50912-59-9Relevant academic research and scientific papers
Discovery of Carboline Derivatives as Potent Antifungal Agents for the Treatment of Cryptococcal Meningitis
Tu, Jie,Li, Zhuang,Jiang, Yanjuan,Ji, Changjin,Han, Guiyan,Wang, Yan,Liu, Na,Sheng, Chunquan
, p. 2376 - 2389 (2019/03/07)
Clinical treatment of cryptococcal meningitis (CM) remains a significant challenge because of the lack of effective and safe drug therapies. Developing novel CM therapeutic agents with novel chemical scaffolds and new modes of action is of great importanc
Design, synthesis, docking studies and biological evaluation of novel dihydro-1,3,5-triazines as human DHFR inhibitors
Zhou, Xiaotian,Lin, Kuaile,Ma, Xiang,Chui, Wai-Keung,Zhou, Weicheng
, p. 1279 - 1288 (2016/11/29)
A novel series of dihydro-1,3,5-triazine derivatives bearing a heteroatom spiro-ring were designed and synthesized on the basis of molecular flexible docking work, and their biological activities were evaluated. Compounds A2, A5, B1 and B3 showed potent human dihydrofolate reductase (hDHFR) inhibitory activity with IC50values of 7.46 nM, 3.72 nM, 6.46 nM, 4.08 nM, versus reference drug methotrexate (MTX). From the molecular docking result we concluded that the conformation space generated by deformation of the flexible residue Phe31 is favorable for the binding of the spiro-ring, and inserting heteroatom into spiro ring might increase the binding affinity. There were 24 compounds with broadspectrum antiproliferative activity against several tumor cell lines (HCT116, A549, HL-60, HepG2 and MDA-MB-231) with IC50values ranging from 0.79 to 0.001 μM. The antitumor activity in?vivo of compound A2 was determined in a human alveolar basal epithelial cell line A549 xenograft model. This study offered novel anticancer agents with high inhibitory activity that target hDHFR and have a binding mode of the novel molecular scaffold with hDHFR. This provides potent support for further development of novel hDHFR inhibitors.
Novel Carboline Derivatives as Potent Antifungal Lead Compounds: Design, Synthesis, and Biological Evaluation
Wang, Shengzheng,Wang, Yan,Liu, Wei,Liu, Na,Zhang, Yongqiang,Dong, Guoqiang,Liu, Yang,Li, Zhengang,He, Xiaomeng,Miao, Zhenyuan,Yao, Jianzhong,Li, Jian,Zhang, Wannian,Sheng, Chunquan
, p. 506 - 511 (2014/06/09)
A series of novel antifungal carboline derivatives was designed and synthesized, which showed broad-spectrum antifungal activity. Particularly, compound C38 showed comparable in vitro antifungal activity to fluconazole without toxicity to human embryonic lung cells. It also exhibited good fungicidal activity against both fluconazole-sensitive and -resistant Candida albicans cells and had potent inhibition activity against Candida albicans biofilm formation and hyphal growth. Moreover, C38 showed good synergistic antifungal activity in combination with fluconazole (FLC) against FLC-resistant Candida species. Preliminary mechanism studies revealed that C38 might act by inhibiting the synthesis of fungal cell wall.
Asymmetric synthesis of nonracemic primary amines via spiroborate-catalyzed reduction of pure (E)- and (Z)-O-benzyloximes: Applications toward the synthesis of calcimimetic agents
Ou, Wenhua,Espinosa, Sandraliz,Meléndez, Héctor J.,Farré, Silvia M.,Alvarez, Jaime L.,Torres, Valerie,Martínez, Ileanne,Santiago, Kiara M.,Ortiz-Marciales, Margarita
, p. 5314 - 5327 (2013/07/25)
Highly enantiopure (1-aryl)- and (1-naphthyl)-1-ethylamines were synthesized by the borane-mediated reduction of single-isomeric (E)- and (Z)-O-benzyloxime ethers using the stable spiroborate ester derived from (S)-diphenyl valinol and ethylene glycol as the chiral catalyst. Primary (R)-arylethylamines were prepared by the reduction of pure (Z)-ethanone oxime ethers in up to 99% ee using 15% of catalyst. Two convenient and facile approaches to the synthesis of new and known calcimimetic analogues employing enantiopure (1-naphthalen-1-yl)ethylamine as chiral precursor are described.
Expeditious synthesis and biological evaluation of novel 2,N 6-disubstituted 1,2-dihydro-1,3,5-triazine-4,6-diamines as potential antimalarials
Gravestock, David,Rousseau, Amanda L.,Lourens, Anna C.U.,Moleele, Simon S.,Van Zyl, Robyn L.,Steenkamp, Paul A.
experimental part, p. 2022 - 2030 (2011/06/21)
A small set of novel 2,N6-disubstituted 1,2-dihydro-1,3,5- triazine-4,6-diamines was prepared possessing a flexible tether between the exocyclic nitrogen bonded to C-6 of the 1,2-dihydro-1,3,5-triazine-4,6-diamine heterocycle and the distal ary
The synthesis and preliminary pharmacological evaluation of a series of substituted 4-phenoxypropyl analogues of the atypical antipsychotic clozapine
Capuano, Ben,Crosby, Ian T.,McRobb, Fiona M.,Podloucka, Anna,Taylor, David A.,Vom, Amelia,Yuriev, Elizabeth
experimental part, p. 116 - 124 (2010/05/18)
Herein we report the synthesis, characterization, and preliminary pharmacological activity of a new series of substituted 4′-phenoxypropyl tricyclic analogues of clozapine as potential antipsychotic agents for the treatment of schizophrenia. The lead comp
Improved model of lanosterol 14α-demethylase by ligand-supported homology modeling: Validation by virtual screening and azole optimization
Sheng, Chunquan,Wang, Wenya,Che, Xiaoying,Dong, Guoqiang,Wang, Shengzheng,Ji, Haitao,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
experimental part, p. 390 - 397 (2010/11/18)
Lanosterol 14α-demethylase (CYP51) is an important target for antifungal drugs. An improved three-dimensional model of CYP51 from Candida albicans (CACYP51) was constructed by ligand-supported homology modeling and molecular dynamics simulations. The accuracy of the constructed model was evaluated by its performance in a small-scale virtual screen. The results show that known CYP51 inhibitors were efficiently discriminated by the model, and it performed better than our previous CACYP51 model. The active site of CACYP51 was characterized by multiple copy simultaneous search (MCSS) calculations. On the basis of the MCSS results, a series of novel azoles were designed and synthesized, and they showed good in vitro antifungal activity with a broad spectrum. The MIC80 value of four of these compounds against C. albicans is 0.001 μgmL-1, indicating that they are promising leads for the discovery of novel antifungal agents.
New azoles with potent antifungal activity: Design, synthesis and molecular docking
Che, Xiaoying,Sheng, Chunquan,Wang, Wenya,Cao, Yongbing,Xu, Yulan,Ji, Haitao,Dong, Guoqiang,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian
scheme or table, p. 4218 - 4226 (2009/12/09)
In response to the urgent need for novel antifungal agents with improved activity and broader spectrum, computer modeling was used to rational design novel antifungal azoles. On the basis of the active site of lanosterol 14α-demethylase from Candida albicans (CACYP51), a series of new azoles with substituted-phenoxypropyl piperazine side chains were rational designed and synthesized. In vitro antifungal activity assay indicates that the new azoles show good activity against most of the tested pathogenic fungi. Interestingly, the designed compounds are also active against an azole-resistant clinical strain. Compared to fluconazole and itraconazole, several compounds (such as 12i, 12j and 12n) show higher antifungal activity and broader spectrum, which are promising leads for the development of novel antifungal agents.
Novel synthetic strategy of N-arylated heterocycles via sequential palladium-catalyzed intra- and inter-arylamination reactions
Omar-Amrani, Rafik,Schneider, Raphael,Fort, Yves
, p. 2527 - 2534 (2007/10/03)
The use of an in situ generated Pd(0) catalyst associated to N,N′-bis(2,6-diisopropylphenyl)dihydroimidazol-2-ylidene (SIPr) as a ligand and t-BuONa as the base for sequential intra- followed by intermolecular aryl animation is described. The method has been applied to the synthesis of N-arylated five-, six- and seven-membered nitrogen heterocycles.
Synthesis and pharmacological evaluation of N-acyl-1,2,3,4- tetrahydroisoquinoline derivatives as novel specific bradycardic agents
Kubota, Hideki,Watanabe, Toshihiro,Kakefuda, Akio,Masuda, Noriyuki,Wada, Kouichi,Ishii, Noe,Sakamoto, Shuichi,Tsukamoto, Shinichi
, p. 871 - 882 (2007/10/03)
A series of N-acyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized and evaluated for their bradycardic activities in isolated guinea pig right atria and in urethane-anesthetized rats. These efforts resulted in identification of the compound 8a
