《Antiviral efficacy against influenza virus and pharmacokinetic analysis of a novel MEK-inhibitor, ATR-002, in cell culture and in the mouse model》 was written by Laure, Martin; Hamza, Hazem; Koch-Heier, Julia; Quernheim, Martin; Mueller, Christin; Schreiber, Andre; Mueller, Gerhard; Pleschka, Stephan; Ludwig, Stephan; Planz, Oliver. Formula: C4H7Br And the article was included in Antiviral Research in 2020. The article conveys some information:
Antiviral therapies against influenza are required, especially for high-risk patients, severe influenza and in case of highly pathogenic influenza virus (IV) strains. This may be overcome by targeting host cell factors that are required for IV propagation. IV induces a variety of host cell signaling cascades, such as the Raf/MEK/ERK kinase pathway. MEK-inhibitors block the activation of the pathway on the bottleneck of the signaling cascade leading to impaired virus propagation. In the present study, we aimed to compare the antiviral potency and bioavailability of the MEK-inhibitor CI-1040 vs. its major active metabolite ATR-002, in vitro as well as in the mouse model. In cell culture assays, an approx. 10-fold higher concentration of ATR-002 is required to generate the same antiviral activity as for CI-1040. Interestingly, we observed that considerably lower concentrations of ATR-002 were required to achieve a reduction of the viral load in vivo. Pharmacokinetic studies with ATR-002 and CI-1040 in mice have found the Cmax and AUC to be far higher for ATR-002 than for CI-1040. Our results thereby demonstrate the in vivo superiority of the active metabolite ATR-002 over CI-1040 as an antiviral agent despite its weaker cell membrane permeability. Therefore, ATR-002 is an attractive candidate for development as an efficient antiviral agent, especially given the fact that a treatment based on cellular pathway inhibition would be far less likely to lead to viral drug resistance. The experimental part of the paper was very detailed, including the reaction process of (Bromomethyl)cyclopropane(cas: 7051-34-5Formula: C4H7Br)
(Bromomethyl)cyclopropane(cas: 7051-34-5) is used as a synthetic building block for the introduction of the cyclopropylmethyl group. It was also used in the synthesis of 1,4-dienes via iron-catalyzed cross-coupling with alkenyl Grignard reagents.Formula: C4H7Br
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary