50824-04-9Relevant articles and documents
Regioselective C-H Trifluoromethylation of Aromatic Compounds by Inclusion in Cyclodextrins
Lu, Xu,Kawazu, Ryohei,Song, Jizhou,Yoshigoe, Yusuke,Torigoe, Takeru,Kuninobu, Yoichiro
supporting information, p. 4327 - 4331 (2021/05/26)
A regioselective radical C-H trifluoromethylation of aromatic compounds was developed using cyclodextrins (CDs) as additives. The C-H trifluoromethylation proceeded with high regioselectivity to afford the product in good yield, even on the gram scale. In the presence of CDs, some substrates underwent a single trifluoromethylation selectively, whereas mixtures of single- and double-trifluoromethylated products were formed in the absence of the CD. 1H NMR experiments indicated that the regioselectivity was controlled by the inclusion of a substrate inside the CD cavity.
Novel pleconaril derivatives: Influence of substituents in the isoxazole and phenyl rings on the antiviral activity against enteroviruses
Egorova, Anna,Ekins, Sean,Jahn, Birgit,Kazakova, Elena,Makarov, Vadim,Schmidtke, Michaela
, (2019/12/28)
Today, there are no medicines to treat enterovirus and rhinovirus infections. In the present study, a series of novel pleconaril derivatives with substitutions in the isoxazole and phenyl rings was synthesized and evaluated for their antiviral activity against a panel of pleconaril-sensitive and -resistant enteroviruses. Studies of the structure-activity relationship demonstrate the crucial role of the N,N-dimethylcarbamoyl group in the isoxazole ring for antiviral activity against pleconaril-resistant viruses. In addition, one or two substituents in the phenyl ring directly impact on the spectrum of antienteroviral activity. The 3-(3-methyl-4-(3-(3-N,N-dimethylcarbamoyl-isoxazol-5-yl)propoxy)phenyl)-5-trifluoromethyl-1,2,4-oxadiazole 10g was among the compounds exhibiting the strongest activity against pleconaril-resistant as well as pleconaril-susceptible enteroviruses with IC50 values from 0.02 to 5.25 μM in this series. Compound 10g demonstrated markedly less CYP3A4 induction than pleconaril, was non-mutagenic, and was bioavailable after intragastric administration in mice. These results highlight compound 10g as a promising potential candidate as a broad spectrum enterovirus and rhinovirus inhibitor for further preclinical investigations.
Hepatitis C replication inhibitors that target the viral NS4B protein
Miller, John F.,Chong, Pek Y.,Shotwell, J. Brad,Catalano, John G.,Tai, Vincent W.-F.,Fang, Jing,Banka, Anna L.,Roberts, Christopher D.,Youngman, Michael,Zhang, Huichang,Xiong, Zhiping,Mathis, Amanda,Pouliot, Jeffery J.,Hamatake, Robert K.,Price, Daniel J.,Seal, John W.,Stroup, Lisa L.,Creech, Katrina L.,Carballo, Luz H.,Todd, Dan,Spaltenstein, Andrew,Furst, Sylvia,Hong, Zhi,Peat, Andrew J.
supporting information, p. 2107 - 2120 (2014/04/03)
We describe the preclinical development and in vivo efficacy of a novel chemical series that inhibits hepatitis C virus replication via direct interaction with the viral nonstructural protein 4B (NS4B). Significant potency improvements were realized through isosteric modifications to our initial lead 1a. The temptation to improve antiviral activity while compromising physicochemical properties was tempered by the judicial use of ligand efficiency indices during lead optimization. In this manner, compound 1a was transformed into (+)-28a which possessed an improved antiviral profile with no increase in molecular weight and only a modest elevation in lipophilicity. Additionally, we employed a chimeric "humanized" mouse model of HCV infection to demonstrate for the first time that a small molecule with high in vitro affinity for NS4B can inhibit viral replication in vivo. This successful proof-of-concept study suggests that drugs targeting NS4B may represent a viable treatment option for curing HCV infection.
