Colin Philip Leslie

Learn More
Selective NPY-Y5 antagonists are known to reduce NPY-evoked increase of food intake under free feeding conditions and drug-reinforced operant responding in rodents suggesting that NPY-Y5 receptors can regulate reinforcers, potentially by modulating the hypothalamic-limbic reward system. However, evidence published to date has revealed a limited expression(More)
Numerous analogues of the naturally occurring antibiotic althiomycin have been synthesised exploiting both total- and semi-synthetic methodologies. The antibacterial activity of these derivatives has been determined in whole cell assays and indicates the natural product exhibits a restricted SAR.
A novel series of trans-8-aminomethyl-1-oxa-3-azaspiro[4.5]decan-2-one derivatives was identified with potent NPY Y5 antagonist activity. Optimization of the original lead furnished compounds 23p and 23u, which combine sub-nanomolar Y5 activity with metabolic stability, oral bioavailability, brain penetration and strong preclinical profile for development.(More)
In an effort to identify selective drug like pan-antagonists of the 5-HT1 autoreceptors, studies were conducted to elaborate a previously reported dual acting 5-HT1 antagonist/SSRI structure. A novel series of compounds was identified showing low intrinsic activities and potent affinities across the 5-HT1A, 5-HT1B, and 5-HT1D receptors as well as high(More)
A novel class of small molecule NPY Y5 antagonists based around an azabicyclo[3.1.0]hexane scaffold was identified through modification of a screening hit. Structure-activity relationships and efforts undertaken to achieve a favourable pharmacokinetic profile in rat are described.
A novel class of benzimidazole NPY Y5 receptor antagonists was prepared exploiting a privileged spirocarbamate moiety. The structure-activity relationship of this series and efforts to achieve a profile suitable for further development and an appropriate pharmacokinetic profile in rat are described. Optimisation led to the identification of the brain(More)
Bioisoteric replacement of the metabolically labile N-methyl amide group of a series of benzoxazinones with small heterocyclic rings has led to novel series of fused tricyclic benzoxazines which are potent 5-HT(1A/B/D) receptor antagonists with and without concomitant human serotonin transporter (hSerT) activity. Optimizing against multiple parameters in(More)
A novel imidazobenzazepine template (5a) with potent dual H(1)/5-HT(2A) antagonist activity was identified. Application of a zwitterionic approach to this poorly selective and poorly developable starting point successfully delivered a class of high quality leads, 3-[4-(3-R(1)-2-R-5H-imidazo[1,2-b][2]benzazepin-11-yl)-1-piperazinyl]-2,2-dimethylpropanoic(More)