Anti-tubercular activities of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues endowed with high activity toward non-replicative Mycobacterium tuberculosis.


:Thirty three derivatives of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues were synthesized by molecular modification of a reported antimycobacterial molecule (GSK163574A). Compounds were evaluated in vitro against actively replicative and nutrient starved non-replicative Mycobacterium tuberculosis (MTB), enzymatic screening and cytotoxicity against RAW 264.7 cell line. Among the compounds, 2-ethyl-N-phenethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine (5c) was found to be the most active compound against non-replicative MTB with 2.7 log reduction of bacteria at 10μg/mL and was more potent than isoniazid (1.2 log reduction) and rifampicin (2.0 log reduction) at same dose level. Compound 5c also showed activity against MTB alanine dehydrogenase enzyme with IC50 of 1.82±0.42μM and showed 25% cytotoxicity against RAW 264.7 cell line at 50μg/mL.


Bioorg Med Chem


Samala G,Brindha Devi P,Saxena S,Gunda S,Yogeeswari P,Sriram D




Has Abstract


2016-11-01 00:00:00














  • In vitro antitumor activities of 2,6-di-[2-(heteroaryl)vinyl]pyridines and pyridiniums.

    abstract::The in vitro antitumor activities of 2,6-di-[2-(heteroaryl)vinyl]pyridines versus the standard National Cancer Institute 60 cell lines panel and of 2,6-di-[2-(heteroaryl)vinyl] pyridinium cations versus MCF7 (human mammary carcinoma) and LNCap (prostate carcinoma) cell lines are reported. Antiproliferative effects in ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Barresi V,Condorelli DF,Fortuna CG,Musumarra G,Scirè S

    更新日期:2002-09-01 00:00:00

  • Structure and functions of gamma-dodecalactone isolated from Antrodia camphorata for NK cell activation.

    abstract::The preserved fungal species Antrodia camphorata has diverse health-promoting effects and has been popularly used in East Asia as a traditional herb. We isolated a volatile compound from the culture medium of A. camphorata and identified it as gamma-dodecalactone (gamma-DDL). Cytomic screening for immune-modulating ac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Chen CJ,Vijaya Krishna R,Tsai CC,Wu WH,Chao LK,Hwang KH,Chien CM,Chang HY,Chen ST

    更新日期:2010-09-15 00:00:00

  • Benzhydrylquinazolinediones: novel cytosolic phospholipase A2alpha inhibitors with improved physicochemical properties.

    abstract::The synthesis and optimization of a class of trisubstituted quinazoline-2,4(1H,3H)-dione cPLA(2)alpha inhibitors are described. Utilizing pharmacophores that were found to be important in our indole series, we discovered inhibitors with reduced lipophilicity and improved aqueous solubility. These compounds are active ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kirincich SJ,Xiang J,Green N,Tam S,Yang HY,Shim J,Shen MW,Clark JD,McKew JC

    更新日期:2009-07-01 00:00:00

  • Structure-activity relationships in platelet-activating factor. Part 13: synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 or pure antiretroviral activity.

    abstract::HIV-1 infection of the brain and PAF neurotoxicity are implicated in AIDS dementia complex. We previously reported that a trisubstituted piperazine derivative is able to diminish both HIV-1 replication in monocyte-derived macrophages and PAF-induced platelet aggregation. We report in this work new compounds obtained b...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Serradji N,Bensaid O,Martin M,Sallem W,Dereuddre-Bosquet N,Benmehdi H,Redeuilh C,Lamouri A,Dive G,Clayette P,Heymans F

    更新日期:2006-12-01 00:00:00

  • Synthesis and pharmacological characterization of functionalized 2-pyridones structurally related to the cardiotonic agent milrinone.

    abstract::A new class of cardiotonic agents characterized by a 2-pyridone structure was synthesized. Appropriate sym-2-dimethylaminomethylene-1,3-diones reacted with methylcyanoacetate to afford the desired compounds. These derivatives were evaluated for their ability in inducing cardiotonic response on guinea pig isolated myoc...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fossa P,Menozzi G,Dorigo P,Floreani M,Mosti L

    更新日期:2003-11-03 00:00:00

  • Structure-activity relationships of truncated adenosine derivatives as highly potent and selective human A3 adenosine receptor antagonists.

    abstract::On the basis of potent and selective binding affinity of truncated 4'-thioadenosine derivatives at the human A(3) adenosine receptor (AR), their bioisosteric 4'-oxo derivatives were designed and synthesized from commercially available 2,3-O-isopropylidene-D-erythrono lactone. The derivatives tested in AR binding assay...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Pal S,Choi WJ,Choe SA,Heller CL,Gao ZG,Chinn M,Jacobson KA,Hou X,Lee SK,Kim HO,Jeong LS

