Carbon analogs of antifungal dioxane-triazole derivatives: synthesis and in vitro activities.

Abstract:

:A new series of triazole compounds possessing a carbon atom in place of a sulfur atom were efficiently synthesized and their in vitro antifungal activities were investigated. The carbon analogs showed excellent in vitro activity against Candida, Cryptococcus, and Aspergillus species. The MICs of compound 1c against C. albicans ATCC24433, C. neoformans TIMM1855, and A. fumigatus ATCC26430 were 0.016, 0.016, and 0.125 microg/mL, respectively (MICs of fluconazole: 0.5, >4, and >4 microg/mL; MICs of itraconazole: 0.125, 0.25, and 0.25 microg/mL).

journal_name

Bioorg Med Chem Lett

authors

Uchida T,Somada A,Kagoshima Y,Konosu T,Oida S

doi

10.1016/j.bmcl.2008.10.055

subject

Has Abstract

pub_date

2008-12-15 00:00:00

pages

6538-41

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(08)01240-7

journal_volume

18

pub_type

杂志文章
  • Synthesis and evaluation of novel prodrugs of caspase inhibitors.

    abstract::A novel type of caspase inhibitor prodrug that improves systemic exposure after oral administration in rats has been designed. Such a prodrug, based on a 6,6a-dihydrofuro[3,2-d]oxazol-5(3aH)-one motif, has the advantage of rapidly liberating the active inhibitor without producing any cleavage by-product. Prodrugs 6-8,...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.10.102

    authors: Charrier JD,Durrant SJ,Studley J,Lawes L,Weber P

    更新日期:2012-01-01 00:00:00

  • Synthesis and biological evaluation of nimesulide based new class of triazole derivatives as potential PDE4B inhibitors against cancer cells.

    abstract::A new class of 1,2,3-triazol derivatives derived from nimesulide was designed as potential inhibitors of PDE4B. Synthesis of these compounds was carried out via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required azide was prepared via th...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.10.035

    authors: Mareddy J,Nallapati SB,Anireddy J,Devi YP,Mangamoori LN,Kapavarapu R,Pal S

    更新日期:2013-12-15 00:00:00

  • Novel small molecule bradykinin B1 receptor antagonists. Part 3: hydroxyurea derivatives.

    abstract::Hydroxy urea moieties are introduced as a new class of bradykinin B(1) receptor antagonists. First, the SAR of the lead compound was systematically explored. Subsequent optimization resulted in the identification of several biaryl-based hydroxyurea bradykinin B(1) receptor antagonists with low-nanomolar activity and v...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.11.121

    authors: Schnatbaum K,Schaudt M,Stragies R,Pfeifer JR,Gibson C,Locardi E,Scharn D,Richter U,Kalkhof H,Dinkel K,Zischinsky G

    更新日期:2010-02-01 00:00:00

  • 4,4,14 alpha-trimethyl 9 beta,19-cyclo-5 alpha-26-homocholesta-24,26-dien-3 beta-ol: a potent mechanism-based inactivator of delta 24(25)- to delta 25(27)-sterol methyl transferase.

    abstract::The title compound (4A) was synthesized and tested as a mechanism-based inactivator of the sterol methyl transferase (SMT) enzyme from Prototheca wickerhamii. Using cycloartenol as substrate, 4A was found to exhibit time-dependent inactivation kinetics, generating a Ki value of 30 microM and Kinact value of 0.30 min-1...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(98)00651-9

    authors: Nes WD,He L,Mangla AT

    更新日期:1998-12-15 00:00:00

  • Diarylacylhydrazones: Clostridium-selective antibacterials with activity against stationary-phase cells.

    abstract::Current antibiotics for treating Clostridium difficile infections (CDI), that is, metronidazole, vancomycin and more recently fidaxomicin, are mostly effective but treatment failure and disease relapse remain as significant clinical problems. The shortcomings of these agents are attributed to their low selectivity for...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.12.015

    authors: Chen C,Doll NK,Casadei G,Bremner JB,Lewis K,Kelso MJ

    更新日期:2014-01-15 00:00:00

  • Discovery and optimization of 2-aminopyridine derivatives as novel and selective JAK2 inhibitors.

    abstract::Janus kinases (JAKs) including JAK1, JAK2, JAK3, and TYK2 are members of a family of intracellular nonreceptor tyrosine kinases, which have been demonstrated to be critical in the cell signaling pathway and involved in inflammatory diseases and cancer. V617F mutation in JAK2 has been implicated in polycythaemia vera (...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2020.127048

    authors: Ma X,Diao Y,Ge H,Xu F,Zhu L,Zhao Z,Li H

    更新日期:2020-04-15 00:00:00

  • Syntheses and biological evaluations of alpha-D-mannosyl [60]fullerenols.

