17064-76-5

Upstream product

• 106-47-8 4-chloro-aniline 
• 552-89-6 2-nitro-benzaldehyde 

Downstream Products

• 129239-65-2 1-(4-chlorophenyl)-5-(2-nitrophenyl)-1,2,3-triazoline 
• 56156-73-1 2-(4-chloro-phenyl)-2H-indazole-3-carbonitrile 
• 56156-68-4 (4-chloro-phenyl)-(3-methoxy-1-oxy-cinnolin-4-yl)-amine 
• 54184-70-2 2-(4-chlorophenyl)-3-phenyl-2H-indazole 
• 61073-53-8 2-(4-chlorophenyl)-2H-indazole 
• 151383-60-7 4-chloro-N-(2-nitrobenzyl)aniline 
• 20887-03-0 N-(2-aminobenzyl)-4-chloroaniline 
• 69914-72-3 diethyl (4-chlorophenylamino)(2-nitrophenyl)methylphosphonate 
• 129239-58-3 1-(4-Chloro-phenyl)-5-(2-nitro-phenyl)-1H-[1,2,3]triazole 
• 1204524-87-7 3,3'-bis(4-chlorophenyl)-3,3',4,4'-tetrahydro-4,4'-biquinazoline-2,2'-dione 

Relevant academic research and scientific papers

Synthesis, antiprotozoal activity, and cheminformatic analysis of 2-phenyl-2h-indazole derivatives

Indazole is an important scaffold in medicinal chemistry. At present, the progress on synthetic methodologies has allowed the preparation of several new indazole derivatives with interesting pharmacological properties. Particularly, the antiprotozoal activity of indazole derivatives have been recently reported. Herein, a series of 22 indazole derivatives was synthesized and studied as antiprotozoals. The 2-phenyl-2H-indazole scaffold was accessed by a one-pot procedure, which includes a combination of ultrasound synthesis under neat conditions as well as Cadogan’s cyclization. Moreover, some compounds were derivatized to have an appropriate set to provide structure-activity relationships (SAR) information. Whereas the antiprotozoal activity of six of these compounds against E. histolytica, G. intestinalis, and T. vaginalis had been previously reported, the activity of the additional 16 compounds was evaluated against these same protozoa. The biological assays revealed structural features that favor the antiprotozoal activity against the three protozoans tested, e.g., electron withdrawing groups at the 2-phenyl ring. It is important to mention that the indazole derivatives possess strong antiprotozoal activity and are also characterized by a continuous SAR.

Synthesis and biological evaluation of 2H-indazole derivatives: Towards antimicrobial and anti-inflammatory dual agents

Indazole is considered a very important scaffold in medicinal chemistry. It is commonly found in compounds with diverse biological activities, e.g., antimicrobial and anti-inflammatory agents. Considering that infectious diseases are associated to an inflammatory response, we designed a set of 2H-indazole derivatives by hybridization of cyclic systems commonly found in antimicrobial and anti-inflammatory compounds. The derivatives were synthesized and tested against selected intestinal and vaginal pathogens, including the protozoa Giardia intestinalis, Entamoeba histolytica, and Trichomonas vaginalis; the bacteria Escherichia coli and Salmonella enterica serovar Typhi; and the yeasts Candida albicans and Candida glabrata. Biological evaluations revealed that synthesized compounds have antiprotozoal activity and, in most cases, are more potent than the reference drug metronidazole, e.g., compound 18 is 12.8 times more active than metronidazole against G. intestinalis. Furthermore, two 2, 3-diphenyl-2H-indazole derivatives (18 and 23) showed in vitro growth inhibition against Candida albicans and Candida glabrata. In addition to their antimicrobial activity, the anti-inflammatory potential for selected compounds was evaluated in silico and in vitro against human cyclooxygenase-2 (COX-2). The results showed that compounds 18, 21, 23, and 26 display in vitro inhibitory activity against COX-2, whereas docking calculations suggest a similar binding mode as compared to rofecoxib, the crystallographic reference.

A Biphilic Phosphetane Catalyzes N-N Bond-Forming Cadogan Heterocyclization via PIII/PV = O Redox Cycling

A small-ring phosphacycle, 1,2,2,3,4,4-hexamethylphosphetane, is found to catalyze deoxygenative N-N bond-forming Cadogan heterocyclization of o-nitrobenzaldimines, o-nitroazobenzenes, and related substrates in the presence of hydrosilane terminal reductant. The reaction provides a chemoselective catalytic synthesis of 2H-indazoles, 2H-benzotriazoles, and related fused heterocyclic systems with good functional group compatibility. On the basis of both stoichiometric and catalytic mechanistic experiments, the reaction is proposed to proceed via catalytic PIII/PV = O cycling, where DFT modeling suggests a turnover-limiting (3+1) cheletropic addition between the phosphetane catalyst and nitroarene substrate. Strain/distortion analysis of the (3+1) transition structure highlights the controlling role of frontier orbital effects underpinning the catalytic performance of the phosphetane.

