56205-88-0Relevant articles and documents
Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite Plasmodium falciparum and Optimization Efforts
Le Manach, Claire,Dam, Jean,Woodland, John G.,Kaur, Gurminder,Khonde, Lutete P.,Brunschwig, Christel,Njoroge, Mathew,Wicht, Kathryn J.,Horatscheck, André,Paquet, Tanya,Boyle, Grant A.,Gibhard, Liezl,Taylor, Dale,Lawrence, Nina,Yeo, Tomas,Mok, Sachel,Eastman, Richard T.,Dorjsuren, Dorjbal,Talley, Daniel C.,Guo, Hui,Simeonov, Anton,Reader, Janette,Van Der Watt, Mari?tte,Erlank, Erica,Venter, Nelius,Zawada, Jacek W.,Aswat, Ayesha,Nardini, Luisa,Coetzer, Theresa L.,Lauterbach, Sonja B.,Bezuidenhout, Belinda C.,Theron, Anjo,Mancama, Dalu,Koekemoer, Lizette L.,Birkholtz, Lyn-Marie,Wittlin, Sergio,Delves, Michael,Ottilie, Sabine,Winzeler, Elizabeth A.,Smith, Dennis,Fidock, David A.,Street, Leslie J.,Basarab, Gregory S.,Duffy, James,Chibale, Kelly
supporting information, p. 2291 - 2309 (2021/03/01)
A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chemistry optimization and biological profiling program. Structure-activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (50 nM) together with strong gametocyte sterilizing properties that translated to transmission-blocking activity in the standard membrane feeding assay. Mechanistic studies through resistance selection with one of the analogues followed by whole-genome sequencing implicated the P. falciparum cyclic amine resistance locus in the mode of resistance.
COMPOUNDS, PHARMACEUTICAL COMPOSITIONS AND USES AS GLUTAMINASE INHIBITORS FOR TREATING CANCERS THEREOF
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Page/Page column 148-149, (2014/06/11)
Provided are compounds of formula (I), wherein X, Y, Z, W, m, n, o, p, R1, R2 and R6 are defined as in the description. Pharmaceutical compositions and uses as glutaminase inhibitors for treating cancers thereof are also provided.
Arylacetamide κ opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity
Le Bourdonnec, Bertrand,Ajello, Christopher W.,Seida, Pamela R.,Susnow, Roberta G.,Cassel, Joel A.,Belanger, Serge,Stabley, Gabriel J.,DeHaven, Robert N.,DeHaven-Hudkins, Diane L.,Dolle, Roland E.
, p. 2647 - 2652 (2007/10/03)
Some κ opioid receptor agonists of the arylacetamide class, for example, ICI 199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6 (CYP2D6) (1: CYP2D6 IC50 = 26 nM). Certain analogs bearing a substituted sulfonylamino group, for example, 13, were discovered to have significantly reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50 > 10 μM) while displaying high affinity toward the cloned human κ opioid receptor, good κ/δ and κ/μ selectivity, and potent in vitro and in vivo agonist activity.
