Discovery of 3-Cyano- N-(3-(1-isobutyrylpiperidin-4-yl)-1-methyl-4-(trifluoromethyl)-1 H-pyrrolo[2,3- b]pyridin-5-yl)benzamide: A Potent, Selective, and Orally Bioavailable Retinoic Acid Receptor-Related Orphan Receptor C2 Inverse Agonist

Autor: Martin Hegen, David C. Wood, Patrik Rhönnstad, Felix Vajdos, Atli Thorarensen, Mark E. Schnute, Timothy Braden, Kimberly Crouse, Maria Sjöberg, John I. Trujillo, Ravi G. Kurumbail, Bolette Husman, Konrad F. Koehler, Mattias Wennerstål, Tomas Bonn, Joakim Löfstedt, Eva Backström-Rydin, Bo Carlsson, Aron Sundell, Ming Z. Chen, Steven E. Heasley, John David Trzupek, Annika Goos-Nilsson, Carol A. Menard, Peter Harris, James R. Kiefer, Martin Bengtsson, Leon P. Collis, Michael J. Prinsen, Philippe Nuhant, Jennifer Alley, Scott A. Long, Alexander E. Hromockyj, Andrew C. Flick, Johnny Sandberg, Christoph W. Zapf, Edouard Zamaratski, Xiao Hu, Lee Napierata, Björn Kauppi, Nicole Caspers, Kimberly F. Fennell, Robert E. Kyne, Gabriel Berstein, Neelu Kaila, Lars Kruger, Wei Li, Li Xing, Ray Unwalla, Elisabet Kallin, Matthew J. Pelc, Susan Fish, James Robert Blinn, Hjalmar Gullberg, Marvin J. Meyers, Scot Richard Mente, Chulho Choi, Falgun Shah, Mathias Färnegårdh, Dean Messing, Peter G. Jones, Yajuan Zhao, Alexandria P. Taylor, Maria Sandström, Charles W. Bolten, Daniel Nöteberg, Robin A. Weinberg, Tomasz Janosik, John D. Knafels, Anna Wilhelmsson

Publikováno v: Journal of medicinal chemistry. 61(23)

The nuclear hormone receptor retinoic acid receptor-related orphan C2 (RORC2, also known as RORγt) is a promising target for the treatment of autoimmune diseases. A small molecule, inverse agonist of the receptor is anticipated to reduce production

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9b335f732a3ffd4d00a80bd0f813c732
https://pubmed.ncbi.nlm.nih.gov/30130103

Synthesis and biological evaluation of substituted benzoxazoles as inhibitors of mPGES-1: Use of a conformation-based hypothesis to facilitate compound design

Autor: Daniel P. Walker, Alexander F. Shaffer, William M. Moore, Michael T. Baratta, Sue Metz, Jeffrey A. Scholten, John Robert Springer, Jeffrey S. Carter, Hwang-Fun Lu, Steven E. Heasley, Yvette M. Fobian, Natasha M. Kablaoui, Francisco M. Franco, Li Xing, Shengtian Yang, Hanau Cathleen E, Michael L. Vazquez, Graciela B. Arhancet, Gina M. Jerome

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 23:1120-1126

Microsomal prostaglandin E(2) synthase-1 (mPGES-1) is a novel therapeutic target for the treatment of inflammation and pain. In the preceding letter, we detailed the discovery of clinical candidate PF-04693627, a potent mPGES-1 inhibitor possessing a

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b2d05bf0698be13f2291735a95c4465f
https://doi.org/10.1016/j.bmcl.2012.11.107

Acidic triazoles as soluble guanylate cyclase stimulators

Autor: Michael A. Tones, Paul A. Bradley, Graham L. Smith, Lee R. Roberts, Geoff E. Gymer, Katherine S. England, Fox David Nathan Abraham, Steven E. Heasley, Michelle Schmidt, Mark E. Bunnage, Yvette M. Fobian, Jerome Molette, David Fairman, Dack Kevin Neil

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 21:6515-6518

A series of acidic triazoles with activity as soluble guanylate cyclase stimulators is described. Incorporation of the CF3 triazole improved the overall physicochemical and drug-like properties of the molecule and is exemplified by compound 25.

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54aefeeb064c19cd276466bf3d396d04
https://doi.org/10.1016/j.bmcl.2011.08.071

Design, Synthesis, and Biological Evaluation of 3-[4-(2-Hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a Potent, Orally Active, Brain Penetrant Inhibitor of Phosphodiesterase 5 (PDE5)

Autor: Sandra W. Curtiss, D. Joseph Rogier, Alan MacInnes, Brown David L, Mike B. Tollefson, Brian R. Bond, Yvette M. Fobian, Maddux Todd Michael, Dafydd R. Owen, Jeanne M. Rumsey, Brent V. Mischke, Jerry W. Cubbage, Alan G. Benson, Robert Hughes, Lena L Zhang, E. Jon Jacobsen, Steven E. Heasley, Joseph B. Moon, Ying Yu, John M. Molyneaux, Yi Zheng, Brad A. Acker, Blevis-Bal Radhika M, John N. Freskos, John K. Walker, Jennie L. Walgren

Publikováno v: Journal of Medicinal Chemistry. 53:2656-2660

We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::892c7788c8aa398973abd4f8bb5a78a5
https://doi.org/10.1021/jm901781q

Design, synthesis, and biological evaluation of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[3,4-b]pyrazin-2(1H)-one, a potent, orally active, brain penetrant inhibitor of phosphodiesterase 5 (PDE5)

Autor: Robert O, Hughes, D Joseph, Rogier, E Jon, Jacobsen, John K, Walker, Alan, Macinnes, Brian R, Bond, Lena L, Zhang, Ying, Yu, Yi, Zheng, Jeanne M, Rumsey, Jennie L, Walgren, Sandra W, Curtiss, Yvette M, Fobian, Steven E, Heasley, Jerry W, Cubbage, Joseph B, Moon, David L, Brown, Brad A, Acker, Todd M, Maddux, Mike B, Tollefson, Brent V, Mischke, Dafydd R, Owen, John N, Freskos, John M, Molyneaux, Alan G, Benson, Rhadika M, Blevis-Bal

Publikováno v: Journal of medicinal chemistry. 53(6)

We recently described a novel series of aminopyridopyrazinones as PDE5 inhibitors. Efforts toward optimization of this series culminated in the identification of 3-[4-(2-hydroxyethyl)piperazin-1-yl]-7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)pyrido[

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::88c2de53db53a1f8525bbef66ae6a7e3
https://pubmed.ncbi.nlm.nih.gov/20196613