Zobrazeno 1 - 10
of 26
pro vyhledávání: '"Joseph G. Bruno"'
Autor:
Christina N. DiMarco, Anthony L. Gotter, Alan T. Savitz, Joanne Stevens, Joseph G. Bruno, Tamara D. Cabalu, John J. Renger, Jason W. Skudlarek, Pamela L. Tannenbaum, Paul J. Coleman, Scott D. Kuduk, Joseph Brunner, Susan L. Garson, Christopher J. Winrow, Julie A. O'Brien, Charles M. Harrell, Mark H. Pausch
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 25:2488-2492
Antagonism of orexin receptors has shown clinical efficacy as a novel paradigm for the treatment of insomnia and related disorders. Herein, molecules related to the dual orexin receptor antagonist filorexant were transformed into compounds that were
Autor:
Christopher J. Winrow, Joanne Stevens, Anthony J. Roecker, Charles M. Harrell, Alan T. Savitz, W. Peter Wuelfing, Kerim Babaoglu, Jason W. Skudlarek, Paul J. Coleman, Steven V. Fox, Christina Ng Dimarco, Pamela L. Tannenbaum, Scott D. Kuduk, Susan L. Garson, Joseph G. Bruno, Joseph Brunner, John J. Renger, Tamara D. Cabalu, Anthony L. Gotter, Mark A. Pausch, Julie A. O'Brien
Publikováno v:
Bioorganicmedicinal chemistry letters. 27(6)
In an ongoing effort to explore the use of orexin receptor antagonists for the treatment of insomnia, dual orexin receptor antagonists (DORAs) were structurally modified, resulting in compounds selective for the OX2R subtype and culminating in the di
Autor:
John J. Renger, Joyce Stellabott, Swati P. Mercer, Wei Lemaire, Thomas S. Reger, Christopher D. Cox, Pamela L. Tannenbaum, Christopher J. Winrow, Joanne Stevens, Donghui Cui, Joseph G. Bruno, Susan L. Garson, Rowena V. Cube, M. Christa Mattern, Dansu Li, C. Meacham Harrell, Paul J. Coleman, John D. Schreier, Tamara D. Cabalu, George D. Hartman, Anthony L. Gotter, Steven V. Fox, Jeffrey M. Bergman, Anthony J. Roecker, Thomayant Prueksaritanont, Steven D. Young
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 24:4884-4890
Orexin receptor antagonists have demonstrated clinical utility for the treatment of insomnia. The majority of clinical efforts to date have focused on the development of dual orexin receptor antagonists (DORAs), small molecules that antagonize both t
Autor:
Pamela L. Tannenbaum, Scott D. Kuduk, Tamara D. Cabalu, Joseph Brunner, Mark A. Pausch, Christina N. Di Marco, Joseph G. Bruno, Paul J. Coleman, Anthony L. Gotter, John J. Renger, Joanne Stevens, Jason W. Skudlarek, Christopher J. Winrow, Julie A. O'Brien
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 24:1784-1789
Analogs of the dual orexin receptor antagonist filorexant were prepared. Replacement of the ether linkage proved highly sensitive toward modification with an acetylene linkage providing compounds with the best in vitro and in vivo potency profiles.
