C-2-aryl O-substituted HI-236 derivatives as non-nucleoside HIV-1 reverse-transcriptase inhibitors.


:Several novel thiourea derivatives of the NNRTI HI-236 substituted at the C-2 oxygen of the phenyl ring have been synthesized and evaluated for their inhibitory activity against HIV-1 (IIIB) replication in MT-2 cell cultures. The compounds were synthesized in order to fine-tune the activity of HI-236 as well as to gain insight into spatial characteristics in the pocket pertaining to the positional choice of tether in the design of [NRTI]-tether-[HI-236] bifunctional inhibitors. Two of the thiourea derivatives bearing a butynyl (6c) or hydroxyethyl tether (6n) were endowed with improved anti-HIV activity compared to HI-236. NNRTI activity was confirmed by a cell-free RT assay on six of the derivatives in which 6c returned an IC(50) of 3.8 nM compared to 28 nM for HI-236, establishing it as an improved lead for HI-236. The structure-activity profile is discussed in terms of potential interactions in the NNRTI pocket as suggested by a docking model using AutoDock, which have a bearing on the bifunctional drug design.


Bioorg Med Chem


Hunter R,Younis Y,Muhanji CI,Curtin TL,Naidoo KJ,Petersen M,Bailey CM,Basavapathruni A,Anderson KS




Has Abstract


2008-12-15 00:00:00














  • Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes.

    abstract::Our present report deals with the preparation of hitherto unreported 7-([carbonyl-14C]-acetyl)paclitaxel 4 and two new bioactive 7-substituted fluorescent taxoids (FITC 9 and rhodamine 11), as well as evaluation towards their applications as biological probes. The results in this report demonstrate that (a) the new pa...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rao CS,Chu JJ,Liu RS,Lai YK

    更新日期:1998-11-01 00:00:00

  • The conformation and activity relationship of fused analogs of DuP753.

    abstract::We have prepared three conformationally restricted analogs of DuP753 in which one of the phenyl rings in the biphenyl moiety is fused to the imidazole ring, and have investigated the conformation-biological activity relationship of these compounds. Conformational analysis on DuP753 and these compounds confirms that a ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yoo SE,Shin YA,Lee SH,Kim NJ

    更新日期:1995-03-01 00:00:00

  • Engineered production of cancer targeting peptide (CTP)-containing C-1027 in Streptomyces globisporus and biological evaluation.

    abstract::Conjugation of cancer targeting peptides (CTPs) with small molecular therapeutics has emerged as a promising strategy to deliver potent (but typically nonspecific) cytotoxic agents selectively to cancer cells. Here we report the engineered production of a CTP (NGR)-containing C-1027 and evaluation of its activity agai...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li W,Li X,Huang T,Teng Q,Crnovcic I,Rader C,Shen B

    更新日期:2016-09-01 00:00:00

  • Structure-activity relationships on adrenoceptors and imidazoline-preferring binding sites (I(1,2)-PBSs). Part 1: Weak intramolecular H-bond and conformational flexibility in a new I1-PBS-selective imidazoline analogue, trans1-(4',5'-dihydro-1'H-imidazol-

    abstract::The highly selective I1-PBS imidazoline analogue PMS 952 has been selected to study the incidence of intramolecular hydrogen bond and molecular flexibility on its biological activity. On one hand, the weak energy difference between three calculated conformers does not support the stabilization of one conformer by an i...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ye HF,Dive G,Dehareng D,Heymans F,Godfroid JJ

    更新日期:2000-08-01 00:00:00

  • Bacterial biofilm formation inhibitory activity revealed for plant derived natural compounds.

    abstract::Use of herbal plant remedies to treat infectious diseases is a common practice in many countries in traditional and alternative medicine. However to date there are only few antimicrobial agents derived from botanics. Based on microbiological screening tests of crude plant extracts we identified four compounds derived ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Artini M,Papa R,Barbato G,Scoarughi GL,Cellini A,Morazzoni P,Bombardelli E,Selan L

    更新日期:2012-01-15 00:00:00

  • Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.

    abstract::The most common lysosomal storage disorder, Gaucher disease, is caused by inefficient folding and trafficking of certain variants of lysosomal beta-glucosidase (beta-Glu, also known as beta-glucocerebrosidase). Recently, Sawker et al. reported that the addition of subinhibitory concentrations (10 microM) of the pharma...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yu L,Ikeda K,Kato A,Adachi I,Godin G,Compain P,Martin O,Asano N

    更新日期:2006-12-01 00:00:00

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

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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

