Zobrazeno 1 - 10
of 14
pro vyhledávání: '"Michael DeGraffenreid"'
Autor:
Stefania Ursu, Daqing Sun, Yosup Rew, Juan C. Jaen, Jay P. Powers, Xiao He, Hua Tu, Dustin McMinn, Michael DeGraffenreid
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 22:3786-3790
A novel series of benzenesulfonanilide derivatives of 11β-HSD1 inhibitors were identified via modification of the sulfonamide core of the arylsulfonylpiperazine lead structures. The synthesis, in vitro biological evaluation, and structure–activity
Autor:
Minqing Rong, Brian Lucas, Wendy Zhong, Guifen Xu, Gary Lee, Ben Jiang, Angela Chong, Qiuping Ye, Michael DeGraffenreid, Tom Huang, Dineli Wickramasinghe, Randall W. Hungate, Wade Aaron, Michael G. Johnson, Jessica Orf, Dustin McMinn, Matthew L. Brown, Richard J. Austin, Maria M. Toteva, Jacob Kaizerman, Jay P. Powers
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 21:5206-5209
A bis-amide antagonist of Smoothened, a seven-transmembrane receptor in the Hedgehog signaling pathway, was discovered via high throughput screening. In vitro and in vivo experiments demonstrated that the bis-amide was susceptible to N-acyl transfera
Autor:
Yosup Rew, Hilary Plake Beck, Anne Y. Saiki, Steven H. Olson, Brian M. Fox, Kevin Salyers, Dongyin Yu, Michael DeGraffenreid, Stephen Schneider, John G. Allen, Jonathan D. Oliner, Qiuping Ye
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 21:2752-2755
Human murine double minute 2 (MDM2) is a negative regulator of p53, which plays an important role in cell cycle and apoptosis. We report several optimizations to the synthesis of the chromenotriazolopyrimidine series of MDM2-p53 protein-protein inter
Autor:
Hua Tu, Lisa Julian, Nigel Walker, Maren Gulsrud Willcockson, Yosup Rew, Michael DeGraffenreid, Zhulun Wang, Juan C. Jaen, Daqing Sun, Ron C. Kelly, Athena Sudom, Seb Caille, Jacob Kaizerman, Jay P. Powers, Xuelei Yan, Qiuping Ye, Stefania Ursu, Ben Jiang, Felix Gonzalez-Lopez de Turiso, Randall W. Hungate, Dustin McMinn
Publikováno v:
Bioorganic & Medicinal Chemistry Letters. 21:405-410
The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11β-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-huma
Autor:
Jinsong Liu, Daqing Sun, Tracy Bostick, Randall W. Hungate, Dustin McMinn, Xiao He, Michael DeGraffenreid, Lisa Julian, Juan C. Jaen, Mario Monshouwer, Qiuping Ye, Athena Sudom, Rebekah Choi, Yongmei Di, Yosup Rew, Zhulun Wang, Stefania Ursu, Xuelei Yan, Hua Tu, Seb Caille, Nigel Walker, Jay P. Powers
Publikováno v:
Journal of Medicinal Chemistry. 51:3953-3960
We report the discovery of potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2,
Autor:
Felix Gonzalez-Lopez de Turiso, Daqing Sun, Yosup Rew, Sarah Bennett, Michael DeGraffenreid, Lisa Julian, Randall W. Hungate, Xuelei Yan, Sebastien Caille, Jay P. Powers, Jacob Kaizerman, Dustin McMinn
Publikováno v:
The Journal of Organic Chemistry. 72:7455-7458
A simple, scalable, and efficient one-pot methodology for the synthesis of 4,4-disubstituted cyclohexane beta-keto esters from benzylic nitriles or esters and methyl acrylate promoted by potassium tert-butoxide is described. The process relies on a t
Autor:
