Understanding the structural requirements of 4-anilidopiperidine analogues for biological activities at mu and delta opioid receptors.

Abstract:

:New 4-anilidopiperidine analogues in which the phenethyl group of fentanyl was replaced by several aromatic ring-contained amino acids (or acids) were synthesized to study the biological effect of the substituents on mu and delta opioid receptor interactions. These analogues showed broad (47 nM-76 microM) but selective (up to 17-fold) binding affinities at the mu opioid receptor over the delta opioid receptor, as predicted from the message-address concept.

journal_name

Bioorg Med Chem Lett

authors

Lee YS,Nyberg J,Moye S,Agnes RS,Davis P,Ma SW,Lai J,Porreca F,Vardanyan R,Hruby VJ

doi

10.1016/j.bmcl.2007.01.114

subject

Has Abstract

pub_date

2007-04-15 00:00:00

pages

2161-5

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(07)00172-2

journal_volume

17

pub_type

杂志文章
  • Resolution of a CPzI precursor, synthesis and biological evaluation of (+) and (-)-N-Boc-CPzI: a further validation of the relationship between chemical solvolytic stability and cytotoxicity.

    abstract::The chemical resolution, using N-tosyl-L-proline as a chiral auxiliary, of a racemate of the pyrazole analog (+/-)-N-Boc-CPzI of the left hand segment (CPI) of the antitumor agent CC-1065, and the cytotoxic evaluation of both enantiomers are described. The reported results further validate the direct relationship betw...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(99)00533-8

    authors: Baraldi PG,Cacciari B,Romagnoli R,Spalluto G,Boyce CW,Boger DL

    更新日期:1999-11-01 00:00:00

  • Eta4-pyrone iron(0)carbonyl complexes as effective CO-releasing molecules (CO-RMs).

    abstract::The CO-releasing properties of iron(0)tricarbonyl complexes bearing a 2-pyrone ligand have been evaluated. In this report, we demonstrate that the intrinsic stability of the (eta4-2-pyrone)Fe(CO)3 complex influences the extent and rate of CO release, which is affected by the presence of a halogen substituent on the 2-...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.10.085

    authors: Fairlamb IJ,Duhme-Klair AK,Lynam JM,Moulton BE,O'Brien CT,Sawle P,Hammad J,Motterlini R

    更新日期:2006-02-15 00:00:00

  • Synthesis and evaluation of alkoxy-phenylamides and alkoxy-phenylimidazoles as potent sphingosine-1-phosphate receptor subtype-1 agonists.

    abstract::In the design of potent and selective sphingosine-1-phosphate receptor agonists, we were able to identify two series of molecules based on phenylamide and phenylimidazole analogs of FTY-720. Several designed molecules in these scaffolds have demonstrated selectivity for S1P receptor subtype 1 versus 3 and excellent in...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2008.11.072

    authors: Evindar G,Bernier SG,Kavarana MJ,Doyle E,Lorusso J,Kelley MS,Halley K,Hutchings A,Wright AD,Saha AK,Hannig G,Morgan BA,Westlin WF

    更新日期:2009-01-15 00:00:00

  • Synthesis and antiplatelet effects of an isoxazole series of glycoprotein IIb/IIIa antagonists.

    abstract::Despite the excellent in vitro potency of a series of benzamide glycoprotein IIb/IIIa antagonists, which have been reported previously, poor in vivo potency in the inhibition of platelet aggregation was observed when the most potent inhibitor XU057 was dosed intravenously to dogs. In this communication, we report that...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(98)00637-4

    authors: Xue CB,Roderick J,Mousa S,Olson RE,DeGrado WF

    更新日期:1998-12-15 00:00:00

  • Ganglioside GM1 mimics: lipophilic substituents improve affinity for cholera toxin.

    abstract::Ganglioside GM1 mimics including (R)-2-hydroxy-3-cyclohexylpropionic acid or (R)-2-hydroxy-3-phenylpropionic acid as replacements for NeuAc are stronger cholera toxin binders than the parent ligand 2, which includes (R)-2-hydroxy-propionic acid. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2003.07.007

    authors: Arosio D,Baretti S,Cattaldo S,Potenza D,Bernardi A

    更新日期:2003-11-03 00:00:00

  • Topological estimation of electronic absorption bands of arene absorption spectra as a tool for modeling their toxicity and environmental pollution.

    abstract::A novel application of distance-based topological indices : Wiener (W)-, Szeged (Sz)-, Padmakar-Ivan (PI)-, and Sadhana (Sd)-indices in modeling electronic absorption bands of arene absorption spectra has been described. It is demonstrated that all these indices correlate linearly with the logarithm of beta and para e...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2004.06.094

    authors: Khadikar PV,Singh S,Jaiswal M,Mandloi D

    更新日期:2004-09-20 00:00:00

  • Learning from our mistakes: the 'unknown knowns' in fragment screening.

