Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors.


:Geranylgeranyl diphosphate synthase (GGDPS) inhibitors are of potential therapeutic interest as a consequence of their activity against the bone marrow cancer multiple myeloma. A series of bisphosphonates linked to an isoprenoid tail through an amide linkage has been prepared and tested for the ability to inhibit GGDPS in enzyme and cell-based assays. The amides were designed as analogues to triazole-based GGDPS inhibitors. Several of the new compounds show GGDPS inhibitory activity in both enzyme and cell assays, with potency dependent on chain length and olefin stereochemistry.


Bioorg Med Chem


Goetz DB,Varney ML,Wiemer DF,Holstein SA




Has Abstract


2020-08-15 00:00:00














  • Imidazolone-amide bridges and their effects on tubulin polymerization in cis-locked vinylogous combretastatin-A4 analogues: synthesis and biological evaluation.

    abstract::A series of novel combretastatin-A4 analogues in which the cis-olefinic bridge is replaced by an imidazolone-amide were synthesized, and their cytotoxicity and tubulin-polymerization inhibitory activities were evaluated. These compounds appear to be potential tubulin-polymerization inhibitors. Compounds 10, 9b and 9c,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li YW,Liu J,Liu N,Shi D,Zhou XT,Lv JG,Zhu J,Zheng CH,Zhou YJ

    更新日期:2011-06-01 00:00:00

  • An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants.

    abstract::An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile 'click' chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure-activity relationships or conjugated to fluorophores to gen...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Phetsang W,Blaskovich MA,Butler MS,Huang JX,Zuegg J,Mamidyala SK,Ramu S,Kavanagh AM,Cooper MA

    更新日期:2014-08-15 00:00:00

  • Development of benzo[d]oxazol-2(3H)-ones derivatives as novel inhibitors of Mycobacterium tuberculosis InhA.

    abstract::A series of twenty seven substituted 2-(2-oxobenzo[d]oxazol-3(2H)-yl)acetamide derivatives were designed based on our earlier reported Mycobacterium tuberculosis (MTB) enoyl-acyl carrier protein reductase (InhA) lead. Compounds were evaluated for MTB InhA inhibition study, in vitro activity against drug-sensitive and ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Pedgaonkar GS,Sridevi JP,Jeankumar VU,Saxena S,Devi PB,Renuka J,Yogeeswari P,Sriram D

    更新日期:2014-11-01 00:00:00

  • New carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, X-ray crystallography and anticancer activity.

    abstract::An amine group was synthesized starting from an optically active bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of a key 6-chloropurine intermediate. This was then reacted with ammonia and selected amines obtaining new adenine- and 6-substituted adenine conformationally constrained carbo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tănase CI,Drăghici C,Căproiu MT,Shova S,Mathe C,Cocu FG,Enache C,Maganu M

    更新日期:2014-01-01 00:00:00

  • Synthesis and cytotoxic activities of goniothalamins and derivatives.

    abstract::Substituted goniothalamins containing cyclopropane-groups were efficiently prepared in high yields and good selectivity. Antiproliferative activity was measured on three human cancer cell lines (A549, MCF-7, HBL-100), to show which of the structural elements of goniothalamins is mandatory for cytotoxicity. We found th...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Weber A,Döhl K,Sachs J,Nordschild ACM,Schröder D,Kulik A,Fischer T,Schmitt L,Teusch N,Pietruszka J

    更新日期:2017-11-15 00:00:00

  • Discovery of 2-(5-nitrothiazol-2-ylthio)benzo[d]thiazoles as novel c-Jun N-terminal kinase inhibitors.

    abstract::A new series of 2-thioether-benzothiazoles has been synthesized and evaluated for JNK inhibition. The SAR studies led to the discovery of potent, allosteric JNK inhibitors with selectivity against p38. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: De SK,Chen LH,Stebbins JL,Machleidt T,Riel-Mehan M,Dahl R,Chen V,Yuan H,Barile E,Emdadi A,Murphy R,Pellecchia M

    更新日期:2009-04-01 00:00:00

  • Investigation into the influence of an acrylic acid acceptor in organic D-π-A sensitizers against phototoxicity.

    abstract::Photodynamic therapy (PDT) is a non-invasive, selective, and cost-effective cancer therapy. We previously reported that thiophene-based organic D-π-A sensitizers consist of an electron-donating (D) moiety, a π-conjugated bridge (π) moiety, and an electron-accepting (A) moiety, and are readily accessible and stable tem...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fuse S,Moriya W,Sato S,Nakamura H

    更新日期:2020-07-01 00:00:00

  • Studies on beta-D-Gal(f)-(1-->4)-alpha-L-Rha(p) octyl analogues as substrates for mycobacterial galactosyl transferase activity.

