当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and evaluation of the 2,4-diaminoquinazoline series as anti-tubercular agents.

Synthesis and evaluation of the 2,4-diaminoquinazoline series as anti-tubercular agents.

Abstract：

:The 2,4-diaminoquinazoline class of compounds has previously been identified as an effective inhibitor of Mycobacterium tuberculosis growth. We conducted an extensive evaluation of the series for its potential as a lead candidate for tuberculosis drug discovery. Three segments of the representative molecule N-(4-fluorobenzyl)-2-(piperidin-1-yl)quinazolin-4-amine were examined systematically to explore structure-activity relationships influencing potency. We determined that the benzylic amine at the 4-position, the piperidine at 2-position and the N-1 (but not N-3) are key activity determinants. The 3-deaza analog retained similar activity to the parent molecule. Biological activity was not dependent on iron or carbon source availability. We demonstrated through pharmacokinetic studies in rats that good in vivo compound exposure is achievable. A representative compound demonstrated bactericidal activity against both replicating and non-replicating M. tuberculosis. We isolated and sequenced M. tuberculosis mutants resistant to this compound and observed mutations in Rv3161c, a gene predicted to encode a dioxygenase, suggesting that the compound may act as a pro-drug.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Odingo J,O'Malley T,Kesicki EA,Alling T,Bailey MA,Early J,Ollinger J,Dalai S,Kumar N,Singh RV,Hipskind PA,Cramer JW,Ioerger T,Sacchettini J,Vickers R,Parish T

doi

10.1016/j.bmc.2014.10.007

subject

Has Abstract

pub_date

2014-12-15 00:00:00

pages

6965-79

issue

24

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(14)00720-2

journal_volume

22

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • No carrier added synthesis of O-(2'-[18F]fluoroethyl)-L-tyrosine via a novel type of chiral enantiomerically pure precursor, NiII complex of a (S)-tyrosine Schiff base.

    abstract：:O-(2'-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of (18)F (110min) allowing remote-site application. Here we present a novel ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.03.040

    authors： Krasikova RN,Kuznetsova OF,Fedorova OS,Maleev VI,Saveleva TF,Belokon YN

    更新日期：2008-05-01 00:00:00

  • Synthesis, molecular modeling and biological evaluation of β-ketoacyl-acyl carrier protein synthase III (FabH) as novel antibacterial agents.

    abstract：:A series of novel cinnamic acid secnidazole ester derivatives have been designed and synthesized, and their biological activities were also evaluated as potential inhibitors of FabH. These compounds were assayed for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.06.021

    authors： Zhang HJ,Zhu DD,Li ZL,Sun J,Zhu HL

    更新日期：2011-08-01 00:00:00

  • Design, synthesis and QSAR studies on N-aryl heteroarylisopropanolamines, a new class of non-peptidic HIV-1 protease inhibitors.

    abstract：:A series of N-aryl heteroarylisopropanolamines in which an indole or a 3-arylpyrrole moiety was linked to an aryl group through an isopropanolamine linker, were designed and synthesized as potential anti-HIV-1-PR agents. Series was tested for their ability in blocking PR activity. As a rule, indole derivatives of clas...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(02)00119-0

    authors： Di Santo R,Costi R,Artico M,Massa S,Ragno R,Marshall GR,La Colla P

    更新日期：2002-08-01 00:00:00

  • Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase.

    abstract：:The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71)...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(02)00253-5

    authors： Chiosis G,Lucas B,Shtil A,Huezo H,Rosen N

    更新日期：2002-11-01 00:00:00

  • Bortezomib inhibits mammalian carbonic anhydrases.

    abstract：:We investigated the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the clinically used antitumor agent bortezomib, a marketed proteasome inhibitor, against all the catalytically active mammalian isoforms CA I-VII, IX, XII-XV. Bortezomib effectively inhibited all these CAs in the micromolar range. hCA II, t...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.10.023

    authors： Supuran CT

    更新日期：2017-10-01 00:00:00

  • The design and optimization of a series of 2-(pyridin-2-yl)-1H-benzimidazole compounds as allosteric glucokinase activators.

