当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and biological evaluation of 14-alkoxymorphinans. 20. 14-phenylpropoxymetopon: an extremely powerful analgesic.

Synthesis and biological evaluation of 14-alkoxymorphinans. 20. 14-phenylpropoxymetopon: an extremely powerful analgesic.

Abstract：

:The synthesis and the biological and pharmacological evaluation of several 14-phenylpropoxy analogues of 14-methoxymetopon are described. Most of the new compounds were nonselective and exhibited binding affinities in the subnanomolar or low nanomolar range at opioid receptors mu, kappa, delta), with 14-phenylpropoxymetopon (PPOM; 7) displaying the highest affinity for all three opioid receptor types. The most striking finding of this study is that the derivatives from the novel series of N-methyl-14-phenylpropoxymorphinans acted as extremely powerful antinociceptives with potencies higher than that of 14-methoxymetopon (1) and even etorphine. 14-Phenylpropoxymetopon (PPOM; 7) showed considerably increased potency in the in vivo assays in mice (25-fold in the tail-flick assay, 10-fold in the hot-plate assay, and 2.5-fold in the paraphenylquinone writhing test) when compared to etorphine, while it was equipotent to dihydroetorphine in the hot-plate assay and the paraphenylquinone writhing test and ca. twice as potent in the tail-flick assay than this reference compound. The 3-O-alkyl ethers of PPOM, compounds 6 and 8, showed less potency in in vivo assays, but partly surpassed the potency of the 3-OH analogue 14-methoxymetopon (1).

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Schütz J,Spetea M,Koch M,Aceto MD,Harris LS,Coop A,Schmidhammer H

doi

10.1021/jm030878b

keywords:

subject

Has Abstract

pub_date

2003-09-11 00:00:00

pages

4182-7

issue

19

eissn

0022-2623

issn

1520-4804

journal_volume

46

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • SH2-directed ligands of the Lck tyrosine kinase.

    abstract：:Two separate libraries, prepared via parallel synthesis, were employed to identify low-molecular-weight SH2-targeted ligands for the Lck tyrosine protein kinase. These libraries were constructed to furnish non-amino acid analogues of the (1) Glu-Glu and (2) Ile residues of the Lck SH2 domain peptide ligand Ac-pTyr-Glu...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm990462r

    authors： Lee TR,Lawrence DS

    更新日期：2000-03-23 00:00:00

  • New dimeric analogues of ethidium; synthesis, interaction with DNA, and antitumor activity.

    abstract：:Three new dimeric analogues of ethidium cation in which the monomeric moieties are linked at the 3' positions by alpha,omega-diethers of varying length and composition have been synthesized. The circular dichroism spectra of all three compounds indicate that they double intercalate, and their effects on the thermal he...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00143a014

    authors： Kuhlmann KF,Mosher CW

    更新日期：1981-11-01 00:00:00

  • Structure-activity relationship studies for the peptide portion of the bladder epithelial cell antiproliferative factor from interstitial cystitis patients.

    abstract：:We performed comprehensive structure-activity relationship (SAR) studies on the peptide portion of antiproliferative factor (APF), a sialylated frizzled-8 related glycopeptide that inhibits normal bladder epithelial and urothelial carcinoma cell proliferation. Glycopeptide derivatives were synthesized by solid-phase m...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm8002763

    authors： Kaczmarek P,Keay SK,Tocci GM,Koch KR,Zhang CO,Barchi JJ Jr,Grkovic D,Guo L,Michejda CJ

    更新日期：2008-10-09 00:00:00

  • Discovery of 8-Methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one Derivatives as Highly Potent and Selective Bromodomain and Extra-Terminal (BET) Bromodomain Inhibitors.

    abstract：:The bromodomain and extra-terminal (BET) family proteins have recently emerged as promising drug targets for cancer therapy. In this study, identification of an 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one fragment (47) as a new binder to the BET bromodomains and the subsequent incorporation of fragment 47 to the scaffold...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01784

    authors： Li Z,Xiao S,Yang Y,Chen C,Lu T,Chen Z,Jiang H,Chen S,Luo C,Zhou B

    更新日期：2020-04-23 00:00:00

  • Potent and selective fluoroketone inhibitors of group VIA calcium-independent phospholipase A2.