    abstract::The biochemically unique structures of sugar residues in the outer cell wall of Mycobacterium tuberculosis (MTB) make the pathways for their biosynthesis and utilization attractive targets for the development of new and selective anti-tubercular agents. A cell-free assay system for galactosyltransferase activity using...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Pathak AK,Besra GS,Crick D,Maddry JA,Morehouse CB,Suling WJ,Reynolds RC

    更新日期:1999-11-01 00:00:00

  • Discovery of potent and selective PARP-1 and PARP-2 inhibitors: SBDD analysis via a combination of X-ray structural study and homology modeling.

    abstract::We disclose herein our efforts aimed at discovery of selective PARP-1 and PARP-2 inhibitors. We have recently discovered several novel classes of quinazolinones, quinazolidinones, and quinoxalines as potent PARP-1 inhibitors, which may represent attractive therapeutic candidates. In PARP enzyme assays using recombinan...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ishida J,Yamamoto H,Kido Y,Kamijo K,Murano K,Miyake H,Ohkubo M,Kinoshita T,Warizaya M,Iwashita A,Mihara K,Matsuoka N,Hattori K

    更新日期:2006-03-01 00:00:00

  • Synthesis and biological evaluation of 1,1-dichloro-2,3-diarylcyclopropanes as antitubulin and anti-breast cancer agents.

    abstract::Z-1,1-Dichloro-2,3-diphenylcyclopropane (1) is an effective anti-breast cancer agent in rodents and in cell culture. We recently determined that 1 inhibits tubulin assembly in vitro and causes microtubule loss in breast cancer cells, leading to accumulation in the G2/M portion of the cell cycle. Aryl ring-halogenated,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Jonnalagadda SS,ter Haar E,Hamel E,Lin CM,Magarian RA,Day BW

    更新日期:1997-04-01 00:00:00

  • Triterpenoids from Momordica balsamina: Reversal of ABCB1-mediated multidrug resistance.

    abstract::The ability as P-glycoprotein (P-gp, ABCB1) modulators of thirty (1-30) triterpenoids of the cucurbitane-type was evaluated on human L5178 mouse T-lymphoma cell line transfected with the human MDR1 gene, through the rhodamine-123 exclusion assay. Compounds (1-26, and 29, 30) were previously obtained from the African m...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ramalhete C,Mulhovo S,Molnar J,Ferreira MU

    更新日期:2016-11-01 00:00:00

  • 1,2,4-triazolo[1,5-a]quinoxaline derivatives and their simplified analogues as adenosine A₃ receptor antagonists. Synthesis, structure-affinity relationships and molecular modeling studies.

    abstract::The 1,2,4-triazolo[1,5-a]quinoxaline (TQX) scaffold was extensively investigated in our previously reported studies and recently, our attention was focused at position 5 of the tricyclic nucleus where different acyl and carboxylate moieties were introduced (compounds 2-15). This study produced some interesting compoun...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Catarzi D,Varano F,Poli D,Squarcialupi L,Betti M,Trincavelli L,Martini C,Dal Ben D,Thomas A,Volpini R,Colotta V

    更新日期:2015-01-01 00:00:00

  • Solution-phase parallel synthesis of substituted chalcones and their antiparasitary activity against Giardia lamblia.

    abstract::A library of 25-membered chalcones was prepared by parallel synthesis. Substituted acetophenones and benzaldehydes were condensed using the Claisen-Schmidt base-catalyzed aldol condensation. Several chalcones showed in vitro antiparasitic activity against Giardia lamblia. The highest activity observed for the IC(50) v...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Montes-Avila J,Díaz-Camacho SP,Sicairos-Félix J,Delgado-Vargas F,Rivero IA

    更新日期:2009-09-15 00:00:00

  • Antimalarial acridines: synthesis, in vitro activity against P. falciparum and interaction with hematin.

    abstract::A series of acridine derivatives were synthesised and their in vitro antimalarial activity was evaluated against one chloroquine-susceptible strain (3D7) and three chloroquine-resistant strains (W2, Bre1 and FCR3) of Plasmodium falciparum. Structure-activity relationship showed that two positives charges as well as 6-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Guetzoyan L,Yu XM,Ramiandrasoa F,Pethe S,Rogier C,Pradines B,Cresteil T,Perrée-Fauvet M,Mahy JP

    更新日期:2009-12-01 00:00:00

  • Synthesis and screening of a cyclic peptide library: discovery of small-molecule ligands against human prolactin receptor.

    abstract::Prolactin receptor is involved in normal lactation and reproduction; however, excessive prolactin levels can cause various reproductive disorders such as prolactinomas. Small-molecule antagonists against the human prolactin receptor (hPRLr) thus have potential clinical applications and may serve as useful molecular pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Liu T,Joo SH,Voorhees JL,Brooks CL,Pei D