    abstract：:The optimization of a series of benzimidazole glucokinase activators is described. We identified a novel and potent achiral benzimidazole derivative as an allosteric GK activator. This activator was designed and synthesized via removal of the chiral center of the lead compound, 6-(N-acylpyrrolidin-2-yl)benzimidazole. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.05.037

    authors： Takahashi K,Hashimoto N,Nakama C,Kamata K,Sasaki K,Yoshimoto R,Ohyama S,Hosaka H,Maruki H,Nagata Y,Eiki J,Nishimura T

    更新日期：2009-10-01 00:00:00

  • Synthesis and biological evaluations of A-ring isomers of 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3.

    abstract：:The activated vitamin D3 derivative 26,27-F6-1alpha,25(OH)2D3 (2a), its three A-ring diastereomers (2b, 2c, 2d), and 5,6-trans isomer (2e) were prepared. Two analogues (2b, 2c) of these isomers were synthesized by a palladium catalyzed coupling reaction using vinyl bromide 5 and enynes (6a, 6b), which were derived fro...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00142-5

    authors： Ikeda M,Takahashi K,Dan A,Koyama K,Kubota K,Tanaka T,Hayashi M

    更新日期：2000-08-01 00:00:00

  • Novel structure-activity relationships and selectivity profiling of cage dimeric 1,4-dihydropyridines as multidrug resistance (MDR) modulators.

    abstract：:Synthesized series of cage dimeric 1,4-dihydropyridines have been systematically evaluated as MDR modulators in in vitro assays to investigate structure-dependent selectivity properties of inhibiting most cancer-relevant efflux pump proteins. Structure-activity relationships of each P-glycoprotein (P-gp) and multidrug...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.06.004

    authors： Coburger C,Wollmann J,Krug M,Baumert C,Seifert M,Molnár J,Lage H,Hilgeroth A

    更新日期：2010-07-15 00:00:00

  • Ophiobolin M and analogues, noncompetitive inhibitors of ivermectin binding with nematocidal activity.

    abstract：:A series of ophiobolins were isolated from a fungal extract based on their nematocidal activity. These compounds are non-competitive inhibitors of ivermectin binding to membranes prepared from the free-living nematode, Caenorhabditis elegans, with an inhibition constant of 15 microM. The ophiobolins which were most po...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/0968-0896(96)00036-3

    authors： Tsipouras A,Adefarati AA,Tkacz JS,Frazier EG,Rohrer SP,Birzin E,Rosegay A,Zink DL,Goetz MA,Singh SB,Schaeffer JM

    更新日期：1996-04-01 00:00:00

  • N-aroyloxylthioxo-naphthalimides as DNA photocleavers of aroyloxyl oxygen radicals: synthesis, evaluation, and substituents' effect.

    abstract：:Novel N-Aroyloxylthioxo-naphthalimides as highly efficient 'time-resolved' DNA photocleavers of aroyloxyl radicals type were designed and synthesized. The substituents at the aroyloxyl moiety have an important and unusual influence on the DNA photocleavage, and DNA photodamages of the compounds were unusually not depe...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.02.013

    authors： Xu Y,Huang X,Qian X,Yao W

    更新日期：2004-05-01 00:00:00

  • Synthesis and biological evaluation of novel pyrazolyl-2,4-thiazolidinediones as anti-inflammatory and neuroprotective agents.

    abstract：:Novel pyrazolyl-2,4-thiazolidinediones were prepared via the reaction of appropriate pyrazolecarboxaldehydes with 2,4-thiazolidinediones and substituted benzyl-2,4-thiazolidinediones. The resultant compounds were first evaluated for their anti-inflammatory and neuroprotective properties in vitro. The active compounds ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.01.021

    authors： Youssef AM,White MS,Villanueva EB,El-Ashmawy IM,Klegeris A

    更新日期：2010-03-01 00:00:00

  • A genetically selected cyclic peptide inhibitor of BCL6 homodimerization.