    abstract：:Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA(2) inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(na...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm901872v

    authors： Kokotos G,Hsu YH,Burke JE,Baskakis C,Kokotos CG,Magrioti V,Dennis EA

    更新日期：2010-05-13 00:00:00

  • Rational design of triazololipopeptides analogs of kisspeptin inducing a long-lasting increase of gonadotropins.

    abstract：:New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-r...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm5019675

    authors： Beltramo M,Robert V,Galibert M,Madinier JB,Marceau P,Dardente H,Decourt C,De Roux N,Lomet D,Delmas AF,Caraty A,Aucagne V

    更新日期：2015-04-23 00:00:00

  • Discovery of potent, highly selective, and orally bioavailable pyridine carboxamide c-Jun NH2-terminal kinase inhibitors.

    abstract：:C-Jun NH2 terminal kinases (JNKs) are important cell signaling enzymes. JNK1 plays a central role in linking obesity and insulin resistance. JNK2 and JNK3 may be involved in inflammatory and neurological disorders, respectively. Small-molecule JNK inhibitors could be valuable tools to study the therapeutic benefits of...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060465l

    authors： Zhao H,Serby MD,Xin Z,Szczepankiewicz BG,Liu M,Kosogof C,Liu B,Nelson LT,Johnson EF,Wang S,Pederson T,Gum RJ,Clampit JE,Haasch DL,Abad-Zapatero C,Fry EH,Rondinone C,Trevillyan JM,Sham HL,Liu G

    更新日期：2006-07-27 00:00:00

  • Specific inhibition of benzodiazepine receptor binding by some N-(indol-3-ylglyoxylyl)amino acid derivatives: stereoselective interactions.

    abstract：:Several optically active N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for [3H]flunitrazepam displacing activity in bovine brain membranes. IC50 values were measured and revealed that the D form of the amino acid moiety of the compounds was more potent than both the L form and racemic form,...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00132a004

    authors： Primofiore G,Marini AM,Da Settimo F,Martini C,Bardellini A,Giannaccini G,Lucacchini A

    更新日期：1989-12-01 00:00:00

  • Quantum chemical studies of meperidine and prodine.

    abstract：:Extensive quantum chemical calculations have been made of the electronic distribution and conformational behavior of meperidine and desmethyl-, (+)-alpha, and (+)-beta-prodine using PCILO, a semiempirical molecular orbital method. For this series of opiates, a phenyl equatorial conformation was preferred over a phenyl...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00245a001

    authors： Loew GH,Jester JR

    更新日期：1975-11-01 00:00:00

  • Systematic synthesis and biological evaluation of alpha- and beta-D-lyxofuranosyl nucleosides of the five naturally occurring nucleic acid bases.

    abstract：:The alpha- and beta-D-lyxofuranosyl analogues of the naturally occurring nucleosides have been synthesized and their antiviral properties examined. The alpha anomers were prepared by glycosylation of purine and pyrimidine aglycons with tetra-O-acetyl-alpha-D-lyxofuranose, followed by removal of the blocking groups. Th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00389a005

    authors： Gosselin G,Bergogne MC,De Rudder J,De Clercq E,Imbach JL

    更新日期：1987-06-01 00:00:00

  • Total synthesis and pharmacological characterization of solomonsterol A, a potent marine pregnane-X-receptor agonist endowed with anti-inflammatory activity.

    abstract：:Recently, we reported the identification of a novel class of pregnane-X-receptor (PXR) agonists, solomonsterols A and B, isolated from the marine sponge Theonella swinhoei. Preliminary pharmacological studies demonstrated that these natural compounds are potential leads for the treatment of human disorders characteriz...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200241s

    authors： Sepe V,Ummarino R,D'Auria MV,Mencarelli A,D'Amore C,Renga B,Zampella A,Fiorucci S

