66532-87-4

Upstream product

• 59-88-1 phenylhydrazine hydrochloride 
• 2142-63-4 1-(3-Bromophenyl)ethanone 
• 100-63-0 phenylhydrazine 

Downstream Products

• 93716-78-0 2-(3-bromophenyl)-1H-indole 
• 914389-67-6 2-(3-iodophenyl)-1H-indole 

Relevant academic research and scientific papers

Acid-catalyzed cleavage of C-C bonds enables atropaldehyde acetals as masked C2 electrophiles for organic synthesis

Acid-catalyzed tandem reactions of atropaldehyde acetals were established for the synthesis of three important molecules, 2,2-disubstituted indolin-3-ones, naphthofurans and stilbenes. The synthesis was realized using novel reaction cascades, which involved the same two initial steps: (i) SN2′ substitution, in which the atropaldehyde acted as an electrophile; and (ii) oxidative cleavage of the carbon-carbon bond of the generated phenylacetaldehyde-type products. Compared with literature methods, the present protocol not only avoided the use of expensive noble metal catalysts, but also enabled a simple operation.

An iron(iii)-catalyzed dehydrogenative cross-coupling reaction of indoles with benzylamines to prepare 3-aminoindole derivatives

We report a green cascade approach to prepare a variety of 3-aminoindole derivatives in good to excellent yields through an iron(iii)-catalyzed dehydrogenative cross-coupling reaction of 2-arylindoles and primary benzylamines under mild reaction conditions. Mechanistic studies show that a cascade reaction involves a tert-butyl nitrite (TBN)-mediated nitrosation of 2-substituted indoles and a 1,5-hydrogen shift to afford indolenine oximes, sequential iron(iii)-catalyzed condensation and a 1,5-hydrogen shift over four steps in a one-pot reaction. The reaction shows a broad substrate scope of indoles and benzylamines and tolerates a wide range of functional groups. Moreover, the reaction is easily performed at the gram scale without producing waste after the reaction is completed. The 3-aminoindole product is purified by simple extraction, washing, and recrystallization without flash column chromatography. A double imine ligand containing the 3-aminoindole unit is facile to obtain in a 52% yield in one step. The present method highlights readily available starting materials, a simple purification procedure, and the usage of cheap, nontoxic, and environmentally benign iron(iii) catalysts. This journal is

Discovery of New 4-Indolyl Quinazoline Derivatives as Highly Potent and Orally Bioavailable P-Glycoprotein Inhibitors

The major drawbacks of P-glycoprotein (P-gp) inhibitors at the clinical stage make the development of new P-gp inhibitors challenging and desirable. In this study, we reported our structure-activity relationship studies of 4-indolyl quinazoline, which led to the discovery of a highly effective and orally active P-gp inhibitor, YS-370. YS-370 effectively reversed multidrug resistance (MDR) to paclitaxel and colchicine in SW620/AD300 and HEK293T-ABCB1 cells. YS-370 bound directly to P-gp, did not alter expression or subcellular localization of P-gp in SW620/AD300 cells, but increased the intracellular accumulation of paclitaxel. Furthermore, YS-370 stimulated the P-gp ATPase activity and had moderate inhibition against CYP3A4. Significantly, oral administration of YS-370 in combination with paclitaxel achieved much stronger antitumor activity in a xenograft model bearing SW620/Ad300 cells than either drug alone. Taken together, our data demonstrate that YS-370 is a promising P-gp inhibitor capable of overcoming MDR and represents a unique scaffold for the development of new P-gp inhibitors.

In vitro studies of potent aldose reductase inhibitors: Synthesis, characterization, biological evaluation and docking analysis of rhodanine-3-hippuric acid derivatives

Inhibitors of aldose reductase are rate-limiting enzymes and could play a key role to prevent the complications of diabetes. In our attempt to develop novel inhibitors of aldose reductase, the derivatives of rhodanine-3-hippuric acid-pyrazole hybrid were synthesized and characterised by spectral data. The biological studies reveal that all the compounds show an excellent activity against ALR2 with IC50 values ranging from 0.04 to 1.36 μM. Among these the synthesised compounds 6a-m, 6g and 6e showed specific inhibitory activity with IC50 values of 0.04 and 0.06 μM respectively against ALR2 and found to be more potent than epalrestat (IC50 = 0.87 μM), the only aldose reductase inhibitor currently used in the therapy. Molecular docking analysis using the AR-NADP+ complex as a receptor was performed with all the synthesized compounds. All the compounds exhibit a well-defined binding mode within the AR active site, similarly to previous described AR inhibitors, with the anion head group bound to the catalytic center, blocking thus its activity. By forming hydrogen bonds with Tyr48 and His110 of the protein from ALR2 (PDB ID: 2FZD), the compounds 6g and 6e interrupt the proton donation mechanism, which is necessary for the catalytic activity of ALR2.

Chiral Br?nsted Acid from Chiral Phosphoric Acid Boron Complex and Water: Asymmetric Reduction of Indoles

A new chiral Br?nsted acid, generated in situ from a chiral phosphoric acid boron (CPAB) complex and water, was successfully applied to asymmetric indole reduction. This “designer acid catalyst”, which is more acidic than TsOH as suggested by DFT calculations, allows the unprecedented direct asymmetric reduction of C2-aryl-substituted N-unprotected indoles and features good to excellent enantioselectivities with broad functional group tolerance. DFT calculations and mechanistic experiments indicates that this reaction undergoes C3-protonation and hydride-transfer processes. Besides, bulky C2-alkyl-substituted N-unprotected indoles are also suitable for this system.

Novel pyrazole-clubbed thiophene derivatives via Gewald synthesis as antibacterial and anti-inflammatory agents

The aim of this study was to synthesize newer potent Schiff bases by condensing 2-amino-5-(2,4-dichlorophenyl)thiophene-3-carbonitrile and 1,3-disubstituted-1H-pyrazole-4-carbaldehydes, and to investigate their biological activity. The compounds were synthesized via Gewald synthesis and characterized by spectral data and elemental analyses. They were screened for their in vitro antibacterial and anti-inflammatory activities. The synthesized compounds were also evaluated for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv using the microplate Alamar Blue assay. Compounds 8b, 8c, 8f, 8g, 8k, 8n, and 8o showed promising antibacterial activity. The interactions between the substituted pyrazoles and bovine protein showed promising anti-inflammatory activity. The experimental results revealed compound 8a as a promising antitubercular agent. Hemolytic assays confirmed that the compounds are nontoxic, with percentage hemolysis ranging from 3.6 to 20.1, at a concentration of 1 mg/ml. The results suggest that the pyrazole ring and the substitution pattern on the heterocyclic moiety have an effect on the bioactivity.

Pyrazolylphenanthroimidazole heterocycles: Synthesis, biological and molecular docking studies

The synthesis of a series of novel pyrazolylphenanthroimidazoles 6a-6j has been accomplished utilizing a multi-step synthetic protocol, and characterized through physical and spectral techniques. Among them, the molecules possessing para-bromo (6d), para-methyl (6f) and para-nitro (6j) phenyl substituents on the pyrazole scaffold displayed similar anti-inflammatory activity and the one with no substituents on the aryl unit (6a) exhibited the highest anti-inflammatory profile. While investigating the DPPH radical scavenging activity, the synthesized chemical entity with a para-methoxyphenyl group attached at the pyrazole structural motif (6i) revealed the highest activity when compared to the other synthesized molecules. Furthermore, the evaluation of cytotoxic activity of the synthesized molecule (6a) exerted significant activity against both the pancreatic cell lines such as AsPC1 and SW1990. Besides, while performing the molecular docking studies of 6a with B-cell lymphoma 2, an appreciable binding affinity (-9.04 kcal mol-1) has been observed. The results of the present examination imply that these chemical entities could be used as efficient intermediates for the construction of biopertinent molecules. This journal is

Design, synthesis, modeling studies and biological screening of novel pyrazole derivatives as potential analgesic and anti-inflammatory agents

Reported herein are the design, synthesis, and pharmacologic evaluation of novel pyrazole and pyrazoline derivatives. The study presents the effect of lengthening of carbon chain in different pyrazole derivatives bearing various amine moieties. Combinatio

Discovery of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups as potential PTP1B inhibitors

Two series of 1,3-diphenyl-1H-pyrazole derivatives containing rhodanine-3-alkanoic acid groups were identified as competitive protein tyrosine phosphatase 1B (PTP1B) inhibitors. Among the compounds studied, IIIv was found to have the best in vitro inhibition activity against PTP1B (IC50 = 0.67 ± 0.09 μM) and the best selectivity (9-fold) between PTP1B and T-cell protein tyrosine phosphatase (TCPTP). Molecular docking studies demonstrated that compounds IIIm, IIIv and IVg could occupy simultaneously at both the catalytic site and the adjacent pTyr binding site. These results provide novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs.

Synthesis and antioxidant evaluation of dihydropyrimidinone integrated pyrazoles

A series of novel ethyl 6-[2-(3-aryl-1-phenyl-1H-pyrazol-4-yl)vinyl]-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylates (9a-9d) has been synthesized by adopting a multistep synthetic strategy. The structure of the targets was confirmed on the basis of physical and spectral techniques. The synthetically achieved targets were evaluated for their antioxidant activity by in-vitro DPPH free radical scavenging assay. Of the chemical entities screened, most of them exhibit good to better radical scavenging profile and among those, the nitro substituent bearing molecule 9c displayed the highest activity (82%) with IC50 value 621.6 μM. Further, as a representative molecule, compound 9a has been subjected to density functional theory calculations employing B3LYP method with 6311(++G) basis set to optimize its structure.