'Carba'-carfentanil (trans isomer): a μ opioid receptor (MOR) partial agonist with a distinct binding mode.


:There is strong evidence to indicate that a positively charged nitrogen of endogenous and exogenous opioid ligands forms a salt bridge with the Asp residue in the third transmembrane helix of opioid receptors. To further examine the role of this electrostatic interaction in opioid receptor binding and activation, we synthesized 'carba'-analogues of the highly potent μ opioid analgesic carfentanil (3), in which the piperidine nitrogen was replaced with a carbon. The resulting trans isomer (8b) showed reduced, but still significant MOR binding affinity (Ki(μ)=95.2nM) with no MOR versus DOR binding selectivity and was a MOR partial agonist. The cis isomer (8a) was essentially inactive. A MOR docking study indicated that 8b bound to the same binding pocket as parent 3, but its binding mode was somewhat different. A re-evaluation of the uncharged morphine derivative N-formylnormorphine (9) indicated that it was a weak MOR antagonist showing no preference for MOR over KOR. Taken together, the results indicate that deletion of the positively charged nitrogen in μ opioid analgesics reduces MOR binding affinity by 2-3 orders of magnitude and may have pronounced effects on the intrinsic efficacy and on the opioid receptor selectivity profile.


Bioorg Med Chem


Weltrowska G,Lemieux C,Chung NN,Guo JJ,Wilkes BC,Schiller PW




Has Abstract


2014-09-01 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

  • Synthesis and bioactive evaluation of novel hybrids of metronidazole and berberine as new type of antimicrobial agents and their transportation behavior by human serum albumin.

    abstract::A series of novel hybrids of metronidazole and berberine as new type of antimicrobial agents were synthesized and characterized by (1)H NMR, (13)C NMR, IR, MS and HRMS spectra. Bioactive assay manifested that most of the prepared compounds exhibited effective antibacterial and antifungal activities and some showed com...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zhang L,Chang JJ,Zhang SL,Damu GL,Geng RX,Zhou CH

    更新日期:2013-07-15 00:00:00

  • The design and synthesis of substituted biphenyl libraries.

    abstract::A novel scaffold system for the generation of diversity libraries has been designed which allows for rapid modification not only of functional groups, but their spatial arrangements as well. The biphenyl scaffold allows for display of three or four diverse functional groups in a wide variety of spatial arrangements de...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Pavia MR,Cohen MP,Dilley GJ,Dubuc GR,Durgin TL,Forman FW,Hediger ME,Milot G,Powers TS,Sucholeiki I,Zhou S,Hangauer DG

    更新日期:1996-05-01 00:00:00

  • PET-compatible endothelin receptor radioligands: synthesis and first in vitro and in vivo studies.

    abstract::The expression and function of endothelin (ET) receptors is abnormal in cardiovascular diseases, tumor progression, and tumor metastasis. In this study, we prepared two [(18)F]-fluorinated derivatives of the non-peptide ET(A) receptor antagonist PD 156707 and evaluated their ET receptor binding potencies. Ex vivo as w...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Höltke C,Law MP,Wagner S,Kopka K,Faust A,Breyholz HJ,Schober O,Bremer C,Riemann B,Schäfers M

    更新日期:2009-10-15 00:00:00

  • Synthesis and evaluation of novel modified γ-lactam prostanoids as EP4 subtype-selective agonists.

    abstract::To identify chemically and metabolically stable subtype-selective EP4 agonists, design and synthesis of a series of modified γ-lactam prostanoids has been continued. Prostanoids bearing 2-oxo-1,3-oxazolidine, 2-oxo-1,3-thiazolidine and 5-thioxopyrrolidine as a surrogate for the γ-hydroxycyclopentanone without a troubl...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kambe T,Maruyama T,Nagase T,Ogawa S,Minamoto C,Sakata K,Maruyama T,Nakai H,Toda M

    更新日期:2012-01-15 00:00:00

  • Tannic acid inhibited norovirus binding to HBGA receptors, a study of 50 Chinese medicinal herbs.

    abstract::Noroviruses (NoVs) are the leading cause of viral acute gastroenteritis affecting people of all ages worldwide. The disease is difficult to control due to its widespread nature and lack of an antiviral or vaccine. NoV infection relies on the interaction of the viruses with histo-blood group antigens (HBGAs) as host re...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zhang XF,Dai YC,Zhong W,Tan M,Lv ZP,Zhou YC,Jiang X

