Design, Synthesis, and Structure–Activity Relationship Optimization of Pyrazolopyrimidine Amide Inhibitors of Phosphoinositide 3-Kinase γ (PI3Kγ)

Autor: Dillon H. Miles, Ada Chen, Manmohan Reddy Leleti, Divyank Soni, Stephen W Young, Artur K. Mailyan, Kenneth V. Lawson, Stefan G Shaqfeh, Ehesan U. Sharif, Jenna L. Jeffrey, Jesus Banuelos, Xuelei Yan, Samuel L Drew, Kimberline Gerrick, Nigel Walker, Puja Dhanota, Lixia Jin, Jay P. Powers, Elaine Ginn, Guillaume Mata, Kent Wong, Hema Singh, Jeremy Fournier, Joel W. Beatty, Ulrike Schindler, Amber Pham, Matthew J. Walters, Jie Chen, Cesar Meleza, Xiaoning Zhao, Nell Narasappa

Publikováno v: Journal of Medicinal Chemistry. 65:1418-1444

Phosphoinositide-3-kinase γ (PI3Kγ) is highly expressed in immune cells and promotes the production and migration of inflammatory mediators. The inhibition of PI3Kγ has been shown to repolarize the tumor immune microenvironment to a more inflammat

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b37aec4464f4375ff8b99d31a40b9e89
https://doi.org/10.1021/acs.jmedchem.1c01153

Discovery of Potent and Selective PI3Kγ Inhibitors

Autor: Dillon H. Miles, Ada Chen, Manmohan Reddy Leleti, Divyank Soni, Stephen W Young, Artur K. Mailyan, Kenneth V. Lawson, Stefan G Shaqfeh, Ehesan U. Sharif, Pei-Yu Chen, Jenna L. Jeffrey, Jesus Banuelos, Xuelei Yan, Samuel L Drew, Nigel Walker, Puja Dhanota, Lixia Jin, Jay P. Powers, Elaine Ginn, Guillaume Mata, Kent Wong, Jeremy Fournier, Joel W. Beatty, Rhiannon Thomas-Tran, Ulrike Schindler, Amber Pham, Matthew J. Walters, Jie Chen, Cesar Meleza, Xiaoning Zhao

Publikováno v: Journal of Medicinal Chemistry. 63:11235-11257

The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homology across the class I

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::237c477c3969b94ce636dfc76aca3e4f
https://doi.org/10.1021/acs.jmedchem.0c01203

Development of a Scalable and Practical Synthesis of AB928, a Dual A2a/A2b Receptor Antagonist

Autor: Jenna L. Jeffrey, Laurent Debien, Dillon H. Miles, Manmohan Reddy Leleti, Brandon Reid Rosen, Jay P. Powers, Ehesan U. Sharif

Publikováno v: Organic Process Research & Development. 24:1254-1261

AB928 is a potent and selective dual antagonist of the A2a and A2b receptors, which is currently in clinical trials. Here, we report the development of two scalable and practical syntheses of AB928...

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::89f6c9ebef3f0788b33a57e7900a3115
https://doi.org/10.1021/acs.oprd.0c00124

Improved synthesis of sterically encumbered heteroaromatic biaryls from aromatic β-keto esters

Autor: Ehesan U. Sharif, Jay P. Powers, Nicholas S. Chan, Dillon H. Miles, Manmohan Reddy Leleti, Brandon Reid Rosen

Publikováno v: Tetrahedron Letters. 61:151855

A protocol for the synthesis of hindered 4-aryl 2-aminopyrimidines from β–keto esters is described. The process employs trifluoroethanol as an essential additive to promote the guanidine condensation reaction, enabling the synthesis of 25 aryl- an

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::1d89cb42bead6f12b2fe690caa28bf58
https://doi.org/10.1016/j.tetlet.2020.151855

Enantioselective Synthesis of N,S-Acetals by an Oxidative Pummerer-Type Transformation using Phase-Transfer Catalysis

Autor: Mathias Turberg, F. Dean Toste, Souvagya Biswas, Matthew S. Sigman, Dillon H. Miles, Koji Kubota, Manuel Orlandi

Publikováno v: Angewandte Chemie (International ed. in English), vol 57, iss 2
Biswas, S; Kubota, K; Orlandi, M; Turberg, M; Miles, DH; Sigman, MS; et al.(2018). Enantioselective Synthesis of N,S-Acetals by an Oxidative Pummerer-Type Transformation using Phase-Transfer Catalysis. Angewandte Chemie-International Edition, 57(2), 589-593. doi: 10.1002/anie.201711277. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/36q8n396

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Reported is the first enantioselective oxidative Pummerer-type transformation using phase-transfer catalysis to deliver enantioenriched sulfur-bearing heterocycles. This reaction includes the direct

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3aa489a33dfd011c6bcb5e7ea0ae2e8
https://escholarship.org/uc/item/36q8n396