  In the drug repurposing approach, the chemically diverse and potentially safe
molecules can be explored as therapeutic potential out of those originally
targeted indications. However, the intellectual property rights, and
competitive over-heating issue from sharing the same drug pipeline information
are drawback of the approach. In current paradigm of drug discovery, despite
approval of new chemical entity, the finding of a new ring system for drug
discovery have stagnated. In addition, there are still rarely used ring systems
from FDA approved drug that can be optimized and used for repurposing purpose.
In the present work, these rarely used drug ring system were re-purposed with
our bidirectional target and ring screening (TR- dual screening) approach
within our defined objectives. The TR-dual screening suggested RARbeta and
cyproheptadine as a pair of target and ring system. The selected ring system
was virtually grown with predefined criterion, ranking of molecular docking and
top score poses made us select test compounds for synthesis and biological
proof. Among the tested compounds, 6c proved RARbeta agonist activity. The
concept of TR dual optimization can contribute to picking either a compound
having acceptable ADMET profile or a target for a selected drug scaffold.
