39643-31-7

Usage

Uses

Used in Pharmaceutical Industry:
2-PIPERIDINOANILINE is used as a key intermediate in the synthesis of oxalylarylaminobenzoic acids, which serve as inhibitors of protein tyrosine phosphatase 1B (PTP1B). PTP1B inhibition is a promising therapeutic strategy for the treatment of type 2 diabetes and obesity, as it helps regulate insulin signaling and glucose homeostasis.
Additionally, 2-PIPERIDINOANILINE is utilized in the preparation of benzimidazole derivatives, which act as activators of AMP-activated protein kinase (AMPK). AMPK activation plays a crucial role in cellular energy homeostasis and has potential applications in the treatment of metabolic disorders, such as diabetes and cardiovascular diseases, as well as in promoting overall cellular health and longevity.

InChI:InChI=1/C11H16N2/c12-10-6-2-3-7-11(10)13-8-4-1-5-9-13/h2-3,6-7H,1,4-5,8-9,12H2

Upstream product

• 857374-62-0 2,2'-dipiperidino-azoxybenzene 
• 5622-83-3 1,2,3,4-tetrahydro-pyrido[1,2-a]benzimidazole 
• 1493-27-2 ortho-nitrofluorobenzene 
• 15822-77-2 1-(2-nitrophenyl)piperidine 
• 88-73-3 2-Chloronitrobenzene 
• 110-89-4 piperidine 

Downstream Products

• 1027049-76-8 2-(2-piperidin-1-yl-phenylamino)-benzoic acid 
• 915006-05-2 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid (2-piperidin-1-yl-phenyl)-amide 
• 535980-13-3 5-bromo-furan-2-carboxylic acid (2-piperidin-1-yl-phenyl)-amide 
• 51317-68-1 1-(2-isothiocyanato-phenyl)-piperidine 
• 131676-40-9 N-methyl-N'-(2-piperidinophenyl)pivalamidine 
• 1579960-77-2 1-(2-(4-bromophenoxy)ethoxy)-3-(4-(2-(piperidin-1-yl)phenyl)piperazin-1-yl)propan-2-ol 

Relevant academic research and scientific papers

Optimisation of 2-(N-phenyl carboxamide) triazolopyrimidine antimalarials with moderate to slow acting erythrocytic stage activity

Malaria is a devastating parasitic disease caused by parasites from the genus Plasmodium. Therapeutic resistance has been reported against all clinically available antimalarials, threatening our ability to control the disease and therefore there is an ongoing need for the development of novel antimalarials. Towards this goal, we identified the 2-(N-phenyl carboxamide) triazolopyrimidine class from a high throughput screen of the Janssen Jumpstarter library against the asexual stages of the P. falciparum parasite. Here we describe the structure activity relationship of the identified class and the optimisation of asexual stage activity while maintaining selectivity against the human HepG2 cell line. The most potent analogues from this study were shown to exhibit equipotent activity against P. falciparum multidrug resistant strains and P. knowlesi asexual parasites. Asexual stage phenotyping studies determined the triazolopyrimidine class arrests parasites at the trophozoite stage, but it is likely these parasites are still metabolically active until the second asexual cycle, and thus have a moderate to slow onset of action. Non-NADPH dependent degradation of the central carboxamide and low aqueous solubility was observed in in vitro ADME profiling. A significant challenge remains to correct these liabilities for further advancement of the 2-(N-phenyl carboxamide) triazolopyrimidine scaffold as a potential moderate to slow acting partner in a curative or prophylactic antimalarial treatment.

Electrochemical Synthesis of Benzo[ d]imidazole via Intramolecular C(sp3)-H Amination

An electrochemical dehydrogenative amination for the synthesis of benzimidazoles was developed. This electrosynthesis method could address the limitations of the C(sp3)-H intramolecular amination synthesis reaction and provide novel access to obtain 1,2-disubstituted benzimidazoles without transition metals and oxidants. Under undivided electrolytic conditions, various benzimidazole derivatives could be synthesized, exhibiting functional group tolerance.

Discovery of Selective Inhibitors of Endoplasmic Reticulum Aminopeptidase 1

ERAP1 is an endoplasmic reticulum-resident zinc aminopeptidase that plays an important role in the immune system by trimming peptides for loading onto major histocompatibility complex proteins. Here, we report discovery of the first inhibitors selective for ERAP1 over its paralogues ERAP2 and IRAP. Compound 1 (N-(N-(2-(1H-indol-3-yl)ethyl)carbamimidoyl)-2,5-difluorobenzenesulfonamide) and compound 2 (1-(1-(4-acetylpiperazine-1-carbonyl)cyclohexyl)-3-(p-tolyl)urea) are competitive inhibitors of ERAP1 aminopeptidase activity. Compound 3 (4-methoxy-3-(N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)sulfamoyl)benzoic acid) allosterically activates ERAP1's hydrolysis of fluorogenic and chromogenic amino acid substrates but competitively inhibits its activity toward a nonamer peptide representative of physiological substrates. Compounds 2 and 3 inhibit antigen presentation in a cellular assay. Compound 3 displays higher potency for an ERAP1 variant associated with increased risk of autoimmune disease. These inhibitors provide mechanistic insights into the determinants of specificity for ERAP1, ERAP2, and IRAP and offer a new therapeutic approach of specifically inhibiting ERAP1 activity in vivo.

A Structure–Activity Study of Nickel NNN Pincer Complexes for Alkyl-Alkyl Kumada and Suzuki–Miyaura Coupling Reactions

A new series of Ni NNN pincer complexes were synthesized and characterized. The main difference among these complexes is the substituents on the side arm amino group(s). No major structural difference was found except for the C–N–C angle of the various substituents and the ‘pseudo bite angle’ of the complexes. Four new complexes were efficient for the alkyl-alkyl Kumada reaction of primary alkyl halides, and among them, one complex was also efficient with secondary alkyl halides. The influence of the substituents on the catalytic performance of the Ni complexes in alkyl-alkyl Kumada and Suzuki–Miyaura cross-coupling reactions was systematically investigated. No correlation was found between the catalytic activity and the key structural parameters (C–N–C angle and ‘pseudo bite angle’), redox properties or Lewis acidity of the complexes.

Synthesis of benzimidazoles via iridium-catalyzed acceptorless dehydrogenative coupling

Iridium-catalyzed acceptorless dehydrogenative coupling of tertiary amines and arylamines has been developed. A number of benzimidazoles were prepared in good yields. An iridium-mediated C-H activation mechanism is suggested. This finding represents a novel strategy for the synthesis of benzimidazoles.

Synthesis of benzimidazoles via iridium-catalyzed acceptorless dehydrogenative coupling

Iridium-catalyzed acceptorless dehydrogenative coupling of tertiary amines and arylamines has been developed. A number of benzimidazoles were prepared in good yields. An iridium-mediated C-H activation mechanism is suggested. This finding represents a novel strategy for the synthesis of benzimidazoles.

Synthesis, antifungal activity and QSAR of some novel carboxylic acid amides

A series of novel aromatic carboxylic acid amides were synthesized and tested for their activities against six phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to good activity. Among them N-(2-(1H-indazol-1-yl)phenyl)-2-(trifluoromethyl)benzamide (3c) exhibited the highest antifungal activity against Pythium aphanidermatum (EC50 = 16.75 μg/mL) and Rhizoctonia solani (EC50 = 19.19 μg/mL), compared to the reference compound boscalid with EC50 values of 10.68 and 14.47 μg/mL, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to develop a three-dimensional quantitative structure-activity relationship model for the activity of the compounds. In the molecular docking, a fluorine atom and the carbonyl oxygen atom of 3c formed hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173.

Synthesis, antifungal activity and structure-activity relationships of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

A convenient synthesis of benzannelated diazacycloalkanes by reductive cleavage of 1,2-polymethylenebenzimidazoles

A facile procedure for the synthesis of benzannelated diazacycloalkanes 3 is elaborated on the basis of reductive cleavage of 1,2- polymethylenebenzimidazoles 2 with DIBAL-H. The reduction of the corresponding salts prepared by treatment of 1,2-polymethylenebenzimidazoles 2 with methyl iodide proceeded differently affording exclusively o-phenylenediamines 10. The limitations and scope of the method were established, and a tentative mechanism proposed.

Potent 2′-aminoanilide inhibitors of cFMS as potential anti-inflammatory agents

A series of 2′-aminoanilides have been identified which exhibit potent and selective inhibitory activity against the cFMS tyrosine kinase. Initial SAR studies within this series are described which examine aroyl and amino group substitutions, as well as the introduction of hydrophilic substituents on the benzene core. Compound 47 inhibits the isolated enzyme (IC50 = 0.027 μM) and blocks CSF-1-induced proliferation of bone marrow-derived macrophages (IC50 = 0.11 μM) and as such, serves as a lead candidate for further optimization studies.