当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Subtlety of the structure-affinity and structure-efficacy relationships around a nonpeptide oxytocin receptor agonist.

Subtlety of the structure-affinity and structure-efficacy relationships around a nonpeptide oxytocin receptor agonist.

Abstract：

:Very few nonpeptide oxytocin agonists have currently been reported, and none of them seem suitable for the in vivo investigation of the oxytocin mediated functions. In an attempt to rationalize the design of better tools, we have systematically studied the structural determinants of the affinity and efficacy of representative ligands of the V(1a), V(2), and OT receptor subtypes. Despite apparently obvious similarity between the ligand structures on one hand, and between the receptor subtypes on the other hand, the binding affinity and the functional activity profiles of truncated and hybrid ligands highlight the subtlety of ligand-receptor interactions for obtaining nonpeptide OT receptor agonists.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Frantz MC,Rodrigo J,Boudier L,Durroux T,Mouillac B,Hibert M

doi

10.1021/jm901084f

subject

Has Abstract

pub_date

2010-02-25 00:00:00

pages

1546-62

issue

4

eissn

0022-2623

issn

1520-4804

journal_volume

53

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Comparison of 5-HT1A and dopamine D2 pharmacophores. X-ray structures and affinities of conformationally constrained ligands.

    abstract：:Conformational and molecular mechanics studies of a new series of tricyclic ligands with affinity for either the dopamine D2 receptor or the 5-HT1A receptor, or both, has enabled us to elaborate considerably on previous pharmacophore models for these receptors. The new tricyclic ligands are either angular, 2,3,3a,4,5,...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00062a001

    authors： Chidester CG,Lin CH,Lahti RA,Haadsma-Svensson SR,Smith MW

    更新日期：1993-05-14 00:00:00

  • Synthesis and activity of 6-substituted purine linker amino acid immunostimulants.

    abstract：:A series of 6-substituted purinyl alkoxycarbonyl amino acids were synthesized and evaluated for their ability to stimulate cytotoxic T lymphocytes (CTLs) and the mixed lymphocyte reaction (MLR). A few of these compounds, in particular [[5-[6-(N,N-dimethylamino)purin-9-yl]pentoxy]-carbonyl]D-arginine (BCH-1393, 4a), di...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960844m

    authors： Zacharie B,Gagnon L,Attardo G,Connolly TP,St-Denis Y,Penney CL

    更新日期：1997-08-29 00:00:00

  • Synthesis of the 2-amino-4-phosphonobutanoic acid analogues (E)- and (Z)-2-amino-2,3-methano-4-phosphonobutanoic acid and their evaluation as inhibitors of hippocampal excitatory neurotransmission.

    abstract：:The cyclopropyl compounds (Z)- and (E)-2-amino-2,3-methano-4-phosphonobutanoic acid, 5 and 6, respectively, were prepared as constrained analogues of 2-amino-4-phosphonobutanoic acid (AP4), a selective glutamate receptor ligand. A Horner-Emmons reaction of trimethyl N-(benzyloxycarbonyl)phosphonoglycinate with 2-(diet...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00109a023

    authors： Kroona HB,Peterson NL,Koerner JF,Johnson RL

    更新日期：1991-05-01 00:00:00

  • Selective thromboxane synthetase inhibitors. 1. 1-[(Aryloxy)alkyl]-1H-imidazoles.

    abstract：:1-(2-Phenoxyethyl)-1H-imidazole was found to be an inhibitor of thromboxane (TxA2) synthetase, but it also inhibited the adrenal cytochrome P-450 enzyme steroid 11 beta-hydroxylase. The preparation of a series of analogues is described, and activity against TxA2 synthetase, PGI2 synthetase, cyclooxygenase, and steroid...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00148a009

    authors： Cross PE,Dickinson RP,Parry MJ,Randall MJ

    更新日期：1985-10-01 00:00:00

  • Simple selection criteria for drug-like chemical matter.

    abstract：:A simple pharmacophore point filter has been developed that discriminates between drug-like and nondrug-like chemical matter. It is based on the observation that nondrugs are often underfunctionalized. Therefore, a minimum count of well-defined pharmacophore points is required to pass the filter. The application of th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm015507e

    authors： Muegge I,Heald SL,Brittelli D

    更新日期：2001-06-07 00:00:00

  • Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotension.

    abstract：:Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0701019

    authors： Zhu GD,Gandhi VB,Gong J,Thomas S,Woods KW,Song X,Li T,Diebold RB,Luo Y,Liu X,Guan R,Klinghofer V,Johnson EF,Bouska J,Olson A,Marsh KC,Stoll VS,Mamo M,Polakowski J,Campbell TJ,Martin RL,Gintant GA,Penning TD,

    更新日期：2007-06-28 00:00:00

  • Novel chemical space exploration via natural products.