    更新日期：2011-07-14 00:00:00

  • Antagonists of slow reacting substance of anaphylaxis. Synthesis of a series of chromone-2-carboxylic acids.

    abstract：:A series of substituted chromone-2-carboxylic acids was synthesized and tested as antagonists of SRS-A induced contractions of isolated guinea pig ileum. This work led to the discovery of sodium 7-[3-(4-acetyl-3hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate (FPL 55712) which is...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00213a012

    authors： Appleton RA,Bantick JR,Chamberlain TR,Hardern DN,Lee TB,Pratt AD

    更新日期：1977-03-01 00:00:00

  • New non-peptide endothelin-A receptor antagonists: synthesis, biological properties, and structure-activity relationships of 5-(dimethylamino)-N-pyridyl-,-N-pyrimidinyl-,-N-pyridazinyl-, and -N-pyrazinyl-1-naphthalenesulfonamides.

    abstract：:Use of automated synthesis led to the discovery of several 6-membered nitrogen heterocycles as replacements for the N-isoxazolyl substituent present in the 1-naphthalenesulfonamides endothelin-A (ETA) antagonist 5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesu lfo namides (BMS 182874). In each of these ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9604585

    authors： Bradbury RH,Bath C,Butlin RJ,Dennis M,Heys C,Hunt SJ,James R,Mortlock AA,Sumner NF,Tang EK,Telford B,Whiting E,Wilson C

    更新日期：1997-03-14 00:00:00

  • 5,6-Cis-penems: broad-spectrum anti-methicillin-resistant Staphylococcus aureus beta-lactam antibiotics.

    abstract：:5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-bind...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9703348

    authors： Ishiguro M,Tanaka R,Namikawa K,Nasu T,Inoue H,Nakatsuka T,Oyama Y,Imajo S

    更新日期：1997-07-04 00:00:00

  • Structural investigation of cycloheptathiophene-3-carboxamide derivatives targeting influenza virus polymerase assembly.

    abstract：:The limited number of drug classes licensed for treatment of influenza virus (Flu), together with the continuous emergence of viral variants and drug resistant mutants, highlights the urgent need to find antivirals with novel mechanisms of action. In this context, the viral RNA-dependent RNA polymerase (RdRP) subunits...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm401560v

    authors： Massari S,Nannetti G,Goracci L,Sancineto L,Muratore G,Sabatini S,Manfroni G,Mercorelli B,Cecchetti V,Facchini M,Palù G,Cruciani G,Loregian A,Tabarrini O

    更新日期：2013-12-27 00:00:00

  • Gliotoxin analogues as inhibitors of reverse transcriptase. 2. Resolution and X-ray crystal structure determination.

    abstract：:A novel, simple, and efficient method for the chemical resolution of epidithiodioxopiperazines is reported, which is based upon covalent formation of diastereomers. This method might be a general one for the resolution of chiral cyclic disulfides. Dithiol 5, prepared from 2 by reduction with NaBH4, was allowed to reac...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00206a016

    authors： Ottenheijm HC,Herscheid JD,Tijhuis MW,Nivard RJ,De Clercq E,Prick PA

    更新日期：1978-08-01 00:00:00

  • Discovery of Benzocycloalkane Derivatives Efficiently Blocking Bacterial Virulence for the Treatment of Methicillin-Resistant S. aureus (MRSA) Infections by Targeting Diapophytoene Desaturase (CrtN).

    abstract：:Antivirulence strategies are now attracting interest for the inherent mechanism of action advantages. In our previous work, diapophytoene desaturase (CrtN) was identified to be an attractive and drugable target for fighting pigmented S. aureus infections. In this research, we developed a series of effective benzocyclo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00122

    authors： Wang Y,Di H,Chen F,Xu Y,Xiao Q,Wang X,Wei H,Lu Y,Zhang L,Zhu J,Lan L,Li J

