6848-16-4

Usage

InChI:InChI=1/C12H14ClN/c1-8-7-12(2,3)14-11-5-4-9(13)6-10(8)11/h4-7,14H,1-3H3

Upstream product

• 141-79-7 4-methyl-pent-3-en-2-one 
• 106-47-8 4-chloro-aniline 
• 67-64-1 acetone 

Downstream Products

• 5361-30-8 1-(6-chloro-4-methylquinazolin-2-yl)guanidine hydrochloride 
• 1492019-83-6 6-chloro-8-cyclohexenyl-1,2-dihydro-2,2,4-trimethylquinoline 

Relevant academic research and scientific papers

C-N coupling of 1,2-dihydro-2,2,4-trimethylquinoline derivatives via a silver(I)-catalyzed direct functionalization of a C-H bond

Two C,N-linked dimeric 1,2-dihydro-2,2,4-trimethylquinolines, namely 6-chloro-1-(6-chloro-1,2-dihydro-2,2,4-trimethylquinolin-8-yl)-1,2-dihydro-2,2, 4-trimethylquinoline (3a) and 6-ethoxy-1-(6-ethoxy-1,2-dihydro-2,2,4- trimethylquinolin-8-yl)-1,2-dihydro-2,2,4-trimethylquinoline (3b), have been prepared through a silver-catalyzed dimerization of their corresponding monomers. The effect of different silver salts on the reaction was also investigated, and the obtained results suggest that silver ions effectively catalyzed the formation of a C-N bond under these mild conditions. This represents one of the rare reports on the silver-catalyzed C-N bond formation through a coupling of a secondary amine and an activated aromatic system, via a direct C-H functionalization. Theoretical studies showed that these dimeric structures favor a conformation in which their monomer units are oriented approximately perpendicular to each other, with an intramolecular hydrogen bond (N-H distance of 2.33 A) forming between the hydrogen atom of the amine in one of the monomeric units and the tertiary nitrogen atom of the other one.

New fluorescence-based high-throughput screening assay for small molecule inhibitors of tyrosyl-DNA phosphodiesterase 2 (TDP2)

Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase II (TOP2) mediated DNA damages and causes resistance to TOP2-targeted cancer therapy. Inhibiting TDP2 could sensitize cancer cells toward TOP2 inhibitors. However, potent TDP2 inhibitors with favorable physicochemical properties are not yet reported. Therefore, there is a need to search for novel molecular scaffolds capable of inhibiting TDP2. We report herein a new simple, robust, homogenous mix-and-read fluorescence biochemical assay based using humanized zebrafish TDP2 (14M_zTDP2), which provides biochemical and molecular structure basis for TDP2 inhibitor discovery. The assay was validated by screening a preselected library of 1600 compounds (Z′ ≥ 0.72) in a 384-well format, and by running in parallel gel-based assays with fluorescent DNA substrates. This library was curated via virtual high throughput screening (vHTS) of 460,000 compounds from Chembridge Library, using the crystal structure of the novel surrogate protein 14M_zTDP2. From this primary screening, we selected the best 32 compounds (2% of the library) to further assess their TDP2 inhibition potential, leading to the IC50 determination of 10 compounds. Based on the dose-response curve profile, pan-assay interference compounds (PAINS) structure identification, physicochemical properties and efficiency parameters, two hit compounds, 11a and 19a, were tested using a novel secondary fluorescence gel-based assay. Preliminary structure-activity relationship (SAR) studies identified guanidine derivative 12a as an improved hit with a 6.4-fold increase in potency over the original HTS hit 11a. This study highlights the importance of the development of combination approaches (biochemistry, crystallography and high throughput screening) for the discovery of TDP2 inhibitors.

