Month: October 2022

Liu, Bin; Xu, Xiaona; Tong, Hongjuan; Zhu, Zhoujing; Tang, Wenqiang; Tang, Chu published the artcile< Synthesis and Antiproliferative Evaluation of Novel 5-Substituted Pyridazin-4-Amine Derivatives>, Synthetic Route of 20744-39-2, the main research area is aminopyridazine preparation antitumor SAR.

A series of 5-substituted pyridazin-4-amine derivatives were synthesized, characterized and evaluated for antitumor activities. The target compounds exhibited moderate to high anti-proliferative activities depending on the type of substituents of the pyridazine skeleton. Preliminary data on their biol. activity against several cancer cell lines of A549, PC3, MCF-7 and HeLa cells was further reported. Specifically, introduction of bulky aromatic substituents onto the pyridazine skeleton have potential benefit against liver cancer cells.

Organic Preparations and Procedures International 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

Xin, Wen-yuan; Li, Jiao; Ma, Dan-wei; Wang, Yanan; Ren, Qiurong; Li, Jia-jia published the artcile< Chemical composition of the essential oil of whole plant of Elsholtizia dense Benth and its anti-tumor effect on human hepatoma cells>, SDS of cas: 20744-39-2, the main research area is Elsholtizia essential oil anticancer agent hepatoma.

To determine the chem. components of the essential oil of Elsholtizia dense in Sichuan Province and evaluate the effect of the oil on human hepatoma cells (SMMC-7721) in vitro. The essential oil was extracted using the modified steam-distillation extraction method, and its chem. components were determined by gas chromatog.-mass spectrometry (GC-MS). The effect of the essential oil on proliferation of SMMC-7721 cells was studied by 3-(4,5-dimethyl-2- thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, with L02 and HeLa cells serving as control groups. GC-MS results show that the essential oil of E. dense contains 40 components. Thirty seven components were identified and accounted for 98.39 % of the essential oil. The two main components were rosefuran epoxide (53.12 %) and 2-Et imidazole (29.8 %). The oil significantly inhibited cell proliferation in a concentration- and time-dependent manner (p < 0.05). SMMC-7721 cells were more inhibited than L02 and HeLa cells by the oil, with half maximal inhibitory concentration (IC50) values of 26.23 and 25.46 μg/mL after 8-h and 24-h treatments, resp. Out of the 40 chem. components of the essential oil of E. dense, rosefuran epoxide and 2-Et imidazole were the most abundant. The oil has a significant anti-tumor effect on SMMC-7721 cells, and thus has a potential to be developed as an anti-liver cancer drug. Tropical Journal of Pharmaceutical Research 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

Tear, Westley F.; Bag, Seema; Diaz-Gonzalez, Rosario; Ceballos-Perez, Gloria; Rojas-Barros, Domingo I.; Cordon-Obras, Carlos; Perez-Moreno, Guiomar; Garcia-Hernandez, Raquel; Martinez-Martinez, Maria Santos; Ruiz-Perez, Luis Miguel; Gamarro, Francisco; Gonzalez Pacanowska, Dolores; Caffrey, Conor R.; Ferrins, Lori; Manzano, Pilar; Navarro, Miguel; Pollastri, Michael P. published the artcile< Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-b]pyridazines for the Treatment of Human African Trypanosomiasis>, Electric Literature of 20744-39-2, the main research area is human african trypanosomiasis Trypanosoma brucei antiparasitic activity trypanosome infection.

From a high-throughput screen of 42 444 known human kinases inhibitors, a pyrazolo[1,5-b]pyridazine scaffold was identified to begin optimization for the treatment of human African trypanosomiasis. Previously reported data for analogous compounds against human kinases GSK-3β, CDK-2, and CDK-4 were leveraged to try to improve the selectivity of the series, resulting in 23a which showed selectivity for T. b. brucei over these three human enzymes. In parallel, properties known to influence the absorption, distribution, metabolism, and excretion (ADME) profile of the series were optimized resulting in 20g being progressed into an efficacy study in mice. Though 20g showed toxicity in mice, it also demonstrated CNS penetration in a PK study and significant reduction of parasitemia in four out of the six mice.

