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 Non-Nucleotide Small Molecule Inhibitors of CD73

Autor: Stephen W Young, Debashis Mandal, Sharon Zhao, Susanne Moschütz, Ada Chen, Elaine Ginn, Lixia Jin, Samuel L Drew, Nigel Walker, Erick Allen Lindsey, Jay P. Powers, Kenneth V. Lawson, Xuelei Yan, Anh Tran, Rhiannon Thomas-Tran, Amber Pham, Manmohan Reddy Leleti, Jenna L. Jeffrey, Steven D. Jacob, Norbert Sträter, Joel W. Beatty, Jeremy Fournier, Laurent Debien

Publikováno v: Journal of Medicinal Chemistry. 63:3935-3955

CD73 is an extracellular mediator of purinergic signaling. When upregulated in the tumor microenvironment, CD73 has been implicated in the inhibition of immune function through overproduction of adenosine. Traditional efforts to inhibit CD73 have inv

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1cb1d479ddd330a628c6dc7fec984840
https://doi.org/10.1021/acs.jmedchem.9b01713

Abstract P206: AB521 potently and selectively inhibits pro-tumorigenic gene transcription by Hypoxia-Inducible Factor (HIF)-2α in vitro and in vivo

Autor: Kelsey E. Sivick Gauthier, Dana Piovesan, Soonweng Cho, Kenneth V. Lawson, Patrick G. Schweickert, Alejandra Lopez, Suan Liu, Timothy Park, Artur Mailyan, Jeremy T. A. Fournier, Joel W. Beatty, Samuel L. Drew, Jarek Kalisiak, Balint Gal, Guillaume Mata, Zhang Wang, Brandon R. Rosen, Clayton Hardman, Matthaw P. Epplin, Kai Yu, Karl T. Haelsig, Lixia Jin, Elaine Ginn, Jennie Au, Cesar A. Meleza, Joel Tencer, Amber Pham, Hyock J. Kwon, Stephen W. Young, Manmohan Leleti, Jay P. Powers, Matthew J. Walters

Publikováno v: Molecular Cancer Therapeutics. 20:P206-P206

Cells in the solid tumor microenvironment are frequently exposed to hypoxic conditions, necessitating molecular adaptations for survival. Of particular importance are transcriptional changes mediated by heterodimeric Hypoxia-Inducible Factor (HIF) pr

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::3dcad50485d58db7e77ba50a6a9d4ed2
https://doi.org/10.1158/1535-7163.targ-21-p206

Total Synthesis of a Dimeric Thymol Derivative Isolated from Arnica sachalinensis

Autor: Gary S. Nichol, Andy Lawrence, Irene De Silvestro, Samuel L. Drew, Fernanda Duarte

Publikováno v: Drew, S L, Duarte Gonzalez, F, De silvestro, I, Lawrence, A & Nichol, G 2017, ' Total Synthesis of a Dimeric Thymol Derivative Isolated from Arnica sachalinensis ', Angewandte Chemie . https://doi.org/10.1002/ange.201701481

The total synthesis of a dimeric thymol derivative (thymarnicol) isolated from Arnica sachalinensis was accomplished in 6 steps. A key biomimetic Diels–Alder dimerization was found to occur at ambient temperature and the final oxidative cyclization

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::32165193025da161c9919c67ff64dd8d
https://doi.org/10.1002/anie.201701481

Pseudopterosin synthesis from a chiral cross-conjugated hydrocarbon through a series of cycloadditions

Autor: Samuel L. Drew, Christopher G. Newton, Anthony C. Willis, Andy Lawrence, Michael N. Paddon-Row, Michael S. Sherburn

Publikováno v: Newton, C G, Drew, S L, Lawrence, A L, Willis, A C, Paddon-Row, M N & Sherburn, M S 2015, ' Pseudopterosin synthesis from a chiral cross-conjugated hydrocarbon through a series of cycloadditions ', Nature Chemistry, vol. 7, pp. 82-86 . https://doi.org/10.1038/NCHEM.2112

The pseudopterosins are a family of diterpene marine natural products, which, by virtue of their interesting anti-inflammatory and analgesic properties, have attracted the attentions of many synthetic chemists. The most efficient syntheses reported t

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e84ad8ef9e829bff37573e7992044c6
https://doi.org/10.1038/nchem.2112