34906-70-2

Upstream product

• 3544-25-0 p-aminophenylacetonitrile 
• 77-78-1 dimethyl sulfate 
• 18293-53-3 2-trimethylsilylacetonitrile 
• 586-77-6 4-bromo-N,N-dimethylaniline 
• 17078-28-3 2-[4-(dimethylamino)phenyl]acetic acid 
• 50-00-0 formaldehyd 
• 58402-54-3 [p-(N,N-dimethylamino)phenyl]-1H-pentazole 
• 75-05-8 acetonitrile 
• 18523-44-9 p-(dimethylamino)phenyl azide 
• 99-98-9 4-amino-N,N-dimethylaniline 
• 38622-91-2 [(p-methylphenyl)sulfonylmethyl]isonitrile 
• 100-10-7 4-dimethylamino-benzaldehyde 

Downstream Products

• 52632-05-0 4-Dimethylaminophenethylamine 
• 111293-79-9 2,3c-bis-(4-dimethylamino-phenyl)-acrylonitrile 
• 810-15-1 3,4,5-Triphenyl-2-<4-dimethylamino-phenyl>-cyclopentadien-(2,4)-on-(1) 
• 810-63-9 4,5-Diphenyl-2,3-bis-<4-dimethylamino-phenyl>-cyclopentadien-(2,4)-on-(1) 
• 91857-66-8 4-Amino-5-(4-dimethylamino-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester 
• 52565-71-6 (E)-2-(4-(dimethylamino)phenyl)-3-phenylacrylonitrile 

Relevant academic research and scientific papers

Accelerated Discovery of α-Cyanodiarylethene Photoswitches

Cyanodiarylethene chromophores are able to undergo constitutional exchange via dynamic covalent chemistry (DCC). During this process, the central ethylene bridge of the molecular scaffold can be broken and thereby enables the assembly of a new combination of aryl moieties around the reformed ethylene bridge. The reversible CC double bond exchange has exemplarily been investigated using α-cyanostilbenes. Establishing a dynamic equilibrium reaction from α-cyanodiarylethene with arylacetonitriles under mild conditions has been the basis to access constitutional libraries of new photoswitches with potentially improved properties. When subject to irradiation with light of adequate wavelength, α-cyanodiarylethenes undergo Z/E isomerization followed by ring-closure. By screening the thus accessible dynamic chromophore libraries using a desired detection wavelength, we could identify specific dithienyl analogues that exhibit three-state photochromism. The combination of dynamic constitutional libraries of functional chromophores in combination with the light-guided screening and selection should lead to more rapid exploration of structural diversity dye chemistry.

Design, synthesis, and biological evaluation of novel EGFR inhibitors containing 5-chloro-3-hydroxymethyl-indole-2-carboxamide scaffold with apoptotic antiproliferative activity

New EGFR inhibitor series of fifteen 5-chloro-3-hydroxymethyl-indole-2-carboxamide derivatives has been designed, synthesized, and tested for antiproliferative activity against a panel of cancer cell lines. The results showed that p-substituted phenethyl derivatives 10, 11, 13, 15 and 17–19 showed superior antiproliferative activity compared to their m-substituted counterparts 12, 14, 16 and 20. Compounds 15, 16, 19 and 20 displayed promising EGFR inhibitory activity as well as an increase in caspase 3 levels. Compounds 15 and 19 increased caspase-8 and 9 levels, as well as inducing Bax and decreasing Bcl-2 protein levels. Compound 19 demonstrated cell cycle arrest at pre-G1 and G2/M phases. The results of the docking study into the active site of EGFR revealed strong fitting of the new compounds with higher binding affinities compared to erlotinib.

Novel 1,5-diaryl pyrazole-3-carboxamides as selective COX-2/sEH inhibitors with analgesic, anti-inflammatory, and lower cardiotoxicity effects

COX-2 selective drugs have been withdrawn from the market due to cardiovascular side effects, just a few years after their discovery. As a result, a new series of 1,5-diaryl pyrazole carboxamides 19–31 was synthesized as selective COX-2/sEH inhibitors wit

Design and synthesis of novel 2,3-dihydropyrazino[1,2-a]indole-1,4-dione derivatives as antiproliferative EGFR and BRAFV600E dual inhibitors