    abstract：:We report an inhibitor of the homodimeric protein-protein interaction of the BCL6 oncoprotein, identified from a genetically encoded SICLOPPS library of 3.2 million cyclic hexapeptides in combination with a bacterial reverse two-hybrid system. This cyclic peptide is shown to bind the BTB domain of BCL6, disrupts its h...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.03.012

    authors： Osher EL,Castillo F,Elumalai N,Waring MJ,Pairaudeau G,Tavassoli A

    更新日期：2018-07-15 00:00:00

  • Synthesis, characterization and biological activity of complexes of lanthanum(III) with 2-(1'-phenyl- 2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline and 2-(1'-p-phenol-2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline.

    abstract：:Two novel ligands 2-(1'-phenyl-2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline (L1) and 2-(1'-p-phenol-2'-carboxyl-3'-aza-butyl)-1,10-phenanthroline (L2), and their La(III) complexes of La(III)L1, La(III)(L1)(2), La(III)L2, and La(III)(L2)(2), were synthesized and characterized by (1)H NMR, elemental analysis, IR, the...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.09.032

    authors： Zhao G,Li F,Lin H,Lin H

    更新日期：2007-01-01 00:00:00

  • Neurotrophic and antileukemic daphnane diterpenoids from Synaptolepis kirkii.

    abstract：:Biological assay guided fractionation of a dichloromethane extract of Synaptolepis kirkii led to the isolation of four new and five known daphnane-type diterpene orthoesters, whose structure was established by spectroscopic data. Full spectroscopic data of the new and known natural products are reported here for the f...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(02)00163-3

    authors： He W,Cik M,Van Puyvelde L,Van Dun J,Appendino G,Lesage A,Van der Lindin I,Leysen JE,Wouters W,Mathenge SG,Mudida FP,De Kimpe N

    更新日期：2002-10-01 00:00:00

  • Synthesis and biological evaluation of 1,4-dihydropyridine calcium channel modulators having a diazen-1-ium-1,2-diolate nitric oxide donor moiety for the potential treatment of congestive heart failure.

    abstract：:A group of racemic 4-aryl(heteroaryl)-1,4-dihydro-2,6-dimethyl-3-nitropyridines possessing nitric oxide donor O(2)-acetoxymethyl-1-(N-ethyl-N-methylamino, or 4-ethylpiperazin-1-yl)diazen-1-ium-1,2-diolate, C-5 ester substituents were synthesized by coupling the respective 4-aryl(heteroaryl)-1,4-dihydro-2,6-dimethyl-3-...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.05.008

    authors： Velázquez C,Knaus EE

    更新日期：2004-07-15 00:00:00

  • Discovery and structure-activity relationship analysis of Staphylococcus aureus sortase A inhibitors.

    abstract：:Methicillin resistant Staphylococcus aureus (MRSA) is a major health problem that has created a pressing need for new antibiotics. Compounds that inhibit the S. aureus SrtA sortase may function as potent anti-infective agents as this enzyme attaches virulence factors to the cell wall. Using high-throughput screening, ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.08.067

    authors： Suree N,Yi SW,Thieu W,Marohn M,Damoiseaux R,Chan A,Jung ME,Clubb RT

    更新日期：2009-10-15 00:00:00

  • The selective quantification of iron by hexadentate fluorescent probes.

    abstract：:The synthesis of four hexadentate fluorescent probes is described, where the fluorescent moiety is based on either coumarin or fluorescein and the chelating moiety is based on either 3-hydroxypyridin-4-one or 3-hydroxypyran-4-one. The fluorescence is quenched when the probe chelating moieties bind iron. The probes wer...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.09.052

    authors： Ma YM,Hider RC

    更新日期：2009-12-01 00:00:00

  • Hydroxy- or methoxy-substituted benzaldoximes and benzaldehyde-O-alkyloximes as tyrosinase inhibitors.

