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X Demographics
Mendeley readers
Attention Score in Context
| Title |
Lead Optimization of a Pyrazole Sulfonamide Series of Trypanosoma brucei N‑Myristoyltransferase Inhibitors: Identification and Evaluation of CNS Penetrant Compounds as Potential Treatments for Stage 2 Human African Trypanosomiasis
|
|---|---|
| Published in |
Journal of Medicinal Chemistry, November 2014
|
| DOI | 10.1021/jm500809c |
| Pubmed ID | |
| Authors |
Stephen Brand, Neil R. Norcross, Stephen Thompson, Justin R. Harrison, Victoria C. Smith, David A. Robinson, Leah S. Torrie, Stuart P. McElroy, Irene Hallyburton, Suzanne Norval, Paul Scullion, Laste Stojanovski, Frederick R. C. Simeons, Daan van Aalten, Julie A. Frearson, Ruth Brenk, Alan H. Fairlamb, Michael A. J. Ferguson, Paul G. Wyatt, Ian H. Gilbert, Kevin D. Read |
| Abstract |
Trypanosoma brucei N-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood-brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 83 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 83 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 18 | 22% |
| Researcher | 17 | 20% |
| Student > Bachelor | 10 | 12% |
| Other | 5 | 6% |
| Professor | 4 | 5% |
| Other | 17 | 20% |
| Unknown | 12 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 42 | 51% |
| Pharmacology, Toxicology and Pharmaceutical Science | 9 | 11% |
| Biochemistry, Genetics and Molecular Biology | 4 | 5% |
| Agricultural and Biological Sciences | 4 | 5% |
| Psychology | 3 | 4% |
| Other | 8 | 10% |
| Unknown | 13 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 11 October 2022.
All research outputs
#6,370,505
of 23,506,079 outputs
Outputs from Journal of Medicinal Chemistry
#12,078
of 22,347 outputs
Outputs of similar age
#86,275
of 365,826 outputs
Outputs of similar age from Journal of Medicinal Chemistry
#63
of 147 outputs
Altmetric has tracked 23,506,079 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 22,347 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
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 365,826 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 76% of its contemporaries.
We're also able to compare this research output to 147 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.