Journal of Medicinal Chemistry published new progress about Central nervous system (CNS penetration). 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

Graves, Alan P.; Shivakumar, Devleena M.; Boyce, Sarah E.; Jacobson, Matthew P.; Case, David A.; Shoichet, Brian K. published the artcile< Rescoring Docking Hit Lists for Model Cavity Sites: Predictions and Experimental Testing>, Computed Properties of 20744-39-2, the main research area is protein ligand docking mol mechanics generalized Born surface area; virtual screening rescoring ligand crystal structure protein conformation.

Mol. docking computationally screens thousands to millions of organic mols. against protein structures, looking for those with complementary fits. Many approximations are made, often resulting in low “”hit rates.””. A strategy to overcome these approximations is to rescore top-ranked docked mols. using a better but slower method. One such is afforded by mol. mechanics-generalized Born surface area (MM-GBSA) techniques. These more phys. realistic methods have improved models for solvation and electrostatic interactions and conformational change compared to most docking programs. To investigate MM-GBSA rescoring, the authors reranked docking hit lists in three small buried sites: a hydrophobic cavity that binds apolar ligands, a slightly polar cavity that binds aryl and hydrogen-bonding ligands, and an anionic cavity that binds cationic ligands. These sites are simple; consequently, incorrect predictions can be attributed to particular errors in the method, and many likely ligands may actually be tested. In retrospective calculations, MM-GBSA techniques with binding-site minimization better distinguished the known ligands for each cavity from the known decoys compared to the docking calculation alone. This encouraged us to test rescoring prospectively on mols. that ranked poorly by docking but that ranked well when rescored by MM-GBSA. A total of 33 mols. highly ranked by MM-GBSA for the three cavities were tested exptl. Of these, 23 were observed to bind-these are docking false negatives rescued by rescoring. The 10 remaining mols. are true negatives by docking and false positives by MM-GBSA. X-ray crystal structures were determined for 21 of these 23 mols. In many cases, the geometry prediction by MM-GBSA improved the initial docking pose and more closely resembled the crystallog. result; yet in several cases, the rescored geometry failed to capture large conformational changes in the protein. Intriguingly, rescoring not only rescued docking false positives, but also introduced several new false positives into the top-ranking mols. The authors consider the origins of the successes and failures in MM-GBSA rescoring in these model cavity sites and the prospects for rescoring in biol. relevant targets.

Journal of Molecular Biology published new progress about Algorithm. 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

Qin, Donghui; Lin, Xiaojuan; Liu, Zhi; Chen, Yan; Zhang, Zhiliu; Wu, Chengde; Liu, Linlin; Pan, Yan; Laquerre, Sylvie; Emery, John; Fergusson, Jeff; Roland, Kimberly; Keenan, Rick; Oliff, Allen; Kumar, Sanjay; Cheung, Mui; Su, Dai-Shi published the artcile< Discovery of Orally Bioavailable Ligand Efficient Quinazolinediones as Potent and Selective Tankyrases Inhibitors>, Formula: C4H5N3, the main research area is quinazolinedione preparation tankyrase inhibitor structure activity pharmacokinetic profile; antitumor quinazolinedione selective tankyrase inhibitor; safety quinazolinedione.

