Repositioning Antitubercular 6‑Nitro-2,3-dihydroimidazo[2,1‑b][1,3]oxazoles for Neglected Tropical Diseases: Structure–Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis
6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole derivatives were initially studied for tuberculosis within a backup program for the clinical trial agent pretomanid (PA-824). Phenotypic screening of representative examples against kinetoplastid diseases unexpectedly led to the identification of DNDI-VL-2098 as a potential first-in-class drug candidate for visceral leishmaniasis (VL). Additional work was then conducted to delineate its essential structural features, aiming to improve solubility and safety without compromising activity against VL. While the 4-nitroimidazole portion was specifically required, several modifications to the aryloxy side chain were well tolerated e.g., exchange of the linking oxygen for nitrogen (or piperazine), biaryl extension, and replacement of phenyl rings by pyridine. Several less lipophilic analogues displayed improved aqueous solubility, particularly at low pH, although stability towards liver microsomes was highly variable. Upon evaluation in a mouse model of acute Leishmania donovani infection, one phenylpyridine derivative (37) stood out, providing efficacy surpassing that of the original preclinical lead.
Pharmacology, Toxicology and Pharmaceutical Science
9
10%
Biochemistry, Genetics and Molecular Biology
4
4%
Immunology and Microbiology
3
3%
Other
8
9%
Unknown
29
32%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 14. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 March 2025.
All research outputs
#3,185,141
of 33,503,639 outputs
Outputs from Journal of Medicinal Chemistry
#3,177
of 27,405 outputs
Outputs of similar age
#38,745
of 334,347 outputs
Outputs of similar age from Journal of Medicinal Chemistry
#43
of 199 outputs
Altmetric has tracked 33,503,639 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 27,405 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.2. This one has done well, scoring higher than 88% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 334,347 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 199 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.
