Heterocyclic Building Blocks-Pyridazine

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

Liu, Yu-Xiu; Wei, Deng-Guo; Zhu, Ye-Rong; Liu, Shao-Hua; Zhang, Yong-Lin; Zhao, Qi-Qi; Cai, Bao-Li; Li, Yong-Hong; Song, Hai-Bin; Liu, Ying; Wang, Yong; Huang, Run-Qiu; Wang, Qing-Min published the artcile< Synthesis, Herbicidal Activities, and 3D-QSAR of 2-Cyanoacrylates Containing Aromatic Methylamine Moieties>, Electric Literature of 120276-59-7, the main research area is hetarylmethylaminoacrylate cyano preparation herbicidal; aminoacrylate cyano preparation herbicidal; arylmethylaminoacrylate cyano preparation herbicidal; cyanoacrylate aromatic methylamine preparation herbicidal.

A series of novel 2-cyanoacrylates containing different aromatic rings, e.g. I (R = MeS, Et, Me2CH; R1 = 4-ClC6H4, 6-bromo-3-pyridinyl, 2-ethoxy-5-thiazolyl, etc) were prepared, and their structures were characterized by 1H NMR, elemental anal., and single-crystal X-ray diffraction anal. Their herbicidal activities against four weeds and inhibition of photosynthetic electron transport against isolated chloroplasts (the Hill reaction) were evaluated. Both in vivo and in vitro data showed that the compounds containing benzene, pyridine, and thiazole moieties gave higher activities than those containing pyrimidine, pyridazine, furan, and THF moieties. To further explore the comprehensive structure-activity relationship on the basis of in vitro data, comparative mol. field anal. (CoMFA) was performed, and the results showed that a bulky and electroneg. group around the para-position of the aromatic rings would have the potential for higher activity, which offered important structural insights into designing highly active compounds prior to the next synthesis.

Journal of Agricultural and Food Chemistry published new progress about Herbicides. 120276-59-7 belongs to class pyridazine, and the molecular formula is C5H4Cl2N2, Electric Literature of 120276-59-7.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Russell, Michael G. N.; Carling, Robert W.; Atack, John R.; Bromidge, Frances A.; Cook, Susan M.; Hunt, Peter; Isted, Catherine; Lucas, Matt; McKernan, Ruth M.; Mitchinson, Andrew; Moore, Kevin W.; Narquizian, Robert; Macaulay, Alison J.; Thomas, David; Thompson, Sally-Anne; Wafford, Keith A.; Castro, Jose L. published the artcile< Discovery of Functionally Selective 7,8,9,10-Tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABAA Receptor Agonists at the α3 Subunit>, COA of Formula: C5H4Cl2N2, the main research area is triazolophthalazine tetrahydroethano preparation human GABA receptor agonist acidity.

7,8,9,10-Tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazine I (R1 = Ph; R2 = 2-pyridylmethyl) was previously identified as a potent partial agonist for the α3 receptor subtype with 5-fold selectivity in binding affinity over α1. This paper describes a detailed investigation of the substituents on this core structure at both the 3- and 6-positions. Despite evaluating a wide range of groups, the maximum selectivity that could be achieved in terms of affinity for the α3 subtype over the α1 subtype was 12-fold (for I [R1 = Ph; R2 = 4-(HOCH2)C6H4CH2]). Although most analogs showed no selectivity in terms of efficacy, some of them, e.g. I (R1 = Ph; R2 = 3,5-dimethyl-2-pyridylmethyl, pyrazol-1-ylmethyl), did show partial agonism at α1 and antagonism at α3. However, two analogs I (R1 = Ph; R2 = 1-methyl-1,2,4-triazol-3-ylmethyl, 2-propyl-1,2,4-triazol-3-ylmethyl), containing triazole substituents in the 6-position, showed significantly higher efficacy for the α3 subtype over the α1 subtype. This was the first indication that selectivity in efficacy in the required direction could be achieved in this series.

Journal of Medicinal Chemistrypublished new progress about Acidity. 120276-59-7 belongs to class pyridazine, and the molecular formula is C5H4Cl2N2, COA of Formula: C5H4Cl2N2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Ren, Huiyu; Bakas, Nicole A.; Vamos, Mitchell; Chaikuad, Apirat; Limpert, Allison S.; Wimer, Carina D.; Brun, Sonja N.; Lambert, Lester J.; Tautz, Lutz; Celeridad, Maria; Sheffler, Douglas J.; Knapp, Stefan; Shaw, Reuben J.; Cosford, Nicholas D. P. published the artcile< Design, Synthesis, and Characterization of an Orally Active Dual-Specific ULK1/2 Autophagy Inhibitor that Synergizes with the PARP Inhibitor Olaparib for the Treatment of Triple-Negative Breast Cancer>, Synthetic Route of 20744-39-2, the main research area is pyrimidine synthesis anticancer ULK1 ULK2 PARP breast cancer autophagy.