    abstract::[60]Fullerenols carrying mono- and bis-alpha-D-mannosyl linkages on the surface were prepared via a [3+2]-cycloaddition reaction between 2-azidoethyl alpha-D-mannoside and C(60) followed by polyhydroxylation with aqueous NaOH. Their biological activity was evaluated in terms of binding affinity to lectins by hemagglut...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(01)00583-2

    authors: Kato H,Yashiro A,Mizuno A,Nishida Y,Kobayashi K,Shinohara H

    更新日期:2001-11-19 00:00:00

  • Activation of antibacterial prodrugs by peptide deformylase.

    abstract::5'-Dipeptidyl derivatives of 5-fluorodeoxyuridine (FdU) (1a-d) were synthesized. These compounds are biologically inactive but can be activated by peptide deformylase, which removes the N-terminal formyl group of the dipeptide, to release the active drug FdU via an intramolecular cyclization reaction. Because the defo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00167-0

    authors: Wei Y,Pei D

    更新日期:2000-05-15 00:00:00

  • Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivity.

    abstract::The concurrent implementation of a proteome-wide serine hydrolase selectivity screen with traditional efforts to optimize fatty acid amide hydrolase (FAAH) inhibition potency led to the expedited discovery of a new class of exceptionally potent (Ki < 300 pM) and unusually selective (> 100-fold selective) inhibitors. T...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2004.12.085

    authors: Leung D,Du W,Hardouin C,Cheng H,Hwang I,Cravatt BF,Boger DL

    更新日期:2005-03-01 00:00:00

  • Catalysis of imido group hydrolysis in a maleimide conjugate.

    abstract::Maleimides are often used for biomolecular conjugation with thiols. An underappreciated aspect of the imido group in a maleimide conjugate is its susceptibility to spontaneous hydrolysis, resulting in undesirable heterogeneity. Here, a chromophoric maleimide is used to demonstrate that both molybdate and chromate cata...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2007.09.002

    authors: Kalia J,Raines RT

    更新日期:2007-11-15 00:00:00

  • Product identification of non-reducing polyketide synthases with C-terminus methyltransferase domain from Talaromyces stipitatus using Aspergillus oryzae heterologous expression.

    abstract::Talaromyces stipitatus ATCC 10500 possesses 17 non-reducing polyketide synthase (NR-PKS) genes. During the course of our functional analysis of PKS genes with a C-terminus methyltransferase domain from T. stipitatus, we expressed tspks2, tspks3 and tspks4 genes in the heterologous host Aspergillus oryzae, respectively...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2015.02.057

    authors: Hashimoto M,Wakana D,Ueda M,Kobayashi D,Goda Y,Fujii I

    更新日期:2015-04-01 00:00:00

  • Design and synthesis of 2-phenylpyrimidine coumarin derivatives as anticancer agents.

    abstract::A series of 2-phenylpyrimidine coumarin derivatives with potential telomerase-inhibiting activity was designed and synthesized. All of the compounds were screened for antiproliferative activity against CNE2, KB, and Cal27 cell lines in vitro. The results showed that most of the derivatives had a favorable effect on re...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2017.08.044

    authors: Lv N,Sun M,Liu C,Li J

    更新日期:2017-10-01 00:00:00

  • Synthesis, spectroscopic studies and biological evaluation of acridine derivatives: The role of aggregation on the photodynamic efficiency.

    abstract::Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very different self-aggregating properties since only 1 present a strong tend...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2018.02.005

    authors: Felip-León C,Martínez-Arroyo O,Díaz-Oltra S,Miravet JF,Apostolova N,Galindo F

    更新日期:2018-03-01 00:00:00

  • Design, synthesis, and analysis of antagonists of GPR55: Piperidine-substituted 1,3,4-oxadiazol-2-ones.

    abstract::A series of 1,3,4-oxadiazol-2-ones was synthesized and tested for activity as antagonists at GPR55 in cellular beta-arrestin redistribution assays. The synthesis was designed to be modular in nature so that a sufficient number of analogues could be rapidly accessed to explore initial structure-activity relationships. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2016.02.030

    authors: Meza-Aviña ME,Lingerfelt MA,Console-Bram LM,Gamage TF,Sharir H,Gettys KE,Hurst DP,Kotsikorou E,Shore DM,Caron MG,Rao N,Barak LS,Abood ME,Reggio PH,Croatt MP