    更新日期:2008-04-01 00:00:00

  • Synthesis, docking studies and anti-inflammatory activity of 4,5,6,7-tetrahydro-2H-indazole derivatives.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rosati O,Curini M,Marcotullio MC,Macchiarulo A,Perfumi M,Mattioli L,Rismondo F,Cravotto G

    更新日期:2007-05-15 00:00:00

  • Synthesis and evaluation of symmetric acyclic nucleoside bisphosphonates as inhibitors of the Plasmodium falciparum, Plasmodium vivax and human 6-oxopurine phosphoribosyltransferases and the antimalarial activity of their prodrugs.

    abstract::Two new series of symmetric acyclic nucleoside bisphosphonates (ANbPs) have been synthesised as potential inhibitors of the Plasmodium falciparum (Pf) and vivax (Pv) 6-oxopurine phosphoribosyltransferases. The structural variability between these symmetric ANbPs lies in the number of atoms in the two acyclic linkers c...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Špaček P,Keough DT,Chavchich M,Dračínský M,Janeba Z,Naesens L,Edstein MD,Guddat LW,Hocková D

    更新日期:2017-08-01 00:00:00

  • Targeting pancreatic cancer with a G-quadruplex ligand.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gunaratnam M,de la Fuente M,Hampel SM,Todd AK,Reszka AP,Schätzlein A,Neidle S

    更新日期:2011-12-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang L,Li L,Fu WT,Jiang ZY,You QD,Xu XL

    更新日期:2017-01-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Eilfeld A,González Tanarro CM,Frizler M,Sieler J,Schulze B,Gütschow M

    更新日期:2008-09-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Balseven H,Mustafa İşgör M,Mert S,Alım Z,Beydemir S,Ok S,Kasımoğulları R

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Hussain I,Yawer MA,Lalk M,Lindequist U,Villinger A,Fischer C,Langer P

    更新日期:2008-12-01 00:00:00

  • Nucleosides with self-complementary hydrogen-bonding motifs: synthesis and base-pairing studies of two nucleosides containing the imidazo[4,5-d]pyridazine ring system.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ujjinamatada RK,Paulman RL,Ptak RG,Hosmane RS

    更新日期:2006-09-15 00:00:00

  • Dolastatin 11 conformations, analogues and pharmacophore.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ali MA,Bates RB,Crane ZD,Dicus CW,Gramme MR,Hamel E,Marcischak J,Martinez DS,McClure KJ,Nakkiew P,Pettit GR,Stessman CC,Sufi BA,Yarick GV

    更新日期:2005-07-01 00:00:00

  • The comparison of characteristics between membrane-active antifungal peptide and its pseudopeptides.

    abstract::By the introduction of various amide surrogates, novel pseudopeptides corresponding to a membrane active depsipeptide were synthesized and their native characteristics compared with that of the peptide. The pseudopeptides had more resistance to serum proteases than the peptide and similar antimicrobial activities to t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Oh JE,Hong SY,Lee KH

    更新日期:1999-11-01 00:00:00

  • Interaction between artemisinin and heme. A Density Functional Theory study of structures and interaction energies.

    abstract::Malaria is an infectious disease caused by the unicellular parasite Plasmodium sp. Currently, the malaria parasite is becoming resistant to the traditional pharmacological alternatives, which are ineffective. Artemisinin is the most recent advance in the chemotherapy of malaria. Since it has been proven that artemisin...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Araújo JQ,Carneiro JW,de Araujo MT,Leite FH,Taranto AG

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Maksay G,Vincze Z,Nemes P

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Boger DL,Yun W,Han N,Johnson DS

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  • Design and synthesis of a multivalent homing device for targeting to murine CD22.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    更新日期:2001-01-01 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:2017-02-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Samosorn S,Bremner JB,Ball A,Lewis K

    更新日期:2006-02-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sol V,Chaleix V,Champavier Y,Granet R,Huang YM,Krausz P

    更新日期:2006-12-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Costa MS,Boechat N,Rangel EA,da Silva Fde C,de Souza AM,Rodrigues CR,Castro HC,Junior IN,Lourenço MC,Wardell SM,Ferreira VF

    更新日期:2006-12-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    更新日期:2017-08-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Askew SC,Butler AR,Flitney FW,Kemp GD,Megson IL

    更新日期:1995-01-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kawakita Y,Seto M,Ohashi T,Tamura T,Yusa T,Miki H,Iwata H,Kamiguchi H,Tanaka T,Sogabe S,Ohta Y,Ishikawa T

    更新日期:2013-04-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Padwal JD,Filippov DV,Narhe BD,Aertssen S,Beuving RJ,Benningshof JC,van der Marel GA,Overkleeft HS,van der Stelt M

    更新日期:2015-06-01 00:00:00