Mei-Chu Lo, Ji Ma, Julio C. Medina, Dineli Wickramasinghe, Mark L. Ragains, Derek E. Piper, Merrill Ayres, Zhihong Li, Alex J. Zhang, Xiaoqi Chen, Jeffrey Deignan, Zhulun Wang, Kanaka Pattabiraman, Kathleen S. Keegan, Xiaoning Zhao, Rachel Ngo, Nigel Walker, Lingming Liang, Margaret F. Weidner, Paul M. Wehn, Christophe Queva, Jason Duquette, Alexander Kamb, Ada Chen, Malgorzata Wanska, Jeffrey T. Mihalic, Kriti Modi, Pingchen Fan, Grace Q. Alba, Yunxiao Li, Michael W. Gribble, John Eksterowicz, Jacob Kaizerman, Dustin McMinn, Xianghong Wang, Michael DeGraffenreid, Steve Thibault, Xiaodong Wang, Kexue Li, Benjamin Fisher, Richard V. Connors, Wen Liu, Sarah E. Lively, Cong Li, Kang Dai, Jiasheng Fu, Justin N. Huard, Robert Cho, Lawrence R. McGee, Timothy J. Carlson, Julia Suchomel
Publikováno v:
Journal of medicinal chemistry. 57(8)
We describe the structural optimization of a lead compound 1 that exhibits dual inhibitory activities against FLT3 and CDK4. A series of pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidine derivatives was synthesized, and SAR analysis, using cell-based assays,
Autor:
Gill Adrian Liam, Csaba Lehel, Mcintosh Joel, Francisco Xavier Talamas, Roland J. Billedeau, Holger Wesche, David Clark, Eric Brian Sjogren, Matt Wright, Nigel Walker, Stacie A. Dalrymple, Sharada Shenvi Labadie, Camran Parast, Timothy D. Cushing, George Tonn, Michelle F. Browner, Keith A. M. Walker, Viola Bordunov, Pu-Ping Lu, Marie-Louise Smith, Chris Whitehead, Xiao He, Mario G. Cardozo, Juan C. Jaen, Chris Allen Broka, Peng Cheng, Youngsook Shin, Karen Berry, Vijay Baichwal, Shichang Miao, Ronald Charles Hawley, Xiaolin Hao, Michael DeGraffenreid, Marc Labelle
Publikováno v:
Bioorganicmedicinal chemistry letters. 21(1)
A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene) thiosemicarbazides was discovered as potent inhibitors of IKKβ. In this Letter we document our early efforts at optimization of the quinoline core, the imidazole and t
Autor:
Karen Berry, Viola Bordunov, Shichang Miao, David Clark, George Tonn, Timothy D. Cushing, Ronald Charles Hawley, Gill Adrian Liam, Marc Labelle, Csaba Lehel, Pu-Ping Lu, Francisco Xavier Talamas, Vijay Baichwal, Roland J. Billedeau, Mario G. Cardozo, Mcintosh Joel, Peng Cheng, Marie-Louise Smith, Michael DeGraffenreid, Chris Whitehead, Stacie A. Dalrymple, Xiao He, Nigel Walker, Camran Parast, Xiaolin Hao, Holger Wesche, Matt Wright, Eric Brian Sjogren, Keith A. M. Walker, Juan C. Jaen, Chris Allen Broka, Sharada Shenvi Labadie, Michelle F. Browner, Youngsook Shin
Publikováno v:
Bioorganicmedicinal chemistry letters. 21(1)
A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene) thiosemicarbazides was discovered as potent inhibitors of IKKβ. In this Letter we document our efforts at further optimization of this series, culminating in 2 with su
Autor:
Pingchen Fan, Dustin McMinn, Shichang Miao, Jinsong Liu, Ji Ma, Liang Tang, Xuelei Yan, Marc Labelle, Athena Sudom, Stefania Ursu, Michael DeGraffenreid, Yongmei Di, Xiao He, Zhulun Wang, Juan C. Jaen, Jay P. Powers, Daqing Sun, Hua Tu, Nigel Walker, Mario G. Cardozo, Qiuping Ye
Publikováno v:
Bioorganicmedicinal chemistry letters. 20(23)
In this communication, human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitory activities of a novel series of diarylsulfones are described. Optimization of this series resulted in several highly potent 11β-HSD1 inhibitors with excelle