    更新日期:2009-05-15 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


    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

  • Novel 5-(2-hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives: promising anticancer agents.

    abstract::A series of 5-(2-hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives was synthesized and 13 of them were selected by the National Cancer Institute (NCI) and evaluated for their in vitro anticancer activity. Seven of the investigated compounds, 3i, 3j, 3k, 3o, 3p, 3q, and 3r, displayed high a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Aboraia AS,Abdel-Rahman HM,Mahfouz NM,El-Gendy MA

    更新日期:2006-02-15 00:00:00

  • Investigation of chalcones and benzochalcones as inhibitors of breast cancer resistance protein.

    abstract::Breast cancer resistance protein (BCRP/ABCG2) belongs to the ATP binding cassette family of transport proteins. BCRP has been found to confer multidrug resistance in cancer cells. A strategy to overcome resistance due to BCRP overexpression is the investigation of potent and specific BCRP inhibitors. The aim of the cu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Juvale K,Pape VF,Wiese M

    更新日期:2012-01-01 00:00:00

  • Synthesis and biological properties of 2-methylene-19-nor-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones--weak agonists.

    abstract::In a continuing effort to explore the 2-methylene-1alpha-hydroxy-19-norvitamin D(3) class of pharmacologically important vitamin D compounds, two novel 2-methylene-19-nor-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones, GC-3 and HLV, were synthesized and biologically tested. Based on reports of similarly structur...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Chiellini G,Grzywacz P,Plum LA,Barycki R,Clagett-Dame M,DeLuca HF

    更新日期:2008-09-15 00:00:00

  • Solution NMR analysis of the binding mechanism of DIVS6 model peptides of voltage-gated sodium channels and the lipid soluble alkaloid veratridine.

    abstract::Voltage-gated sodium channels (VGSCs) are responsible for generating action potentials in nervous systems. Veratridine (VTD), a lipid soluble alkaloid isolated from sabadilla lily seed, is believed to bind to segment 6 of VGSCs and act as a partial agonist. However, high resolution structural interaction mechanism bet...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yoshinaka-Niitsu A,Yamagaki T,Harada M,Tachibana K

    更新日期:2012-05-01 00:00:00

  • Amino derivatives of glycyrrhetinic acid as potential inhibitors of cholinesterases.

    abstract::The development of remedies against the Alzheimer's disease (AD) is one of the biggest challenges in medicinal chemistry nowadays. Although not completely understood, there are several strategies fighting this disease or at least bringing some relief. During the progress of AD, the level of acetylcholine (ACh) decreas...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Schwarz S,Lucas SD,Sommerwerk S,Csuk R

    更新日期:2014-07-01 00:00:00

  • Cytotoxic palladium complexes of bioreductive quinoxaline N1,N4-dioxide prodrugs.

    abstract::Four new palladium(II) complexes with the formula Pd(L)(2), where L are quinoxaline-2-carbonitrile N(1),N(4)-dioxide derivatives, were synthesized as a contribution to the chemistry and pharmacology of metal compounds with this class of pharmacologically interesting bioreductive prodrugs. Compounds were characterized ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Urquiola C,Vieites M,Torre MH,Cabrera M,Lavaggi ML,Cerecetto H,González M,Cerain AL,Monge A,Smircich P,Garat B,Gambino D

    更新日期:2009-02-15 00:00:00

  • 2,4-Disubstituted oxazoles and thiazoles as latent pharmacophores for diacylhydrazine of SC-51089, a potent PGE2 antagonist.

    abstract::8-Chlorodibenz[b,f][1,4]oxazepine-10(11H)-carboxylic acid, 2-[1-oxo-3-(4-pyridinyl)propyl]hydrazide, monohydrochloride (1, SC-51089) is a functional PGE2 antagonist selective for the EP1 receptor subtype with antinociceptive activity. Analogues of SC-51089, in which the diacylhydrazine moiety has been replaced with 2,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Hallinan EA,Hagen TJ,Tsymbalov S,Stapelfeld A,Savage MA

    更新日期:2001-01-01 00:00:00

  • Synthesis and biological evaluation of SANT-2 and analogues as inhibitors of the hedgehog signaling pathway.

    abstract::Hedgehog (Hh) signaling plays an important role in cell signaling of embryonic development and adult tissue homeostasis. In vertebrates, the hh gene encodes three different unique proteins: sonic hedgehog (Shh), desert hedgehog (Dhh) and indian hedgehog (Ihh). Disruption of the Hh signaling pathway leads to severe dis...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Büttner A,Seifert K,Cottin T,Sarli V,Tzagkaroulaki L,Scholz S,Giannis A

    更新日期:2009-07-15 00:00:00

  • Design, synthesis, and biological activity of novel tetrahydropyrazolopyridone derivatives as FXa inhibitors with potent anticoagulant activity.

    abstract::A series of novel tetrahydropyrazolopyridone derivatives containing 1,3,4-triazole, triazolylmethyl, and partially saturated heterocyclic moieties as P2 binding element was designed, synthesized, and evaluated in vitro for anticoagulant activity in human and rabbit plasma. All compounds showed moderate to significant ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sun X,Hong Z,Liu M,Guo S,Yang D,Wang Y,Lan T,Gao L,Qi H,Gong P,Liu Y

    更新日期:2017-05-15 00:00:00

  • Fluorinated methylenecyclopropane analogues of nucleosides. Synthesis and antiviral activity of (Z)- and (E)-9-{[(2-fluoromethyl-2-hydroxymethyl)-cyclopropylidene]methyl}adenine and -guanine.

    abstract::Synthesis and antiviral activity of the title fluoromethylenecyclopropane analogues 15a, 15b, 16a, and 16b is described. Methylenecyclopropane carboxylate was first transformed to 2,2-bis-hydroxymethylmethylenecyclopropane. Selective monoacetylation followed by introduction of fluorine gave 2-acetoxymethyl-2-fluoromet...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li C,Prichard MN,Korba BE,Drach JC,Zemlicka J

    更新日期:2008-03-01 00:00:00

  • Design, synthesis and biological evaluation of inhibitors of cathepsin K on dedifferentiated chondrocytes.

    abstract::Selective proteinase inhibitors have demonstrated utility in the investigation of cartilage degeneration mechanisms and may have clinical use in the management of osteoarthritis. The cysteine protease cathepsin K (CatK) is an attractive target for arthritis therapy. Here we report the synthesis of two cathepsin K inhi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yuan XY,Ren Z,Wu Y,Bougault C,Brizuela L,Magne D,Buchet R,Mebarek S

    更新日期:2019-03-15 00:00:00

  • Novel quinolinequinone antitumor agents: structure-metabolism studies with NAD(P)H:quinone oxidoreductase (NQO1).

    abstract::A series of quinolinequinones bearing various substituents has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (hNQO1) was studied. A range of quinolinequinones were selected for study, and were specifically designed to probe the e...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fryatt T,Pettersson HI,Gardipee WT,Bray KC,Green SJ,Slawin AM,Beall HD,Moody CJ

    更新日期:2004-04-01 00:00:00

  • Cloning, isolation and characterization of the Thermotoga maritima KDPG aldolase.

    abstract::The Thermotoga maritima aldolase gene has been cloned into a T7 expression vector and overexpressed in Escherichia coli. The preparation yields 470 UL(-1) of enzyme at a specific activity of 9.4 U mg(-1). During retroaldol cleavage of KDPG, the enzyme shows a k(cat) that decreases with decreasing temperature. A more t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Griffiths JS,Wymer NJ,Njolito E,Niranjanakumari S,Fierke CA,Toone EJ

    更新日期:2002-03-01 00:00:00

  • Design, synthesis and biological activity of 3-pyrazine-2-yl-oxazolidin-2-ones as novel, potent and selective inhibitors of mutant isocitrate dehydrogenase 1.

    abstract::Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate (α-KG) generating carbon dioxide and NADPH/NADH. Evidence suggests that the specific mutations in IDH1 are critical to the growth and reproduction of some tumor cells such as gliomas and acute myeloid leukemia,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ma T,Zou F,Pusch S,Yang L,Zhu Q,Xu Y,Gu Y,von Deimling A,Zha X

    更新日期:2017-12-15 00:00:00

  • A strategic approach to the synthesis of ferrocene appended chalcone linked triazole allied organosilatranes: Antibacterial, antifungal, antiparasitic and antioxidant studies.

    abstract::A series of ferrocene appended chalcone allied triazole coupled organosilatranes (FCTSa 7-FCTSa 12) were synthesised with the aim of amalgamating the pharmacological action of the constituting moieties into a single molecular scaffold. All the synthesised silatranes were well characterized by various spectroscopic tec...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Singh G,Arora A,Kalra P,Maurya IK,Ruizc CE,Estebanc MA,Sinha S,Goyal K,Sehgal R

    更新日期:2019-01-01 00:00:00

  • In vitro cytotoxicity of 5-aminosubstituted 20(S)-camptothecins. Part 1.