    abstract：:Several benzaldoximes, benzaldehyde-O-ethyloximes, and acetophenonoximes were synthesized and evaluated as tyrosinase inhibitors by an assay based on tyrosinase catalyzed L-DOPA oxidation. Whereas benzaldoxime itself is only a weak inhibitor, its derivatives with one or two hydroxy or methoxy moieties in para and meta...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(01)00084-0

    authors： Ley JP,Bertram HJ

    更新日期：2001-07-01 00:00:00

  • Pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones as selective human A(1) adenosine receptor ligands.

    abstract：:A series of pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones was synthesized and tested in radioligand binding assays to determine their affinities for the human adenosine A(1), A(2A), A(2B) and A(3) receptors. Results indicated that this scaffold is appropriate for adenosine receptor subtype A(1) ligands and th...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.09.043

    authors： Giovannoni MP,Vergelli C,Cilibrizzi A,Crocetti L,Biancalani C,Graziano A,Dal Piaz V,Loza MI,Cadavid MI,Díaz JL,Gavaldà A

    更新日期：2010-11-15 00:00:00

  • The evaluation of quinonoid compounds against Trypanosoma cruzi: synthesis of imidazolic anthraquinones, nor-beta-lapachone derivatives and beta-lapachone-based 1,2,3-triazoles.

    abstract：:In continuing our screening program of naphthoquinone activity against Trypanosoma cruzi, the aetiological agent of Chagas' disease, new beta-lapachone-based 1,2,3-triazoles, 3-arylamino-nor-beta-lapachones, 3-alkoxy-nor-beta-lapachones and imidazole anthraquinones were synthesised and evaluated against bloodstream tr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.03.029

    authors： da Silva EN Jr,Guimarães TT,Menna-Barreto RF,Pinto Mdo C,de Simone CA,Pessoa C,Cavalcanti BC,Sabino JR,Andrade CK,Goulart MO,de Castro SL,Pinto AV

    更新日期：2010-05-01 00:00:00

  • NO-glibenclamide derivatives: prototypes of a new class of nitric oxide-releasing anti-diabetic drugs.

    abstract：:Endothelial dysfunction and consequent reduction of biosynthesis of endogenous nitric oxide (NO) play an important pathogenetic role in the cardiovascular complications associated with type II diabetes. In this work, the hybrid drugs 3a and 3b, nitrooxymethylbenzoate-derivatives of 1 (which is a hydroxylated active me...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.06.049

    authors： Calderone V,Rapposelli S,Martelli A,Digiacomo M,Testai L,Torri S,Marchetti P,Breschi MC,Balsamo A

    更新日期：2009-08-01 00:00:00

  • C-nucleoside analogues of furanfurin as ligands to A1 adenosine receptors.

    abstract：:Furanfurin (2-beta-D-ribofuranosylfuran-4-carboxamide) derivatives and analogues were synthesized and their affinity for adenosine receptors was determined. The agonistic behavior of furanfurin against A1 receptors is preserved only when the furan ring is substituted with isosteric pentatomic ring systems such as oxaz...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00167-x

    authors： Franchetti P,Cappellacci L,Marchetti S,Martini C,Costa B,Varani K,Borea PA,Grifantini M

    更新日期：2000-09-01 00:00:00

  • Synthesis and DNA cleavage activity of 2-hydrazinyl-1,4,5,6-tetrahydropyrimidine containing hydroxy group.

    abstract：:2-Hydrazinyl-1,4,5,6-tetrahydropyrimidin-5-ol dihydrochloride 2, as well as 2-hydrazinyl-4,5-dihydro-1H-imidazole dihydrochloride 1, was synthesized as metal-free DNA cleaving agent. Agarose gel electrophoresis was used to assess the plasmid pUC 19 DNA cleavage activities in the presence of 1 and 2. DNA cleavage effic...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.05.044

    authors： Shao Y,Ding Y,Jia ZL,Lu XM,Ke ZH,Xu WH,Lu GY

    更新日期：2009-07-01 00:00:00

  • Biaryl diacid inhibitors of human s-PLA2 with anti-inflammatory activity.

