6711-46-2Relevant articles and documents
Design, synthesis and biological activity of a novel ethylenediamine derivatives as H1 receptor antagonists
Chen, Guangying,Huang, Gangliang,Zhou, Shiyang
, (2019/11/21)
In this study, a series of novel ethylenediamine compounds were obtained by structural modification of the lead compounds with thonzylamine, and using the principle of modifying by bioisostere formation and modification with alkyl groups. In vitro assay, the biological activities showed that the target compounds have good properties in inhibiting mast cell degranulation and releasing histamine and β-aminohexidase, such as the compounds 5c, 5g, 5k, 5l and 5o, especially of compound 5k to mast cell degranulation is IC50 = 0.0106 ± 0.001 μmol?L?1, histamine release was IC50 = 0.0192 ± 0.005 μmol?L?1 and β-hexosaminidase release was IC50 = 0.0455 ± 0.002 μmol?L?1 in vitro. At the same time, in vivo biological activities assay results showed that have a good Histamie induce bronchospasm effect with relatively long duration and good protective effect in vivo, among which the protective effect of compound 5k was 79.74 ± 0.30%, compounds 5c, 5g, 5k, 5l and 5o could inhibit the capillary permeability of increasing which were caused by histamine.
Dihydridoboranes: Selective Reagents for Hydroboration and Hydrodefluorination
Phillips, Nicholas A.,O'hanlon, James,Hooper, Thomas N.,White, Andrew J. P.,Crimmin, Mark R.
supporting information, p. 7289 - 7293 (2019/10/08)
The preparation of a new series of dihydridoboranes supported by N,N-chelating ligands, [R2NCH2CH2NAr]- (R = alkyl, Ar = aryl), is reported. These new boranes react selectively with carbonyls, imines, and a series of electron-deficient fluoroarenes. The reactivity is complementary to recognized reagents such as pinacolborane, catecholborane, NHC-BH3, and borane (BH3) itself. Selectivities are rationalized by invoking both open- A nd closed-chain forms of the reagents as part of equilibrium mixtures.
SULFONYLAMINOPYRIDINE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
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Page/Page column 112, (2016/01/25)
Provided are sulfonylaminopyridine compounds that are inhibitors of ITK kinase, compositions containing these compounds and methods for treating diseases mediated by ITK kinase. In particular, provided are compounds of Formula (I), (II) or (III), stereoisomers, tautomers, solvates, prodrugs or pharmaceutically acceptable salts thereof, where n, R1, R2, R3, R6 and R7 are defined herein, pharmaceutical compositions comprising the compound and a pharmaceutically acceptable carrier, adjuvant or vehicle, methods of using the compound or composition in therapy, for example, for treating a disease or condition mediated by ITK kinase in a patient.
Halogen bonding enhances activity in a series of dual 5-HT6/D2 ligands designed in a hybrid bioisostere generation/virtual screening protocol
Staroń, Jakub,Warszycki, Dawid,Kurczab, Rafa?,Sata?a, Grzegorz,Bugno, Ryszard,Hogendorf, Adam,Bojarski, Andrzej J.
, p. 54918 - 54925 (2016/07/06)
A novel hybrid bioisostere generation/virtual screening method combined with narrowing of chemical space through similarity to compounds that are active at the second target was successfully applied for the development of structurally new dual 5-HT6/D2 receptor ligands. Consequently, a series of derivatives of the found hit 1d (N-[2-(dimethylamino)ethyl]-N-(2-phenylethyl)aniline) was synthesized. The most active 5-HT6/D2 ligands also showed affinity for 5-HT7R and 5-HT2AR. The para-chloroaniline derivative was identified as a potent dual 5-HT6/5-HT7 receptor antagonist (Ki = 24 nM and Kb = 30 nM, Ki = 4 nM and Kb = 1.4 nM, respectively). In the case of halogen-containing compounds, interesting structure-activity relationships were observed at 5-HT6, D2 and 5-HT7 receptors, and the ligand-receptor complexes were subsequently examined using a molecular modelling approach that combined quantum-polarized ligand docking (QPLD) and Molecular-Mechanics-Generalized-Born/Surface Area (MM/GBSA) free-energy calculation, which permitted the identification of putative halogen binding pockets.
Design, synthesis, and biological evaluation of novel FAK scaffold inhibitors targeting the FAK-VEGFR3 protein-protein interaction
Gogate, Priyanka N.,Ethirajan, Manivannan,Kurenova, Elena V.,Magis, Andrew T.,Pandey, Ravindra K.,Cance, William G.
, p. 154 - 156 (2014/05/20)
Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor 3 (VEGFR3) are tyrosine kinases, which function as key modulators of survival and metastasis signals in cancer cells. Previously, we reported that small molecule chlorpyramine hydrochloride (C4) specifically targets the interaction between FAK and VEGFR3 and exhibits anti-tumor efficacy. In this study, we designed and synthesized a series of 1 (C4) analogs on the basis of structure activity relationship and molecular modeling. The resulting new compounds were evaluated for their binding to the FAT domain of FAK and anti-cancer activity. Amongst all tested analogs, compound 29 augmented anti-proliferative activity in multiple cancer cell lines with stronger binding to the FAT domain of FAK and disrupted the FAK-VEGFR3 interaction. In conclusion, we hope that this work will contribute to further studies of more potent and selective FAK-VEGFR3 protein-protein interaction inhibitors.
Substrate-promoted copper-catalyzed N-arylation of amino alcohols with aryl iodides in water
Jin, Ming,Zhao, Dan,He, Guozhen,Tong, Yao,Han, Shiqing
, p. 1651 - 1655 (2013/10/21)
An efficient method has been developed for the N-arylation of a variety of water-soluble amino alcohols (1.2 mmol) with aryl iodides (1.0 mmol) in water under CuI-catalyzed conditions. The reaction was conducted via substrate-promoted action and did not require an additional ligand or phase-transfer catalyst, and afforded the desired N-aryl amines in acceptable to excellent yields (64%-93%) under mild reaction conditions with a small excess of the amino alcohol.
Discovery of a novel series of quinolone α7 nicotinic acetylcholine receptor agonists
McDonald, Ivar M.,Mate, Robert A.,Zusi, F. Christopher,Huang, Hong,Post-Munson, Debra J.,Ferrante, Meredith A.,Gallagher, Lizbeth,Bertekap Jr., Robert L.,Knox, Ronald J.,Robertson, Barbara J.,Harden, David G.,Morgan, Daniel G.,Lodge, Nicholas J.,Dworetzky, Steven I.,Olson, Richard E.,MacOr, John E.
, p. 1684 - 1688 (2013/04/10)
High throughput screening led to the identification of a novel series of quinolone α7 nicotinic acetylcholine receptor (nAChR) agonists. Optimization of an HTS hit (1) led to 4-phenyl-1-(quinuclidin-3-ylmethyl) quinolin-2(1H)-one, which was found to be potent and selective. Poor brain penetrance in this series was attributed to transporter-mediated efflux, which was in turn due to high pKa. A novel 4-fluoroquinuclidine significantly lowered the pKa of the quinuclidine moiety, reducing efflux as measured by a Caco-2 assay.
Microwave-promoted mono-N-alkylation of aromatic amines in water: A new efficient and green method for an old and problematic reaction
Marzaro, Giovanni,Guiotto, Adriano,Chilin, Adriana
supporting information; experimental part, p. 774 - 776 (2010/04/23)
A greener improvement to direct mono-N-alkylation of aromatic amines by alkyl halides was achieved using microwave irradiation in water without any catalyst.
7-Fluoroindazoles as potent and selective inhibitors of factor Xa
Lee, Yu-Kai,Parks, Daniel J.,Lu, Tianbao,Thieu, Tho V.,Markotan, Thomas,Pan, Wenxi,McComsey, David F.,Milkiewicz, Karen L.,Crysler, Carl S.,Ninan, Nisha,Abad, Marta C.,Giardino, Edward C.,Maryanoff, Bruce E.,Damiano, Bruce P.,Player, Mark R.
, p. 282 - 297 (2008/09/17)
We have developed a novel series of potent and selective factor Xa inhibitors that employ a key 7-fluoroindazolyl moiety. The 7-fluoro group on the indazole scaffold replaces the carbonyl group of an amide that is found in previously reported factor Xa inhibitors. The structure of a factor Xa cocrystal containing 7-fluoroindazole 51a showed the 7-fluoro atom hydrogen-bonding with the N-H of Gly216 (2.9 ?) in the peptide backbone. Thus, the 7-fluoroindazolyl moiety not only occupied the same space as the carbonyl group of an amide found in prior factor Xa inhibitors but also maintained a hydrogen bond interaction with the protein's β-sheet domain. The structure-activity relationship for this series was consistent with this finding, as the factor Xa inhibitory potencies were about 60-fold greater (ΔΔG ≈ 2.4 kcal/mol) for the 7-fluoroindazoles 25a and 25c versus the corresponding indazoles 25b and 25d. Highly convergent synthesis of these factor Xa inhibitors is also described.
Potassium iodide catalysed monoalkylation of anilines under microwave irradiation
Romera, Juan L.,Cid, José M.,Trabanco, Andrés A.
, p. 8797 - 8800 (2007/10/03)
A potassium iodide catalysed method for the selective N-monoalkylation anilines with alkylhalides and alkyltosylates under microwave irradiation is described. The corresponding N-alkylanilines are obtained in good yields with only minor quantities of dialkylation by-products.