    更新日期：2016-05-26 00:00:00

  • Structure-activity analysis of a class of orally active hydroxamic acid inhibitors of leukotriene biosynthesis.

    abstract：:The nature of the carbonyl and nitrogen substituents of hydroxamic acids has a major influence on the biological profile of these compounds. Hydroxamates with small groups such as methyl appended to the carbonyl and relatively large nitrogen substituents generally have longer duration in vivo, produce greater plasma c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00118a016

    authors： Summers JB,Gunn BP,Martin JG,Martin MB,Mazdiyasni H,Stewart AO,Young PR,Bouska JB,Goetze AM,Dyer RD

    更新日期：1988-10-01 00:00:00

  • Design, synthesis, and biological activity of isophthalic acid derivatives targeted to the C1 domain of protein kinase C.

    abstract：:Protein kinase C (PKC) is a widely studied molecular target for the treatment of cancer and other diseases. We have approached the issue of modifying PKC function by targeting the C1 domain in the regulatory region of the enzyme. Using the X-ray crystal structure of the PKC delta C1b domain, we have discovered conveni...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900229p

    authors： Boije af Gennäs G,Talman V,Aitio O,Ekokoski E,Finel M,Tuominen RK,Yli-Kauhaluoma J

    更新日期：2009-07-09 00:00:00

  • Voltage-Gated Sodium Channels: Structure, Function, Pharmacology, and Clinical Indications.

    abstract：:The tremendous therapeutic potential of voltage-gated sodium channels (Na(v)s) has been the subject of many studies in the past and is of intense interest today. Na(v)1.7 channels in particular have received much attention recently because of strong genetic validation of their involvement in nociception. Here we summa...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/jm501981g

    authors： de Lera Ruiz M,Kraus RL

    更新日期：2015-09-24 00:00:00

  • Identification of Inhibitors for the DEDDh Family of Exonucleases and a Unique Inhibition Mechanism by Crystal Structure Analysis of CRN-4 Bound with 2-Morpholin-4-ylethanesulfonate (MES).

    abstract：:The DEDDh family of exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human DEDDh exonucleases can serve as antiviral drug targets due to their critical roles in virus replication. Here using RNase T and CRN-4 as the model systems, we identify potential inhibitors ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00794

    authors： Huang KW,Hsu KC,Chu LY,Yang JM,Yuan HS,Hsiao YY

    更新日期：2016-09-08 00:00:00

  • Synthetic HIV V3 Glycopeptide Immunogen Carrying a N334 N-Glycan Induces Glycan-Dependent Antibodies with Promiscuous Site Recognition.

    abstract：:The N332 high-mannose glycan on the HIV-1 gp120 V3-loop is the target of many bNAbs. About 17% HIV isolates carry the N332 to N334 mutation, but the antibody recognition of the N334 N-glycan and its immunogenicity are not well characterized. Here we report the chemoenzymatic synthesis, antigenicity, and immunogenicity...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b01290

    authors： Cai H,Zhang RS,Orwenyo J,Giddens J,Yang Q,LaBranche CC,Montefiori DC,Wang LX

    更新日期：2018-11-21 00:00:00

  • Structure-activity relationships of 1,4-dihydro-(1H,4H)-quinoxaline-2,3-diones as N-methyl-D-aspartate (glycine site) receptor antagonists. 1. Heterocyclic substituted 5-alkyl derivatives.

    abstract：:A series of 6,7-dichloro-1,4-dihydro-(1H, 4H)-quinoxaline-2,3-diones (1-17) were prepared in which the 5-position substituent was a heterocyclylmethyl or 1-(heterocyclyl)-1-propyl group. Structure-activity relationships were evaluated where binding affinity for the glycine site of the N-methyl-D-aspartate (NMDA) recep...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm001124p

    authors： Fray MJ,Bull DJ,Carr CL,Gautier EC,Mowbray CE,Stobie A

    更新日期：2001-06-07 00:00:00

  • Disulfiram facilitates intracellular Cu uptake and induces apoptosis in human melanoma cells.