    abstract::In the past 15 years, fragment-based lead discovery (FBLD) has been adopted widely throughout academia and industry. The approach entails discovering very small molecular fragments and growing, merging, or linking them to produce drug leads. Because the affinities of the initial fragments are often low, detection meth...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.03.028

    authors: Davis BJ,Erlanson DA

    更新日期:2013-05-15 00:00:00

  • Discovery of new diphenyloxazole derivatives containing a pyrrolidine ring: orally active prostacyclin mimetics. Part 2.

    abstract::Synthetic and biological evaluation of novel diphenyloxazole derivatives containing a pyrrolidine ring, as a prostacyclin mimetic without the PG skeleton, are described. Asymmetric reduction of a ketone using a chiral Ru complex and reductive amination by NaBH(4) produces four isomers of the tetrahydronaphthalene ring...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.04.042

    authors: Hattori K,Okitsu O,Tabuchi S,Taniguchi K,Nishio M,Koyama S,Seki J,Sakane K

    更新日期:2005-07-01 00:00:00

  • Anthranilic sulfonamide CCK1/CCK2 dual receptor antagonists II: tuning of receptor selectivity and in vivo efficacy.

    abstract::In the previous article we demonstrated how certain CCK2R-selective anthranilic amides could be structurally modified to afford high-affinity, selective CCK1R activity. We now describe our efforts at modulating and optimizing the CCK1R and CCK2R affinities aimed at producing compounds with good pharmacokinetics proper...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.09.065

    authors: Pippel M,Boyce K,Venkatesan H,Phuong VK,Yan W,Barrett TD,Lagaud G,Li L,Morton MF,Prendergast C,Wu X,Shankley NP,Rabinowitz MH

    更新日期:2009-11-15 00:00:00

  • Identification of free fatty acid receptor 2 agonists using virtual screening.

    abstract::Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analyzed for their effectiveness in virtual screening against FFAR2. To evaluate the performance of these methods, retrospective virtual screening was performed. Statistical quality of the methods was evaluated by BED...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2020.127460

    authors: Fells JI,Ai X,Weinglass A,Feng W,Lei Y,Finley M,Hoveyda HR,Fraser GL,Machacek M

    更新日期:2020-11-01 00:00:00

  • Shikonin derivatives: synthesis and inhibition of human telomerase.

    abstract::We synthesized DL-shikonin, shikonin, alkanin, and their cyclo-derivatives and acyl-derivatives. These compounds have low cytotoxicity, as well as inhibitory activity against the telomerase enzyme, except cyclo-derivatives. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(02)00158-0

    authors: Lu Q,Liu W,Ding J,Cai J,Duan W

    更新日期:2002-05-20 00:00:00

  • Quantitating the concentration of Py-Im polyamide-fluorescein conjugates in live cells.

    abstract::Quantitative fluorescence-based methods have been developed to determine the nuclear concentration of polyamide-fluorescein conjugates in cell culture. Confocal laser scanning microscopy and flow cytometry techniques are utilized to plot calibration curves, from which the nuclear concentration can be interpolated. Upo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2008.05.063

    authors: Hsu CF,Dervan PB

    更新日期:2008-11-15 00:00:00

  • Design of selective Cathepsin inhibitors.

    abstract::A number of molecular recognition features have been exploited in structure-based design of selective Cathepsin inhibitors. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.06.090

    authors: Bethel PA,Gerhardt S,Jones EV,Kenny PW,Karoutchi GI,Morley AD,Oldham K,Rankine N,Augustin M,Krapp S,Simader H,Steinbacher S

    更新日期:2009-08-15 00:00:00

  • The bioisosteric modification of pyrazinamide derivatives led to potent antitubercular agents: Synthesis via click approach and molecular docking of pyrazine-1,2,3-triazoles.

    abstract::Tuberculosis remains as a major public health risk which causes the highest mortality rate globally and an improved regimen is required to treat the drug-resistant strains. Pyrazinamide is a first-line antitubercular drug used in combination therapy with other anti-TB drugs. Herein, we describe the modification of pyr...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2019.126846

    authors: Reddyrajula R,Dalimba U

    更新日期:2020-01-15 00:00:00

  • Chemo-enzymatic synthesis of imidazolium-tagged sialyllactosamine probes.