    更新日期:2012-02-15 00:00:00

  • Synthesis of plaunotol derivatives and their antibacterial activities against Helicobacter pylori.

    abstract::Plaunotol, a known antiulcer drug, has antibacterial activities against Helicobacter pylori. Plaunotol thiourea derivatives 2--4 and diol derivatives 6--10 were designed in search for a compound with high antibacterial activities. Thiourea derivatives 2--4 were synthesized regioselectively using our effective syntheti...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tago K,Minami E,Masuda K,Akiyama T,Kogen H

    更新日期:2001-07-01 00:00:00

  • Structure-based design of parasitic protease inhibitors.

    abstract::To streamline the preclinical phase of pharmaceutical development, we have explored the utility of structural data on the molecular target and synergy between computational and medicinal chemistry. We have concentrated on parasitic infectious diseases with a particular emphasis on the development of specific noncovale...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li R,Chen X,Gong B,Selzer PM,Li Z,Davidson E,Kurzban G,Miller RE,Nuzum EO,McKerrow JH,Fletterick RJ,Gillmor SA,Craik CS,Kuntz ID,Cohen FE,Kenyon GL

    更新日期:1996-09-01 00:00:00

  • Synthesis and biological evaluation of 1,4-dihydropyridine calcium channel modulators having a diazen-1-ium-1,2-diolate nitric oxide donor moiety for the potential treatment of congestive heart failure.

    abstract::A group of racemic 4-aryl(heteroaryl)-1,4-dihydro-2,6-dimethyl-3-nitropyridines possessing nitric oxide donor O(2)-acetoxymethyl-1-(N-ethyl-N-methylamino, or 4-ethylpiperazin-1-yl)diazen-1-ium-1,2-diolate, C-5 ester substituents were synthesized by coupling the respective 4-aryl(heteroaryl)-1,4-dihydro-2,6-dimethyl-3-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Velázquez C,Knaus EE

    更新日期:2004-07-15 00:00:00

  • Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosphonate linkages.

    abstract::Bacterial DNA and synthetic oligodeoxynucleotides containing unmethylated CpG-motifs in a particular sequence context activate vertebrate immune cells. We examined the significance of negatively charged internucleoside linkages in the flanking sequences 5' and 3' to the CpG-motif on immunostimulatory activity. Cell pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yu D,Kandimalla ER,Zhao Q,Cong Y,Agrawal S

    更新日期:2001-11-01 00:00:00

  • An evaluation of central penetration from a peripherally administered oxytocin receptor selective antagonist in nonhuman primates.

    abstract::The physiology of the oxytocin receptor has increasingly become a focus of scientific investigation due to its connection with social behavior and psychiatric disorders with impairments in social funciton. Experimental utilization of small molecule and peptide antagonists for the oxytocin receptor has played a role in...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Smith AL,Walum H,Connor-Stroud F,Freeman SM,Inoue K,Parr LA,Goodman MM,Young LJ

    更新日期:2017-01-01 00:00:00

  • The evaluation of quinonoid compounds against Trypanosoma cruzi: synthesis of imidazolic anthraquinones, nor-beta-lapachone derivatives and beta-lapachone-based 1,2,3-triazoles.

    abstract::In continuing our screening program of naphthoquinone activity against Trypanosoma cruzi, the aetiological agent of Chagas' disease, new beta-lapachone-based 1,2,3-triazoles, 3-arylamino-nor-beta-lapachones, 3-alkoxy-nor-beta-lapachones and imidazole anthraquinones were synthesised and evaluated against bloodstream tr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: da Silva EN Jr,Guimarães TT,Menna-Barreto RF,Pinto Mdo C,de Simone CA,Pessoa C,Cavalcanti BC,Sabino JR,Andrade CK,Goulart MO,de Castro SL,Pinto AV

    更新日期:2010-05-01 00:00:00

  • Structure-based virtual screening of Src kinase inhibitors.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lee K,Kim J,Jeong KW,Lee KW,Lee Y,Song JY,Kim MS,Lee GS,Kim Y

    更新日期:2009-04-15 00:00:00

  • 1,2,4-Thiadiazole acyclic nucleoside phosphonates as inhibitors of cysteine dependent enzymes cathepsin K and GSK-3β.

