Abstract:
:The synthesis and biological activity of a novel series of 2-alkyl-4-pyrrolidinylthio-beta-methylcarbapenems containing a variety of cationic heteroaromatic substituents linked via a C-C bond is described. As a result of these studies, we selected FR21818 (In) as a candidate compound for development. FR21818 exhibited a well balanced spectrum of antibacterial activity, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), excellent urinary recovery, good stability against renal dehydropeptidase-I (DHP-I). no antigenicity and mutagenicity, weak toxicities, and good efficacy and therapeutic effect on mice systemic infections. Affinities to PBP's, permeability of outer membrane, and plasma levels in mice, dog, and cynomolgous monkey of FR21818 are also reported.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Zam HA,Barrett D,Tanaka A,Sasaki H,Matsuda K,Sakurai M,Terasawa T,Shirai F,Chiba T,Matsumoto Y,Tawara Sdoi
10.1016/s0968-0896(00)00314-xsubject
Has Abstractpub_date
2001-04-01 00:00:00pages
961-82issue
4eissn
0968-0896issn
1464-3391pii
S096808960000314Xjournal_volume
9pub_type
杂志文章abstract::Analogs of the antibiotic fosmidomycin, an inhibitor of the methylerythritol phosphate pathway to isoprenoids, were synthesized and evaluated against the recombinant Synechocystis sp. PCC6803 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR). Fosfoxacin, the phosphate analog of fosmidomycin, and its acetyl congene...
journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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abstract::Previously, we reported 2-N-carbamoylguanine (cmG) as a guanine analog. We further studied the synthetic protocol and hybridization properties of oligodeoxynucleotides (ODNs) incorporating cmG. These ODNs were synthesized using the phosphoramidite of cmG without protection of the 6-O position. However, the isolated pr...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.11.042
更新日期:2009-02-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.07.071
更新日期:2008-09-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00603-x
更新日期:2003-04-03 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
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更新日期:2020-09-15 00:00:00
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pub_type: 杂志文章
doi:10.1016/j.bmc.2004.11.030
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(02)00564-3
更新日期:2003-03-20 00:00:00
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journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2011.09.020
更新日期:2011-11-01 00:00:00
abstract::Ethacrynic acid (EA), an alpha,beta-unsaturated carbonyl compound, is a glutathione S-transferase P1-1 (GSTP1-1) inhibitor. Twenty-one novel EA derivatives have been synthesized. The effects of these compounds on GSTP1-1 activity and on the proliferation of human leukemia HL-60 cells have been determined. Compounds wi...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2007.01.037
更新日期:2007-04-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2012.06.032
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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journal_title:Bioorganic & medicinal chemistry
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abstract::3-(4-Piperidinyl)-5-arylpyrazoles, such as 1, were selective for the cloned human dopamine D4 receptor (hD4), but also showed affinity at voltage sensitive calcium, sodium and potassium ion channels. A combination of substituent changes to reduce the basicity of the piperidine nitrogen and conformational restriction t...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(98)00028-5
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abstract::A novel 7,6 fused bicyclic scaffold, pyrimido[4,5-b]azepine was designed to fit into the ATP binding site of the HER2/EGFR proteins. The synthesis of this scaffold was accomplished by an intramolecular Claisen-type condensation. As the results of optimization lead us to 4-anilino and 6-functional groups, we discovered...
journal_title:Bioorganic & medicinal chemistry
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doi:10.1016/j.bmc.2013.02.014
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abstract::We report the synthesis of several highly functionalized biotinylated philanthotoxin (PhTX) analogues (7, 8, 10, 13-16) designed on the basis of earlier structure-activity relationship studies. Despite the extensive modifications, the binding to nicotinic acetylcholine receptor (nAChR) is in the low micromolar range a...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/s0968-0896(99)00054-1
更新日期:1999-06-01 00:00:00
abstract::The tremendous increase in crop yields associated with the 'green' revolution has been possible in part by the discovery and utilization of chemicals for pest control. However, concerns over the potential impact of pesticides on human health and the environment has led to the introduction of new pesticide registration...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
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abstract::A series of N-methyl rac-cis-4a-aralkyl- and alkyl-substituted-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols have been prepared (2a-l) using a simple previously designed synthetic route, in order to find a ligand that would interact with both μ- and δ-opioid receptors. A C4a-phenethyl derivative 2a, was found t...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2013.02.060
更新日期:2013-06-01 00:00:00
abstract::In order to develop structure-activity relationships and to provide access to antibacterial agents for dual action studies, a variety of aryl group-substituted 2-aryl-5-nitro-1H-indoles were synthesized and the activity of the compounds assessed as inhibitors of the NorA multidrug resistance pump in the bacterium Stap...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2005.09.019
更新日期:2006-02-01 00:00:00
abstract::The risk of the presence of haloacetic acids in drinking water as chlorination by-products and the shortage of experimental mutagenicity data for most of them requires a research work. This paper describes a QSAR model to predict direct mutagenicity for these chemicals. The model, able to describe more than 90% of the...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.03.070
更新日期:2008-05-15 00:00:00
abstract::New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 microg/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivat...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章
doi:10.1016/j.bmc.2008.10.086
更新日期:2009-01-01 00:00:00
abstract::This review summarises current knowledge on adenosine receptors, an important G protein-coupled receptor. The four known adenosine receptor subtypes A1, A2A, A2B, and A3 are discussed with special reference to the opportunities for drug development. ...
journal_title:Bioorganic & medicinal chemistry
pub_type: 杂志文章,评审
doi:10.1016/s0968-0896(98)00038-8
更新日期:1998-06-01 00:00:00