Recent studies have shown additive and synergistic effects associated with the combination of kinase inhibitors. BRAFV600E and EGFR are attractive targets for many diseases treatments and have been studied extensively. In keeping with our interest in developing anticancer targeting EGFR and BRAFV600E, a novel series of 2,3-dihydropyrazino[1,2-a]indole-1,4-dione has been rationally designed, synthesized and evaluated for their antiproliferative activity against a panel of four human cancer cell lines. Compounds 20–23, 28–31, and 33 showed promising antiproliferative activities. These compounds were further tested for their inhibitory potencies against EGFR and BRAFV600E kinases with erlotinib as a reference drug. Compounds 23 and 33 exhibited equipotency to doxorubicin against the four cell lines and efficiently inhibited both EGFR (IC50 = 0.08 and 0.09 μM, respectively) and BRAFV600E (IC50 = 0.1 and 0.29 μM, respectively). In cell cycle study of MCF-7 cell line, compounds 23 and 33 induced apoptosis and exhibited cell cycle arrest in both Pre-G1 and G2/M phases. Molecular docking analyses revealed that the new compounds can fit snugly into the active sites of EGFR, and BRAFV600E kinases. Compound 23, 31 and 33 adopted similar binding orientations and interactions to those of erlotinib and vemurafenib.

Design, synthesis and pharmacophoric model building of new 3-alkoxymethyl/3-phenyl indole-2-carboxamides with potential antiproliferative activity

Novel 3-alkoxymethyl/3-phenyl indole-2-carboxamide derivatives were synthesized and evaluated for their anticancer activity. Most of the tested compounds showed moderate to excellent activity against the tested cell lines (MCF7 and HCT116). 3-Phenyl substitution on indole with p-piperidinyl phenethyl 24a and p-dimethylamino phenethyl 24c exhibited anticancer activity against MCF7 with IC50 of 0.13 and 0.14?μm, respectively. Further mechanistic study of the most active compounds through their action on cell cycle showed disturbance in cell cycle progression and cell cycle arrest. For future development of this series of compounds, pharmacophore study was conducted which indicated that the enhancement of the activity could be achieved through the addition of acceptor or donating groups to the already-present indole nucleus.

Synthesis, biological evaluation, docking study and ulcerogenicity profiling of some novel quinoline-2-carboxamides as dual COXs/LOX inhibitors endowed with anti-inflammatory activity

A series of novel quinoline-2-carboxamides 15–28 was synthesized and evaluated in?vitro as dual COXs/LOX inhibitors. Compounds 19 and 27 exhibited the highest potency and selectivity for COX-2 inhibitory activity (IC50?=?1.21 and 1.13?μM, respe

Two-step cyanomethylation protocol: Convenient access to functionalized aryl- and heteroarylacetonitriles

A two-step protocol has been developed for the introduction of cyanomethylene groups to metalated aromatics through the intermediacy of substituted isoxazoles. A palladium-mediated cross-coupling reaction was used to introduce the isoxazole unit, followed by release of the cyanomethylene function under thermal or microwave-assisted conditions. The intermediate isoxazoles were shown to be amenable to further functionalization prior to deprotection of the sensitive cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl-substituted acetonitrile building blocks.

Solution photochemistry of [ p -(Dimethylamino)phenyl]pentazole (DMAPP) at 193 and 300 nm

The photochemistry of [p-(dimethylamino)phenyl]pentazole (DMAPP) at 193 nm and in the near UV is reported, with emphasis on the nature of the final stable products. The (dimethylamino)phenyl azide (DMAPA) is found as a major product in MeCN, but not in dichloromethane (DCM). (In this paper the acronyms DMAPP and DMAPA refer to the para isomers.) The photochemistry of DMAPA is also explored for comparison. The data obtained in MeCN solutions are consistent with the initial formation of the corresponding nitrene, but in DCM, different products are found, on the basis of NMR data. In the case of high reactant concentration in DCM (10-2 M), quantitative conversion of DMAPP and DMAPA is observed, indicating a high quantum yield. In contrast, MeCN solutions react much more slowly. A radical-type chain reaction mechanism is proposed to account for this observation. At high dilution, DMAPP is completely converted to products in both solvents. Possible mechanisms accounting for these results are discussed.

N- (ARYLALKYL) - 1H- INDOLE- 2 - SULFONIC ACID AMIDE COMPOUNDS AND THEIR THERAPEUTIC USE AS CANNABINOID ALLOSTERIC MODULATORS

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain /V-(arylalkyl)-1 H-indole- 2-sulfonic acid amide compounds that, inter alia, inhibit cannabinoid receptor signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit cannabinoid receptor signalling; to treat disorders that are ameliorated by the inhibition of cannabinoid receptor signalling; to treat metabolic syndrome, type-2 diabetes, dyslipidaemia, obesity, eating disorders, cardiovascular diseases and disorders, and other conditions as described herein.

Controlled conversion of phenylacetic acids to phenylacetonitriles or benzonitriles using bis(2-methoxyethyl)aminosulfur trifluoride

A mild, efficient, and practical method for the one-step synthesis of benzonitriles from phenylacetic acids using bis(2-methoxyethyl)aminosulfur trifluoride is described. The reaction was easily extended to the synthesis of the corresponding phenylacetonitriles by inclusion of triethylphosphine.