Drug design and synthesis of epsilon opioid receptor agonist: 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821) inducing antinociception mediated by putative epsilon opioid


:Here we report the new drug design and synthesis of a series of 6,14-endoethenomorphinan-7-carboxamide derivatives as a putative epsilon opioid receptor agonist. One of these compounds, 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821), showed agonistic activity for a putative epsilon opioid receptor (IC(50) = 71.71nM) in the rat vas deferens (RVD) preparations. TAN-821 stimulated the binding of the nonhydrolyzable guanosine 5'-triphosphate analog, guanosine 5'-(gamma-thio)-triphosphate (GTPgammaS), to the mouse pons/medulla membrane via the activation of putative epsilon opioid receptor. Moreover, TAN-821 given intracerebroventricularly (i.c.v.) produced a marked antinociception in the tail-flick test (ED(50) = 1.73 microg) and the hot-plate test (ED(50) = 2.05 microg) in a dose-dependent manner. The antinociception induced by TAN-821 administered i.c.v. was blocked by the i.c.v.-pretreatment with a putative epsilon opioid receptor partial agonist beta-endorphin [1-27], but not a mu opioid receptor antagonist beta-FNA, a delta opioid receptor antagonist NTI, or a kappa opioid receptor antagonist nor-BNI. The present results suggest that TAN-821 may be a useful tool for the investigation on the pharmacological properties of the putative epsilon opioid receptor.


Bioorg Med Chem


Fujii H,Narita M,Mizoguchi H,Murachi M,Tanaka T,Kawai K,Tseng LF,Nagase H




Has Abstract


2004-08-01 00:00:00














  • Acetyltransfer in natural product biosynthesis--functional cloning and molecular analysis of vinorine synthase.

    abstract::Vinorine synthase (EC catalyses the acetyl-CoA- or CoA-dependent reversible formation of the alkaloids vinorine (or 11-methoxy-vinorine) and 16-epi-vellosimine (or gardneral). The forward reaction leads to vinorine, which is a direct biosynthetic precursor along the complex pathway to the monoterpenoid indo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bayer A,Ma X,Stöckigt J

    更新日期:2004-05-15 00:00:00

  • QSAR models for Daphnia toxicity of pesticides based on combinations of topological parameters of molecular structures.

    abstract::A topological parameter is defined as an integer value of a given local or global invariant of a molecular graph. We examined three types of local graph invariants, the vertex degrees (0EC), the extended connectivity of first order (1EC), and the numbers of paths of length two (P2), as elementary invariants for constr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Toropov AA,Benfenati E

    更新日期:2006-04-15 00:00:00

  • Thionation of segetalins A and B, cyclic peptides with estrogen-like activity from seeds of Vaccaria segetalis.

    abstract::Thionation of estrogen-like active cyclic peptides, segetalins A (1) and B (2), with Lawesson's reagent provided each two thiosegetalins; thiosegetalin A1 [Gly-1-psi(CS-NH)-Val-2; Trp-5-psi (CS-NH)-Ala-6]segetalin A, thiosegetalin A2 [Gly-1-psi(CS-NH)-Val-2; Ala-6-psi(CS-NH)-Gly-1]segetalin A, thiosegetalin B1 [Gly-1-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Morita H,Yun YS,Takeya K,Itokawa H,Shirota O

    更新日期:1997-03-01 00:00:00

  • Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent.

    abstract::Here we report on a novel fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2 incorporated a heptyl side chain and dansyl moiety onto the parent compound phenytoin and produced greater displacement of BTX from sodium channels and greater funct...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Walls TH,Grindrod SC,Beraud D,Zhang L,Baheti AR,Dakshanamurthy S,Patel MK,Brown ML,MacArthur LH

    更新日期:2012-09-01 00:00:00

  • 4-Anilino-7-alkenylquinoline-3-carbonitriles as potent MEK1 kinase inhibitors.

    abstract::A series of substituted 7-alkenyl 4[3-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-3-quinolinecarbonitrile analogs were synthesized and evaluated as MEK1 kinase inhibitors. The synthetic details, structure-activity relationships, biological activity, and selected oral exposure studies of these analogs are desc...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Berger DM,Dutia M,Powell D,Floyd MB,Torres N,Mallon R,Wojciechowicz D,Kim S,Feldberg L,Collins K,Chaudhary I

    更新日期:2008-10-15 00:00:00

  • Chemical and enzymatic synthesis of fructose analogues as probes for import studies by the hexose transporter in parasites.

    abstract::Various D-fructose analogues modified at C-1 or C-6 positions were synthesized from D-glucose by taking advantage of the Amadori rearrangement or using the aldol condensation between dihydroxyacetone phosphate and appropriate aldehyde catalyzed by fructose 1,6-diphosphate aldolase from rabbit muscle. The affinities of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Azéma L,Bringaud F,Blonski C,Périé J

    更新日期:2000-04-01 00:00:00

  • Characterization and in vitro activity of a branched peptide boronic acid that interacts with HIV-1 RRE RNA.

    abstract::A branched peptide containing multiple boronic acids was found to bind RRE IIB selectively and inhibit HIV-1 p24 capsid production in a dose-dependent manner. Structure-activity relationship studies revealed that branching in the peptide is crucial for the low micromolar binding towards RRE IIB, and the peptide demons...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wynn JE,Zhang W,Tebit DM,Gray LR,Hammarskjold ML,Rekosh D,Santos WL

    更新日期:2016-09-01 00:00:00

  • Structure-activity relationship of leucyladenylate sulfamate analogues as leucyl-tRNA synthetase (LRS)-targeting inhibitors of Mammalian target of rapamycin complex 1 (mTORC1).

    abstract::Leucyl-tRNA synthetase (LRS) plays an important role in amino acid-dependent mTORC1 signaling, which is known to be associated with cellular metabolism and proliferation. Therefore, LRS-targeting small molecules that can suppress mTORC1 activation may provide an alternative strategy to current anticancer therapy. In t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yoon S,Kim SE,Kim JH,Yoon I,Tran PT,Ann J,Kim C,Byun WS,Lee S,Kim S,Lee J,Lee J

    更新日期:2019-03-15 00:00:00

  • Synthesis and physical characterization of a P1 arginine combinatorial library, and its application to the determination of the substrate specificity of serine peptidases.

    abstract::Serine peptidases are a large, well-studied, and medically important class of peptidases. Despite the attention these enzymes have received, details concerning the substrate specificity of even some of the best known enzymes in this class are lacking. One approach to rapidly characterizing substrate specificity for pe...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Furlong ST,Mauger RC,Strimpler AM,Liu YP,Morris FX,Edwards PD

    更新日期:2002-11-01 00:00:00

  • Enhanced RNA binding of dimerized aminoglycosides.

    abstract::Aminoglycoside antibiotics have recently emerged as an intriguing family of RNA binding molecules and they became leading structures for the design of novel RNA ligands. The demystification of the aminoglycoside-RNA recognition phenomenon is required for the development of superior binders. To explore the existence of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Michael K,Wang H,Tor Y

    更新日期:1999-07-01 00:00:00

  • Salicylanilide diethyl phosphates: synthesis, antimicrobial activity and cytotoxicity.

    abstract::A series of 27 salicylanilide diethyl phosphates was prepared as a part of our on-going search for new antimicrobial active drugs. All compounds exhibited in vitro activity against Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium strains, with minimum inhibitory concentration (MIC) values of ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Vinšová J,Kozic J,Krátký M,Stolaříková J,Mandíková J,Trejtnar F,Buchta V

    更新日期:2014-01-15 00:00:00

  • New insights into the conformational requirements of B2 bradykinin antagonism.

    abstract::The conformational profiles of a selected group of a new series of small linear and cyclic penta- and hexapeptides, inspired on the C-terminal segment of second-generation bradykinin (BK) antagonists, were independently computed in order to assess the chemical and geometrical requirements necessary for BK antagonism. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Filizola M,Llorens O,Cartení-Farina M,Perez JJ

    更新日期:1998-09-01 00:00:00

  • Analgesic agents without gastric damage: design and synthesis of structurally simple benzenesulfonanilide-type cyclooxygenase-1-selective inhibitors.

    abstract::In order to create novel analgesic agents without gastric disturbance, structurally simple cyclooxygenase-1 (COX-1) inhibitors with a benzenesulfonanilide skeleton were designed and synthesized. As a result, compounds 11f and 15a, which possess a p-amino group on the benzenesulfonyl moiety and p-chloro group on the an...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zheng X,Oda H,Takamatsu K,Sugimoto Y,Tai A,Akaho E,Ali HI,Oshiki T,Kakuta H,Sasaki K

    更新日期:2007-01-15 00:00:00

  • Design, synthesis, and activity of caffeoyl pyrrolidine derivatives as potential gelatinase inhibitors.

    abstract::The synthesis and biological evaluation of caffonyl pyrrolidine derivatives as MMPs inhibitors are reported in this paper. Inhibiting activities of synthesized compounds on gelatinase (MMP-2 and -9) were tested by using succinylated gelatin as substrate. Structure-activity relationship results from these tested compou...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li YL,Xu WF

    更新日期:2004-10-01 00:00:00

  • Deoxyiminoalditols from aldonolactones--V. Preparation of the four stereoisomers of 1,5-dideoxy-1,5-iminopentitols. Evaluation of these iminopentitols and three 1,5-dideoxy-1,5-iminoheptitols as glycosidase inhibitors.

    abstract::The four stereoisomeric 1,5-dideoxy-1,5-iminopentitols with D-arabino-(D-lyxo-) (3), ribo- (9), L-lyxo (L-arabino-) (13) and xylo-(18) configurations were synthesized. The corresponding aldonolactones (1, 7 and 11) or aldonic acid ester (15b) having a leaving group at C-5 gave by reaction with aqueous ammonia, the 5-a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Godskesen M,Lundt I,Madsen R,Winchester B

    更新日期:1996-11-01 00:00:00

  • Novel semicarbazide-derived inhibitors of human dipeptidyl peptidase I (hDPPI).

    abstract::Human dipeptidyl peptidase I (hDPPI, cathepsin C, EC is a novel putative drug target for the treatment of inflammatory diseases. Using 1 as a starting point (IC50>10 microM), we have improved potency by more than 500-fold and successfully identified novel inhibitors of DPPI via screening of a one-bead-two-co...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bondebjerg J,Fuglsang H,Valeur KR,Kaznelson DW,Hansen JA,Pedersen RO,Krogh BO,Jensen BS,Lauritzen C,Petersen G,Pedersen J,Naerum L

    更新日期:2005-07-15 00:00:00

  • Synthesis and receptor binding affinity of new selective GluR5 ligands.

    abstract::Two hybrid analogues of the kainic acid receptor agonists, 2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) and (2S,4R)-4-methylglutamic acid ((2S,4R)-4-Me-Glu), were designed, synthesized, and characterized in radioligand binding assays using cloned ionotropic and metabotropic glutamic acid recept...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bunch L,Johansen TH,Bräuner-Osborne H,Stensbøl TB,Johansen TN,Krogsgaard-Larsen P,Madsen U

    更新日期:2001-04-01 00:00:00

  • Evaluation of PI polyamide conjugates with eight-base pair recognition and improvement of the aqueous solubility by PEGylation.

    abstract::To investigate the effect of elongating base-pair (bp) recognition sequences, we synthesized N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates with eight-bp recognition (3-5). The DNA alkylating activities of conjugates 3-5 were evaluated by high-resolution denaturing polyacrylamide gel electrophoresis with ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Takagaki T,Bando T,Kitano M,Hashiya K,Kashiwazaki G,Sugiyama H

    更新日期:2011-10-01 00:00:00

  • A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids.

    abstract::The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellul...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zhu M,Harshbarger WD,Robles O,Krysiak J,Hull KG,Cho SW,Richardson RD,Yang Y,Garcia A,Spiegelman L,Ramirez B,Wilson CT,Yau JA,Moore JT,Walker CB,Sacchettini JC,Liu WR,Sieber SA,Smith JW,Romo D

    更新日期:2017-06-01 00:00:00

  • A credit-card library approach for disrupting protein-protein interactions.

    abstract::Protein-protein interfaces are prominent in many therapeutically important targets. Using small organic molecules to disrupt protein-protein interactions is a current challenge in chemical biology. An important example of protein-protein interactions is provided by the Myc protein, which is frequently deregulated in h...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Xu Y,Shi J,Yamamoto N,Moss JA,Vogt PK,Janda KD

    更新日期:2006-04-15 00:00:00

  • An approach to identifying novel substrates of bacterial arylamine N-acetyltransferases.

    abstract::Arylamine N-acetyltransferases (NATs) catalyse the acetylation of arylamine, arylhydrazine and arylhydroxylamine substrates by acetyl Coenzyme A. NAT has been discovered in a wide range of eukaryotic and prokaryotic species. Although prokaryotic NATs have been implicated in xenobiotic metabolism, to date no endogenous...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Brooke EW,Davies SG,Mulvaney AW,Pompeo F,Sim E,Vickers RJ

    更新日期:2003-04-03 00:00:00

  • Cosmomycin C inhibits signal transducer and activator of transcription 3 (STAT3) pathways in MDA-MB-468 breast cancer cell.

    abstract::The signal transducer and activator of transcription 3 (STAT3) is constitutively activated in cancer cells. Therefore, blocking the aberrant activity of STAT3 in tumor cells is a validated therapeutic strategy. To discover novel inhibitors of STAT3 activity, we screened against microbial natural products using a dual-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kim J,Lee YJ,Shin DS,Jeon SH,Son KH,Han DC,Jung SN,Oh TK,Kwon BM

    更新日期:2011-12-15 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


    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

  • Effective syntheses of 2',4'-BNANC monomers bearing adenine, guanine, thymine, and 5-methylcytosine, and the properties of oligonucleotides fully modified with 2',4'-BNANC.

    abstract::We efficiently synthesized 2'-O,4'-C-aminomethylene-bridged nucleic acid (2',4'-BNANC) monomers bearing the four nucleobases, guanine, adenine, thymine, and 5-methylcytosine and incorporated these monomers into oligonucleotides. Initially, we carried out the transglycosylation reaction on several 2'-O-substituted 5-me...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fujisaka A,Hari Y,Takuma H,Rahman SMA,Yoshikawa H,Pang J,Imanishi T,Obika S

    更新日期:2019-04-15 00:00:00

  • 1-(1-Arylethylidene)thiosemicarbazide derivatives: a new class of tyrosinase inhibitors.

    abstract::A series of 1-(1-arylethylidene)thiosemicarbazide compounds and their analogues were synthesized and characterized by 1H NMR, MS. Their tyrosinase inhibitory activities were investigated by an assay based on the catalyzing ability of tyrosinase for the oxidation of L-DOPA, comparing with 4-methoxycinnamic acid and arb...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Liu J,Yi W,Wan Y,Ma L,Song H

    更新日期:2008-02-01 00:00:00

  • Concise syntheses of arabinogalactans with beta-(1-->6)-linked galactopyranose backbones and alpha-(1-->3)- and alpha-(1-->2)-linked arabinofuranose side chains.

    abstract::4-methoxyphenyl glycosides of 2,3''-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl tetraose (16), 3',2''''-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl hexaose (27), and a twentyose (42) consisting of beta-(1-->6)-linked D-galactopyranosyl pentadecaoligosac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li A,Kong F

    更新日期:2005-02-01 00:00:00

  • Quantitative structure and aldose reductase inhibitory activity relationship of 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone derivatives.

    abstract::We investigate the quantitative structure-activity relationship of spirosuccinimide-fused tetrahydropyrrolo[1,2-a]pyrazine-1,3-dione derivatives acting as aldose reductase inhibitors, which contain a chiral center. The published assay data of 30 training compounds are not for optically pure enantiomer preparations but...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ko K,Won Y

    更新日期:2005-03-01 00:00:00

  • Enantioselective syntheses of (R)- and (S)-argentilactone and their cytotoxic activities against cancer cell lines.

    abstract::Concise total syntheses of (R)- and (S)-argentilactone have been developed via enantioselective catalytic allylation (ECA) and ring-closing metathesis pathways (four steps, 39% overall yield and 82-84% ee) from 2-octynal and their in vitro activity against cancer cells is described. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: de Fatima A,Kohn LK,Antônio MA,de Carvalho JE,Pilli RA

    更新日期:2004-10-15 00:00:00

  • Interaction between double helix DNA fragments and a new topopyrone acting as human topoisomerase I poison.

    abstract::A water soluble derivative (2) of topopyrones was selected for NMR studies directed to elucidate the mode of binding with specific oligonucleotides. Topopyrone 2 can intercalate into the CG base pairs, but the residence time into the double helix is very short and a fast chemical exchange averaging occurs at room temp...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Scaglioni L,Mazzini S,Mondelli R,Dallavalle S,Gattinoni S,Tinelli S,Beretta GL,Zunino F,Ragg E

    更新日期:2009-01-15 00:00:00

  • TRH mimetics: differentiation of antiamnesic potency from antidepressant effect.

    abstract::For the purpose of rational modification of the TRH molecule, we were pursuing an approach that consists of two steps: (1) 'obligatory' replacement of histidine with glutamine in TRH and (2) the application of conformational constraints for putative bioactive conformation I stabilized by an intramolecular hydrogen bon...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mazurov AA,Andronati SA,Korotenko TI,Sokolenko NI,Dyadenko AI,Shapiro YE,Gorbatyuk VYa,Voronina TA

    更新日期:1997-11-01 00:00:00