In spite of their various pharmacological properties the anti-inflammatory potential of benzo[c]phenanthridines remained underexplored. Thus, for the first time PDE4 inhibitory potential of 11,12-dihydro benzo[c]phenanthridine/benzo[c]phenanthridine was assessed in vitro. Elegant synthesis of these compounds was performed via a multi-step sequence consisting of a Pd-catalyzed unusual construction of 4-allyl isocoumarin ring and FeCl-mediated intramolecular regio- as well as site-selective arene-allyl cyclization as key steps. The overall strategy involved Sonogashira coupling followed by isocoumarin and isoquinolone synthesis, then chlorination and subsequent cyclization to afford a range of 11,12-dihydro derivatives. One of these dihydro compounds was converted to the corresponding benzo[c]phenanthridine that showed concentration dependent inhibition of PDE4B affording an initial hit molecule. The SAR study suggested that 11,12-dihydro analogs were less potent than the compound having unsaturation at the same part of the ring.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioorg.2020.103691DOI Listing

Publication Analysis

Top Keywords

pd-catalyzed unusual
8
unusual construction
8
arene-allyl cyclization
8
synthesis 1112-dihydro
4
1112-dihydro benzo[c]phenanthridines
4
benzo[c]phenanthridines pd-catalyzed
4
construction isocoumarin
4
isocoumarin ring/fecl-mediated
4
ring/fecl-mediated intramolecular
4
intramolecular arene-allyl
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!