131362-25-9Relevant academic research and scientific papers
Chromium-Salen Complex/Nitroxyl Radical Cooperative Catalysis: A Combination for Aerobic Intramolecular Dearomative Coupling of Phenols
Nagasawa, Shota,Fujiki, Shogo,Sasano, Yusuke,Iwabuchi, Yoshiharu
, p. 6952 - 6968 (2021/05/29)
We describe an aerobic intramolecular dearomative coupling reaction of tethered phenols using a catalytic system consisting of a chromium-salen (Cr-salen) complex combined with a nitroxyl radical. This novel catalytic system enables formation of various spirocyclic dienone products including those unable to be accessed by previously reported methods efficiently under mild reaction conditions.
Influences of Histidine-1 and Azaphenylalanine-4 on the Affinity, Anti-inflammatory, and Antiangiogenic Activities of Azapeptide Cluster of Differentiation 36 Receptor Modulators
Chignen Possi, Kelvine,Mulumba, Mukandila,Omri, Samy,Garcia-Ramos, Yesica,Tahiri, Houda,Chemtob, Sylvain,Ong, Huy,Lubell, William D.
, p. 9263 - 9274 (2017/11/30)
Azapeptide analogues of growth hormone releasing peptide-6 (GHRP-6) exhibit promising affinity, selectivity, and modulator activity on the cluster of differentiation 36 receptor (CD36). For example, [A1, azaF4]- and [azaY4
Indazole-oxadiazole derivative, medicinal composition containing derivative, and application of derivative in tumor prevention
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, (2017/07/25)
The invention discloses an indazole-oxadiazole derivative with the structure represented by general formula a shown in the description, or a pharmaceutically acceptable salt or solvate thereof. In the formula, X is O or N, Y is N, Z is N or O, and all groups are as defined in the description. The invention also discloses a medicinal composition adopting the derivative as an active component, and a use of the derivative. Compounds synthesized in the invention have an HIF-1 inhibition effect, and most of the compounds have a substantial HIF-1 inhibition effect, have strong in-vivo and in-vitro anti-HIF-1 effect on human colorectal carcinoma cell strains (HCT116) and other tumor cell strains, and can be used for treating tumor diseases.
Modular construction of quaternary hemiaminal-based inhibitor candidates and their in cellulo assessment with HIV-1 protease
Gros, Guillaume,Martinez, Lorena,Gimenez, Anna Servat,Adler, Paula,Maurin, Philippe,Wolkowicz, Roland,Falson, Pierre,Hasserodt, Jens
, p. 5407 - 5413 (2013/09/02)
Non-peptidomimetic drug-like protease inhibitors have potential for circumventing drug resistance. We developed a much-improved synthetic route to our previously reported inhibitor candidate displaying an unusual quaternized hemi-aminal. This functional group forms from a linear precursor upon passage into physiological media. Seven variants were prepared and tested in cellulo with our HIV-1 fusion-protein technology that result in an eGFP-based fluorescent readout. Three candidates showed inhibition potency above 20 μM and toxicity at higher concentrations, making them attractive targets for further refinement. Importantly, our class of original inhibitor candidates is not recognized by two major multidrug resistance pumps, quite in contrast to most clinically applied HIV-1 protease inhibitors.
Asymmetric total synthesis of (-)-quinocarcin
Wu, Yan-Chao,Liron, Melanie,Zhu, Jieping
, p. 7148 - 7152 (2008/12/20)
(-)-Quinocarcin (1) has been synthesized in a longest linear sequence of 22 steps from 3-hydroxybenzaldehyde in 16% overall yield. The Pictet-Spengler reaction of L-tert-butyl-2-bromo-5-hydroxy phenylalanate (17), synthesized according to Corey-Lygo's enantioselective alkylation process, with benzoxyacetaldehyde (12) under mild acidic conditions afforded 1,3-cis tetrahydroisoquinoline 20 as an only isolable stereomer in 91% yield. The diazabicycle[3,2,1]-octane ring system of 28 was constructed by a silver tetrafluoroborate-promoted intramolecular Mannich reaction using amino thioether as a latent N-acyliminium species and tethered silyl enol ether as a nucleophile. Using amino thioether instead of aminal as a precursor of N-acyliminium was of high importance to the success of this otherwise disfavored 5-endo-Trig cyclization. A Hf(OTf)4-catalyzed (0.1 equiv) transformation of aminal to amino thioether was uncovered in the course of this study, allowing the conversion of tricyclic aminal 24 to amino thioether 25 to be realized in high yield. From the bridged tetracyclic compound 28, a sequence of oxidation of aldehyde to acid, global deprotection under hydrogenolysis conditions, and one-pot partial reduction of lactam to aminal/oxazolidine formation completed the total synthesis of the pentacyclic (-)-quinocarcine.
