56568-99-1

Upstream product

• 529-19-1 2-Methylbenzonitrile 
• 603-35-0 triphenylphosphine 
• 22115-41-9 2-(bromomethyl)benzonitrile 

Downstream Products

• 98460-06-1 2-[(E)-2-(11-Fluoro-dibenzo[c,g]phenanthren-9-yl)-vinyl]-benzonitrile 
• 1372123-33-5 C₁₇H₁₄N₂O₂ 
• 1372123-37-9 C₁₇H₁₄N₂O 
• 161447-52-5 2-{2-[1-(4-Chloro-benzyl)-4-methyl-6-(5-phenyl-pyridin-2-ylmethoxy)-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]-ethyl}-benzonitrile 
• 908863-84-3 2-(9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazol-4-yl)benzamide 
• 908863-83-2 2-(9-methoxy-1,3-dioxo-3,6-dihydro-1H-furo[3,4-c]carbazol-4-yl)benzamide 
• 622861-40-9 2-(9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo[3,4-c]carbazol-4-yl)benzonitrile 
• 926933-87-1 4-[4-(2-cyano-benzylidene)-piperidin-1-yl]-benzoic acid 
• 622861-39-6 2-[(E)-2-(5-methoxy-1H-indol-2-yl)ethenyl]benzonitrile 
• 170243-08-0 2-{(E)-2-[1-(4-Chloro-benzyl)-4-methyl-6-(5-phenyl-pyridin-2-ylmethoxy)-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]-vinyl}-benzonitrile 
• 80663-50-9 2-((1E)-2-phenylvinyl)benzenecarbonitrile 

Relevant academic research and scientific papers

Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters

A set of new substituted dienes were synthesized from betulinic acid by its oxidation to 30-oxobetulinic acid followed by the Wittig reaction. Cytotoxicity of all compounds was tested in vitro in eight cancer cell lines and two noncancer fibroblasts. Almost all dienes were more cytotoxic than betulinic acid. Compounds 4.22, 4.30, 4.33, 4.39 had IC50 below 5 μmol/L; 4.22 and 4.39 were selected for studies of the mechanism of action. Cell cycle analysis revealed an increase in the number of apoptotic cells at 5 × IC50 concentration, where activation of irreversible changes leading to cell death can be expected. Both 4.22 and 4.39 led to the accumulation of cells in the G0/G1 phase with partial inhibition of DNA/RNA synthesis at 1 × IC50 and almost complete inhibition at 5 × IC50. Interestingly, compound 4.39 at 5 × IC50 caused the accumulation of cells in the S phase. Higher concentrations of tested drugs probably inhibit more off-targets than lower concentrations. Mechanisms disrupting cellular metabolism can induce the accumulation of cells in the S phase. Both compounds 4.22 and 4.39 trigger selective apoptosis in cancer cells via intrinsic pathway, which we have demonstrated by changes in the expression of the crucial apoptosis-related protein. Pharmacological parameters of derivative 4.22 were superior to 4.39, therefore 4.22 was the finally selected candidate for the development of anticancer drug.

Synthesis, optical and nonlinear optical properties of new pyrazoline derivatives

We report on synthesis and optical properties of new organic compounds based on substituted pyrazole ring. The investigated pyrazoline derivatives (PRDs) exhibit efficient broadband photoluminescence which covers nearly whole visible spectrum. The experimental results are compared to quantum chemical calculations. Amplified spontaneous emission and photodegradation measurements were performed for hybrid systems based on selected PRDs doped into poly(methyl methacrylate) matrix proving the potential utility of such systems in lasing applications. Two-photon absorption (TPA) properties were characterized by the femtosecond Z-scan technique.

A catalytic metal-free Ritter reaction to 3-substituted 3-aminooxindoles

The first Ritter reaction of 3-substituted 3-hydroxyoxindoles with nitriles, catalyzed by HClO4, is developed, which enables the synthesis of 3-substituted 3-aminooxindoles in good to excellent yield with rich diversity.

Photochemical and thermal intramolecular 1,3-dipolar cycloaddition reactions of new o-stilbenemethylene-3-sydnones and their synthesis

New trans-and cis-o-stilbene-methylene-sydnones 3a,b were synthesized by transforming the trans-and cis-o-aminomethylstilbene derivative, obtained by reduction of corresponding o-cyano derivatives, into glycine ester derivatives (43 and 31% yield) followed by hydrolysis (90 and 96% yield), nitrosation and ring closure with acetic acid anhydride (30 and 40% yield). The products were submitted to photochemical and thermal intramolecular [3 + 2] cycloadditions to afford diverse heteropolycyclic compounds. Photochemical reactions afforded cis-3-(4-methylphenyl)-3a,8-dihydro-3H-pyrazolo[5,1-a]isoindole (11, 12.5% yield) and trans-3-(4-methylphenyl)-3a,8-dihydro-3H-pyrazolo[5,1-a]isoindole (12, 5% yield). Thermal reactions afforded 3-(4-methylphenyl)-3,3a,8,8a- tetrahydroindeno[2,1-c]pyrazole (14, 50% yield) and 11-(4-methylphenyl)-9,10- diazatricyclo[7.2.1.02,7]dodeca-2,4,6,10-tetraene (15, 22% yield).

Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL

Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.

4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. structure-activity relationships for chromophore modification and phenyl ring substitution

High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]-carbazole-1,3(2H,6H)- dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2′-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.

Thiopyranoindoles as Inhibitors of 5-Lipoxygenase, 5-Lipoxygenase-Activating Protein, and Leukotriene C4 Synthase

The attachment of an arylacetic or benzoic acid moiety to the thiopyranoindole nucleus results in compounds which are highly potent and selective 5-lipoxygenase (5-LO) inhibitors.These compounds are structurally simpler than previous compounds

ARYL THIOPYRANO[2,3,4-C,D]INDOLES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS

Compounds having the formula I: are inhibitors of 5-lipoxygenase and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cyto-protective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, psoriasis, uveitis, and allograft rejection and in preventing the formation of atherosclerotic plaques.

HELICENES : SYNTHESE PHOTOCHIMIQUE ET ETUDE RMN 19F, 13 C ET 1H DE FLUORO-1-HEXAHELICENES ET FLUORO-1-HEPTAHELICENES.

1-Fluorohexahelicene, 1-fluoroheptahelicene and 12 substituted derivatives of these fluorohelicenes have been synthesized by the photocyclodehydrogenation of 1-fluro-11-styrylbenzophenanthrenes (Table 2) and 1-fluoro-13-styrylpentahelicenes (Table 4) respectively.The photocyclisations to heptahelicenes were accompanied in five cases, by a side reaction, namely a photodefluoration.A new synthesis of heptahelicenes is described (25-->18 : 40 percent). 1H, 19F and 13C-NMR spectra are discussed. 19F and 13C-NMR spectra of 1-fluoro-, 1-fluoro-13-methyl- and 1-fluoro-13-methoxycarbonylpentahelicene (8d, 8a and 8 R=-CO2CH3) are also included.