Bryan Roberts

Molybdenum-Mediated Carbonylation of Aryl Halides with Nucleophiles Using Microwave Irradiation

A new, efficient, and practical molybdenum-mediated carbonylation of aryl and heteroaryl halides with a variety of nucleophiles is described using microwave irradiation. A range of reactions illustrating the wide scope of this chemistry were carried out and proceeded in good to excellent yields.

Hit-to-lead studies: the discovery of potent, orally bioavailable triazolethiol CXCR2 receptor antagonists.

A Hit-to-Lead optimisation programme was carried out on the high throughput screening hit, the triazolethiol 1, resulting in the discovery of the potent, orally bioavailable triazolethiol CXCR2 receptor antagonist 45.

Novel Aryl and Heteroaryl Acyl Sulfamide Synthesis via Microwave-Assisted Palladium-Catalyzed Carbonylation

A novel, simple synthesis of aryl and heteroaryl acyl sulfamides has been developed via palladium-catalyzed carbonylation of aryl or heteroaryl halides in the presence of sulfamide nucleophiles. A range of reactions illustrating the wide scope of this reaction was carried out under microwave irradiation in a vessel equipped with a gas inlet adapter and proceeded in good to excellent yields.

Investigation of (E)-3-[4-(2-Oxo-3-aryl-chromen-4-yl)oxyphenyl]acrylic Acids as Oral Selective Estrogen Receptor Down-Regulators

A novel estrogen receptor down-regulator, 7-hydroxycoumarin (5, SS5020), has been reported with antitumor effects against chemically induced mammary tumors. Here, we report on our own investigation of 7-hydroxycoumarins as potential selective estrogen receptor down-regulators, which led us to the discovery of potent down-regulating antagonists, such as 33. Subsequent optimization and removal of the 7-hydroxy group led to coumarin 59, which had increased potency and improved rat bioavailability relative to SS5020.

Discovery of pyrazoles as novel FPR1 antagonists

A series of pyrazole inhibitors of the human FPR1 receptor have been identified from high throughput screening. The compounds demonstrate potent inhibition in human neutrophils and attractive physicochemical and in vitro DMPK profiles to be of further interest.

Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat

A series of tetrahydroisoquinoline phenols was modified to give an estrogen receptor downregulator-antagonist profile. Optimization around the core, alkyl side chain, and pendant aryl ring resulted in compounds with subnanomolar levels of potency. The phenol functionality was shown to be required to achieve highly potent compounds, but unusually this was compatible with obtaining high oral bioavailabilities in rat.

Lead optimisation of pyrazoles as novel FPR1 antagonists.

Optimisation of a series of pyrazole inhibitors of the human FPR1 receptor has been achieved. The use of an in vitro media loss assay was utilised to identify sub-series with more robust DMPK profiles. These were subsequently improved to generate analogues with attractive overall profiles.

Discovery of AZD-2098 and AZD-1678, Two Potent and Bioavailable CCR4 Receptor Antagonists

N-(5-Bromo-3-methoxypyrazin-2-yl)-5-chlorothiophene-2-sulfonamide 1 was identified as a hit in a CCR4 receptor antagonist high-throughput screen (HTS) of a subset of the AstraZeneca compound bank. As a hit with a lead-like profile, it was an excellent starting point for a CCR4 receptor antagonist program and enabled the rapid progression through the Lead Identification and Lead Optimization phases resulting in the discovery of two bioavailable CCR4 receptor antagonist candidate drugs.

Design and Implementation of a Rugbyspecific Garment Evaluation Trial (P30)

A structured rugby-specific wearer trial to extract meaningful on-field garment performance data does not exist. To address this, a novel rugby-specific garment evaluation protocol was developed and trialled using a rugby-union international prototype shirt. Three wearer trial elements were investigated namely, rugby-specific wear-service conditions, players’ perceptions of the shirt and, the determination of garment performance on the field of play. Methods: A field test mimicking the demands of the game was devised using published international match-play time-motion analysis. Fifteen non-professional club players (age 26.1 yrs ± 5.2 SD, height 1.83 m ± 0.05 SD, pre-trial body mass 95.8 kg ± 10.7 SD) participated and completed the aforementioned field test. Heart rate was recorded throughout and protocol intensity determined. Garment performance was assessed using controlled visual assessment techniques and dimensional stability measurements. Structured questionnaires were administered during and post-trial to determine player perceptions. Results: Forwards’mean and peak heart rates (153.3 bpm ± 24.1SD and 181.9 bpm ± 10.0 SD) were lower than match-play target values. Backs’mean and peak heart rates (147.2 bpm ± 26.8 SD and 185.0 bpm ± 10.7 SD) were similar to target values. Dimensional changes and defects were identified and quantified successfully. Players conformed well to the protocol and responded favourably to the questionnaire. Conclusion: The protocol described represents the first rugby-specific garment evaluation protocol to be documented. It is hoped that this will be adopted and refined thereby adding structure to the sports-specific garment development process.

Benchmarking the ball–garment frictional properties of rugby union shirts

Recently, rugby shirt manufacturers have added grip textures to the front of shirts in an attempt to enhance their frictional properties, however, the shirt–ball interaction has yet to be systematically studied. Using a sled-type tribometer, the mean dynamic friction forces and quality energy values of seven distinct match-play shirts were determined in two fabric directions and conditions, respectively. Fabric and ball characteristics were determined using an optical measurement device. Significant differences in mean friction force between respective shirts and conditions but not orientations were observed. Adding grip textures to the front of shirts does not necessarily increase mean friction force. No correlations exist between shirt–ball characteristics and mean friction force. The study described represents the first attempt to characterise the rugby shirt–ball frictional interaction. It is hoped that the methods outlined will be adopted and refined, thereby adding structure to the rugby shirt design process.