    abstract::Two novel α-linked sialyltrisaccharide imidazolium-type probes (ITags) based on the structures of biologically relevant 6'-sialyllactosamine and 3'-sialyllactosamine were efficiently and stereoselectively prepared using a chemo-enzymatic approach. The apparent kinetic parameters for the enzyme catalyzed transformation...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2015.07.049

    authors: Sittel I,Galan MC

    更新日期:2015-10-01 00:00:00

  • Novel BACE1 inhibitors possessing a 5-nitroisophthalic scaffold at the P2 position.

    abstract::Recently, we reported substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. These inhibitors showed potent inhibitory activities in enzymatic and cell assays. We also designed and synthesized non-peptidic and small-sized inhibitors possessing ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.05.089

    authors: Hamada Y,Nakanishi T,Suzuki K,Yamaguchi R,Hamada T,Hidaka K,Ishiura S,Kiso Y

    更新日期:2012-07-15 00:00:00

  • Novel naftopidil derivatives containing methyl phenylacetate and their blocking effects on α1D/1A-adrenoreceptor subtypes.

    abstract::α1-Adrenoceptor (α1-AR) antagonists are considered to be the most effective monotherapy agents for lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). In this study, we synthesized compounds 2-17, which are novel piperazine derivatives that contain methyl phenylacetate. We then evalua...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2018.01.068

    authors: Huang JJ,Zhang ZH,He F,Liu XW,Xu XJ,Dai LJ,Liu QM,Yuan M

    更新日期:2018-02-15 00:00:00

  • Synthesis of a novel universal opioid receptor agonist with the 1,3,5-trioxazatriquinane skeleton and its pharmacologies.

    abstract::We designed and synthesized of 1,3,5-trioxazatriquinanes with o- or p-hydroxyphenyl rings as analogs of the κ opioid receptor agonist SYK-146 with m-hydroxyphenyl groups. Although almost all tested compounds did not bind to the opioid receptors, only 17b (SYK-524) with two o-hydroxyphenyl rings showed moderate or pote...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2014.08.012

    authors: Hirayama S,Wada N,Kuroda N,Iwai T,Yamaotsu N,Hirono S,Fujii H,Nagase H

    更新日期:2014-10-15 00:00:00

  • Synthesis of new cis-fused tetrahydrochromeno[4,3-b]quinolines and their antiproliferative activity studies against MDA-MB-231 and MCF-7 breast cancer cell lines.

    abstract::New cis-fused tetrahydrochromeno[4,3-b]quinolines have been synthesized by intramolecular [4+2] imino-Diels-Alder reactions of 2-azadienes derived in situ from aromatic amines and 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones in the presence of 20mol% Yb(OTf)(3) in acetonitrile under reflux conditio...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.04.061

    authors: Nagaiah K,Venkatesham A,Srinivasa Rao R,Saddanapu V,Yadav JS,Basha SJ,Sarma AV,Sridhar B,Addlagatta A

    更新日期:2010-06-01 00:00:00

  • Detection of NAD(P)H-dependent enzyme activity by time-domain ratiometry of terbium luminescence.

    abstract::NAD(P)H-dependent oxidoreductases play important roles in biology. Recently, we reported that the luminescence lifetime of some Tb(3+) complexes is sensitive to NAD(P)H, and we used this phenomenon to detect activities of these enzymes. However, conventional time-resolved luminescence assays are susceptible to static ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2016.03.038

    authors: Terai T,Ito H,Hanaoka K,Komatsu T,Ueno T,Nagano T,Urano Y

    更新日期:2016-05-01 00:00:00

  • Impact of protein binding cavity volume (PCV) and ligand volume (LV) in rigid and flexible docking of protein-ligand complexes.

    abstract::The importance of protein binding cavity volume (PCV) and ligand volume (LV) in rigid and flexible docking has been studied in 48 protein-ligand complexes belonging to eight protein families. In continuation of our earlier study on protein flexibility in relationship to PCV and LV, this study analyzes the importance o...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.10.018

    authors: Saranya N,Jeyakanthan J,Selvaraj S

    更新日期:2012-12-15 00:00:00

  • Synthesis and biological evaluation of a series of novel pyridinecarboxamides as potential multi-receptor antipsychotic drugs.

    abstract::In previous study, a series of benzamides was identified as potent antipsychotic agents. As a continuation of the program to discover novel antipsychotics, herein we reported the evaluation of a series of pyridinecarboxamide derivatives. The most promising compound 7h not only held good activities on dopamine D2, sero...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2018.01.038

    authors: Xu M,Wang Y,Yang F,Wu C,Wang Z,Ye B,Jiang X,Zhao Q,Li J,Liu Y,Zhang J,Tian G,He Y,Shen J,Jiang H

    更新日期:2018-02-15 00:00:00

  • Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity.

    abstract::A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained w...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2017.03.051

    authors: Artyushin OI,Sharova EV,Vinogradova NM,Genkina GK,Moiseeva AA,Klemenkova ZS,Orshanskaya IR,Shtro AA,Kadyrova RA,Zarubaev VV,Yarovaya OI,Salakhutdinov NF,Brel VK

    更新日期:2017-05-15 00:00:00

  • Discovery of imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors.

    abstract::The synthesis and structure-activity relationships (SAR) of novel, potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors are described. The X-ray crystal structure of imidazo[1,2-a]pyrazine Aurora inhibitor 1j is disclosed. Compound 10i was identified as lead compound with a promising overall profile. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.07.008

    authors: Belanger DB,Curran PJ,Hruza A,Voigt J,Meng Z,Mandal AK,Siddiqui MA,Basso AD,Gray K

    更新日期:2010-09-01 00:00:00

  • Highly increased cellular accumulation of vincristine, a useful hydrophobic antitumor-drug, in multidrug-resistant solid cancer cells induced by a simply reduced taxinine.

    abstract::Regio- and/or chemo-selective reductions of taxinine (1a), a taxane diterpenoid readily obtainable from the needles of a Japanese yew (Taxus cuspidata), at the 5-O-cinnamoyl and 4-exo-methylene moieties have been accomplished by the catalytic hydrogenation over Pd/C or Rh/C to obtain 5-O-phenylpropionylated taxinine A...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(99)00620-4

    authors: Sako M,Suzuki H,Yamamoto N,Hirota K

    更新日期:1999-12-20 00:00:00

  • Design and synthesis of potent, isoxazole-containing renin inhibitors.

    abstract::The design and optimization of a novel isoxazole S(1) linker for renin inhibitor is described herein. This effort culminated in the identification of compound 18, an orally bioavailable, sub-nanomolar renin inhibitor even in the presence of human plasma. When compound 18 was found to inhibit CYP3A4 in a time dependent...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2012.03.014

    authors: Fournier PA,Arbour M,Cauchon E,Chen A,Chefson A,Ducharme Y,Falgueyret JP,Gagné S,Grimm E,Han Y,Houle R,Lacombe P,Lévesque JF,MacDonald D,Mackay B,McKay D,Percival MD,Ramtohul Y,St-Jacques R,Toulmond S

    更新日期:2012-04-15 00:00:00

  • New strigolactone mimics: structure-activity relationship and mode of action as germinating stimulants for parasitic weeds.

    abstract::Strigolactones (SLs) are new plant hormones with varies important bio-functions. This Letter deals with germination of seeds of parasitic weeds. Natural SLs have a too complex structure for synthesis. Therefore, there is an active search for SL analogues and mimics with a simpler structure with retention of activity. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.07.004

    authors: Zwanenburg B,Nayak SK,Charnikhova TV,Bouwmeester HJ

    更新日期:2013-09-15 00:00:00

  • Design and synthesis of a hybrid potentiator-corrector agonist of the cystic fibrosis mutant protein DeltaF508-CFTR.

    abstract::A developing therapy of cystic fibrosis caused by the DeltaF508 mutation in CFTR employs correction of defective CFTR chloride channel gating by a 'potentiator' and of defective CFTR protein folding by a 'corrector'. Based on SAR data for phenylglycine-type potentiators and bithiazole correctors, we designed a hybrid ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.11.020

    authors: Mills AD,Yoo C,Butler JD,Yang B,Verkman AS,Kurth MJ

    更新日期:2010-01-01 00:00:00

  • Synthesis of miltirone analogues as inhibitors of Cdc25 phosphatases.

    abstract::Miltirone analogues were synthesized and evaluated for inhibitory activity against Cdc25 and PTP1B. Most of the compounds demonstrated potent Cdc25 inhibitory activity, and several exhibited higher selectivity for Cdc25 than for PTP1B. In a cytotoxic assay, most of the compounds displayed cytotoxicity against the tumo...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.12.080

    authors: Huang W,Li J,Zhang W,Zhou Y,Xie C,Luo Y,Li Y,Wang J,Li J,Lu W

    更新日期:2006-04-01 00:00:00

  • Synthesis of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine as potential prodrug of L-dopa.

    abstract::The synthesis and in vitro chemical and enzymatic stability of L-(+)-3-(3-hydroxy-4-pivaloyloxybenzyl)-2,5-diketomorpholine (9) as L-Dopa prodrug are described. Prodrug 9 possesses a good lipophilicity (log P = 2.153 +/- 0.017), is stable in aqueous buffer solutions (pH 1.3 and 7.4), and in 80% rat and human plasma it...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00249-3

    authors: Cingolani GM,Di Stefano A,Mosciatti B,Napolitani F,Giorgioni G,Ricciutelli M,Claudi F

    更新日期:2000-06-19 00:00:00