Discovery of Novel Potent Reversible and Irreversible Myeloperoxidase Inhibitors Using Virtual Screening Procedure

The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great interest in the development of new efficient and specific inhibitors. Here, we have performed a novel virtual screening procedure, depending on ligand-based pharmacophore modeling followed by structure-based virtual screening. Starting from a set of 727842 compounds, 28 molecules were selected by this virtual method and tested on MPO in vitro. Twelve out of 28 compounds were found to have an IC50 less than 5 μM. The best inhibitors were 2-(7-methoxy-4-methylquinazolin-2-yl)guanidine (28) and (R)-2-(1-((2,3-dihydro-1H-imidazol-2-yl)methyl)pyrrolidin-3-yl)-5-fluoro-1H-benzo[d]imidazole (42) with IC50 values of 44 and 50 nM, respectively. Studies on the mechanism of inhibition suggest that 28 is the first potent mechanism-based inhibitor and inhibits irreversibly MPO at nanomolar concentration.

The catalytic enantioselective synthesis of tetrahydroquinolines containing all-carbon quaternary stereocenters via the formation of aza-ortho-xylylene with 1,2-dihydroquinoline as a precursor

Tetrahydroquinolines (THQs) with an all-carbon quaternary stereocenter were effectively obtained via the in situ formation of aza-ortho-xylylene (AOX) with easily accessible 1,2-dihydroquinolines as precursors. The reaction was rationalized with chiral phosporic acid to afford chiral THQs with high yield and excellent enantioselectivity.

Enantioselective Organocatalytic Transfer Hydrogenation of 1,2-Dihydroquinoline through Formation of Aza-o-xylylene

A new way of forming the aza-o-xylylene with easily accessible 1,2-dihydroquinolines as precursor has been developed. The presence of an electron-donating group at the proper position of 1,2-dihydroquinoline was crucial for protonation of the alkene through dearomatization with a simple Bronsted acid. The in situ forming reactive intermediate was trapped with Hantzsch ester to afford tetrahydroquinolines in excellent yield and enantioselectivity.

Iodine-catalyzed cycloalkenylation of dihydroquinolines and arylamines through a reaction with cyclic ketones under neat conditions

An iodine-catalyzed direct cycloalkenylation of dihydroquinolines and arylamines has been developed. This method consists of a Friedel-Crafts reaction between dihydroquinolines (or arylamines) and cyclic ketones in which the double bond is selectively generated throughout the course of the reaction resulting in a direct cycloalkenylation, under neat conditions.

Ceric ammonium nitrate: An efficient catalyst for one-pot synthesis of 2,2,4-trimethyl-1,2-dihydroquinolines

Ceric ammonium nitrate (CAN) catalyzed the one-pot synthesis of 2,2,4-trirnethyl-1,2-dihydroquinoline derivatives from substituted anilines and acetone via a modified Skraup reaction. The methodology was used to synthesize a novel dihydroquinoline-based compound derived from an anti-inflammatory agent nimesulide.

A facile synthesis of 2,2,4-trisubstituted-1,2-dihydroquinolines catalyzed by zinc triflate under solvent-free conditions

An efficient process has been developed for the synthesis of 2,2,4-trisubstituted-1,2-dihydroquinolines in good yields through a simple one-pot condensation between anilines and ketones in the presence of zinc triflate as a catalyst at room temperature under solvent-free conditions.

Mild and convenient synthesis of 1,2-dihydroquinolines from anilines and acetone catalyzed by ytterbium(III) triflate in ionic liquids

A mild, convenient, and efficient process has been developed for the synthesis of 2,2,4-trimethyl-1,2-dihydroquinolines by the reaction of anilines with acetone catalyzed by ytterbium(III) triflate [Yb(OTf)3] in ionic liquids. The catalyst and ionic liquids can be easily recovered and reused, making this method friendly and environmentally acceptable. Copyright Taylor & Francis Group, LLC.

Efficient microwave-assisted synthesis of quinolines and dihydroquinolines under solvent-free conditions

A convenient and efficient procedure for the synthesis of quinolines and dihydroquinolines has been developed by a simple one-pot reaction of anilines with alkyl vinyl ketones on the surface of silica gel impregnated with indium(III) chloride under microwave irradiation without any solvent.