    abstract：:Natural products (NPs) are a rich source of novel compound classes and new drugs. In the present study we have used the chemical space navigation tool ChemGPS-NP to evaluate the chemical space occupancy by NPs and bioactive medicinal chemistry compounds from the database WOMBAT. The two sets differ notably in coverage...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm801514w

    authors： Rosén J,Gottfries J,Muresan S,Backlund A,Oprea TI

    更新日期：2009-04-09 00:00:00

  • Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis.

    abstract：:The dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered, providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagon...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm501512b

    authors： Keck TM,John WS,Czoty PW,Nader MA,Newman AH

    更新日期：2015-07-23 00:00:00

  • Synthesis of analogues of N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea for evaluation as anticancer agents.

    abstract：:The superior activity of N-(2-chloroethyl)-N'-(trans-4-methylcyclohexyl)-N-nitrosourea (MeCCNU) against advanced murine Lewis lung carcinoma in comparisons with the cis form and other nitrosoureas prompted the synthesis of a number of MeCCNU analogues, including several cis-trans pairs. The methyl group was replaced b...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00212a019

    authors： Johnston TP,McCaleb GS,Clayton SD,Frye JL,Krauth CA,Montgomery JA

    更新日期：1977-02-01 00:00:00

  • Antifilarial agents. 3-Aminopyrrolidine and 1,4-diazabicyclo[3.2.1]octane derivatives as analogues of diethylcarbamazine.

    abstract：:3-Aminopyrrolidines bearing acyl substituents on either nitrogen and N-acylated 1,4-diazabicyclo[3.2.1]octanes are potent microfilaricides in the Litomosoides carinii gerbil test system but have no effect on adult worms. The high activity of the pyrrolidine derivatives establishes that diethylcarbamazine (DEC) like an...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00220a021

    authors： Sturm P,Cory M,Henry DW

    更新日期：1977-10-01 00:00:00

  • Major effect of pyrrolic N-benzylation in norbinaltorphimine, the selective kappa-opioid receptor antagonist.

    abstract：:Indolic N-benzylation of naltrindole reportedly extends the duration of delta-opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low potency mu-opioid receptor (MOR) partial agonist, was found to affect predominantly th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049172n

    authors： Chauvignac C,Miller CN,Srivastava SK,Lewis JW,Husbands SM,Traynor JR

    更新日期：2005-03-10 00:00:00

  • Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development.

    abstract：:The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clinically, res...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00389

    authors： Blake JF,Burkard M,Chan J,Chen H,Chou KJ,Diaz D,Dudley DA,Gaudino JJ,Gould SE,Grina J,Hunsaker T,Liu L,Martinson M,Moreno D,Mueller L,Orr C,Pacheco P,Qin A,Rasor K,Ren L,Robarge K,Shahidi-Latham S,Stults J,S

    更新日期：2016-06-23 00:00:00

  • Long-acting opiate agonists and antagonists: 14-hydroxydihydromorphinone hydrazones.

    abstract：:Two new long-acting hydrazone derivatives of 14-hydroxydihydromorphinones have been synthesized, oxymorphazone and naltrexazone. Both derivatives show high affinity for opiate binding sites in vitro, similar to naloxazone, the hydrazone analogue of naloxone. Sodium and manganese shifts imply that naltrexazone, like na...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00180a019

    authors： Pasternak GW,Hahn EF

    更新日期：1980-06-01 00:00:00

  • Synthesis and biological evaluation of a fluorine-18 derivative of dasatinib.

    abstract：:Tyrosine kinases often play pivotal roles in the pathogenesis of cancer and are good candidates for therapeutic intervention and targeted molecular imaging. The precursor synthesis, radiosynthesis, and biological characterization of a fluorine-18 analog of dasatinib, a multitargeted kinase inhibitor, are reported. Com...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm070342g

    authors： Veach DR,Namavari M,Pillarsetty N,Santos EB,Beresten-Kochetkov T,Lambek C,Punzalan BJ,Antczak C,Smith-Jones PM,Djaballah H,Clarkson B,Larson SM

    更新日期：2007-11-15 00:00:00

  • Can amphipathic helices influence the CNS antinociceptive activity of glycopeptides related to β-endorphin?

    abstract：:Glycosylated β-endorphin analogues of various amphipathicity were studied in vitro and in vivo in mice. Opioid binding affinities of the O-linked glycopeptides (mono- or disaccharides) and unglycosylated peptide controls were measured in human receptors expressed in CHO cells. All were pan-agonists, binding to μ-, δ-,...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm400879w

    authors： Li Y,St Louis L,Knapp BI,Muthu D,Anglin B,Giuvelis D,Bidlack JM,Bilsky EJ,Polt R

    更新日期：2014-03-27 00:00:00

  • Synthesis, structure, dopamine transporter affinity, and dopamine uptake inhibition of 6-alkyl-3-benzyl-2-[(methoxycarbonyl)methyl]tropane derivatives.

