Tag: M.W:0-100

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

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

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

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

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

Yamagami, Chisako; Takao, Narao; Fujita, Toshio published the artcile< Hydrophobicity parameter of diazines. 1. Analysis and prediction of partition coefficients of monosubstituted diazines>, Synthetic Route of 20744-39-2, the main research area is hydrophobicity diazine LFER; partition coefficient diazine.

The octanol/water partition coefficient (P) of a number of monosubstituted diazines was measured. The composition of the π value of substituents, the increment in the log P value accompanying the introduction of substituents, was examined in terms of physicochem. substituent parameters and correlation anal. The diazine-π value of substituents was generally higher than the pyridine-π value of corresponding substituents, indicating that the intramol. electronic interactions between the ring-N atoms and substituent are more pronounced than those in substituted pyridines in governing the log P value of the mol. Except for 2-substituted pyrimidines, the π value of substituents in each series of monosubstituted diazines was in general nicely correlated with the π value of the corresponding substituents in substituted pyridines along with electronic parameter terms representing bidirectional electronic effects on the relative solvation of the ring-N atom(s) and the hydrogen-bondable substituents with partitioning solvents according to the procedure proposed previously for the anal. of the π value in disubstituted benzenes and monosubstituted pyridines. Keeping in mind that 2-pyrimidines substituted by hydrogen-bondable groups sometimes behave as outliers, the correlations were believed to be usable for prediction of log P values of monosubstituted diazines.

Quantitative Structure-Activity Relationships published new progress about Hydrophobicity. 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

Qu, Ren-Yu; Nan, Jia-Xu; Yan, Yao-Chao; Chen, Qiong; Ndikuryayo, Ferdinand; Wei, Xue-Fang; Yang, Wen-Chao; Lin, Hong-Yan; Yang, Guang-Fu published the artcile< Structure-Guided Discovery of Silicon-Containing Subnanomolar Inhibitor of Hydroxyphenylpyruvate Dioxygenase as a Potential Herbicide>, Application of C4H5N3, the main research area is triketonequinazolinedione preparation hydroxyphenylpyruvate dioxygenase inhibitor herbicide; crop safety weed control wheat peanut MBQ derivative; 4-dione; herbicide; hydrophobic interaction; hydroxyphenylpyruvate dioxygenase; lead optimization; quinazoline-2.

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been recognized as one of the most promising targets in the field of herbicide innovation considering the severity of weed resistance currently. In a persistent effort to develop effective HPPD-inhibiting herbicides, a structure-guided strategy was carried out to perform the structural optimization for triketone-quinazoline-2,4-diones, a novel HPPD inhibitor scaffold first discovered in our laboratory Herein, starting from the crystal structure of Arabidopsis thaliana (At)HPPD complexed with 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-(o-tolyl)quinazoline-2,4(1H,3H)-dione (MBQ), three subseries of quinazoline-2,4-dione derivatives were designed and prepared by optimizing the hydrophobic interactions between the side chain of the core structure at the R1 position and the hydrophobic pocket at the active site entrance of AtHPPD. 6-(2-Hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-(3-(trimethylsilyl)prop-2-yn-1-yl)quinazoline-2,4(1H,3H)-dione (I) with the best inhibitory activity against AtHPPD was identified to be the first subnanomolar-range AtHPPD inhibitor (Ki = 0.86 nM), which significantly outperformed that of the lead compound MBQ (Ki = 8.2 nM). Further determination of the crystal structure of AtHPPD in complex with compound 60 (1.85 Å) and the binding energy calculation provided a mol. basis for the understanding of its high efficiency. Addnl., the greenhouse assay indicated that 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-propylquinazoline-2,4(1H,3H)-dione (II) and compound I showed acceptable crop safety against peanut and good herbicidal activity with a broad spectrum. Moreover, compound II also showed superior selectivity for wheat at the dosage of 120 g ai/ha and favorable herbicidal efficacy toward the gramineous weeds at the dosage of as low as 30 g ai/ha. We believe that compounds II and I have promising prospects as new herbicide candidates for wheat and peanut fields.

Journal of Agricultural and Food Chemistry published new progress about Abutilon theophrasti. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Application of C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Deyrup, J. A.; Gingrich, H. L. published the artcile< Cycloadditions of 4-oxazolin-2-ones>, Product Details of C4H5N3, the main research area is oxazolinone cycloaddition cyclopentadiene anthracene; chloranil cycloaddition oxazolinone; tetrazine pyridyl cycloaddition oxazolinone.

The 4-oxazolin-2-ones I (R = H, Ac, R1 = H; R = Ac, R1 = Ph) underwent cycloaddition reactions with a variety of cyclic unsaturated compounds, e.g. cyclopentadiene, o-chloranil, anthracene. E.g., I (R = Ac, R1 = H) with anthracene in o-xylene at 144° for 72 h gave 87% adduct II. Hydrolysis of II in refluxing alc. aqueous NaOH gave 74% amino alc. III.

Tetrahedron Letters published new progress about Cycloaddition reaction. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Product Details of C4H5N3.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Barlin, Gordon B. published the artcile< Methylation of aminopyridazines>, HPLC of Formula: 20744-39-2, the main research area is methylation aminopyridazine; pyridazine amino methylation; aminopyridazinium iodide UV NMR; acidity aminopyridazine.

Treatment of 3- and 4-amino- and 3,5-diaminopyridazine with MeI in MeOH gave mixtures of the corresponding 1- and 2-methyl iodides whereas 3,4-, 3,6-, and 4,5-diaminopyridazines gave only one methiodide, in the first case identified as 3,4-diamino-1-methylpyridazinium iodide. No ammonio compounds were detected. The ionization constants and uv and PMR spectra of the pyridazines, their methiodides, and related compounds were determined and discussed.

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) published new progress about Acidity. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, HPLC of Formula: 20744-39-2.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem

Lambert, William T.; Buysse, Ann M.; Wessels, Frank J. published the artcile< Discovery of novel insecticidal 3-aminopyridyl ureas>, Name: Pyridazin-4-amine, the main research area is aminopyridyl urea insecticidal synthesis activity; Bemisia tabaci; Myzus persicae; agrochemical discovery; commercial compounds; insecticidal spectrum; insecticide discovery; structure-activity relationship (SAR); urea.

Com. compound databases represent rich sources of potential starting points for pharmaceutical and agrochem. product development. Routine insecticidal screening of compounds ordered from these sources led to the identification of a 3-aminopyridyl urea with activity against Myzus persicae (Sulzer) (green peach aphid). Based on this activity and its structural novelty, further exploration of the chem. space around this hit was initiated. A series of ureas based on the structure of the initial hit were synthesized and screened for insecticidal activity. A broad range of tail groups derived from cyclic secondary amines were explored, and many of these compounds were found to be insecticidally active. However, only compounds featuring a 3-aminopyridine or 4-aminopyridazine head group exhibited significant insecticidal potency. Although activity against M. persicae was consistently observed, these ureas were largely inactive against another key sap-feeding insect pest, Bemisia tabaci (Glennadius) (sweetpotato whitefly). Follow-up of an insecticide hit identified from com. compound acquisition led to the discovery of a novel class of ureas with activity against M. persicae. Despite considerable effort to identify related compounds with addnl. insecticidal spectrum, however, activity on other important pests remains limited.

Pest Management Science published new progress about Bemisia tabaci. 20744-39-2 belongs to class pyridazine, and the molecular formula is C4H5N3, Name: Pyridazin-4-amine.

Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem