19342-88-2Relevant articles and documents
Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists
Xia, Yuehan,Yu, Mingcheng,Zhao, Yunpeng,Xia, Li,Huang, Yafei,Sun, Nannan,Song, Meiqi,Guo, Huimin,Zhang, Yunyi,Zhu, Di,Xie, Qiong,Wang, Yonghui
supporting information, (2020/12/04)
The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound 1 was identified as a weak RORγt agonist during in-house library screening. Changes in LHS core of 1 led to the identification of tetrahydroquinoline compound 6 as a partial RORγt agonist (max. act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound 8g (EC50 = 8.9 ± 0.4 nM, max. act. = 104.5%) and benzomorpholine compound 9g (EC50 = 7.5 ± 0.6 nM, max. act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of 8g; 59.4% activation at 300 nM of 9g). The binding modes of 8g and 9g as well as the two RORγt inverse agonists accidentally discovered were also discussed.
Synthesis, in silico Study and Antileishmanial Evaluation of New Selenides Derived from 7-Chloro-quinoline and N-Phenylacetamides
Huang, Min-Fu N.,Luis, José A.S.,da Silva, Alison P.,Rocha, Juliana C.,Lima, Tatjana K.S.,Scotti, Marcus T.,Scotti, Luciana,de Oliveira, Rafael F.,Souza, Helivaldo D.S.,de Athayde-Filho, Petr?nio F.,Barbosa-Filho, José M.
, p. 712 - 721 (2021/03/17)
This study describes a virtual screening performed for two series of selenides (28 compounds), derived from N-phenylacetamides chlorides and 7-chloro-quinoline, to determine their potential for leishmanicidal activity against Leishmania amazonensis and Leishmania donovani. Seven compounds were predicted as potential leishmanicides; therefore, they were synthesized from elemental selenium, as a precursor for the production of NaHSe, and subsequent reactions with 4,7-dichloro-quinoline and N-phenylacetamides chlorides were performed. The compounds were characterized by infrared (IR), 1H and 13C nuclear magnetic resonance (NMR), and sent for in vitro cytotoxicity tests against L. amazonensis and were found to be active and selective, and two compounds presented half-maximal inhibitory concentrations (IC50) of 5.67 and 10.81 μg mL-1. They also presented good interaction energies in the docking study, suggesting that may exert their effects by inhibiting the N-myristoyltransferase and O-acetylserine sulfhydrylase enzymes in parasites.
A one pot protocol to convert nitro-arenes into: N-aryl amides
Massolo, Elisabetta,Pirola, Margherita,Puglisi, Alessandra,Rossi, Sergio,Benaglia, Maurizio
, p. 4040 - 4044 (2020/02/04)
A two-step one pot, experimentally simple protocol, based on readily available and inexpensive reagents allowed the conversion of nitro-arenes directly to N-aryl amides. A metal-free reduction of the nitro group, mediated by trichlorosilane, followed by the addition of an anhydride afforded the corresponding N-aryl carboxyamide, that was isolated after a simple aqueous work up in good-excellent yields. When the methodology was applied to the reaction with γ-butyrolactone, the desired N-aryl butanamide derivative was obtained, featuring a chlorine atom at the γ-position, a functionalized handle that can be used for further synthetic manipulation of the reaction product. Such an intermediate has already been employed as a key advanced precursor of pharmaceutically active compounds.
Discovery of new potent protein arginine methyltransferase 5 (PRMT5) inhibitors by assembly of key pharmacophores from known inhibitors
Zhu, Kongkai,Song, Jia-Li,Tao, Hong-Rui,Cheng, Zhi-Qiang,Jiang, Cheng-Shi,Zhang, Hua
supporting information, p. 3693 - 3699 (2018/10/24)
Protein arginine methyltransferase 5 (PRMT5) is an epigenetics related enzyme that has been validated as a promising therapeutic target for human cancer. Up to now, two small molecule PRMT5 inhibitors has been put into phase I clinical trial. In the prese
Synthesis of some 1,2,4-triazoles as potential anti-tubercular agents
Vijayaraghavan,Shirodkar
, p. 1149 - 1153 (2015/09/28)
A series of 5-(N-substituted carboxamidoethylthio)-3-(3'pyridyl)-4- amino-1,2,4-triazole derivatives 6a-j have been synthesized and evaluated for anti-tubercular activity. They are screened in-vitro at 10μg/mL concentration against Mycobacterium tuberculosis H37RV (ATCC 27294). All the compounds are showing antitubercular activity when compared with the standard drug Amikacin. Compounds 6e and 6h are found active as they displayed IC50 and IC90 values at 100μg/mL.
Synthesis and biological screening of novel derivatives of 3-(N-substituted carboxamidoethylthio)-(4H)-1,2,4-triazoles
Manikrao, Anil M.,Fursule, Ravindra A.,Rajesh,Kunjwani, Harish K.,Sabale, Prafulla M.
experimental part, p. 1642 - 1647 (2011/03/17)
3-Mercapto-(4H)-1,2,4-triazole has been synthesized from 1-formylthiosemicarbazide. Different N-substituted β-chloropropionamides have been prepared by reacting substituted amines with β- chloropropionylchloride. Different Nsubstituted β-chloropropionamides have been condensed with 3-mercapto-(4H)-1,2,4-triazole in basic medium to obtain various 3-(N-substituted carboxamidoethylthio)-(4H)-1,2,4-triazoles. The structure of the synthesized compounds are confirmed by IR, 1H NMR spectra and elemental analysis. All the compounds have been screened for their analgesic, anti-inflammatory and anxiolytic activity.
Anticancer activities of some arylcarbamoylalkyltriphenylphosphonium chlorides
Zhaowen, Lou,Li, Zhou,Chunfen, Xiao,Yong, Ye,Fanbo, Zeng,Kaixun, Huang
, p. 380 - 391 (2008/12/21)
A series of novel arylcarbamoylalkyltriphenylphosphonium chlorides were synthesized. The newly synthesized compounds, [R-(p-C6H 4)-NH-CO-R1P⊕(C6H 4)3]Clθ, R = H (2), CH3 (4), NO2 (6), R1 = -CH2- (b), CH3CH2CH2- (c), -CH2CH2CH 2 (d), the analogs of an anticancer drug, were characterized by infrared (IR), 1H nuclear magnetic resonance (NMR), 13C-NMR, 31P-NMR, mass spectrometry (MS), thermogravimetry (TG), and conductivity measurements. The anticancer activities of the obtained compounds were measured by MTT. The preliminary results indicated that some compounds showed potent anticancer activities against HCT-8, Bel-7402, A549, and S180.
Benzo[c]quinolizin-3-ones: A novel class of potent and selective nonsteroidal inhibitors of human steroid 5α-reductase 1
Guarna,Machetti,Occhiato,Scarpi,Comerci, Alessandra,Danza, Giovanna,Mancina, Rosa,Serio, Mario,Hardy, Kimber
, p. 3718 - 3735 (2007/10/03)
The synthesis and biological evaluation of a series of novel, selective inhibitors of isoenzyme 1 of human 5α-reductase (5αR) (EC 1.3.99.5) are reported. The inhibitors are 4aH- (19-29) or 1H-tetrahydrobenzo[c]quinolizin-3-ones (35-47) bearing at position
Aluminium chloride-catalyzed intermolecular vs intramolecular friedel-crafts reaction of acrylanilides and 3-chloropropanamides
Chen, I.-Li,Wang, Tai-Chi,Chen, Yeh-Long,Tzeng, Cherng-Chyi
, p. 155 - 162 (2007/10/03)
3-Phenylpropionanilide (4a) is obtained in a yield of 89% from acrylanilide by the treatment with AlCl3/ benzene, compared with a yield of 39% by the 1,4-conjugate addition of phenyllithium. The formation of 4a indicated that an intermolecular Friedel-Crafts reaction occurred, rather than the relatively more facile intramolecular ring cyclization, and provided a more efficient route than a conjugate addition of phenyllithium for the preparation of 3-phenylpropionanilide and its derivatives. Although the methoxy group is an activator of the nucleophilic substitution, introduction of a methoxy substituent at N-phenyl did not increase the competitive capability of the intramolecular cyclization because of AlCl3-catalyzed demethylation to form the ArOAlCl2 complex which decreased the availability of the π-electron in the N-phenyl aromatic system.
