排序方式: 共有30条查询结果,搜索用时 0 毫秒
1.
Rowbottom MW Vickers TD Tamiya J Zhang M Dyck B Grey J Schwarz D Heise CE Hedrick M Wen J Tang H Wang H Fisher A Aparicio A Saunders J Goodfellow VS 《Bioorganic & medicinal chemistry letters》2007,17(8):2171-2178
The design, synthesis, and SAR of a series of substituted spirohydantoins are described. Optimization of an in-house screening hit gave compounds that exhibited potent binding affinity and functional activity at MCH-R1. 相似文献
2.
Rowbottom DP 《Studies in History and Philosophy of Science Part C: Studies in History and Philosophy of Biological and Biomedical Sciences》2011,42(2):145-154
This paper, which is based on recent empirical research at the University of Leeds, the University of Edinburgh, and the University of Bristol, presents two difficulties which arise when condensed matter physicists interact with molecular biologists: (1) the former use models which appear to be too coarse-grained, approximate and/or idealized to serve a useful scientific purpose to the latter; and (2) the latter have a rather narrower view of what counts as an experiment, particularly when it comes to computer simulations, than the former. It argues that these findings are related; that computer simulations are considered to be undeserving of experimental status, by molecular biologists, precisely because of the idealizations and approximations that they involve. The complexity of biological systems is a key factor. The paper concludes by critically examining whether the new research programme of 'systems biology' offers a genuine alternative to the modelling strategies used by physicists. It argues that it does not. 相似文献
3.
A M Bonin T M Banks J J Campbell S A Glover G P Hammond A S Prakash C A Rowbottom 《Mutation research》2001,494(1-2):115-134
N-acyloxy-N-alkoxybenzamides are mutagenic in TA100 without the need for metabolic activation with S9. Electronic effects of substituents on both the benzamide ring in N-acetoxy-N-butoxybenzamides or the benzyloxy ring in N-acetoxy-N-benzyloxybenzamides do not influence mutagenicity levels. For N-benzoyloxy-N-benzyloxybenzamides, mutagenicity levels are inversely related to the electron-withdrawing effect of substituents on the benzoyloxy leaving group. Since reactivities increase with increasing electron-withdrawing effects, mutagenicity correlates with stability rather than reactivity of these mutagens. Hydrophobicity is the dominant factor controlling mutagenicity levels and data for all mutagens correlate with computed logP values with a lower dependence (h=0.22) than that recorded for indirect mutagens (h=1.0), except where a sterically demanding p-tert-butyl substituent or a naphthyl group is present. N-acetoxy-N-butoxynaphthamide exhibits a much higher level of mutagenicity than predicted by its logP value and activity may be ascribed to an intercalative binding process with DNA rather than straightforward hydrophobic binding in the major or minor groove. Since these are direct-acting mutagens, structural factors influence binding and reactivity towards DNA. 相似文献
4.
Guo Z Wu D Zhu YF Tucci FC Regan CF Rowbottom MW Struthers RS Xie Q Reijmers S Sullivan SK Sai Y Chen C 《Bioorganic & medicinal chemistry letters》2005,15(16):3685-3690
SAR studies of 1,3,5-triazine-2,4,6-triones as human gonadotropin-releasing hormone receptor antagonists resulted in potent compounds. The best compound from the series had a binding affinity of 2 nM. 相似文献
5.
Guo Z Chen Y Huang CQ Gross TD Pontillo J Rowbottom MW Saunders J Struthers S Tucci FC Xie Q Wade W Zhu YF Wu D Chen C 《Bioorganic & medicinal chemistry letters》2005,15(10):2519-2522
Uracil derivatives were designed and synthesized to avoid atropisomers observed in the 6-methyluracils as antagonists of the human GnRH receptor. Optimization at the 1- and 5-positions of the uracil resulted in potent compounds such as 24 (Ki=0.45 nM). 相似文献
6.
Hudson S Kiankarimi M Rowbottom MW Vickers TD Wu D Pontillo J Ching B Dwight W Goodfellow VS Schwarz D Heise CE Madan A Wen J Ban W Wang H Wade WS 《Bioorganic & medicinal chemistry letters》2006,16(18):4922-4930
The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas are described. Compounds from this series exhibited considerable binding affinity (Ki = 1 nM) and functional activity at MCH-R1, acceptable CYP2D6 inhibition, and good rat brain exposure. 相似文献
7.
Rowbottom MW Vickers TD Dyck B Grey J Tamiya J Zhang M Kiankarimi M Wu D Dwight W Wade WS Schwarz D Heise CE Madan A Fisher A Petroski R Goodfellow VS 《Bioorganic & medicinal chemistry letters》2006,16(17):4450-4457
The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas are described. Compounds from this series exhibited potent binding affinity and functional activity at MCH-R1, and good oral bioavailability in rat. 相似文献
8.
Edwards J Quinn D Rowbottom KA Whittingham JL Thomson MJ Moir JW 《The Biochemical journal》2012,445(1):69-79
9.
Rowbottom MW Tucci FC Connors PJ Gross TD Zhu YF Guo Z Moorjani M Acevedo O Carter L Sullivan SK Xie Q Fisher A Struthers RS Saunders J Chen C 《Bioorganic & medicinal chemistry letters》2004,14(19):4967-4973
The synthesis of a series of (R)-3-[2-(2-amino)phenethyl]-1-(2,6-difluorobenzyl)-6-methyluracils containing a substituted thiophene or thiazole at C-5 is described. SAR around C-5 of the uracil led to the discovery that a 2-thienyl or (2-phenyl)thiazol-4-yl group is required for optimal receptor binding. The best compound from the series had a binding affinity of 2 nM (K(i)) for the human GnRH receptor. A novel and convenient preparation of N-1-(2,6-difluorobenzyl)-6-methyluracil is also described. 相似文献
10.
Rowbottom MW Tucci FC Zhu YF Guo Z Gross TD Reinhart GJ Xie Q Struthers RS Saunders J Chen C 《Bioorganic & medicinal chemistry letters》2004,14(9):2269-2274
The synthesis of a series of (R)-1-alkyl-3-[2-(2-amino)phenethyl]-5-(2-fluorophenyl)-6-methyluracils is discussed. SAR around N-1 of the uracil was explored, which led to the discovery that an electron-deficient 2,6-disubstituted benzyl group is required for optimal receptor binding. The best compound from the series had binding affinity of 0.7 nM (K(i) for the human GnRH receptor, which was 8-fold better than the 2,6-difluorobenzyl analog. 相似文献