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981.
982.
983.
Bussenius J Anand NK Blazey CM Bowles OJ Bannen LC Chan DS Chen B Co EW Costanzo S DeFina SC Dubenko L Engst S Franzini M Huang P Jammalamadaka V Khoury RG Kim MH Klein RR Laird D Le DT Mac MB Matthews DJ Markby D Miller N Nuss JM Parks JJ Tsang TH Tsuhako AL Wang Y Xu W Rice KD 《Bioorganic & medicinal chemistry letters》2012,22(6):2283-2286
984.
Boyer SJ Burke J Guo X Kirrane TM Snow RJ Zhang Y Sarko C Soleymanzadeh L Swinamer A Westbrook J Dicapua F Padyana A Cogan D Gao A Xiong Z Madwed JB Kashem M Kugler S O'Neill MM 《Bioorganic & medicinal chemistry letters》2012,22(1):733-737
A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were identified through high throughput screening. An RSK crystal structure and exploratory SAR were used to define the series pharmacophore. Compounds with good cell potency, such as compounds 43, 44, and 55 were identified, and form the basis for subsequent kinase selectivity optimization. 相似文献
985.
Xianfeng Li Yang Liu Yong-Kang Zhang Jacob J. Plattner Stephen J. Baker Wei Bu Liang Liu Yasheen Zhou Charles Z. Ding Suoming Zhang Wieslaw M. Kazmierski Robert Hamatake Maosheng Duan Lois L. Wright Gary K. Smith Richard L. Jarvest Jing-Jing Ji Joel P. Cooper Matthew D. Tallant Renae M. Crosby Amy Wang 《Bioorganic & medicinal chemistry letters》2012,22(24):7351-7356
We have synthesized and evaluated a series of novel HCV NS3 protease inhibitors with various P4 capping groups, which include urea, carbamate, methoxy-carboxamide, cyclic carbamate and amide, pyruvic amide, oxamate, oxalamide and cyanoguanidine. Most of these compounds are remarkably potent, exhibiting single-digit to sub-nanomolar activity in the enzyme assay and cell-based replicon assay. Selected compounds were also evaluated in the protease-inhibitor-resistant mutant transient replicon assay, and they were found to show quite different potency profiles against a panel of HCV protease-inhibitor-resistant mutants. 相似文献
986.
MH Kim AL Tsuhako EW Co DT Aftab F Bentzien J Chen W Cheng S Engst L Goon RR Klein DT Le M Mac JJ Parks F Qian M Rodriquez TJ Stout JH Till KA Won X Wu FM Yakes P Yu W Zhang Y Zhao P Lamb JM Nuss W Xu 《Bioorganic & medicinal chemistry letters》2012,22(15):4979-4985
Variously substituted indolin-2-ones were synthesized and evaluated for activity against KDR, Flt-1, FGFR-1 and PDGFR. Extension at the 5-position of the oxindole ring with ethyl piperidine (compound 7i) proved to be the most beneficial for attaining both biochemical and cellular potencies. Further optimization of 7i to balance biochemical and cellular potencies with favorable ADME/ PK properties led to the identification of 8h, a compound with a clean CYP profile, acceptable pharmacokinetic and toxicity profiles, and robust efficacy in multiple xenograft tumor models. 相似文献
987.
Powell NA Kohrt JT Filipski KJ Kaufman M Sheehan D Edmunds JE Delaney A Wang Y Bourbonais F Lee DY Schwende F Sun F McConnell P Catana C Chen H Ohren J Perrin LA 《Bioorganic & medicinal chemistry letters》2012,22(1):190-193
We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall. 相似文献
988.
Fragrance is a putatively important character in the evolution of flowering plants, but natural selection on scent is rarely studied and thus poorly understood. We characterized floral scent composition and emission in a common garden of Penstemon digitalis from three nearby source populations. We measured phenotypic selection on scent as well as floral traits more frequently examined, such as floral phenology, display size, corolla pigment, and inflorescence height. Scent differed among populations in a common garden, underscoring the potential for scent to be shaped by differential selection pressures. Phenotypic selection on flower number and display size was strong. However, selection favoured scent rather than flower size or colour, suggesting that smelling stronger benefits reproductive success in P. digitalis. Linalool was a direct target of selection and its high frequency in floral-scent bouquets suggests that further studies of both pollinator- and antagonist-mediated selection on this compound would further our understanding of scent evolution. Our results indicate that chemical dimensions of floral display are just as likely as other components to experience selective pressure in a nonspecialized flowering herb. Therefore, studies that integrate visual and chemical floral traits should better reflect the true nature of floral evolutionary ecology. 相似文献
989.
990.
Harnessing the rhizosphere microbiome through plant breeding and agricultural management 总被引:2,自引:0,他引:2
Matthew G. Bakker Daniel K. Manter Amy M. Sheflin Tiffany L. Weir Jorge M. Vivanco 《Plant and Soil》2012,360(1-2):1-13