    abstract：:A series of 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl)methyl]tropane analogues were synthesized and evaluated as cocaine binding site ligands at the dopamine transporter (DAT). The in vitro affinity (Ki) for the DAT of the 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl) methyl]tropane analogues was determined by inhibition...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970549h

    authors： Lomenzo SA,Izenwasser S,Katz JL,Terry PD,Zhu N,Klein CL,Trudell ML

    更新日期：1997-12-19 00:00:00

  • Nucleoside conjugates. 6. Synthesis and comparison of antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugates of corticosteroids and selected lipophilic alcohols.

    abstract：:Five new P1-(steroid-21-yl)-P2-(1-beta-D-arabinofuranosylcytosin-5'-yl)pyro phosphates (ara-CDP-steroids), five 1-beta-D-arabinofuranosylcytosine 5'-O-(alkyl)phosphates (ara-CMP-alkyl esters), and two P1-(alkyl)-P2-(1-beta-D-arabinofuranosylcytosin-5'-yl)pyrophosphat e (ara-CDP-alkyl esters) have been prepared and eva...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00380a004

    authors： Hong CI,Kirisits AJ,Nechaev A,Buchheit DJ,West CR

    更新日期：1985-02-01 00:00:00

  • Discovery of 4-[(2S)-2-{[4-(4-chlorophenoxy)phenoxy]methyl}-1-pyrrolidinyl]butanoic acid (DG-051) as a novel leukotriene A4 hydrolase inhibitor of leukotriene B4 biosynthesis.

    abstract：:Both in-house human genetic and literature data have converged on the identification of leukotriene 4 hydrolase (LTA(4)H) as a key target for the treatment of cardiovascular disease. We combined fragment-based crystallography screening with an iterative medicinal chemistry effort to optimize inhibitors of LTA(4)H. Lig...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900838g

    authors： Sandanayaka V,Mamat B,Mishra RK,Winger J,Krohn M,Zhou LM,Keyvan M,Enache L,Sullins D,Onua E,Zhang J,Halldorsdottir G,Sigthorsdottir H,Thorlaksdottir A,Sigthorsson G,Thorsteinnsdottir M,Davies DR,Stewart LJ,Zembower DE

    更新日期：2010-01-28 00:00:00

  • Design and synthesis of small molecule RhoA inhibitors: a new promising therapy for cardiovascular diseases?

    abstract：:RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200161c

    authors： Deng J,Feng E,Ma S,Zhang Y,Liu X,Li H,Huang H,Zhu J,Zhu W,Shen X,Miao L,Liu H,Jiang H,Li J

    更新日期：2011-07-14 00:00:00

  • Preparation and analgesic activity of (-)-11 alpha-substituted 1,2,3,4,5,6-hexahydro-6 alpha,7-(methyleneoxy)-2,6-methano-3-benzazocines.

    abstract：:Dihydrocodeinone oxime (1) under Beckmann rearrangement conditions gave a product (2) that facilitated the preparation of (-)-11 alpha-substituted 1,2,3,4,5,6-hexahydro-6 alpha,7-(methyleneoxy)-2,6-methano-3-benzazocines, a hitherto little-examined series of morphine partial structures. Compounds 7a and 12 gave good l...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00160a022

    authors： Cittern PA,Kapoor VK,Parfitt RT

    更新日期：1986-10-01 00:00:00

  • Binding structures and potencies of oxidosqualene cyclase inhibitors with the homologous squalene-hopene cyclase.

    abstract：:The binding structures of 11 human oxidosqualene cyclase inhibitors designed as cholesterol-lowering agents were determined for the squalene-hopene cyclase from Alicyclobacillus acidocaldarius, which is the only structurally known homologue of the human enzyme. The complexes were produced by cocrystallization, and the...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0211218

    authors： Lenhart A,Reinert DJ,Aebi JD,Dehmlow H,Morand OH,Schulz GE

    更新日期：2003-05-22 00:00:00

  • Identification of a new scaffold for opioid receptor antagonism based on the 2-amino-1,1-dimethyl-7-hydroxytetralin pharmacophore.

    abstract：:The trans-(3,4)-dimethyl-4-(3-hydroxyphenyl)piperidines are a unique class of opioid antagonists that have recently provided selective antagonists for mu-opioid receptors (MOR) and kappa-opioid receptors (KOR). Molecular modeling indicated a strong structural similarity between the parent of this series and 2-amino-1,...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm040807s

    authors： Grundt P,Williams IA,Lewis JW,Husbands SM

    更新日期：2004-10-07 00:00:00

  • Structure-activity relationships of cyclic opioid peptide analogues containing a phenylalanine residue in the 3-position.

    abstract：:Ten analogues of the highly mu-receptor selective cyclic opioid peptide H-Tyr-D-Orn-Phe-Asp-NH2 (1) were synthesized by the solid phase method and were characterized in vitro in mu- and delta-receptor representative binding assays and bioassays. These cyclic analogues are structurally related to the linear opioid pept...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00394a027

    authors： Schiller PW,Nguyen TM,Maziak LA,Wilkes BC,Lemieux C

    更新日期：1987-11-01 00:00:00

  • New inhibitors of human renin that contain novel replacements at the P2 site.

    abstract：:A series of renin inhibitors with novel modifications at the P2 site has been prepared. Structure-activity relationships reveal that for a particular P2 fragment the in vitro potency is highly dependent on the nature of the P2' portion in addition to the P1-P1' group. The length of the P2 side chain and choice of epsi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00108a004

    authors： Doherty AM,Kaltenbronn JS,Hudspeth JP,Repine JT,Roark WH,Sircar I,Tinney FJ,Connolly CJ,Hodges JC,Taylor MD

    更新日期：1991-04-01 00:00:00

  • Noncataleptogenic, centrally acting dopamine D-2 and serotonin 5-HT2 antagonists within a series of 3-substituted 1-(4-fluorophenyl)-1H-indoles.

    abstract：:A series of 1-(4-fluorophenyl)-1H-indoles substituted at the 3-position with 1-piperazinyl, 1,2,3,6-tetrahydro-4-pyridinyl, and 4-piperidinyl was synthesized. Within all three subseries potent dopamine D-2 and serotonin 5-HT2 receptor affinity was found in ligand binding studies. Quipazine-induced head twitches in rat...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00084a014

    authors： Perregaard J,Arnt J,Bøgesø KP,Hyttel J,Sánchez C

    更新日期：1992-03-20 00:00:00

  • Dermorphin and deltorphin glycosylated analogues: synthesis and antinociceptive activity after systemic administration.

    abstract：:In the present paper we describe the synthesis of some dermorphin and deltorphin analogues beta-O- and alpha-C-glycosylated on the C-terminal amino acid residue and report their opioid receptor affinity and selectivity as well as their analgesic potency after subcutaneous injection in mice. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9810699

    authors： Negri L,Lattanzi R,Tabacco F,Orrù L,Severini C,Scolaro B,Rocchi R

    更新日期：1999-02-11 00:00:00

  • Hemolytic effects of water-soluble fullerene derivatives.

    abstract：:A series of water-soluble fullerene C(60) derivatives has been investigated for their cytotoxic and hemolytic properties, with the aim to correlate structure with toxicity. We observed that cationic chains induce significant toxicity while the presence of neutral or anionic moieties did not produce any response in our...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0497489

    authors： Bosi S,Feruglio L,Da Ros T,Spalluto G,Gregoretti B,Terdoslavich M,Decorti G,Passamonti S,Moro S,Prato M

    更新日期：2004-12-30 00:00:00

  • Discovery of highly selective brain-penetrant vasopressin 1a antagonists for the potential treatment of autism via a chemogenomic and scaffold hopping approach.

    abstract：:From a micromolar high throughput screening hit 7, the successful complementary application of a chemogenomic approach and of a scaffold hopping exercise rapidly led to a low single digit nanomolar human vasopressin 1a (hV1a) receptor antagonist 38. Initial optimization of the mouse V1a activities delivered suitable t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm501745f

    authors： Ratni H,Rogers-Evans M,Bissantz C,Grundschober C,Moreau JL,Schuler F,Fischer H,Alvarez Sanchez R,Schnider P

    更新日期：2015-03-12 00:00:00

  • General pseudoreceptor model for sweet compounds: a semiquantitative prediction of binding affinity for sweet-tasting molecules.

    abstract：:The chemical structures of sweet compounds are very different, ranging from sugars to amino acids and peptides or other compounds such as saccharin. The biological mechanism underlying the generation of sweet taste is still unknown, although in the past few years much research has provided evidence for the existence o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020833v

    authors： Bassoli A,Drew MG,Merlini L,Morini G

    更新日期：2002-09-26 00:00:00

  • (S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide: an orally bioavailable KCNQ2 opener with significant activity in a cortical spreading depression model of migraine.

    abstract：:(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as an orally bioavailable KCNQ2 potassium channel opener. In a rat model of migraine, 2 demonstrated significant oral activity in reducing the total number of cortical spreading depressions induced by potassium chloride. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm034073f

    authors： Wu YJ,Boissard CG,Greco C,Gribkoff VK,Harden DG,He H,L'Heureux A,Kang SH,Kinney GG,Knox RJ,Natale J,Newton AE,Lehtinen-Oboma S,Sinz MW,Sivarao DV,Starrett JE Jr,Sun LQ,Tertyshnikova S,Thompson MW,Weaver D,Wong HS

    更新日期：2003-07-17 00:00:00