Integration of Bromine and Cyanogen Bromide Generators for the Continuous-Flow Synthesis of Cyclic Guanidines

A continuous-flow process for the in situ on-demand generation of cyanogen bromide (BrCN) from bromine and potassium cyanide that makes use of membrane-separation technology is described. In order to circumvent the handling, storage, and transportation of elemental bromine, a continuous bromine generator using bromate–bromide synproportionation can optionally be attached upstream. Monitoring and quantification of BrCN generation was enabled through the implementation of in-line FTIR technology. With the Br2 and BrCN generators connected in series, 0.2 mmol BrCN per minute was produced, which corresponds to a 0.8 m solution of BrCN in dichloromethane. The modular Br2/BrCN generator was employed for the synthesis of a diverse set of biologically relevant five- and six-membered cyclic amidines and guanidines. The set-up can either be operated in a fully integrated continuous format or, where reactive crystallization is beneficial, in semi-batch mode.

Synthesis, X-ray crystal structure, DNA/protein binding and cytotoxicity studies of five α-aminophosphonate N-derivatives

Five new α-aminophosphonates are synthesized and characterized by EA, FT-IR, 1H NMR, 13C NMR, 31P NMR, ESI-MS and X-ray crystallography. The X-ray analyses reveal that the crystal structures of 1–5 are monoclinic or triclinic system with the space group P 21/c, P ? 1, P ? 1, P2(1)/c and P ? 1, respectively. All P atoms of 1–5 have tetrahedral geometries involving two O-ethyl groups, one Cα atom, and a double bond O atom. The binding interaction of five new α-aminophosphonate N-derivatives (1–5) with calf thymus(CT)-DNA have been investigated by UV–visible and fluorescence emission spectrometry. The apparent binding constant (Kapp) values follows the order: 1 (3.38 × 105 M?1) > 2 (3.04 × 105 M?1) > 4 (2.52 × 105 M?1) > 5 (2.32 × 105 M?1) > 3 (2.10 × 105 M?1), suggesting moderate intercalative binding mode between the compounds and DNA. In addition, fluorescence spectrometry of bovine serum albumin (BSA) with the compounds 1–5 showed that the quenching mechanism might be a static quenching procedure. For the compounds 1–5, the number of binding sites were about one for BSA and the binding constants follow the order: 1 (2.72 × 104 M?1) > 2 (2.27 × 104 M?1) > 4 (2.08 × 104 M?1) > 5 (1.79 × 104 M?1) > 3 (1.17 × 104 M?1). Moreover, the DNA cleavage abilities of 1 exhibit remarkable changes and the in vitro cytotoxicity of 1 on tumor cells lines (MCF-7, HepG2 and HT29) have been examined by MTT and shown antitumor effect on the tested cells.

A Facile One-Step Synthesis of 2-Arylindazoles via Reductive Cyclization of N-(2-nitroarylidene)amines

A mild and efficient synthesis of 2-arylindazole derivatives via the reductive cyclization of nitro-aryl substrates mediated by a low-valent titanium reagent (TiCl4/Sm/Et3N) has been developed. The attractive features of the current method include an N-N bond formation and the selective reduction of the =C-N bond and nitro group, both of which were easily achieved in one-pot by controlling the pH of the reaction mixture.

Regioselective synthesis of 2 H-indazoles using a mild, one-pot condensation-cadogan reductive cyclization

An operationally simple and efficient one-pot synthesis of 2H-indazoles from commercially available reagents is reported. Ortho-imino-nitrobenzene substrates, generated via condensation, undergo reductive cyclization promoted by tri-n-butylphosophine to afford substituted 2H-indazoles under mild reaction conditions. A variety of electronically diverse ortho-nitrobenzaldehydes and anilines were examined. To further extend the scope of the transformation, aliphatic amines were also employed to form N2-alkyl indazoles selectively under the optimized reaction conditions.

Oriented synthesis and in vitro anticancer activity of biquinazoline-2,2'- diones

The synthesis of a series of biquinazoline-2,2'-diones starting from o-nitrobenzaldehydes, anilines, and triphosgene is presented. This general approach features a novel and easy way for access to the target products. The mechanistic course of the reaction suggests the involvement of reduction, coupling, and cyclization by one-pot. These compounds were also investigated in vitro for anticancer activity, and some were found to have good anticancer activity.

o-Nitrobenzylidene Compounds. Part 3. Formation of 4-Arylamino-3-methoxycinnoline 1-Oxides from N-o-Nitrobenzylideneanilines, Cyanide Ion, and Methanol: the Intermediacy of 2-Aryl-3-cyano-2H-indazole 1-Oxides

The N-o-nitrobenzylidene derivatives of variously substituted anilines (7) have been cyclised by potassium cyanide in methanol, to give 4-arylamino-3-methoxycinnoline 1-oxides (9), the structures of which have been confirmed by independent synthesis of one representative .These cinnoline oxides are the main products (sometimes the only isolated products) when the amine-derived ring in (7) is ortho-substituted; in other cases the cinnoline oxides are minor products formed along with 2-aryl-3-cyano-2H-indazoles (10).In the latter group of reactions, the primary cyclisation products are 2-aryl-3-cyano-2H-indazole 1-oxides (8): these have then either been reduced to the indazoles in the basic methanolic medium, or have undergone ring-opening and recyclisation to give the cinnoline oxides (9).In the other group, where indazole oxides (8) cannot usually be isolated, their intermediacy in cinnoline oxide formation remains a possibility, although other mechanistic pathways can be envisaged.Some 'borderline' cases are identified and discussed.