Autor:
Samuel L. Graham, Joseph G. Bruno, Scott D. Mosser, Harold G. Selnick, Sandra M. Sanabria-Bohórquez, Christopher A. Salvatore, Rebecca B. White, Melody Mcwherter, Hong Fan, Mangay Williams, Jacquelynn J. Cook, Kerry Riffel, Richard Hargreaves, Ian M. Bell, Craig A. Stump, Eric L. Moore, Liza Gantert, Steven N. Gallicchio, Mona Purcell, C. Blair Zartman, Amanda L. Kemmerer, Eric D. Hostetler, Donnette D. Staas, Stefanie A. Kane
Publikováno v:
ACS Medicinal Chemistry Letters. 4:863-868
Rational modification of the potent calcitonin gene-related peptide (CGRP) receptor antagonist MK-3207 led to a series of analogues with enhanced CNS penetrance and a convenient chemical handle for introduction of a radiolabel. A number of (11)C-trac
Autor:
Christopher J. Winrow, John J. Renger, Craig A. Stump, Tamara D. Cabalu, Terrence P. McDonald, C. Meacham Harell, Scott D. Kuduk, Anthony L. Gotter, Julie A. O'Brien, Cooke Andrew John, Paul J. Coleman, Peter D. Williams, Joseph G. Bruno
Publikováno v:
Bioorganicmedicinal chemistry letters. 26(23)
While a correlation between blockade of the orexin 2 receptor (OX2R) with either a dual orexin receptor antagonist (DORA) or a selective orexin 2 receptor antagonist (2-SORA) and a decrease of wakefulness is well established, less is known about sele
Autor:
Samuel L. Graham, Christine Fandozzi, Eric L. Moore, Donnette D. Staas, Ian M. Bell, Nova Sain, Joseph G. Bruno, Steven N. Gallicchio, Harold G. Selnick, Christopher A. Salvatore, Mark O. Urban, Rebecca B. White, Matthew M. Zrada, Amy Calamari, C. Blair Zartman, Amanda L. Kemmerer, Joseph P. Vacca, Stefanie A. Kane, Craig A. Stump, Scott D. Mosser
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 22:3941-3945
Rational modification of the clinically tested CGRP receptor antagonist MK-3207 (3) afforded an analogue with increased unbound fraction in rat plasma and enhanced aqueous solubility, 2-[(8R)-8-(3,5-difluorophenyl)-8-methyl-10-oxo-6,9-diazaspiro[4.5]
Autor:
Reshma Panemangalore, Judith A. Johnson, Colin M. Tice, Wei He, Brian M. McKeever, Yi Zhao, Zhenrong Xu, Peter Lindblom, Joseph G. Bruno, Yuri Bukhtiyarov, Joan Guo, Salvacion Cacatian, Wei Zhao, Jennifer Berbaum, Jennifer Togias, Boyd B. Scott, David A. Claremon, Rong Guo, Linghang Zhuang, Barbara A. Kruk, Yuanjie Ye, Suresh B. Singh, Paula Krosky, Richard K. Harrison, Gerard McGeehan, Patrick J. Carroll
Publikováno v:
Journal of Medicinal Chemistry. 54:6050-6062
Structure based design led directly to 1,3-oxazinan-2-one 9a with an IC(50) of 42 nM against 11β-HSD1 in vitro. Optimization of 9a for improved in vitro enzymatic and cellular potency afforded 25f with IC(50) values of 0.8 nM for the enzyme and 2.5
Autor:
Scott D. Mosser, Joseph P. Vacca, Eric L. Moore, Rodney A. Bednar, Shane Roller, John F. Fay, Kathy M. Schirripa, Harold G. Selnick, Michael R. Wood, June J. Kim, Joseph G. Bruno, Christopher A. Salvatore
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 20:6827-6830
A previously utilized quinoline-for- N -phenylamide replacement strategy was employed against a central amide in a novel class of CGRP receptor antagonists. A unique and unexpected substitution pattern was ultimately required to maintain reasonable a
Autor:
Joseph P. Vacca, Eric L. Moore, Joseph G. Bruno, Craig A. Stump, Christopher A. Salvatore, Harold G. Selnick, Stefanie A. Kane, Amy G. Quigley, Rodney A. Bednar, Ian M. Bell, Kathy M. Schirripa, John F. Fay, Scott D. Mosser, Shane Roller, Michael R. Wood, June J. Kim
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 19:5787-5790
A novel class of CGRP receptor antagonists was rationally designed by modifying a highly potent, but structurally complex, CGRP receptor antagonist. Initial modifications focused on simplified structures, with increased flexibility. Subsequent to the