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排序方式: 共有177条查询结果,搜索用时 471 毫秒
91.
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Bart H. Harper Liping Wang Cheng Zhu Nam F. Kar Bing Li Christopher R. Moyes Stephen D. Goble Melissa Costa Karen Dingley Jerry Di Salvo Sookhee N. Ha Amanda Hurley Xiaofang Li Randy R. Miller Hiroshi Nagabukuro Gino M. Salituro Sean Smith Mary Struthers Richard Berger 《Bioorganic & medicinal chemistry letters》2017,27(4):1094-1098
The synthesis of a novel class of piperazine benzamide (reverse amides) targeting the human β3-adrenergic receptor for the treatment of overactive bladder (OAB) is described. The SAR studies directed towards maintaining well established β3 potency and selectivities while improving the overall pharmacokinetic profile in the reverse amide class will be evaluated. The results and consequences associated with functional activity at the norepinephrine transporter (NET) will also be discussed. 相似文献
93.
Scott B. Hoyt Jerry Taylor Clare London Amjad Ali Feroze Ujjainwalla Jim Tata Mary Struthers Doris Cully Tom Wisniewski Ning Ren Charlene Bopp Andrea Sok Andreas Verras Daniel McMasters Qing Chen Elaine Tung Wei Tang Gino Salituro Yusheng Xiong 《Bioorganic & medicinal chemistry letters》2017,27(11):2384-2388
We report the discovery and hit-to-lead optimization of a structurally novel indazole series of CYP11B2 inhibitors. Benchmark compound 34 from this series displays potent inhibition of CYP11B2, high selectivity versus related steroidal and hepatic CYP targets, and lead-like physical and pharmacokinetic properties. On the basis of these and other data, the indazole series was progressed to lead optimization for further refinement. 相似文献
94.
Phytophthora ramorum is an oomycete plant pathogen classified in the kingdom Stramenopila. P. ramorum is the causal agent of sudden oak death on coast live oak and tanoak as well as ramorum blight on woody ornamental and forest understorey plants. It causes stem cankers on trees, and leaf blight or stem dieback on ornamentals and understorey forest species. This pathogen is managed in the USA and Europe by eradication where feasible, by containment elsewhere and by quarantine in many parts of the world. Genomic resources provide information on genes of interest to disease management and have improved tremendously since sequencing the genome in 2004. This review provides a current overview of the pathogenicity, population genetics, evolution and genomics of P. ramorum. Taxonomy: Phytophthora ramorum (Werres, De Cock & Man in't Veld): kingdom Stramenopila; phylum Oomycota; class Peronosporomycetidae; order Pythiales; family Pythiaceae; genus Phytophthora. Host range: The host range is very large and the list of known hosts continues to expand at the time of writing. Coast live oak and tanoak are ecologically, economically and culturally important forest hosts in the USA. Rhododendron, Viburnum, Pieris, Syringa and Camellia are key ornamental hosts on which P. ramorum has been found repeatedly, some of which have been involved in moving the pathogen via nursery shipments. Disease symptoms: P. ramorum causes two different diseases with differing symptoms: sudden oak death (bleeding lesions, stem cankers) on oaks and ramorum blight (twig dieback and/or foliar lesions) on tree and woody ornamental hosts. Useful websites: http://nature.berkeley.edu/comtf/ , http://rapra.csl.gov.uk/ , http://www.aphis.usda.gov/plant_health/plant_pest_info/pram/index.shtml , http://genome.jgi‐psf.org/Phyra1_1/Phyra1_1.home.html , http://pamgo.vbi.vt.edu/ , http://pmgn.vbi.vt.edu/ , http://vmd.vbi.vt.edu./ , http://web.science.oregonstate.edu/bpp/labs/grunwald/resources.htm , http://www.defra.gov.uk/planth/pramorum.htm , http://www.invasive.org/browse/subject.cfm?sub=4603 , http://www.forestry.gov.uk/forestry/WCAS‐4Z5JLL 相似文献
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Gross TD Zhu YF Saunders J Wilcoxen KM Gao Y Connors PJ Guo Z Struthers RS Reinhart GJ Chen C 《Bioorganic & medicinal chemistry letters》2002,12(16):2185-2187
SAR studies of lead GnRH receptor antagonists 2a and 2b reported earlier resulted in the discovery of compound 10b which showed much higher potency (K(i)=4.6 nM, compared with 2b, K(i)=230 nM) in which the 7-position of the imidazolo[1,2-a]pyrimidone core was substituted with a methyl group, and the ester at the 6-position was replaced by the 3-methoxyphenyl group. 相似文献
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98.
