Challenges in the development of an M4 PAM preclinical candidate: The discovery, SAR, and in vivo characterization of a series of 3-aminoazetidine-derived amides
Published in
Bioorganic & Medicinal Chemistry Letters, May 2017
This letter details the continued chemical optimization of a novel series of M4 positive allosteric modulators (PAMs) based on a 5-amino-thieno[2,3-c]pyridazine core by incorporating a 3-amino azetidine amide moiety. The analogs described within this work represent the most potent M4 PAMs reported for this series to date. The SAR to address potency, clearance, subtype selectivity, CNS exposure, and P-gp efflux are described. This work culminated in the discovery of VU6000918, which demonstrated robust efficacy in a rat amphetamine-induced hyperlocomotion reversal model at a minimum efficacious dose of 0.3mg/kg.
Pharmacology, Toxicology and Pharmaceutical Science
3
14%
Biochemistry, Genetics and Molecular Biology
3
14%
Neuroscience
3
14%
Chemistry
3
14%
Agricultural and Biological Sciences
1
5%
Other
1
5%
Unknown
7
33%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 10. 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 09 July 2026.
All research outputs
#4,096,330
of 30,385,879 outputs
Outputs from Bioorganic & Medicinal Chemistry Letters
#1,100
of 14,528 outputs
Outputs of similar age
#57,316
of 337,380 outputs
Outputs of similar age from Bioorganic & Medicinal Chemistry Letters
#10
of 145 outputs
Altmetric has tracked 30,385,879 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 14,528 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.1. This one has done particularly well, scoring higher than 92% 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 337,380 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 82% of its contemporaries.
We're also able to compare this research output to 145 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 92% of its contemporaries.