    更新日期:2016-04-01 00:00:00

  • A new insight on the hypochlorous acid scavenging mechanism of tryptamine and tryptophan derivatives.

    abstract::The reaction mechanisms of hypochlorous acid (HOCl) with several tryptophan and tryptamine derivatives, previously reported to scavenge this powerful oxidant, was investigated to determine whether ionic or radical pathways were involved. For this purpose, the reaction of tryptamine and tryptophan derivatives with HOCl...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.09.067

    authors: Carvalho LC,Estevão MS,Ferreira LM,Fernandes E,Marques MM

    更新日期:2010-11-15 00:00:00

  • An analysis of the 'legal high' mephedrone.

    abstract::'Legal highs' are compounds, plant or fungal material which can be readily bought from the internet without legal restriction and the single chemicals may be structurally related to illegal drugs of abuse such as the amphetamines. Several recent deaths in the UK have been attributed to these legal highs and unfortunat...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.05.065

    authors: Gibbons S,Zloh M

    更新日期:2010-07-15 00:00:00

  • Benzimidazole-carboxamides as potent and bioavailable stearoyl-CoA desaturase (SCD1) inhibitors from ligand-based virtual screening and chemical optimization.

    abstract::The discovery of potent benzimidazole stearoyl-CoA desaturase (SCD1) inhibitors by ligand-based virtual screening is described. ROCS 3D-searching gave a favorable chemical motif that was subsequently optimized to arrive at a chemical series of potent and promising SCD1 inhibitors. In particular, compound SAR224 was se...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.01.030

    authors: Matter H,Zoller G,Herling AW,Sanchez-Arias JA,Philippo C,Namane C,Kohlmann M,Pfenninger A,Voss MD

    更新日期:2013-03-15 00:00:00

  • Small-molecule microarrays: development of novel linkers and an efficient detection method for bound proteins.

    abstract::Novel isocyanate and diazoketone linkers possessing polyoxypropylenediamine as a spacer for small-molecule microrray are developed. White light interferometry is introduced to detect bound proteins on the glass slides without using chemically modified proteins. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2006.04.057

    authors: Kurosu M,Mowers WA

    更新日期:2006-07-01 00:00:00

  • Chemical constituents of Callistemon citrinus from Egypt and their antiausterity activity against PANC-1 human pancreatic cancer cell line.

    abstract::Human pancreatic cancer is resistant to almost all conventional chemotherapeutic agents. It is known to proliferate aggressively within hypovascular tumor microenvironment by exhibiting remarkable tolerance to nutrition starvation,  a phenomenon termed as "austerity". Search for the new agents that eliminate the toler...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2020.127352

    authors: Tawila AM,Sun S,Kim MJ,Omar AM,Dibwe DF,Ueda JY,Toyooka N,Awale S

    更新日期:2020-08-15 00:00:00

  • Evaluation of triazolamers as active site inhibitors of HIV-1 protease.

    abstract::Proteases typically recognize their peptide substrates in extended conformations. General approaches for designing protease inhibitors often consist of peptidomimetics that feature this conformation. Herein we discuss a combination of computational and experimental studies to evaluate the potential of triazole-linked ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.09.049

    authors: Jochim AL,Miller SE,Angelo NG,Arora PS

    更新日期:2009-11-01 00:00:00

  • SAR studies of 9-norbornylpurines as Coxsackievirus B3 inhibitors.

    abstract::Coxsackievirus and related enteroviruses are important human pathogens that cause various diseases with clinical manifestations ranging from trivial flu-like syndromes to dangerous or even fatal diseases such as myocarditis, meningitis and encephalitis. Here, we report on our continuous SAR study focused on 9-(bicyclo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.05.070

    authors: Sála M,De Palma AM,Hřebabecký H,Dejmek M,Dračínský M,Leyssen P,Neyts J,Mertlíková-Kaiserová H,Nencka R

    更新日期:2011-07-15 00:00:00

  • Synthesis and evaluation of a cyclic imine derivative conjugated to a fluorescent molecule for labeling of proteins.

    abstract::A cyclic imine conjugated to a fluorescent dansyl group was synthesized and used for covalent labeling of proteins. The covalent attachment to proteins was confirmed by gel electrophoresis and mass analysis. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2008.12.071

    authors: Guo HM,Minakawa M,Ueno L,Tanaka F

    更新日期:2009-02-15 00:00:00

  • Design and synthesis of pregnenolone/2-cyanoacryloyl conjugates with dual NF-κB inhibitory and anti-proliferative activities.

