ArticleBioorganic & medicinal chemistry2016
Synthesis of novel amide and urea derivatives of thiazol-2-ethylamines and their activity against Trypanosoma brucei rhodesiense.
Article in Bioorganic & medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Optimization of Orally Bioavailable Antileishmanial 2,4,5-Trisubstituted Benzamides.Journal of medicinal chemistry · 2023Article
- Development of Urea-Bond-Containing Michael Acceptors as Antitrypanosomal Agents Targeting Rhodesain.ACS medicinal chemistry letters · 2022Article
- Thiazole Ring-A Biologically Active Scaffold.Molecules (Basel, Switzerland) · 2021Review
- Synthesis and Structure-Activity Relationships of Imidazopyridine/Pyrimidine- and Furopyridine-Based Anti-infective Agents against Trypanosomiases.ChemMedChem · 2021Article
- Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.Journal of medicinal chemistry · 2020Review
- Urea Derivatives in Modern Drug Discovery and Medicinal Chemistry.Journal of medicinal chemistry · 2020Article
- Phenotypic Drug Discovery for Human African Trypanosomiasis: A Powerful Approach.Tropical medicine and infectious disease · 2020Article
- Synthesis and evaluation of novel 2,4-disubstituted arylthiazoles againstRSC medicinal chemistry · 2020Article
- Article
- Novel lead compounds in pre-clinical development against African sleeping sickness.MedChemComm · 2017Review
- Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery.Antimicrobial agents and chemotherapy · 2017Article
- New Class of Antitrypanosomal Agents Based on Imidazopyridines.ACS medicinal chemistry letters · 2017Article
- Urea Derivatives of 2-Aryl-benzothiazol-5-amines: A New Class of Potential Drugs for Human African Trypanosomiasis.Journal of medicinal chemistry · 2017Article
- Synthesis and biological evaluation of N-cyanoalkyl-, N-aminoalkyl-, and N-guanidinoalkyl-substituted 4-aminoquinoline derivatives as potent, selective, brain permeable antitrypanosomal agents.Bioorganic & medicinal chemistry · 2016Article
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7 authors.
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Abstract
2-(2-Benzamido)ethyl-4-phenylthiazole (1) was one of 1035 molecules (grouped into 115 distinct scaffolds) found to be inhibitory to Trypanosoma brucei, the pathogen causing human African trypanosomiasis, at concentrations below 3.6μM and non-toxic to mammalian (Huh7) cells in a phenotypic high-throughput screen of a 700,000 compound library performed by the Genomics Institute of the Novartis Research Foundation (GNF). Compound 1 and 72 analogues were synthesized in this lab by one of two general pathways. These plus 10 commercially available analogues were tested against T. brucei rhodesiense STIB900 and L6 rat myoblast cells (for cytotoxicity) in vitro. Forty-four derivatives were more potent than 1, including eight with IC50 values below 100nM. The most potent and most selective for the parasite was the urea analogue 2-(2-piperidin-1-ylamido)ethyl-4-(3-fluorophenyl)thiazole (70, IC50=9nM, SI>18,000). None of 33 compounds tested were able to cure mice infected with the parasite; however, seven compounds caused temporary reductions of parasitemia (⩾97%) but with subsequent relapses. The lack of in vivo efficacy was at least partially due to their poor metabolic stability, as demonstrated by the short half-lives of 15 analogues against mouse and human liver microsomes.
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