Tanya Coleman

Design and synthesis of 6-phenylnicotinamide derivatives as antagonists of TRPV1

6-Phenylnicotinamide (2) was previously identified as a potent TRPV1 antagonist with activity in an in vivo model of inflammatory pain. Optimization of this lead through modification of both the biaryl and heteroaryl components has resulted in the discovery of 6-(4-fluorophenyl)-2-methyl-N-(2-methylbenzothiazol-5-yl)nicotinamide (32; SB-782443) which possesses an excellent overall profile and has been progressed into pre-clinical development.

Identification of a novel series of selective 5-HT7 receptor antagonists

Novel 5-HT(7) receptor antagonists containing the benzocycloheptanone core were identified from high throughput screening. Molecular modelling and SAR studies have converted these intractable hits into a more potent, selective and tractable series, exemplified by compound (25), SB-691673.

Occupational Exposure to Animals and Risk of Zoonotic Illness in a Cohort of Farmers, Farmworkers, and Their Families in England

We recruited a representative population-based sample of 606 farmers, farmworkers, and their families from three areas of England. By defining and measuring animal exposure (type, frequency, and species range) we were able not only to measure the incidence and prevalence of markers of exposure to zoonotic organisms in this sentinel group, but also to determine the risk of exposure to zoonotic organisms associated with a variety of defined occupational exposures. Prevalence of antibodies to Coxiella burnetii (the cause of Q fever) (29.2%) and toxoplasma (50.2%) were high; whereas, prevalence of antibodies to Borrelia burgdorferi (the cause of Lyme disease) (0.2%), leptospira (0.2%), and brucella (0.7%) were low. The cohort was also exposed to hantavirus (seroprevalence 4.7%), orthopoxvirus (0.7%), parapoxvirus (4.5%), Bartonella spp. (2.0%) Ehrlichia chaffeensis (0.2%), human granulocytic ehrlichiosis agent (1.5%), and Echinococcus granulosis 3/202 (1.5%). Coxiella seropositivity was associated with exposure to dairy cattle (odds ratio: 1.48, 95% confidence interval: 1.03-2.12); cowpox with exposure to rats (odds ratio: 18.7, 95% confidence interval: 1.7-201.8). Self-reported clinical orf (contagious pustular dermatitis) was associated with exposure to sheep (risk ratio: 7.64, 95% confidence interval: 1.93-30.26) and rats (risk ratio 4.54, 95% confidence interval: 1.16-17.70); ringworm (dermatophytosis) with cattle (risk ratio: 1.76; 95% confidence interval: 1.17-2.64).

Incidence of Helicobacter pylori in Farmworkers and the Role of Zoonotic Spread

Although Helicobacter pylori is probably the most common human pathogen worldwide, it’s epidemiology is largely unknown. To determine it’s occupational significance, if any, and mode of transmission, we measured the prevalence and incidence of IgG specific antibody to H.pylori in a representative cohort of farmworkers and collected detailed exposure data.