Synthesis and methemoglobinemia-inducing properties of benzocaine isosteres designed as humane rodenticides.


:A number of isosteres (oxadiazoles, thiadiazoles, tetrazoles and diazines) of benzocaine were prepared and evaluated for their capacity to induce methemoglobinemia-with a view to their possible application as humane pest control agents. It was found that an optimal lipophilicity for the formation of methemoglobin (metHb) in vitro existed within each series, with 1,2,4-oxadiazole 3 (metHb%=61.0±3.6) and 1,3,4-oxadiazole 10 (metHb%=52.4±0.9) demonstrating the greatest activity. Of the 5 candidates (compounds 3, 10, 11, 13 and 23) evaluated in vivo, failure to induce a lethal end-point at doses of 120mg/kg was observed in all cases. Inadequate metabolic stability, particularly towards hepatic enzymes such as the CYPs, was postulated as one reason for their failure.


Bioorg Med Chem


Conole D,Beck TM,Jay-Smith M,Tingle MD,Eason CT,Brimble MA,Rennison D




Has Abstract


2014-04-01 00:00:00














  • Synthesis and monoamine transporter binding properties of 2beta-[3'-(substituted benzyl)isoxazol-5-yl]- and 2beta-[3'-methyl-4'-(substituted phenyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes.

    abstract::A series of 2beta-[3'-(substituted benzyl)isoxazol-5-yl]- and 2beta-[3'-methyl-4'-(substituted phenyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes were prepared and evaluated for affinities at dopamine, serotonin, and norepinephrine transporters using competitive radioligand binding assays. The 2beta-[3'-(substit...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Jin C,Navarro HA,Page K,Carroll FI

    更新日期:2008-07-15 00:00:00

  • Cyclic MOG35-55 ameliorates clinical and neuropathological features of experimental autoimmune encephalomyelitis.

    abstract::EAE is induced to susceptible mice using linear peptides of myelin proteins of the central nervous system. Specific peptide motifs within the peptide-binding groove of the MHC peptide-complex determines the affinity of the peptide in each animal and the consequent T-cell receptor recognition and activation of the cell...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lourbopoulos A,Deraos G,Matsoukas MT,Touloumi O,Giannakopoulou A,Kalbacher H,Grigoriadis N,Apostolopoulos V,Matsoukas J

    更新日期:2017-08-01 00:00:00

  • Baylis-Hillman reaction assisted parallel synthesis of 3,5-disubstituted isoxazoles and their in vivo bioevaluation as antithrombotic agents.

    abstract::The solution-phase parallel synthesis involving reactions of Baylis-Hillman products of 3-substituted-5-isoxazolecarbaldehydes with nucleophiles and their in vivo antithrombotic evaluations are described along with the results of in vitro platelet aggregation inhibition assay of a few compounds. Results of the detaile...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Batra S,Roy AK,Patra A,Bhaduri AP,Surin WR,Raghavan SA,Sharma P,Kapoor K,Dikshit M

    更新日期:2004-05-01 00:00:00

  • Inhibition of bovine plasma amine oxidase by 1,4-diamino-2-butenes and -2-butynes.

    abstract::Bovine plasma amine oxidase (BPAO) was previously shown to be irreversibly inhibited by propargylamine and 2-chloroallylamine. 1,4-Diamine versions of these two compounds are here shown to be highly potent inactivators, with IC50 values near 20 microM. Mono-N-alkylation or N,N-dialkylation greatly lowered the inactiva...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Jeon HB,Lee Y,Qiao C,Huang H,Sayre LM

    更新日期:2003-10-15 00:00:00

  • Direct PCR amplification of various modified DNAs having amino acids: convenient preparation of DNA libraries with high-potential activities for in vitro selection.

    abstract::We synthesized modified 2'-deoxyuridine triphosphates bearing amino acids at the C5 position and investigated their substrate properties for KOD Dash DNA polymerase during polymerase chain reaction (PCR). PCR using C5-modified dUTP having an amino acyl group (arginyl, histidyl, lysyl, phenylalanyl, tryptophanyl, leucy...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kuwahara M,Hanawa K,Ohsawa K,Kitagata R,Ozaki H,Sawai H

    更新日期:2006-04-15 00:00:00

  • CC-1065 CBI analogs: an example of enhancement of DNA alkylation efficiency through introduction of stabilizing electrostatic interactions.

    abstract::The three trimethylammonium salts 3-5 proved to be 100 times more efficient at alkylating DNA than 2 and exhibited DNA alkylation efficiencies identical to that of (+)-CC-1065 (1). In addition, the agents 3 and 4 exhibited DNA alkylation selectivities identical to that of 2. This may be attributed to spatially well-de...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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

    更新日期:1995-06-01 00:00:00

  • Preparation of two sets of 5,6,7-trioxygenated dihydroflavonol derivatives as free radical scavengers and neuronal cell protectors to oxidative damage.

    abstract::An unusual class of 5,6,7-trioxygenated dihydroflavonols (3a-e and 4a-j) were designed and prepared. Their antioxidative properties were assessed by examining their capacities in several in vitro models, including superoxide anion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, rat liver homogenate lipid ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gong J,Huang K,Wang F,Yang L,Feng Y,Li H,Li X,Zeng S,Wu X,Stöckigt J,Zhao Y,Qu J

    更新日期:2009-05-01 00:00:00

  • Identification of 5-nitrofuran-2-amide derivatives that induce apoptosis in triple negative breast cancer cells by activating C/EBP-homologous protein expression.

    abstract::The transcription factor C/EBP-homologous protein (CHOP) is a key component of the terminal unfolded protein response (UPR) that mediates unresolvable endoplasmic reticulum stress-induced apoptosis. CHOP induction is known to cause cancer cell death. Chemicals that induce CHOP expression would thus be valuable as pote...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Duan H,Li Y,Lim HY,Wang W

    更新日期:2015-08-01 00:00:00

  • Analogues of DNA minor groove cross-linking agents incorporating aminoCBI, an amino derivative of the duocarmycins: Synthesis, cytotoxicity, and potential as payloads for antibody-drug conjugates.

    abstract::A Pd-catalysed amination method is used to convert seco-CBI, a synthetic analogue of the alkylating subunit of the duocarmycin natural products, from the phenol to amino form. This allows efficient enantioselective access to the more potent S enantiomer of aminoCBI and its incorporation into analogues of DNA minor gro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Giddens AC,Lee HH,Lu GL,Miller CK,Guo J,Lewis Phillips GD,Pillow TH,Tercel M

    更新日期:2016-11-15 00:00:00

  • New mimics of the acetate function in pheromone-based attraction.

    abstract::Several analogues of (Z)-8-dodecenyl acetate (1a), the major pheromone component of the Oriental fruit moth, Cydia molesta, with chloroformate and lactone functional groups in place of the acetate moiety, were synthesized and investigated for their biological activity at four evaluation levels, i.e. by electroantennog...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Hoskovec M,Hovorka O,Kalinová B,Koutek B,Streinz L,Svatos A,Sebek P,Saman D,Vrkoc J

    更新日期:1996-03-01 00:00:00

  • Bromo-deaza-SAH: a potent and selective DOT1L inhibitor.

    abstract::Chemical inhibition of proteins involved in chromatin-mediated signaling is an emerging strategy to control chromatin compaction with the aim to reprogram expression networks to alter disease states. Protein methyltransferases constitute one of the protein families that participate in epigenetic control of gene expres...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yu W,Smil D,Li F,Tempel W,Fedorov O,Nguyen KT,Bolshan Y,Al-Awar R,Knapp S,Arrowsmith CH,Vedadi M,Brown PJ,Schapira M

    更新日期:2013-04-01 00:00:00

  • Probing linker design in citric acid-ciprofloxacin conjugates.

    abstract::A series of structurally related citric acid-ciprofloxacin conjugates was synthesised to investigate the influence of the linker between citric acid and ciprofloxacin on antibacterial activities. Minimum inhibitory concentrations (MICs) were determined against a panel of reference strains and clinical isolates of bact...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Milner SJ,Snelling AM,Kerr KG,Abd-El-Aziz A,Thomas GH,Hubbard RE,Routledge A,Duhme-Klair AK

    更新日期:2014-08-15 00:00:00

  • Novel symmetrical ureas as modulators of protein arginine methyl transferases.

    abstract::Methylation of histone arginine residues is an epigenetic mark related to gene expression that is implicated in a variety of biological processes and can be reversed by small-molecule modulators of protein arginine methyltransferases (PRMTs). A series of symmetrical ureas, designed as analogues of the known PRMT1 inhi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fontán N,García-Domínguez P,Álvarez R,de Lera ÁR

    更新日期:2013-04-01 00:00:00

  • Effects of charge and hydrophobicity on the oligomerization of peptides derived from IAPP.

    abstract::Changes in pH resulting in modifications of charge can dramatically alter the folding and interaction of proteins. This article probes the effects of charge and hydrophobicity on the oligomerization of macrocyclic β-sheet peptides derived from residues 11-17 of IAPP (RLANFLV). Previous studies have shown that a macroc...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang Y,Truex NL,Vo NDP,Nowick JS

    更新日期:2018-03-15 00:00:00

  • Assessing the physiological relevance of alternate architectures of the p7 protein of hepatitis C virus in different environments.

    abstract::The viroporin p7 of the hepatitis C virus forms multimeric channels eligible for ion transport across the endoplasmic reticulum membrane. Currently the subject of many studies and discussion, the molecular assembly of the ion channel and the structural characteristics of the p7 monomer are not yet fully understood. St...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Holzmann N,Chipot C,Penin F,Dehez F

    更新日期:2016-10-15 00:00:00

  • Novel FXR (farnesoid X receptor) modulators: Potential therapies for cholesterol gallstone disease.

    abstract::Metabolic disorders such as diabetes are known risk factors for developing cholesterol gallstone disease (CGD). Cholesterol gallstone disease is one of the most prevalent digestive diseases, leading to considerable financial and social burden worldwide. Ursodeoxycholic acid (UDCA) is the only bile acid drug approved b...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yu DD,Andrali SS,Li H,Lin M,Huang W,Forman BM

    更新日期:2016-09-15 00:00:00

  • Synthesis and muscarinic activities of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives.

    abstract::A series of 3-(pyrazolyl)-1,2,5,6-tetrahydropyridine derivatives (B) was synthesized and tested for muscarinic activity in receptor binding assays using [3H]-oxotremorine-M (3H-OXO-M) and [3H]-pirenzepine (3H-PZ) as ligands. Potential muscarinic agonistic or antagonistic properties of the compounds were determined usi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Plate R,Plaum MJ,de Boer T,Andrews JS,Rae DR,Gibson S

    更新日期:1996-02-01 00:00:00

  • Carbonic anhydrases as targets for medicinal chemistry.

    abstract::Carbonic anhydrases (CAs, EC are zinc enzymes acting as efficient catalysts for the reversible hydration of carbon dioxide to bicarbonate. 16 different alpha-CA isoforms were isolated in mammals, where they play crucial physiological roles. Some of them are cytosolic (CA I, CA II, CA III, CA VII, CA XIII), ot...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Supuran CT,Scozzafava A

    更新日期:2007-07-01 00:00:00

  • Anti-HBV and cytotoxic activities of pyranocoumarin derivatives.

    abstract::Four natural pyranocoumarins clausenidin (1), nordentatin (2), clausarin (3), and xanthoxyletin (4) were isolated from the medicinal plant Clausena excavata. Recently, we found that 1 and 2 suppressed hepatitis B virus surface antigen in HepA2 cells, and in addition, 1-3 showed cytotoxic activity against four human ca...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Su CR,Yeh SF,Liu CM,Damu AG,Kuo TH,Chiang PC,Bastow KF,Lee KH,Wu TS

    更新日期:2009-08-15 00:00:00

  • Synthesis and antitumor activity of novel per-butyrylated glycosides of podophyllotoxin and its derivatives.

    abstract::A series of perbutyrylated glycosides of podophyllotoxin and its derivatives were synthesized and evaluated for their antitumor activity in vitro. Most of them exhibit cytotoxic activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Among the synthesized comp...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zi CT,Yang D,Dong FW,Li GT,Li Y,Ding ZT,Zhou J,Jiang ZH,Hu JM

    更新日期:2015-04-01 00:00:00

  • Novel and potent calcium-sensing receptor antagonists: discovery of (5R)-N-[1-ethyl-1-(4-ethylphenyl)propyl]-2,7,7-trimethyl-5-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide monotosylate (TAK-075) as an orally active bone anabolic agent.

    abstract::The calcium-sensing receptor antagonist (CaSR) has been recognized as a promising target of anabolic agents for treating osteoporosis. In the course of developing a new drug candidate for osteoporosis, we found tetrahydropyrazolopyrimidine derivative 1 to be an orally active CaSR antagonist that stimulated transient P...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yoshida M,Mori A,Morimoto S,Kotani E,Oka M,Notoya K,Makino H,Ono M,Shirasaki M,Tada N,Fujita H,Ban J,Ikeda Y,Kawamoto T,Goto M,Kimura H,Baba A,Yasuma T

    更新日期:2011-03-15 00:00:00

  • Discovery of 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate as a potential antiproliferative agent by inhibiting histone deacetylase.

    abstract::Twenty-one benzotriazoles (3-16 and 18-24) were synthesized and half of them (5, 8-16, 20, and 21) were reported for the first time. Their antiproliferative activities against three human cancer cells were assayed. It revealed that 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate (9) showed considerable activit...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fu J,Yang Y,Zhang XW,Mao WJ,Zhang ZM,Zhu HL

    更新日期:2010-12-15 00:00:00

  • Preparation of N-tBoc L-glutathione dimethyl and di-tert-butyl esters: versatile synthetic building blocks.

    abstract::The title l-glutathione derivatives, containing acid- and base-labile esters, respectively, were obtained in good overall yields. N-(t)Boc l-glutathione dimethyl ester was prepared via Fischer esterification of l-glutathione disulfide (GSSG) using HCl in dry methanol, protection of the amine with (t)Boc(2)O, and tribu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Falck JR,Sangras B,Capdevila JH

    更新日期:2007-01-15 00:00:00

  • Construction of a chemically and conformationally self-replicating system of amyloid-like fibrils.

    abstract::The amyloid-like fibril is considered to be a macromolecular self-assemblage with a highly-ordered quaternary structure, in which numerous beta-stranded polypeptide chains align regularly. Therefore, this kind of fibril has the potential to be engineered into proteinaceous materials, although conformational alteration...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Takahashi Y,Mihara H

    更新日期:2004-02-15 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


    authors: Ma YM,Hider RC

    更新日期:2009-12-01 00:00:00

  • Identification of 2-[2-(4-tert-butylphenyl)ethyl]-N-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (29) as an orally available MGAT2 inhibitor.

    abstract::MGAT2 (monoacylglycerol acyltransferase 2) is expected to be an attractive target for the drug treatment of obesity, diabetes, and other disease. We describe our exploration and structure-activity relationship (SAR) study of 2,3-dihydro-1H-isoindole-5-sulfonamide derivatives. In this study, we identified 29 as an oral...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Busujima T,Tanaka H,Shirasaki Y,Munetomo E,Saito M,Kitano K,Minagawa T,Yoshida K,Osaki N,Sato N

    更新日期:2015-09-01 00:00:00

  • Synthesis of functionalized 2-aryl-5-nitro-1H-indoles and their activity as bacterial NorA efflux pump inhibitors.

    abstract::In order to develop structure-activity relationships and to provide access to antibacterial agents for dual action studies, a variety of aryl group-substituted 2-aryl-5-nitro-1H-indoles were synthesized and the activity of the compounds assessed as inhibitors of the NorA multidrug resistance pump in the bacterium Stap...

    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

  • G-quadruplex DNA cleavage preference and identification of a perylene diimide G-quadruplex photocleavage agent using a rapid fluorescent assay.

    abstract::A rapid fluorescence assay for G-quadruplex DNA cleavage was used to investigate the preference of TMPyP4 photochemical and Mn·TMPyP4 oxidative cleavage. Both agents most efficiently cleave the c-Myc promoter G-quadruplex. Direct PAGE analysis of selected assay samples showed that for a given cleavage agent, different...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Schoonover M,Kerwin SM

    更新日期:2012-12-15 00:00:00

  • Quinazolines as adenosine receptor antagonists: SAR and selectivity for A2B receptors.

    abstract::We have recently reported the discovery of numerous new compounds that are selective inhibitors of all of the subtypes of the adenosine receptor family via a pharmacophore database searching and screening strategy. During the course of this work we made the unexpected discovery of a potent A(2B) receptor antagonist, 4...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Webb TR,Lvovskiy D,Kim SA,Ji Xd,Melman N,Linden J,Jacobson KA

    更新日期:2003-01-02 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