Design and elaboration of a tractable tricyclic scaffold to synthesize druglike inhibitors of dipeptidyl peptidase-4 (DPP-4), antagonists of the C–C Chemokine Receptor Type 5 (CCR5), and highly potent and selective phosphoinositol-3 Kinase δ (PI3Kδ) inhibitors

Schwehm, Carolin; Kellam, Barrie; Garces, Aimie; Hill, Stephen J.; Kindon, Nicholas; Bradshaw, Tracey D.; Li, Jin; Macdonald, Simon J.F.; Rowedder, James E.; Stoddart, Leigh A.; Stocks, Michael

doi:10.1021/acs.jmedchem.6b01801

All Outputs (4)

From UTP to AR-C118925, the discovery of a potent non nucleotide antagonist of the P2Y2 receptor (2017)
Journal Article

The G protein-coupled P2Y2 receptor, activated by ATP and UTP has been reported as a potential drug target for a wide range of important clinical conditions, such as tumor metastasis, kidney disorders, and in the treatment of inflammatory conditions.... Read More about From UTP to AR-C118925, the discovery of a potent non nucleotide antagonist of the P2Y2 receptor.

Discovery of AZD-2098 and AZD-1678, two potent and bioavailable CCR4 receptor antagonists (2017)
Journal Article

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 sub-set of the AstraZeneca compound bank. As a hit with a lead-like profile, it was an excelle... Read More about Discovery of AZD-2098 and AZD-1678, two potent and bioavailable CCR4 receptor antagonists.

Ipratropium is ‘luminally recycled’ by an inter-play between apical uptake and efflux transporters in Calu-3 bronchial epithelial cell layers (2017)
Journal Article

The mechanism by which quaternized anticholinergic bronchodilators permeate the airway epithelium remains controversial to date. In order to elucidate the role of drug transporters, ipratropium bidirectional transport as well as accumulation and rele... Read More about Ipratropium is ‘luminally recycled’ by an inter-play between apical uptake and efflux transporters in Calu-3 bronchial epithelial cell layers.

Design and elaboration of a tractable tricyclic scaffold to synthesize druglike inhibitors of dipeptidyl peptidase-4 (DPP-4), antagonists of the C–C Chemokine Receptor Type 5 (CCR5), and highly potent and selective phosphoinositol-3 Kinase δ (PI3Kδ) inhibitors (2017)
Journal Article

A novel molecular scaffold has been synthesized, and its incorporation into new analogues of biologically active molecules across multiple target classes will be discussed. In these studies, we have shown use of the tricyclic scaffold to synthesize p... Read More about Design and elaboration of a tractable tricyclic scaffold to synthesize druglike inhibitors of dipeptidyl peptidase-4 (DPP-4), antagonists of the C–C Chemokine Receptor Type 5 (CCR5), and highly potent and selective phosphoinositol-3 Kinase δ (PI3Kδ) inhibitors.