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Optimization of 2-(1H-imidazo-2-yl)piperazines series of Trypanosoma brucei growth inhibitors as potential treatment for the second stage of HAT
- Publication Year :
- 2020
-
Abstract
- A previous publication from our laboratory reported the identification of a new class of 2-(1H-imidazo-2-yl)piperazines as potent T. brucei growth inhibitors as potential treatment for Human African Trypanosomiasis (HAT). This work describes the structure–activity relationship (SAR) around the hit compound 1, which led to the identification of the optimized compound 18, a single digit nanomolar inhibitor (EC50 7 nM), not cytotoxic and with optimal in vivo profile that made it a suitable candidate for efficacy studies in a mouse model mimicking the second stage of disease.
- Subjects :
- Antiparasitic
Cell Survival
medicine.drug_class
Morpholines
Trypanosoma brucei brucei
Clinical Biochemistry
Drug Evaluation, Preclinical
Pharmaceutical Science
Pharmacology
Trypanosoma brucei
01 natural sciences
Biochemistry
Piperazines
Structure-Activity Relationship
Isomerism
In vivo
Sleeping sickne
Drug Discovery
Human Umbilical Vein Endothelial Cells
medicine
Humans
African trypanosomiasis
Molecular Biology
biology
010405 organic chemistry
Chemistry
Organic Chemistry
medicine.disease
biology.organism_classification
Human African Trypanosomiasis (HAT)
Trypanocidal Agents
Growth Inhibitors
0104 chemical sciences
010404 medicinal & biomolecular chemistry
Trypanosomiasis, African
Quinolines
Molecular Medicine
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1eb99b1d9838b8c3597fae42fc68fd91