Synthesis of (-)-quinocarcin by directed condensation of α-amino aldehydes
Kwon, Soojin,Myers, Andrew G.
, p. 16796 - 16797 (2007/10/03)
An enantioselective synthesis of the natural antiproliferative agent quinocarcin was achieved by the directed condensation of optically active α-amino aldehyde intermediates. Condensation of the N-protected α-amino aldehyde 1, prepared in eight steps (19% yield) from (R,R)-pseudoephedrine glycinamide, with the C-protected α-amino aldehyde derivative 2, prepared in seven steps (34% yield) from (R,R)-pseudoephedrine glycinamide, afforded the corresponding imine in quantitative yield. Without isolation, direct treatment of this imine intermediate with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and hydrogen cyanide led to cleavage of the fluorenylmethoxycarbonyl (Fmoc) protective group followed by addition of cyanide (Strecker reaction) to form the bis-amino nitriles 3 as a mixture of diastereomers, in 91% yield. Treatment of the diastereomers 3 with trimethylsilyl cyanide and zinc chloride in 2,2,2-trifluoroethanol at 60 °C led to stepwise cyclization to form the tetracyclic product 4 (42% yield from 1 and 2). The latter intermediate was transformed into (-)-quinocarcin (1) in five steps (45% yield). The yield of quinocarcin was 19% from 1 and 2 (7 steps), and 4% from pseudoephedrine glycinamide (15 steps). Copyright
AN ASYMMETRIC SYNTHESIS OF S-(-)-NORANICANINE
Meyers, Albert I.,Nguyen, Thanh H.
, p. 513 - 518 (2007/10/02)
The absolute configuration of the titled natural alkaloid has been confirmed as R-(+) through a chiral formamidine-assisted total synthesis.
PYRAN DERIVATIVES AND THEIR USE AS INHIBITORS OF 5-LIPOXYGENASE
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, (2008/06/13)
The invention concerns a cyclic ether derivative of the formula I, wherein Ar1 is optionally substituted phenyl, naphthyl or a 9-or 10-membered bicyclic heterocyclic moiety; A1 is a direct link to X1 or (l-3C)alkylene; X1 is oxy, thio, sulphinyl, sulphony
Nonprostanoid prostacyclin mimetics. 3. Structural variations of the diphenyl heterocycle moiety
Meanwell,Rosenfeld,Trehan,Romine,Wright,Brassard,Buchanan,Federici,Fleming,Gamberdella,Zavoico,Seiler
, p. 3498 - 3512 (2007/10/02)
4,5-Diphenyl-2-oxazolenonanoic acid (2) and 2-[3-[2-(4,5-diphenyl-2- oxazolyl)ethyl]phenoxy]acetic acid (3) were previously identified as nonprostanoid prostacyclin (PGI2) mimetics that inhibit ADP-induced aggregation of human platelets in vitro. The effects on biological activity of substitution and structural modification of the 4- and 5-phenyl rings of 3 was examined. Potency showed a marked sensitivity to the introduction of substituents to these aromatic rings and only the bis-4-methyl derivative 9j, IC50 = 0.34 μM, demonstrated enhanced potency compared to the parent structure 3, IC50 = 1.2 μM. Substitution at the ortho or meta positions of the phenyl rings, replacement by thiopheneyl or cyclohexyl moieties, or constraining in a planar phenanthrene system resulted in compounds that were less effective inhibitors of ADP-induced platelet aggregation. In contrast, variation of the heterocycle moiety revealed a much less stringent SAR and many 5- and 6-membered heterocycles were found to effectively substitute for the oxazole ring of 2 and 3. The diphenylmethyl moiety functioned as an effective isostere for 4,5-diphenylated heterocycles since 13aad showed similar platelet inhibitory activity to 3. With the exception of the 3,4,5- triphenylpyrazole derivative 13g, compounds presenting the (m- ethylphenoxy)acetic acid side chain discovered with 3 demonstrated enhanced potency compared to the analogously substituted alkanoic acid derivative. The structure-activity findings led to a refinement of a model of the nonprostanoid PGI2 mimetic pharmacophore.