Review and phylogeny of the New Zealand hagfishes (Myxiniformes: Myxinidae), with a description of three new species 下载免费PDF全文
Vincent Zintzen Clive D. Roberts Lara Shepherd Andrew L. Stewart Carl D. Struthers Marti J. Anderson Margaret McVeagh Michael Noren Bo Fernholm 《Zoological Journal of the Linnean Society》2015,174(2):363-393
Hagfishes from New Zealand are reviewed and a phylogeny proposed using morphological and genetic data (DNA sequences of cytochrome c oxidase subunit I gene, COI, and the small subunit RNA, 16S). E ptatretus cryptus sp. nov. was previously confused with Eptatretus cirrhatus (Forster in Bloch & Schneider, 1801) because of their similar morphology, and is found from the Three Kings Islands to Stewart Island and in the eastern part of the Chatham Rise (at depths of 96–922 m). E ptatretus poicilus sp. nov. is endemic to the Three Kings Islands, where it is common and associated with soft sediment and deep‐sea coral‐sponge habitats (114–842 m). N eomyxine caesiovitta sp. nov. is a slender hagfish found along the east coast of the North Island south to the Chatham Rise (430–1083 m). A neotype is erected for E. cirrhatus (type locality: Breaksea Sound, Fiordland), occurring widely in New Zealand coastal, shelf, and slope waters (1–922 m), but not at the Three Kings Islands. Eptatetrus goliath Mincarone & Stewart, 2006, Neomyxine biniplicata (Richardson & Jowett, 1951), and Nemamyxine elongata Richardson, 1958 are further described using additional material. Rubicundus eos (Fernholm, 1991) is still only known from the holotype (type locality: Challenger Plateau). Genetic results showed that the New Zealand Eptatretus species form a monophyletic group within the subfamily Eptatretinae, indicating likely speciation from a single common ancestor within the area. E ptatretus poicilus sp. nov. is the sister species of E. cirrhatus, and E . cryptus sp. nov. is closely associated with the clade formed by these two species. Eptatretus goliath is most closely associated with Eptatretus minor Fernholm & Hubbs, 1981 (Gulf of Mexico), these two species basally diverging within New Zealand hagfishes. The endemic genus Neomyxine forms a well‐supported monophyletic group of as yet uncertain position within the phylogenetic tree. A key to the New Zealand hagfishes, fresh colour photographs, distribution maps, and in situ video recordings are presented. © 2015 The Linnean Society of London 相似文献
99.
Andrew Tuplin Madeleine Struthers Jonathan Cook Kirsten Bentley David J. Evans 《Nucleic acids research》2015,43(5):2914-2926
A phylogenetically conserved RNA structure within the NS5B coding region of hepatitis C virus functions as a cis-replicating element (CRE). Integrity of this CRE, designated SL9266 (alternatively 5BSL3.2), is critical for genome replication. SL9266 forms the core of an extended pseudoknot, designated SL9266/PK, involving long distance RNA–RNA interactions between unpaired loops of SL9266 and distal regions of the genome. Previous studies demonstrated that SL9266/PK is dynamic, with ‘open’ and ‘closed’ conformations predicted to have distinct functions during virus replication. Using a combination of site-directed mutagenesis and locked nucleic acids (LNA) complementary to defined domains of SL9266 and its interacting regions, we have explored the influence of this structure on genome translation and replication. We demonstrate that LNAs which block formation of the closed conformation inhibit genome translation. Inhibition was at least partly independent of the initiation mechanism, whether driven by homologous or heterologous internal ribosome entry sites or from a capped message. Provision of SL9266/PK in trans relieved translational inhibition, and mutational analysis implied a mechanism in which the closed conformation recruits a cellular factor that would otherwise suppresses translation. We propose that SL9266/PK functions as a temporal switch, modulating the mutually incompatible processes of translation and replication. 相似文献
100.
Pinkerton AB Huang D Cube RV Hutchinson JH Struthers M Ayala JM Vicario PP Patel SR Wisniewski T DeMartino JA Vernier JM 《Bioorganic & medicinal chemistry letters》2007,17(3):807-813
We have identified and synthesized a series of diaryl substituted pyrazoles as potent antagonists of the chemokine receptor subtype 2. Structure-activity relationship studies directed toward improving the potency led to the discovery of 23 (IC50 = 6 nM). 相似文献