    abstract：:Twenty-four hydrophobic dicarboxylic acids are described which were evaluated as inhibitors of 14 kDa human platelet phospholipase A2 (HP-PLA2). In general, biarylacetic acid derivatives were found to be more active than biaryl acids or biarylpropanoic acids. More potent inhibitors were obtained when hydrophobic group...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00047-x

    authors： Springer DM,Luh BY,Bronson JJ,McElhone KE,Mansuri MM,Gregor KR,Nettleton DO,Stanley PL,Tramposch KM

    更新日期：2000-05-01 00:00:00

  • Synthesis and cytotoxic activities of usnic acid derivatives.

    abstract：:Nine usnic acid-amine conjugates were evaluated on murine and human cancer cell lines. The polyamine derivatives showed significant cytotoxicity in L1210 cells. Their activities appeared to be independent of the polyamine transport system (PTS). Indeed, their activities were similar in chinese hamster ovary (CHO) and ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.05.069

    authors： Bazin MA,Le Lamer AC,Delcros JG,Rouaud I,Uriac P,Boustie J,Corbel JC,Tomasi S

    更新日期：2008-07-15 00:00:00

  • Modeling and synthesis of novel tight-binding inhibitors of cytochrome P450 2C9.

    abstract：:Cytochrome P450 2C9 (2C9) is one of the three major drug metabolizing cytochrome P450 enzymes in human liver. Although the crystal structure of 2C9 has been solved, the important physicochemical properties of substrate-enzyme interactions remain difficult to be determined. This is due in part to the conformational fle...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.01.021

    authors： Peng CC,Rushmore T,Crouch GJ,Jones JP

    更新日期：2008-04-01 00:00:00

  • Adenosine receptors: new opportunities for future drugs.

    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

    authors： Poulsen SA,Quinn RJ

    更新日期：1998-06-01 00:00:00

  • Systematic synthesis of N-methyl-1-deoxynojirimycin-containing, Le(x), Le(a), sialyl-Le(x) and sialyl-Le(a) epitopes recognized by selectins.

    abstract：:A systematic synthesis of the N-methyl-1-deoxynojirimycin-containing oligosaccharides related to the Lewis x, Lewis a, sialyl-Lewis x and sialyl-Lewis a antigens has been achieved. The couplings of the suitably protected 1-deoxynojirimycin derivative 10 with methyl-1-thioglycosides (glycosyl donors) of L-fucose (11), ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)82080-5

    authors： Kiso M,Furui H,Ando K,Ishida H,Hasegawa A

    更新日期：1994-11-01 00:00:00

  • Cembrane diterpenoids from the soft coral Sarcophyton trocheliophorum Marenzeller as a new class of PTP1B inhibitors.

    abstract：:A detailed investigation of the South China Sea soft coral Sarcophyton trocheliophorum Marenzeller yielded, along with six known terpenes (6-11), the new sarcophytonolides N-R (1-5), whose structures have been elucidated by detailed spectroscopic analysis. Sarcophytonolides N-R are mono- or bicyclic cembranoids charac...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.06.043

    authors： Liang LF,Gao LX,Li J,Taglialatela-Scafati O,Guo YW

    更新日期：2013-09-01 00:00:00

  • Synthesis, biological evaluation, and modeling studies of inhibitors aimed at the malarial proteases plasmepsins I and II.

    abstract：:The increasing resistance of the malarial parasite to antimalarial drugs is a major contributor to the reemergence of the disease and increases the need for new drug targets. The two aspartic proteases, plasmepsins I and II, from Plasmodium falciparum have recently emerged as potential targets. In an effort to inhibit...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.06.048

    authors： Muthas D,Nöteberg D,Sabnis YA,Hamelink E,Vrang L,Samuelsson B,Karlén A,Hallberg A

    更新日期：2005-09-15 00:00:00