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91.
Krueger AC Madigan DL Green BE Hutchinson DK Jiang WW Kati WM Liu Y Maring CJ Masse SV McDaniel KF Middleton TR Mo H Molla A Montgomery DA Ng TI Kempf DJ 《Bioorganic & medicinal chemistry letters》2007,17(8):2289-2292
Substituted 1-hydroxy-4,4-dialkyl-3-oxo-3,4-dihydronaphthalene benzothiadiazine derivatives were investigated as inhibitors of genotype 1 HCV polymerase. Structure-activity relationship patterns for this class of compounds are discussed. It was found that the saturated alkane dialkyl units provided the most active analogs. 相似文献
92.
Chiu G Li S Connolly PJ Pulito V Liu J Middleton SA 《Bioorganic & medicinal chemistry letters》2007,17(12):3292-3297
Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS) can be effectively treated by alpha(1)-adrenergic receptor antagonists. Unfortunately, all currently marketed alpha(1) blockers produced CV related side effects that are caused by the subtype non-selective nature of the drugs. To overcome this problem, it was postulated that a alpha(1a/1d) subtype selective antagonist would bring more benefit for the treatment of BPH/LUTS. In developing selective alpha(1a/1d) ligands, (arylpiperazinyl)cyclohexylsulfonamides were synthesized and their binding profiles against three cloned human alpha(1)-adrenergic receptor subtypes were evaluated. Many compounds show equal affinity for both alpha(1a) and alpha(1d) subtypes with good selectivity against the alpha(1b) subtype. They also overcome the problem of dopamine receptor affinity that previous analogues had exhibited. 相似文献
93.
Huang S Lin R Yu Y Lu Y Connolly PJ Chiu G Li S Emanuel SL Middleton SA 《Bioorganic & medicinal chemistry letters》2007,17(5):1243-1245
The novel compound 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2-b]pyridine was discovered to be a potent CDK1 inhibitor. Described here is the chemistry for its synthesis, including Pd(II) catalyzed Stille coupling reaction and sulfur(0) induced benzimidazole formation. Its effects on VEGFR-2 kinase activity and tumour cell proliferation are also described. 相似文献
94.
Lin R Connolly PJ Lu Y Chiu G Li S Yu Y Huang S Li X Emanuel SL Middleton SA Gruninger RH Adams M Fuentes-Pesquera AR Greenberger LM 《Bioorganic & medicinal chemistry letters》2007,17(15):4297-4302
A series of 3,5-disubstituted pyrazolo[3,4-b]pyridine cyclin-dependent kinase (CDK) inhibitors was synthesized. These compounds showed potent and selective CDK inhibitory activities and inhibited in vitro cellular proliferation in cultured human tumor cells. Selected compounds were evaluated in an in vivo tumor xenograft model. The synthesis and biological evaluation of these pyrazolo[3,4-b]pyridines and related compounds are reported. 相似文献
95.
Li S Chiu G Pulito VL Liu J Connolly PJ Middleton SA 《Bioorganic & medicinal chemistry letters》2007,17(6):1646-1650
Subtype-selective alpha-1a and/or alpha-1d adrenergic receptor antagonists may be useful for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) with fewer adverse effects than non-selective drugs. A series of 1-arylpiperazinyl-4-cyclohexylamine derived isoindole-1,3-diones has been synthesized, displaying in vitro alpha(1a) and alpha(1d) binding affinity K(i) values in the range of 0.09-38nM with K(i)(alpha1b)/K(i)(alpha1a) and K(i)(alpha1b)/K(i)(alpha1d) selectivity ratios up to 3607-fold. 相似文献
96.
97.
Ahrman E Gustavsson N Hultschig C Boelens WC Emanuelsson CS 《Extremophiles : life under extreme conditions》2007,11(5):659-666
Citrate synthase (CS) is often used in chaperone assays since this thermosensitive enzyme aggregates at moderately increased
temperatures. Small heat shock proteins (sHsps) are molecular chaperones specialized in preventing the aggregation of other
proteins, termed substrate proteins, under conditions of transient heat stress. To investigate the mechanism whereby sHsps
bind to and stabilize a substrate protein, we here used peptide array screening covering the sequence of porcine CS (P00889).
Strong binding of sHsps was detected to a peptide corresponding to the most N-terminal α-helix in CS (amino acids Leu13 to Gln27). The N-terminal α-helices in the CS dimer intertwine with the C-terminus in the other subunit and together form a stem-like
structure which is protruding from the CS dimer. This stem-like structure is absent in thermostable forms of CS from thermophilic
archaebacteria like Pyrococcus furiosus and Sulfolobus solfatacarium. These data therefore suggest that thermostabilization of thermosensitive CS by sHsps is achieved by stabilization of the
C- and N-terminae in the protruding thermosensitive softspot, which is absent in thermostable forms of the CS dimer. 相似文献
98.
Bett Nolan N. Hinch Scott G. Bass Arthur L. Braun Douglas C. Burnett Nicholas J. Casselman Matthew T. Cooke Steven J. Drenner S. Matthew Gelchu Ahmed Harrower William L. Ledoux Roxx Lotto Andrew G. Middleton Collin T. Minke-Martin Vanessa Patterson David A. Zhang Wenming Zhu David Z. 《Hydrobiologia》2022,849(2):385-405
Hydrobiologia - Many of the world’s rivers are dammed, altering the physiology, behaviour, ecology and survival of fish. Integrative research has the potential to improve our understanding of... 相似文献
99.
100.
Raina K. Plowright Peggy Eby Peter J. Hudson Ina L. Smith David Westcott Wayne L. Bryden Deborah Middleton Peter A. Reid Rosemary A. McFarlane Gerardo Martin Gary M. Tabor Lee F. Skerratt Dale L. Anderson Gary Crameri David Quammen David Jordan Paul Freeman Lin-Fa Wang Jonathan H. Epstein Glenn A. Marsh Nina Y. Kung Hamish McCallum 《Proceedings. Biological sciences / The Royal Society》2015,282(1798)
Viruses that originate in bats may be the most notorious emerging zoonoses that spill over from wildlife into domestic animals and humans. Understanding how these infections filter through ecological systems to cause disease in humans is of profound importance to public health. Transmission of viruses from bats to humans requires a hierarchy of enabling conditions that connect the distribution of reservoir hosts, viral infection within these hosts, and exposure and susceptibility of recipient hosts. For many emerging bat viruses, spillover also requires viral shedding from bats, and survival of the virus in the environment. Focusing on Hendra virus, but also addressing Nipah virus, Ebola virus, Marburg virus and coronaviruses, we delineate this cross-species spillover dynamic from the within-host processes that drive virus excretion to land-use changes that increase interaction among species. We describe how land-use changes may affect co-occurrence and contact between bats and recipient hosts. Two hypotheses may explain temporal and spatial pulses of virus shedding in bat populations: episodic shedding from persistently infected bats or transient epidemics that occur as virus is transmitted among bat populations. Management of livestock also may affect the probability of exposure and disease. Interventions to decrease the probability of virus spillover can be implemented at multiple levels from targeting the reservoir host to managing recipient host exposure and susceptibility. 相似文献