    abstract::Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was con...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2017.09.013

    authors: Song JL,Zhang J,Liu CL,Liu C,Zhu KK,Yang FF,Liu XG,Figueiró Longo JP,Alexandre Muehlmann L,Azevedo RB,Zhang YY,Guo YW,Jiang CS,Zhang H

    更新日期:2017-10-15 00:00:00

  • Development of amino-pyrimidine inhibitors of c-Jun N-terminal kinase (JNK): kinase profiling guided optimization of a 1,2,3-benzotriazole lead.

    abstract::A series of amino-pyrimidines was developed based upon an initial kinase cross-screening hit from a CDK2 program. Kinase profiling and structure-based drug design guided the optimization from the initial 1,2,3-benzotriazole hit to a potent and selective JNK inhibitor, compound 24f (JNK1 and 2 IC(50)=16 and 66 nM, resp...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.12.047

    authors: Palmer WS,Alam M,Arzeno HB,Chang KC,Dunn JP,Goldstein DM,Gong L,Goyal B,Hermann JC,Hogg JH,Hsieh G,Jahangir A,Janson C,Jin S,Ursula Kammlott R,Kuglstatter A,Lukacs C,Michoud C,Niu L,Reuter DC,Shao A,Silva T,Tr

    更新日期:2013-03-01 00:00:00

  • Novel lactam NK1 antagonists with anti-emetic activity.

    abstract::A series of 4,4-disubstituted cyclohexylamine NK(1) antagonists containing a lactam ring is described. The compounds are brain penetrant and activity is demonstrated in a ferret emesis model. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.11.111

    authors: Hollingworth GJ,Carlson EJ,Castro JL,Chicchi GG,Clark N,Cooper LC,Dirat O,Salvo JD,Elliott JM,Kilburn R,Kurtz MM,Rycroft W,Tattersall FD,Tsao KL,Swain CJ

    更新日期:2006-03-01 00:00:00

  • Synthesis and methemoglobin toxicity of the amides of 6/7 mono or disubstituted quinolone.

    abstract::A series of 6/7-mono and disubstituted quinolone-3-carboxamide derivatives (1-12) were synthesized and their in vitro methemoglobin producing capacity have been delineated. The compounds 5, 6, 9 and 10 showed minimum methemoglobin toxicity. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(98)00688-x

    authors: Srivastava S,Srivastava SK,Shukla A,Chauhan PM,Puri SK,Bhaduri AP,Pandey VC

    更新日期:1999-01-04 00:00:00

  • Syntheses and studies of quinolone-cephalosporins as potential anti-tuberculosis agents.

    abstract::The syntheses and anti-tuberculosis activity of quinolone-cephalosporin conjugates (1 and 2) are described. Both showed broad-spectrum antibacterial activity and significant anti-TB activity. The carbamate-linked quinolone-cephem 2 showed better antimycobacterial activity, including anti-TB activity, than the direct a...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2006.08.045

    authors: Zhao G,Miller MJ,Franzblau S,Wan B,Möllmann U

    更新日期:2006-11-01 00:00:00

  • Enantioselective biocatalytic synthesis of (S)-monastrol.

    abstract::The first enantioselective biocatalytic synthesis of (S)-monastrol has been developed via an unexpected and unusual enzymatic pathway as suitable route. Whereas attempts for a direct hydrolysis of racemic monastrol were not successful, formation of racemic O-butanoyl monastrol and subsequent enantioselective hydrolysi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.05.063

    authors: Blasco MA,Thumann S,Wittmann J,Giannis A,Gröger H

    更新日期:2010-08-01 00:00:00

  • Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series.

    abstract::Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Changes made to the 6-furanyl group had little impact on the enzyme a...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2006.05.090

    authors: Petrov KG,Zhang YM,Carter M,Cockerill GS,Dickerson S,Gauthier CA,Guo Y,Mook RA Jr,Rusnak DW,Walker AL,Wood ER,Lackey KE

    更新日期:2006-09-01 00:00:00

  • Conformationally restricted analogs of Combretastatin A-4 derived from SU5416.

    abstract::A series of compounds originally derived from the vascular endothelial growth factor receptor tyrosine kinase inhibitor, SU5416, was synthesized and evaluated. The most potent compound in this series, compound 7, structurally resembles the potent anti-microtubule agent Combretastatin A-4, inhibited tubulin polymerizat...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.09.001

    authors: Li PK,Xiao Z,Hu Z,Pandit B,Sun Y,Sackett DL,Werbovetz K,Lewis A,Johnsamuel J

    更新日期:2005-12-15 00:00:00