Discovery of potent and orally bioavailable indazole-based glucagon receptor antagonists for the treatment of type 2 diabetes

Autor: Fuyong Du, Brian C. Shook, Karen DiLoreto, Guozhang Xu, Fengbin Song, Yin Liang, Michael David Gaul, Rosie Santulli, Dennis Rentzeperis, Annette Eckardt, Keith T. Demarest, Renee L. DesJarlais

Publikováno v: Bioorganicmedicinal chemistry letters. 29(20)

Type 2 diabetes mellitus (T2DM) is characterized by chronically elevated plasma glucose levels. The inhibition of glucagon-induced hepatic glucose output via antagonism of the glucagon receptor (GCGR) using a small-molecule antagonist is a promising

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0b30b8f1be120fa7a91abbdd01da299a
https://pubmed.ncbi.nlm.nih.gov/31519374

Characterization of the trigeminovascular actions of several adenosine A2A receptor antagonists in an in vivo rat model of migraine

Autor: Paul F. Jackson, Christopher M. Flores, Antoinette MaassenVanDenBrink, Kristian Agmund Haanes, Kayi Y. Chan, Brian C. Shook, Jimmy Zhang, Alejandro Labastida-Ramírez, Alexander H. J. Danser, René de Vries, Carlos M. Villalón

Publikováno v: Journal of Headache and Pain, 19:41. Springer-Verlag Italia
The Journal of Headache and Pain
The Journal of Headache and Pain, Vol 19, Iss 1, Pp 1-10 (2018)

Background Migraine is considered a neurovascular disorder, but its pathophysiological mechanisms are not yet fully understood. Adenosine has been shown to increase in plasma during migraine attacks and to induce vasodilation in several blood vessels

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f32dfcb4d99f07e443809e06b8a7c6dc
https://doi.org/10.1186/s10194-018-0867-x

Substituted thieno[2,3-d]pyrimidines as adenosine A2A receptor antagonists

Autor: Lori Westover, Nathaniel H. Wallace, Paul F. Jackson, Brian C. Shook, Lisa Lampron, Devraj Chakravarty, J. Kent Barbay, Mark T. Powell, Aihua Wang, Robert H. Scannevin, Kenneth J. Rhodes, Mark Ault, Vernon C. Alford, Jeffrey Crooke, Kristi A. Leonard, Stefanie Rassnick, Karen Carroll

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 23:2688-2691

A novel series of benzyl substituted thieno[2,3-d]pyrimidines were identified as potent A2A receptor antagonists. Several five- and six-membered heterocyclic replacements for the optimized methylfuran were explored. Select compounds effectively rever

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb0e7d68d61aecf41c3f65b13066a52c
https://doi.org/10.1016/j.bmcl.2013.02.078

Overcoming the Genotoxicity of a Pyrrolidine Substituted Arylindenopyrimidine As a Potent Dual Adenosine A2A/A1 Antagonist by Minimizing Bioactivation to an Iminium Ion Reactive Intermediate

Autor: Jose Silva, Heng-Keang Lim, Vedwatee Gopaul, Tynisha Thomas, Rhys Salter, Paul F. Jackson, Kevin Cook, Kenneth J. Rhodes, Carlo Sensenhauser, Stefanie Rassnick, David C. Evans, Chen Jie, Robert Preston, Brian C. Shook

Publikováno v: Chemical Research in Toxicology. 24:1012-1030

2-Amino-4-phenyl-8-pyrrolidin-1-ylmethyl-indeno[1,2-d]pyrimidin-5-one (1) is a novel and potent selective dual A(2A)/A(1) adenosine receptor antagonist from the arylindenopyrimidine series that was determined to be genotoxic in both the Ames and Mous

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41e7471f9a767bbd6ed26775c7fa579a
https://doi.org/10.1021/tx1004437

Methylene amine substituted arylindenopyrimidines as potent adenosine A2A/A1 antagonists

Autor: Sandra Damon, Lori Westover, Kenneth C. Rupert, Ronald K. Russell, Xun Li, Devraj Chakravarty, Paul F. Jackson, Brian Magliaro, Yuting Tang, Geoffrey R. Heintzelman, Kenneth M. Wells, Stefanie Rassnick, Shawn Branum, Mel Osbourne, Karen Carroll, Kenneth J. Rhodes, James L. Bullington, Robert H. Scannevin, Keith T. Demarest, Lisa Lampron, Brian C. Shook, Scott Youells, Kristen Hansen, Hall Daniel A

Publikováno v: Bioorganic & Medicinal Chemistry Letters. 20:2864-2867

A novel series of arylindenopyrimidines were identified as A(2A) and A(1) receptor antagonists. The series was optimized for in vitro activity by substituting the 8- and 9-positions with methylene amine substituents. The compounds show excellent acti

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f81d5b2a5b35b6c6aec43edf95869ec0
https://doi.org/10.1016/j.bmcl.2010.03.042