Inhibition of autophagy, the major cellular recycling pathway in mammalian cells, is a promising strategy for the treatment of triple-neg. breast cancer (TNBC). We previously reported SBI-0206965, a small mol. inhibitor of unc-51-like autophagy activating kinase 1 (ULK1), which is a key regulator of autophagy initiation. Herein, we describe the design, synthesis, and characterization of new dual inhibitors of ULK1 and ULK2 (ULK1/2). One inhibitor, SBP-7455 (compound 26), displayed improved binding affinity for ULK1/2 compared with SBI-0206965, potently inhibited ULK1/2 enzymic activity in vitro and in cells, reduced the viability of TNBC cells and had oral bioavailability in mice. SBP-7455 inhibited starvation-induced autophagic flux in TNBC cells that were dependent on autophagy for survival and displayed synergistic cytotoxicity with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib against TNBC cells. These data suggest that combining ULK1/2 and PARP inhibition may have clin. utility for the treatment of TNBC.

Journal of Medicinal Chemistrypublished 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>, Category: pyridazine, 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 Letterspublished new progress about Antitumor agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Category: pyridazine.

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>, Product Details of C4H5N3, 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 Chemistrypublished new progress about Antitumor agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Product Details of C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Dong, Jianyang; Yue, Fuyang; Xu, Wentao; Song, Hongjian; Liu, Yuxiu; Wang, Qingmin published the artcile< Visible-light-mediated Minisci C-H alkylation of heteroarenes with 4-alkyl-1,4-dihydropyridines using O2 as an oxidant>, SDS of cas: 64067-99-8, the main research area is alkylated heteroarene green preparation; heteroarene alkyl dihydropyridine alkylation iridium photocatalyst.

A protocol for direct visible-light-mediated Minisci C-H alkylation reactions of N-heteroarenes with 4-alkyl-1,4-dihydropyridines for synthesis of alkylated N-heteroarenes such as I at room temperature with mol. oxygen as an oxidant was reported. The protocol permitted efficient functionalization of various N-heteroarenes with a broad range of cyclic and acyclic primary, secondary and tertiary alkyl groups and was scalable to the gram level. This mild protocol used an inexpensive, green oxidant and was suitable for late-stage C-H alkylation of complex nitrogen-containing mols. Its utility was demonstrated by preparing or functionalizing several pharmaceuticals and natural products.

Green Chemistrypublished new progress about Dihydropyridines Role: RCT (Reactant), RACT (Reactant or Reagent). 64067-99-8 belongs to class pyridazine, and the molecular formula is C9H8ClN3O2, SDS of cas: 64067-99-8.

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>, Reference 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 Chemistrypublished new progress about Aphicides. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Reference of 20744-39-2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Jiang, Li-wen published the artcile< Analysis of volatile substances from Psophocarpus tetragonolobus D. C. seeds>, SDS of cas: 20744-39-2, the main research area is volatile substance Psophocarpus seed.

Objective: To analyze volatile substances from Psophocarpus tetragonolobus D. C seeds, so as to provide a basis to make better use of this resources. Method: Volatile substances extracted from Psophocarpus tetragonolobus D. C seeds were identified by GC-MS, and their relative contents were determined through area normalization method. Result: 125 kinds of compounds in 10 types including alkanes, olefine, acids, aromatic compounds, esters, ketone, ethers and heterlcyclic series were identified from 4 Psophocarpus tetragonolobus D. C seeds. Moreover each kind of seeds had 42 volatile substances mainly referred to ketone, alc. and esters. There was no significant difference regarding types and total amount of volatile substances from Psophocarpus tetragonolobus D. C seeds among different species, but their relative contents were differed obviously. Conclusion: The existence and differences of volatile substances formed their own characteristic flavors that could contribute to products variation in the processing of Psophocarpus tetragonolobus D. C.

Anhui Nongye Kexuepublished new progress about Psophocarpus tetragonolobus. 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

Xiao, Fang; Lin, Jin-Hong; Hao, Fei; Zheng, Xing; Guo, Yu; Xiao, Ji-Chang published the artcile< Visible light mediated C-H trifluoromethylation of (hetero)arenes>, Quality Control of 64067-99-8, the main research area is trifluoromethyl heteroarene preparation; aromatic heterocycle visible light trifluoromethylation.

A protocol for visible light mediated C-H trifluoromethylation of unactivated (hetero)arenes under blue LED irradiation has been developed. The reaction enables the rapid construction of a range of CF3-containing (hetero)arenes in moderate to high yields from the readily accessible trifluoromethylsulfonyl-pyridinium salt (TFSP). This protocol is also suitable for nitrogen-containing aromatic heterocycles, which are potentially useful in medicinal chem.

Organic Chemistry Frontierspublished new progress about Heterocyclic aromatic compounds Role: RCT (Reactant), SPN (Synthetic Preparation), RACT (Reactant or Reagent), PREP (Preparation). 64067-99-8 belongs to class pyridazine, and the molecular formula is C9H8ClN3O2, Quality Control of 64067-99-8.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem