 5 cc. EtOH, and 3 cc. 28% aqueous NH3 heated 4 hrs. at 120° in a sealed tube, the mixture treated with C, the solution evaporated in vacuo, the residue extracted repeatedly with hot EtOAc, and the combined extracts evaporated gave 0.05 g. XI, m. 140-1° (EtOAc). XIII (0.17 g.) in 10 cc. MeOH treated with NaOMe solution (prepared from 30 mg. Na and 5 cc. MeOH), the mixture kept overnight at room temperature, evaporated in vacuo, the residue treated with a little H2O, the mixture extracted with CHCl3, the extract dried, evaporated, and the residue chromatographed on Al2O3 with C6H6 gave 130 mg. XII, m. 78-80°. XIII (0.05 g.) and 0.04 cc. 80% N2H4.H2O in 1 cc. 95% EtOH refluxed 1 hr., cooled, evaporated in vacuo, the residue dissolved in 1 cc. AcOH, the solution treated with 0.03 g. NaNO2 in H2O with cooling, and the precipitate collected gave 30 mg. 3-azido derivative of I, m. 155-6° (99% MeOH), ν (KBr) 2180, 2150, and 1250 cm.-1 IV shown no activity of Ehrlich ascite carcinoma in vivo, it showed strong activity against Staphylococcus aureus, Escherichia coli, Shigella flexneri, and Candida albicans in vitro.

Chemical & Pharmaceutical Bulletin published new progress about IR spectra. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Category: pyridazine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem