Novel 12N-substituted matrinanes as potential anti-coxsackievirus agents.

Authors :: Li YH
Tang S
Li YH
Cheng XY
Zhang X
Wang YX
Su F
Song DQ
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 Feb 15; Vol. 27 (4), pp. 829-833. Date of Electronic Publication: 2017 Jan 10.
Publication Year :: 2017
Abstract: A series of novel 12N-substituted matrinane derivatives were synthesized and evaluated for their activities against coxsackievirus type B3 (CVB3) taking compound 1 as the lead. SAR analysis indicated that the introduction of a suitable heteroaromatic ring on the 12N-atom might be beneficial for the activity. Among them, compound 8a exhibited the highest potency against all CVB serotypes as well as CVA16 with IC <subscript>50</subscript> values ranging from 2.02μM to 7.41μM, indicating a broad-spectrum anti-coxsackieviruse effect. Furthermore, compound 8a demonstrated a good safety profile in vivo. Thus, we consider 12N-substituted matrinanes to be a promising family of anti-coxsackievirus agents, and compound 8a to be a promising drug candidate in the treatment of various diseases related to coxsackievirus infection.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)