This work describes the identification of a novel class of octahydrobenzo[f]quinolines as dopamine D(3)-selective full agonists. We developed a facile method that utilizes Suzuki coupling for easy incorporations of various substituted pendant rings into the scaffold. A small focused library of octahydrobenzo[f]quinolines 5 was synthesized, and these compounds demonstrated at least 14-fold D(2)-like selectivity over D(1) in native porcine striatal tissue. Furthermore, n-propyl analog 5f was found to be a high affinity (K(i)=1.1 nM) D(3) dopamine full agonist with 145-fold selectivity over the D(2) receptor and about 840-fold selectivity over the D(1) receptor.
This work describes the identification of a novel class of octahydrobenzo[f]quinolines as n class="Chemical">dopamine D(3)-selective full agonists. We developed a facile method that utilizes Suzuki coupling for easy incorporations of various substituted pendant rings into the scaffold. A small focused library of octahydrobenzo[f]quinolines 5 was synthesized, and these compounds demonstrated at least 14-fold D(2)-like selectivity over D(1) in native porcine striatal tissue. Furthermore, n-propyl analog 5f was found to be a high affinity (K(i)=1.1 nM) D(3) dopamine full agonist with 145-fold selectivity over the D(2) receptor and about 840-fold selectivity over the D(1) receptor.
Authors: John A Allen; Julianne M Yost; Vincent Setola; Xin Chen; Maria F Sassano; Meng Chen; Sean Peterson; Prem N Yadav; Xi-ping Huang; Bo Feng; Niels H Jensen; Xin Che; Xu Bai; Stephen V Frye; William C Wetsel; Marc G Caron; Jonathan A Javitch; Bryan L Roth; Jian Jin Journal: Proc Natl Acad Sci U S A Date: 2011-10-24 Impact factor: 11.205
Authors: W K Brewster; D E Nichols; R M Riggs; D M Mottola; T W Lovenberg; M H Lewis; R B Mailman Journal: J Med Chem Date: 1990-06 Impact factor: 7.446