    更新日期:2009-02-01 00:00:00

  • Design and analysis of molecular motifs for specific recognition of RNA.

    abstract::Selective targeting of RNA has become a recent priority in drug design strategies due to the emergence of retroviruses, the need for new antibiotics to counter drug resistance, and our increased awareness of the essential role RNA and RNA structures play in the progression of disease. Most organic compounds known to s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li K,Fernandez-Saiz M,Rigl CT,Kumar A,Ragunathan KG,McConnaughie AW,Boykin DW,Schneider HJ,Wilson WD

    更新日期:1997-06-01 00:00:00

  • Exploring new Probenecid-based carbonic anhydrase inhibitors: Synthesis, biological evaluation and docking studies.

    abstract::Novel Probenecid-based amide derivatives, incorporating different natural amino acids, were synthesized and assayed to test their effect on the human carbonic anhydrase (hCA, EC transmembrane isoforms hCA IX and XII over the ubiquitous isoforms hCA I and II. Most of them presented a complete loss of hCA II in...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mollica A,Costante R,Akdemir A,Carradori S,Stefanucci A,Macedonio G,Ceruso M,Supuran CT

    更新日期:2015-09-01 00:00:00

  • Design, synthesis and evaluate of novel dual FGFR1 and HDAC inhibitors bearing an indazole scaffold.

    abstract::Both histone deacetylase (HDAC) and fibroblast growth factor receptor (FGFR) are important targets for cancer therapy. Although combining dual HDAC pharmacophore with tyrosine kinase inhibitors (TKIs) had achieved a successful progress, dual HDAC/FGFR1 inhibitors haven't been reported yet. Herein, we designed a series...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Liu J,Qian C,Zhu Y,Cai J,He Y,Li J,Wang T,Zhu H,Li Z,Li W,Hu L

    更新日期:2018-02-01 00:00:00

  • Nanomolar affinity, iminosugar-based chemical probes for specific labeling of lysosomal glucocerebrosidase.

    abstract::Three different photoprobes were synthesized to label beta-glucosidases; one probe was based on glucose, two probes on the iminosugar deoxynojirimycin. The affinity of the probes for three different beta-glucosidases was determined. Furthermore, their labeling efficiencies, binding specificities through competition wi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: van Scherpenzeel M,van den Berg RJ,Donker-Koopman WE,Liskamp RM,Aerts JM,Overkleeft HS,Pieters RJ

    更新日期:2010-01-01 00:00:00

  • N-substituted aminohydroxypyridines as potential non-opioid analgesic agents.

    abstract::A series of new N-substituted aminohydroxypyridines have been synthesized, pharmacologically evaluated and compared with their N-substituted oxazolopyridone analogs. The compound with the maximal combination of safety and analgesic efficacy was 3-[2-[4-(4-fluorophenyl)-1-piperazinyl]ethyl]amino-2-hydroxypyridine (comp...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Viaud MC,Jamoneau P,Bizot-Espiard JG,Pfeiffer B,Renard P,Caignard DH,Adam G,Guillaumet G

    更新日期:1995-07-01 00:00:00

  • Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA--II. Modification of pyrrolidine ring at P1' proline.

    abstract::Systematic replacement in the 3- or 4-position of the pyrrolidine ring at P1' proline was carried out. Compound 26, which has a Cl atom in the 4(S)-position was the most active among inhibitors substituted with other halogen atoms or other substituents. Furthermore, the replacement of the Z group in compound 26 with f...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Komai T,Higashida S,Sakurai M,Nitta T,Kasuya A,Miyamaoto S,Yagi R,Ozawa Y,Handa H,Mohri H,Yasuoka A,Oka S,Nishigaki T,Kimura S,Shimada K,Yabe Y

    更新日期:1996-08-01 00:00:00

  • Synthesis of 11C-labelled (R)-OHDMI and CFMME and their evaluation as candidate radioligands for imaging central norepinephrine transporters with PET.

    abstract::(R)-1-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-3-methylamino-propan-2-ol ((R)-OHDMI) and (S,S)-1-cyclopentyl-2-(5-fluoro-2-methoxy-phenyl)-1-morpholin-2-yl-ethanol (CFMME) were synthesized and found to be potent inhibitors of norepinephrine reuptake. Each was labelled efficiently in its methyl group with carbon-11 (t(1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Schou M,Pike VW,Sóvágó J,Gulyás B,Gallagher PT,Dobson DR,Walter MW,Rudyk H,Farde L,Halldin C

    更新日期:2007-01-15 00:00:00

  • Synthesis and evaluation of 4- and 5-pyridazin-3-one phenoxypropylamine analogues as histamine-3 receptor antagonists.

