Abstract for PubMed entry 25728130

Title		Structure-based design of inhibitors of coagulation factor XIa with novel P1 moieties.
Authors		D.J.Pinto, J.M.Smallheer, J.R.Corte, E.J.Austin, C.Wang, T.Fang, L.M.Smith, K.A.Rossi, A.R.Rendina, J.M.Bozarth, G.Zhang, A.Wei, V.Ramamurthy, S.Sheriff, J.E.Myers, P.E.Morin, J.M.Luettgen, D.A.Seiffert, M.L.Quan, R.R.Wexler.
Ref.		Bioorg Med Chem Lett, 2015, 25, 1635-1642.
PubMed id		25728130
Abstract
Compound 2 was previously identified as a potent inhibitor of factor XIa lacking oral bioavailability. A structure-based approach was used to design analogs of 2 with novel P1 moieties with good selectivity profiles and oral bioavailability. Further optimization of the P1 group led to the identification of a 4-chlorophenyltetrazole P1 analog, which when combined with further modifications to the linker and P2' group provided compound 32 with FXIa Ki=6.7nM and modest oral exposure in dogs.