Nicholas A. Meanwell

WORK HISTORY

EDUCATION

SKILLS

ABOUT NICHOLAS A. MEANWELL

CV drug discovery: Developed a series of imidazo[4,5-b]quinolin-2-ones as selective PDE inhibitors and blood platelet aggregation inhibitors. Mapped the non-prostanoid prostacyclin mimetic pharmacophore, defined most effectively by BMY-45778, a potent partial agonist. Contributed to the design of inhibitors of thrombin. CNS drug discovery: led the early phase team that explored the potential of Ca2+-dependent K+ channel modulators leading to the Maxi K ion channel opener flindokalner (MaxiPostTM) which was advanced into Phase clinical trials for the treatment of stroke. Antiviral drug discovery chemistry: BMS-433771 was characterized as an inhibitor of RSV fusion, the first small molecule to interfere with 6 helical bundle function. BMS-488043 established clinical proof-of-concept for inhibition of HIV-1 attachment, a first in class small molecule that prevents virus gp120 and CD4 receptor interaction. BMS-663068, a phosphonooxymethyl prodrug of temsavir (BMS-626529), has completed Phase 2 clinical trials and has entered Phase 3 studies. HCV inhibitor drug discovery: daclatasvir (DaklinzaTM), the first-in-class NS5A inhibitor that established this protein as a clinically-relevant target; the HCV NS3 protease inhibitor asunaprevir (SunvepraTM), which incorporates the cyclopropyl acylsulfonamide moiety that has been widely adopted. The combination of daclatasvir and asunaprevir established that an HCV infection could be cured by direct acting antiviral agents in the absence of immune stimulation. Beclabuvir, a thumb site inhibitor of HCV NS5B polymerase, has completed Phase 3 trials as a fixed-dose combination therapy with daclatasvir and asunaprevir. Author/co-author of over 200 publications, 170 meeting abstracts, co-inventor of more than 110 granted U.S. Patents. I have presented over 120 invited lectures at National and International meetings, Universities and Schools on Medicinal Chemistry.