title: Identification and optimization of an aminoalcohol-carbazole series with antimalarial properties.
abstract: Recent observations on the emergence of artemisinin resistant parasites have highlighted the need for new antimalarial treatments. An HTS campaign led to the identification of the 1-(1-aminopropan-2-ol)carbazole analogues as potent hits against Plasmodium falciparum K1 strain. The SAR study and optimization of early ADME and physicochemical properties direct us to the selection of a late lead compound that shows good efficacy when orally administrated in the in vivo P. berghei mouse model.
authors.affiliation: Merck Serono, 9 chemin des mines, 1202 Geneva, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Molette
authors.affiliation: Merck Serono, 9 chemin des mines, 1202 Geneva, Switzerland.
authors.forename: Julie
authors.initials: J
authors.lastname: Routier
authors.affiliation: Merck Serono, 9 chemin des mines, 1202 Geneva, Switzerland.
authors.forename: Nada
authors.initials: N
authors.lastname: Abla
authors.affiliation: Special Program for Research & Training in Tropical Diseases (TDR), World Health Organization , Avenue Appia 20, 1211 Geneva 27, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Besson
authors.affiliation: Merck Serono, 9 chemin des mines, 1202 Geneva, Switzerland.
authors.forename: Agnes
authors.initials: A
authors.lastname: Bombrun
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse. 57, 4051 Basel, Switzerland , and University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.affiliation: Merck Serono, 9 chemin des mines, 1202 Geneva, Switzerland.
authors.forename: Howard
authors.initials: H
authors.lastname: Burt
authors.affiliation: Merck Serono, 9 chemin des mines, 1202 Geneva, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Georgi
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse. 57, 4051 Basel, Switzerland , and University of Basel, Petersplatz 1, 4003 Basel, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Special Program for Research & Training in Tropical Diseases (TDR), World Health Organization , Avenue Appia 20, 1211 Geneva 27, Switzerland.
authors.forename: Solomon
authors.initials: S
authors.lastname: Nwaka
authors.affiliation: Merck Serono, 9 chemin des mines, 1202 Geneva, Switzerland.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Muzerelle
authors.affiliation: Merck Serono, 9 chemin des mines, 1202 Geneva, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Scheer
keywords: IC50; Malaria; Plasmodium berghei; Plasmodium falciparum; SAR; WHO; carbazole; hERG