    abstract：:The alcohol-abuse deterrent disulfiram (DSF) is shown to have a highly selective toxicity against melanoma in culture, inducing a largely apoptotic response, with much lower toxicity against several other cell lines. Melanoma cell lines derived from different stages (radial, vertical, and metastatic phase) were all se...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049568z

    authors： Cen D,Brayton D,Shahandeh B,Meyskens FL Jr,Farmer PJ

    更新日期：2004-12-30 00:00:00

  • Prolyl oligopeptidase inhibition by N-acyl-pro-pyrrolidine-type molecules.

    abstract：:Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm800944x

    authors： Kánai K,Arányi P,Böcskei Z,Ferenczy G,Harmat V,Simon K,Bátori S,Náray-Szabo G,Hermecz I

    更新日期：2008-12-11 00:00:00

  • Design, Synthesis, and Biological Evaluation of Quinazolin-4-one-Based Hydroxamic Acids as Dual PI3K/HDAC Inhibitors.

    abstract：:A series of quinazolin-4-one based hydroxamic acids was rationally designed and synthesized as novel dual PI3K/HDAC inhibitors by incorporating an HDAC pharmacophore into a PI3K inhibitor (Idelalisib) via an optimized linker. Several of these dual inhibitors were highly potent (IC50 < 10 nM) and selective against PI3K...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c00193

    authors： Thakur A,Tawa GJ,Henderson MJ,Danchik C,Liu S,Shah P,Wang AQ,Dunn G,Kabir M,Padilha EC,Xu X,Simeonov A,Kharbanda S,Stone R,Grewal G

    更新日期：2020-04-23 00:00:00

  • Investigation of a novel series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones as human immunodeficiency virus type 1 integrase inhibitors.

    abstract：:We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs). Substitution of the N-hydroxyimide two-metal binding pharmacophore at position 4 by carboxamido side chains was previously shown by us to be fruitful for this scaffold, since strong ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500109z

    authors： Suchaud V,Bailly F,Lion C,Calmels C,Andréola ML,Christ F,Debyser Z,Cotelle P

    更新日期：2014-06-12 00:00:00

  • Carbocyclic prostaglandin analogs. 1. Steroid carboxylic acids.

    abstract：:Certain structural similarities between prostaglandins with close-packed side chains and the perhydrocyclopentanophenanthrene nucleus of steroids prompted the synthesis and biological evaluation of 6beta, 17 beta-dihydroxy-5alpha-androstane-2alpha-carboxylic acid (30), its 6-deoxy derivative 28, and the corresponding ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00235a002

    authors： Venton DL,Counsell RE,Sanner JH,Sierra K

    更新日期：1975-01-01 00:00:00

  • Intensely potent doxorubicin analogues: structure-activity relationship.

    abstract：:N-(5,5-Diacetoxypent-1-yl)doxorubicin (1b) is an intensely cytotoxic doxorubicin analogue that retains full potency against tumor cells that express elevated levels of P-glycoprotein and are resistant to doxorubicin. 1b was designed to be hydrolyzed in the presence of carboxylate esterases to N-(5-oxypent-1-yl)doxorub...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9706980

    authors： Farquhar D,Cherif A,Bakina E,Nelson JA

    更新日期：1998-03-12 00:00:00

  • Structure-Activity Relationship of 2,4-Dichloro-N-(3,5-dichloro-4-(quinolin-3-yloxy)phenyl)benzenesulfonamide (INT131) Analogs for PPARγ-Targeted Antidiabetics.

    abstract：:Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor central to fatty acid and glucose homeostasis. PPARγ is the molecular target for type 2 diabetes mellitus (T2DM) therapeutics TZDs (thiazolidinediones), full agonists of PPARγ with robust antidiabetic properties, which are confounded with signi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01727

    authors： Frkic RL,He Y,Rodriguez BB,Chang MR,Kuruvilla D,Ciesla A,Abell AD,Kamenecka TM,Griffin PR,Bruning JB

    更新日期：2017-06-08 00:00:00