The authors report the discovery of quinazolinediones as potent and selective tankyrase inhibitors. Elucidation of the structure-activity relationship of the lead compound I (R1 = R2 = R3 = H, R4 = NHCH2Ph), led to truncated analogs, e.g., I (R1 = H, F, Cl, OMe, Me, R2 = H, F, Me, CONH2, R3 = H, CF3, Me, Cl, R4 = OH, 4-pyridylamino, 1-methyl-4-pyrazolylamino, etc.), that have good potency in cells, pharmacokinetic (PK) properties, and excellent selectivity. Compound I (R1 = R2 = H, R3 = CF3, R4 = OH) (II) exhibited excellent potencies in cells and proliferation studies, good selectivity, in vitro activities, and an excellent PK profile. Compound II also inhibited H292 xenograft tumor growth in nude mice. The synthesis, biol., pharmacokinetic, in vivo efficacy studies, and safety profiles of compounds are presented.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Formula: C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Tong, Chao-Lai; Xu, Xiu-Hua; Qing, Feng-Ling published the artcile< Nucleophilic and Radical Heptafluoroisopropoxylation with Redox-Active Reagents>, Name: Ethyl 6-chloroimidazo[1,2-b]pyridazine-2-carboxylate, the main research area is heptafluoroisopropyl ether preparation; hydroxylamine oxidative heptafluoroisopropyl silver heptafluoroisopropylation; conformation; heptafluoroisopropoxylation; nucleophilic reactions; radical reactions; redox-active reagents.

The practical and efficient heptafluoroisopropoxylation reactions through the invention of a series of redox-active N-OCF(CF3)2 reagents e.g., I were described. These reagents were readily prepared from the oxidative heptafluoroisopropylation of hydroxylamines e.g., II with AgCF(CF3)2. The substitutions on the nitrogen atom significantly affected the properties and reactivities of N-OCF(CF3)2 reagents. Accordingly, two types of N-OCF(CF3)2 reagents including I and III were used as OCF(CF3)2 anion and radical precursors, resp. This protocol enables the direct heptafluoroisopropoxylation of a range of substrates, delivering the corresponding products in moderate to excellent yields.

Angewandte Chemie, International Edition published new progress about Alcohols Role: RCT (Reactant), RACT (Reactant or Reagent). 64067-99-8 belongs to class pyridazine, and the molecular formula is C9H8ClN3O2, Name: Ethyl 6-chloroimidazo[1,2-b]pyridazine-2-carboxylate.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Moriya, Koichi; Shibuya, Katsuhiko; Hattori, Yumi; Tsuboi, Shinichi; Shiokawa, Kozo; Kagabu, Shinzo published the artcile< 1-Diazinylmethyl-2-nitromethylene- and 2-nitroimino-imidazolidines as new potential insecticides>, Reference of 120276-59-7, the main research area is insecticide diazinylmethyl nitromethylene imidazolidine; nitroiminoimidazolidine insecticide structure activity.

The insecticidal properties of diazinylmethylimidazolidines and compared them with the corresponding Ph and pyridyl homologs. Me group and chlorine atom were selected as ring substituents to simplify the comparison. The bioassay was carried out using green rice leafhoppers as test species.

Journal of Pesticide Science (International Edition) published new progress about Insecticides. 120276-59-7 belongs to class pyridazine, and the molecular formula is C5H4Cl2N2, Reference of 120276-59-7.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

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

Hara, Hiroshi; Van der Plas, Henk C. published the artcile< On the amination of azaheterocycles. A new procedure for the introduction of an amino group>, Recommanded Product: Pyridazin-4-amine, the main research area is amination azaheterocycle; heterocycle aza amination; diazine amination; triazine amination; pyrimidine amination; pyridazine amination.

Diazines and triazines were aminated using KNH2, liquid NH3 and KMnO4. Thus, 4-aminopyridazine was obtained in 91% yield from pyridazine.

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

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Venturello, P.; Barbero, M. published the artcile< Product subclass 6: potassium amides and phosphides>, Related Products of 20744-39-2, the main research area is review potassium amide organic synthesis; potassium phosphide organic synthesis review.

A review of the application of potassium amides and phosphides to organic synthesis.

Science of Synthesis published new progress about Organic synthesis. 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