    abstract::A number of 5-aminosubstituted 20(S)-camptothecin analogues were prepared via semi-synthesis starting from 20(S)-camptothecin and 9-methoxy 20(S)-camptothecin. In vitro anti-cancer activity of these analogues was determined using 60 human tumor cell line assay. Although water solubility of most of these compounds was ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Subrahmanyam D,Sarma VM,Venkateswarlu A,Sastry TV,Kulakarni AP,Rao DS,Reddy KV

    更新日期:1999-09-01 00:00:00

  • Solution-phase microwave assisted parallel synthesis, biological evaluation and in silico docking studies of N,N'-disubstituted thioureas derived from 3-chlorobenzoic acid.

    abstract::A facile and robust microwave-assisted solution phase parallel synthesis protocol was exercised for the development of a 38-member library of N,N'-disubstituted thiourea analogues (1-38) by using an identical set of conditions. The reaction time for synthesis of N,N'-disubstituted thiourea analogues was drastically re...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rauf MK,Zaib S,Talib A,Ebihara M,Badshah A,Bolte M,Iqbal J

    更新日期:2016-09-15 00:00:00

  • Mechanism-based inhibitors of serine proteases with high selectivity through optimization of S' subsite binding.

    abstract::A series of mechanism-based inhibitors designed to interact with the S' subsites of serine proteases was synthesized and their inhibitory activity toward the closely-related serine proteases human neutrophil elastase (HNE) and proteinase 3 (PR 3) was investigated. The compounds were found to be time-dependent inhibito...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li Y,Dou D,He G,Lushington GH,Groutas WC

    更新日期:2009-05-15 00:00:00

  • Asymmetric reduction of 3-aryl-3-keto esters using Rhizopus species.

    abstract::Ethyl 3-aryl-3-oxopropanoates (aryl: phenyl, 2-fluorophenyl, 3-nitrophenyl, and 4-nitrophenyl) were reduced enantioselectively to the corresponding (S)-alcohols by the fungus Rhizopus arrhizus and other Rhizopus sp. The best results were generally obtained with Rhizopus arrhizus (wild type) and Rhizopus nivius NCIM 95...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Salvi NA,Chattopadhyay S

    更新日期:2006-07-15 00:00:00

  • Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents.

    abstract::We designed, synthesized and evaluated 13 novel tricyclic indeno[2,1-d]pyrimidines as RTK inhibitors. These analogues were synthesized via a Dieckmann condensation of 1,2-phenylenediacetonitrile followed by cyclocondensation with guanidine carbonate to afford the 2-amino-3,9-dihydro-indeno[2,1-d]pyrimidin-4-one. Sulfo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gangjee A,Zhao Y,Ihnat MA,Thorpe JE,Bailey-Downs LC,Kisliuk RL

    更新日期:2012-07-15 00:00:00

  • Structure-based design and synthesis of covalent-reversible inhibitors to overcome drug resistance in EGFR.

    abstract::The clinical success of covalent kinase inhibitors in the treatment of EGFR-dependent non-small cell lung cancer (NSCLC) has rejuvenated the appreciation of reactive small molecules. Acquired drug resistance against first-line EGFR inhibitors remains the major bottleneck in NSCLC and is currently addressed by the appl...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Basu D,Richters A,Rauh D

    更新日期:2015-06-15 00:00:00

  • 18F-Labeled indole-based analogs as highly selective radioligands for imaging sigma-2 receptors in the brain.

    abstract::We have designed and synthesized a series of indole-based σ2 receptor ligands containing 5,6-dimethoxyisoindoline or 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline as pharmacophore. In vitro competition binding assays showed that all ten ligands possessed low nanomolar affinity (Ki=1.79-5.23nM) for σ2 receptors and high...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang L,Ye J,He Y,Deuther-Conrad W,Zhang J,Zhang X,Cui M,Steinbach J,Huang Y,Brust P,Jia H

    更新日期:2017-07-15 00:00:00

  • Synthesis of the (1→6)-linked thiodisaccharide of galactofuranose: inhibitory activity against a β-galactofuranosidase.

    abstract::A new (1→6)-linked thiodisaccharide formed by two galactofuranosyl units has been synthesized. Methyl (methyl α,β-D-galactofuranosid)uronate was employed as the starting compound, which was per-O-silylated with TBSCl and reduced with LiAlH4 to afford methyl 2,3,5-tri-O-tert-butyldimethylsilyl-β-D-galactofuranoside (2β...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Repetto E,Marino C,Varela O

    更新日期:2013-06-01 00:00:00