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
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 potent inhibitors of the serine peptidase DPP-4, an...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
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American Chemical Society
2017
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| Online Access: | https://eprints.nottingham.ac.uk/44065/ |
| _version_ | 1848796828687925248 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Schwehm, Carolin |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 potent inhibitors of the serine peptidase DPP-4, antagonists of the CCR5 receptor, and highly potent and selective PI3K δ isoform inhibitors. We also describe the predicted physicochemical properties of the resulting inhibitors and conclude that the tractable molecular scaffold could have potential application in future drug discovery programs. |
| first_indexed | 2025-11-14T19:54:11Z |
| format | Article |
| id | nottingham-44065 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:54:11Z |
| publishDate | 2017 |
| publisher | American Chemical Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-440652020-05-04T18:29:22Z https://eprints.nottingham.ac.uk/44065/ 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 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 potent inhibitors of the serine peptidase DPP-4, antagonists of the CCR5 receptor, and highly potent and selective PI3K δ isoform inhibitors. We also describe the predicted physicochemical properties of the resulting inhibitors and conclude that the tractable molecular scaffold could have potential application in future drug discovery programs. American Chemical Society 2017-01-27 Article PeerReviewed 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. and Stocks, Michael (2017) 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. Journal of Medicinal Chemistry, 60 (4). pp. 1534-1554. ISSN 1520-4804 http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.6b01801 doi:10.1021/acs.jmedchem.6b01801 doi:10.1021/acs.jmedchem.6b01801 |
| spellingShingle | 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 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://eprints.nottingham.ac.uk/44065/ https://eprints.nottingham.ac.uk/44065/ https://eprints.nottingham.ac.uk/44065/ |