    abstract::In analogy to antiviral acyclic nucleoside phosphonates, a series of 5-amino-3-oxo-1,2,4-thiadiazol-3(2H)-ones bearing a 2-phosphonomethoxyethyl (PME) or 3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) group at the position 2 of the heterocyclic moiety has been synthesized. Diisopropyl esters of PME- and HPMP-amines have ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Pomeislová A,Otmar M,Rubešová P,Benýšek J,Matoušová M,Mertlíková-Kaiserová H,Pohl R,Poštová Slavětínská L,Pomeisl K,Krečmerová M

    更新日期:2021-01-06 00:00:00

  • A new dihydroxanthenone from a plant-associated strain of the fungus Chaetomium globosum demonstrates anticancer activity.

    abstract::Bioassay-guided fractionation of a cytotoxic EtOAc extract of the fungal strain, Chaetomium globosum, inhabiting the rhizosphere of the Christmas cactus, Opuntia leptocaulis, of the Sonoran desert afforded a new dihydroxanthenone, globosuxanthone A (1), a new tetrahydroxanthenone, globosuxanthone B (2), two new xantho...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wijeratne EM,Turbyville TJ,Fritz A,Whitesell L,Gunatilaka AA

    更新日期:2006-12-01 00:00:00

  • Neurotrophic and antileukemic daphnane diterpenoids from Synaptolepis kirkii.

    abstract::Biological assay guided fractionation of a dichloromethane extract of Synaptolepis kirkii led to the isolation of four new and five known daphnane-type diterpene orthoesters, whose structure was established by spectroscopic data. Full spectroscopic data of the new and known natural products are reported here for the f...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: He W,Cik M,Van Puyvelde L,Van Dun J,Appendino G,Lesage A,Van der Lindin I,Leysen JE,Wouters W,Mathenge SG,Mudida FP,De Kimpe N

    更新日期:2002-10-01 00:00:00

  • Synthesis and biological evaluation of scopoletin derivatives.

    abstract::A series of new scopoletin derivatives were designed and synthesized. Their anti-proliferative effect was initially evaluated against various human cancer cell lines. Among the tested compounds, A1, A2, and D6 showed significant anti-proliferative activities. Angiogenesis was detected by endothelial cell migration ass...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Cai X,Yang J,Zhou J,Lu W,Hu C,Gu Z,Huo J,Wang X,Cao P

    更新日期:2013-01-01 00:00:00

  • Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin-4-ones.

    abstract::A series of 2-sec-amino-3H-quinazolin-4-ones (4a-p) and 4-sec-amino-2-chloroquinazolines (5a-b) have been synthesized by nucleophilic substitution reaction of 2-chloro-4(3H)-quinazolones (3) and 2,4-dichloroquinazolines (2) with amines, respectively. Most of the synthesized compounds were evaluated for antihyperglycem...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ram VJ,Farhanullah,Tripathi BK,Srivastava AK

    更新日期:2003-05-29 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

  • Synthesis and biological evaluation of 1,8-naphthyridin-4(1H)-on-3-carboxamide derivatives as new ligands of cannabinoid receptors.

    abstract::Cannabinoid receptors have been studied extensively in view of their potential functional role in several physiological and pathological processes. For this reason, the search for new potent, selective ligands for subtype CB receptors, CB(1) and CB(2), is still of great importance, in order to investigate their role i...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ferrarini PL,Calderone V,Cavallini T,Manera C,Saccomanni G,Pani L,Ruiu S,Gessa GL

    更新日期:2004-04-15 00:00:00

  • Synthesis, insecticidal activities and SAR of novel phthalamides targeting calcium channel.

    abstract::In order to find novel and environmental friendly insecticides targeting the ryanodine receptor, three series of novel phthalamides containing heptafluoroisopropyl group, low fluorine atoms group and non-fluorine group were designed and synthesized. 35 novel structures of three series were obtained. Insecticidal activ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Chen Y,Li Y,Pan L,Liu J,Wan Y,Chen W,Xiong L,Yang N,Song H,Li Z

    更新日期:2014-11-15 00:00:00

  • Small-molecules that bind to the ubiquitin-binding motif of REV1 inhibit REV1 interaction with K164-monoubiquitinated PCNA and suppress DNA damage tolerance.

    abstract::REV1 protein is a mutagenic DNA damage tolerance (DDT) mediator and encodes two ubiquitin-binding motifs (i.e., UBM1 and UBM2) that are essential for the DDT function. REV1 interacts with K164-monoubiquitinated PCNA (UbPCNA) in cells upon DNA-damaging stress. By using AlphaScreen assays to detect inhibition of REV1 an...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Vanarotti M,Evison BJ,Actis ML,Inoue A,McDonald ET,Shao Y,Heath RJ,Fujii N

    更新日期:2018-05-15 00:00:00

  • Synthesis and biological activity of (24E)- and (24Z)-26-hydroxydesmosterol.

    abstract::Using 3β-hydroxychol-5-en-24-oic acid (4) as starting material, the diastereoisomeric allylic alcohols (24E)-26-hydroxydesmosterol (2) and (24Z)-26-hydroxydesmosterol (3) have been synthesised in six steps with 67% and 12% overall yield, respectively. Both of these isomers are found in newborn mouse brain where sterol...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Saini R,Kataeva O,Schmidt AW,Wang Y,Meljon A,Griffiths WJ,Knölker HJ

    更新日期:2013-09-15 00:00:00

  • Photo-control of nitric oxide synthase activity using a caged isoform specific inhibitor.

    abstract::Nitric oxide (NO) plays a critical role in a number of physiological processes and is produced in mammalian cells by nitric oxide synthase (NOS) isozymes. Because of the diverse functions of NO, pharmaceutical interventions which seek to abrogate adverse effects of excess NOS activity must not interfere with the norma...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Montgomery HJ,Perdicakis B,Fishlock D,Lajoie GA,Jervis E,Guy Guillemette J

    更新日期:2002-06-01 00:00:00

  • 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives as a new class of potent inhibitors of Interleukin-8-induced neutrophil chemotaxis.

    abstract::A series of 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives was synthesized. The compounds demonstrated to be novel, potent and selective inhibitors of Interleukin-8-induced human neutrophil chemotaxis. A SAR study was performed by varying the carbonyl function at position 5 and...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Cesarini S,Spallarossa A,Ranise A,Bruno O,Arduino N,Bertolotto M,Dallegri F,Tognolini M,Gobbetti T,Barocelli E

    更新日期:2009-05-15 00:00:00

  • Synthesis, in vitro antibacterial and carbonic anhydrase II inhibitory activities of N-acylsulfonamides using silica sulfuric acid as an efficient catalyst under both solvent-free and heterogeneous conditions.

    abstract::Silica sulfuric acid catalyzes efficiently the reaction of sulfonamides with both carboxylic acid anhydrides and chlorides under solvent-free and heterogeneous conditions. All the reactions were done at room temperature and the N-acylsulfonamides were obtained with high yields and purity via an easy work-up procedure....

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Massah AR,Adibi H,Khodarahmi R,Abiri R,Majnooni MB,Shahidi S,Asadi B,Mehrabi M,Zolfigol MA

    更新日期:2008-05-15 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.

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    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

  • Design and synthesis of 8-hydroxyquinoline-based radioprotective agents.

    abstract::In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ariyasu S,Sawa A,Morita A,Hanaya K,Hoshi M,Takahashi I,Wang B,Aoki S

    更新日期:2014-08-01 00:00:00

  • Synthesis and evaluation of a radioiodinated bladder cancer specific peptide.

    abstract::Bladder cancer is the second most common cancer of the urinary tract, however the invasive cystoscopy is still the standard technique for diagnosis and surveillance of bladder cancer. Herein, we radiolabel bladder cancer specific peptide with radioactive iodine ((131/124)I) and evaluate its potential as a new radiopha...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ha YS,Lee HY,An GI,Kim J,Kwak W,Lee EJ,Lee SM,Lee BH,Kim IS,Belay T,Lee W,Ahn BC,Lee J,Yoo J

    更新日期:2012-07-15 00:00:00

  • The role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D.

    abstract::Extensive molecular modeling based on crystallographic data was used to aid the design of synthetic analogues of the fungicidal naturally occurring respiration inhibitors crocacins A and D, and an inhibitor binding model to the mammalian cytochrome bc(1) complex was constructed. Simplified analogues were made which sh...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Crowley PJ,Berry EA,Cromartie T,Daldal F,Godfrey CR,Lee DW,Phillips JE,Taylor A,Viner R

    更新日期:2008-12-15 00:00:00