排序方式: 共有19条查询结果,搜索用时 15 毫秒
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Jenifer L. Smith Kassandra I. Rossiter Christopher M. Semko Ying-Zi Xu David A. Quincy Jacek Jagodzinski Michael S. Dappen Andrei W. Konradi Christopher Vandevert Caroline Garrido Wenxian Mao F. Bong San Pablo Brian Wipke Lilibeth Dofiles Angie Wadsworth Eric Peterson Carlos Lorenzana Stellanie Simmonds Ted A. Yednock 《Bioorganic & medicinal chemistry letters》2013,23(14):4117-4119
Mitsunobu reactions were employed to link t-butyl esters of α4 integrin inhibitors at each of the termini of a three-arm, 40 kDa, branched PEG. Cleavage of the t-butyl esters using HCO2H provided easily isolated PEG derivatives, which are potent α4 integrin inhibitors, and which achieve sustained levels and bioactivity in vivo, following subcutaneous administration to rats. 相似文献
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Anh P. Truong Danielle L. Aubele Gary D. Probst Martin L. Neitzel Chris M. Semko Simeon Bowers Darren Dressen Roy K. Hom Andrei W. Konradi Hing L. Sham Albert W. Garofalo Pamela S. Keim Jing Wu Michael S. Dappen Karina Wong Erich Goldbach Kevin P. Quinn John-Michael Sauer Elizabeth F. Brigham William Wallace Guriqbal Basi 《Bioorganic & medicinal chemistry letters》2010,20(24):7553
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Huryn DM Ashwell S Baudy R Dressen DB Gallaway W Grant FS Konradi A Ley RW Petusky S Pleiss MA Sarantakis D Semko CM Sherman MM Tio C Zhang L 《Bioorganic & medicinal chemistry letters》2004,14(7):1651-1654
A pro-drug strategy to identify orally efficacious VLA-4 antagonists is described. Potential pro-drugs were evaluated for their physical chemical characteristics and in vitro properties, including solubility, stability, permeability and plasma stability. Based on this characterization, promising compounds were identified for in vivo pharmacokinetic evaluation. These studies resulted in the identification of a pro-drug that exhibited desirable blood levels in PK studies in several different species. 相似文献
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Ying-zi Xu Andrei W. Konradi Frederique Bard Michael Dappen Lilibeth Dofiles Mark Dreyer Ian Gallager Caroline Garrido Mike Krimm Zhenmei Liao Elizabeth Messersmith Linda Mutter Michael A. Pleiss Bhushan Samant Christopher M. Semko Jennifer Smith Frank Stappenbeck Brian Stupi Ted Yednock 《Bioorganic & medicinal chemistry letters》2013,23(10):3070-3074
A series of (S)-2-(2-(diethylamino)-5-(N-alkyl-N-sulfonamido)pyrimidin-4-ylamino)-3-(4-(carbamoyloxy)phenyl)propanoic acid is discovered as orally available VLA-4 antagonists. Representative compounds 11b and 11p showed efficacy in multiple in vivo animal models. The in vitro selectivity of 11p is also described. 相似文献
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Ying-zi Xu Jenifer L. Smith Christopher M. Semko Kassandra I. Rossiter Juri Y. Fukuda Michael S. Dappen David A. Quincy Andrei W. Konradi Wenxian Mao Brent Welch Mark L. Dreyer Bhushan Samant Hongbin Zhang Judevin Lugar Zhenmei Liao Carrol Henschel Eric Petersen Christopher Vandevert Ted A. Yednock 《Bioorganic & medicinal chemistry letters》2013,23(15):4370-4373
A series of potent α4β1/α4β7 integrin inhibitors is reported, including an inhibitor 12d with remarkable oral exposure and efficacy in rat models of rheumatoid arthritis and Crohn’s disease. 相似文献
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Semko CM Chen L Dressen DB Dreyer ML Dunn W Farouz FS Freedman SB Holsztynska EJ Jefferies M Konradi AW Liao A Lugar J Mutter L Pleiss MA Quinn KP Thompson T Thorsett ED Vandevert C Xu YZ Yednock TA 《Bioorganic & medicinal chemistry letters》2011,21(6):1741-1743
A series of N-(pyrimidin-4-yl)-phenylalanine VLA-4 antagonists is described. Optimization of substituents at the 2 and 5 positions of the pyrimidine ring gave 14, a very potent VLA-4 inhibitor which is orally active in a sheep asthma model. 相似文献
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Anh P. Truong Danielle L. Aubele Gary D. Probst Martin L. Neitzel Chris M. Semko Simeon Bowers Darren Dressen Roy K. Hom Andrei W. Konradi Hing L. Sham Albert W. Garofalo Pamela S. Keim Jing Wu Michael S. Dappen Karina Wong Erich Goldbach Kevin P. Quinn John-Michael Sauer Elizabeth F. Brigham William Wallace Guriqbal Basi 《Bioorganic & medicinal chemistry letters》2009,19(17):4920-4923
In this Letter, we report our strategy to design potent and metabolically stable γ-secretase inhibitors that are efficacious in reducing the cortical Aβx-40 levels in FVB mice via a single PO dose. 相似文献
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Aubele DL Truong AP Dressen DB Probst GD Bowers S Mattson MN Semko CM Sun M Garofalo AW Konradi AW Sham HL Zmolek W Wong K Goldbach E Quinn KP Sauer JM Brigham EF Wallace W Nguyen L Bova MP Hemphill SS Basi G 《Bioorganic & medicinal chemistry letters》2011,21(19):5791-5794
The structure-activity relationship (SAR) of a novel, potent and metabolically stable series of sulfonamide-pyrazoles that attenuate β-amyloid peptide synthesis via γ-secretase inhibition is detailed herein. Sulfonamide-pyrazoles that are efficacious in reducing the cortical Aβx-40 levels in FVB mice via a single PO dose, as well as sulfonamide-pyrazoles that exhibit selectivity for inhibition of APP versus Notch processing by γ-secretase, are highlighted. 相似文献