    abstract::A novel series of 4-pyridazin-3-one and 5-pyridazin-3-one analogues were designed and synthesized as H(3)R antagonists. Structure-activity relationship revealed the 5-pyridazin-3-ones 8a and S-methyl 8b had excellent human and rat H(3)R affinities, and acceptable pharmacokinetic properties. In vivo evaluation of 8a sh...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Becknell NC,Lyons JA,Aimone LD,Huang Z,Gruner JA,Raddatz R,Hudkins RL

    更新日期:2012-06-15 00:00:00

  • 11H-Isoquino[4,3-c]cinnolin-12-ones; novel anticancer agents with potent topoisomerase I-targeting activity and cytotoxicity.

    abstract::Recent studies have identified 2,3-dimethoxy-8,9-methylenedioxy-11-[(2-dimethylamino)ethyl]-11H-isoquino[4,3-c]cinnolin-12-one (1a) as a novel topoisomerase I-targeting agent with potent cytotoxic activity. The effect of varied substituents at the 11-position of 2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinn...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ruchelman AL,Singh SK,Ray A,Wu X,Yang JM,Zhou N,Liu A,Liu LF,LaVoie EJ

    更新日期:2004-02-15 00:00:00

  • Studies on 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole/2-hydroxypropyl-β-cyclodextrin association: Characterization, molecular modeling studies, and in vivo anthelminthic activity.

    abstract::The purpose of this work is to study the molecular association that occurs between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20), an antiparasitic compound recently found by our research group, with poor aqueous solubility. The complex stability cons...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rojas-Aguirre Y,Yépez-Mulia L,Castillo I,López-Vallejo F,Soria-Arteche O,Hernández-Campos A,Castillo R,Hernández-Luis F

    更新日期:2011-01-15 00:00:00

  • Synthesis, semipreparative HPLC separation, biological evaluation, and 3D-QSAR of hydrazothiazole derivatives as human monoamine oxidase B inhibitors.

    abstract::The present study reports on synthesis in high yields (70-99%), HPLC enantioseparation, inhibitory activity against human monoamino oxidases, and molecular modeling including 3D-QSAR studies, of a large series of (4-aryl-thiazol-2-yl)hydrazones (1-45). Most of the synthesized compounds proved to be potent and selectiv...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Chimenti F,Secci D,Bolasco A,Chimenti P,Granese A,Carradori S,Maccioni E,Cardia MC,Yáñez M,Orallo F,Alcaro S,Ortuso F,Cirilli R,Ferretti R,Distinto S,Kirchmair J,Langer T

    更新日期:2010-07-15 00:00:00

  • N-thiolated beta-lactams: Studies on the mode of action and identification of a primary cellular target in Staphylococcus aureus.

    abstract::This study focuses on the mechanism of action of N-alkylthio beta-lactams, a new family of antibacterial compounds that show promising activity against Staphylococcus and Bacillus microbes. Previous investigations have determined that these compounds are highly selective towards these bacteria, and possess completely ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Revell KD,Heldreth B,Long TE,Jang S,Turos E

    更新日期:2007-03-15 00:00:00

  • Synthesis, biological evaluation, and molecular docking of N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives as xanthine oxidase and tyrosinase inhibitors.

    abstract::Claisen-Schmidt condensation of 3-formyl-9-methylcarbazole with various amides of 3-aminoacetophenone afforded N-{3-[3-(9-methyl-9H-carbazol-3-yl)-acryloyl]-phenyl}-benzamide/amide derivatives. All compounds were investigated for their in vitro xanthine oxidase (XO), tyrosinase and melanin production inhibitory activi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bandgar BP,Adsul LK,Chavan HV,Shringare SN,Korbad BL,Jalde SS,Lonikar SV,Nile SH,Shirfule AL

    更新日期:2012-09-15 00:00:00

  • Synthesis of (+)-crocacin D and simplified bioactive analogues.

    abstract::The total synthesis of (+)-crocacin D has been achieved in 15 steps (9 isolated intermediates) and 14% overall yield from commercially available starting materials and using (+)-crocacin C as a key intermediate. A number of simplified analogues and their biological activities are also reported. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Pasqua AE,Ferrari FD,Crawford JJ,Whittingham WG,Marquez R

    更新日期:2015-03-01 00:00:00

  • Cytotoxicity of new polyfluorinated 1,4-naphtoquinones with diverse substituents in the quinone moiety.

    abstract::Fluorinated derivatives of 1,4-naphthoquinones are highly potent inhibitors of Cdc25A and Cdc25B phosphatases and growth of tumor cells. Eight new derivatives of polyfluoro-1,4-naphthoquinone were synthesized and their cytotoxicity in human myeloma, human mammary adenocarcinoma, mouse fibroblasts and primary mouse fib...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zakharova OD,Ovchinnikova LP,Goryunov LI,Troshkova NM,Shteingarts VD,Nevinsky GA

    更新日期:2011-01-01 00:00:00