当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Specific inhibition of benzodiazepine receptor binding by some N-(indol-3-ylglyoxylyl)amino acid derivatives: stereoselective interactions.

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, suggesting a key role of the amino acid stereochemistry on the affinity to the benzodiazepine receptors. GABA ratio and proconvulsant/convulsant data reported for the most active compounds reveal they behave as inverse agonists at the benzodiazepine receptor.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

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

doi

10.1021/jm00132a004

subject

Has Abstract

pub_date

1989-12-01 00:00:00

pages

2514-8

issue

12

eissn

0022-2623

issn

1520-4804

journal_volume

32

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Isotope effects in enzymatic N-demethylation of tertiary amines.

    abstract：:The N-demethylation of 1-(N-methyl-N-trideuteriomethylamino)-3-phenylpropane (1) by rodent liver homogenates was studied. The ratio of 1-trideuteriomethylamino-3-phenylpropane (2)/1-methylamino-3-phenylpropane (3) was determined by gc-ms. The ratio of 2/3 in the product of N-demethylation of 1 by liver homogenate from...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00238a021

    authors： Abdel-Monem MM

    更新日期：1975-04-01 00:00:00

  • Design and synthesis of renin inhibitors: incorporation of transition-state isostere side chains that span from the S1 to the S3 binding pockets and examination of P3-modified renin inhibitors.

    abstract：:A series of renin inhibitors were designed to examine the topography of the contiguous binding pocket of renin that is normally occupied by the P1 and P3 side chains. Molecular modeling suggested that extending the P1 hydrophobic side chain into the adjacent hydrophobic S3 enzyme pocket was feasible. Novel transition ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00015a012

    authors： Plummer MS,Shahripour A,Kaltenbronn JS,Lunney EA,Steinbaugh BA,Hamby JM,Hamilton HW,Sawyer TK,Humblet C,Doherty AM

    更新日期：1995-07-21 00:00:00

  • Inhibition Mechanisms of Indoleamine 2,3-Dioxygenase 1 (IDO1).

    abstract：:Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway of tryptophan metabolism, which is involved in immunity, neuronal function, and aging. Its implication in pathologies such as cancer and neurodegenerative diseases has stimulated the development of IDO1 inhibitors. However,...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00942

    authors： Röhrig UF,Reynaud A,Majjigapu SR,Vogel P,Pojer F,Zoete V

    更新日期：2019-10-10 00:00:00

  • Synthesis and preliminary binding studies of 4,4-ditritio-(-)-nicotine of high specific activity.

    abstract：:4,4-Ditritio-(-)-nicotine (5) of high specific activity (4.7 Ci/mmol) has been synthesized from (-)-nicotine via the readily prepared 4,4-dibromocotinine (3). Scatchard analysis of the binding of 5 to the crude mitochondrial fraction of whole rat brain revealed a Ka of 4.7 X 10(6) M-1 and 13 fmol of binding sites/mg o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00182a028

    authors： Vincek WC,Martin BR,Aceto MD,Bowman ER

    更新日期：1980-08-01 00:00:00

  • Synthesis and evaluation of a new generation of orally efficacious benzimidazole-based poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agents.

    abstract：:Small molecule inhibitors of PARP-1 have been pursued by various organizations as potential therapeutic agents either capable of sensitizing cytotoxic treatments or acting as stand-alone agents to combat cancer. As one of the strategies to expand our portfolio of PARP-1 inhibitors, we pursued unsaturated heterocycles ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900697r

    authors： Tong Y,Bouska JJ,Ellis PA,Johnson EF,Leverson J,Liu X,Marcotte PA,Olson AM,Osterling DJ,Przytulinska M,Rodriguez LE,Shi Y,Soni N,Stavropoulos J,Thomas S,Donawho CK,Frost DJ,Luo Y,Giranda VL,Penning TD

    更新日期：2009-11-12 00:00:00

  • Analysis of the binding of mixed lineage leukemia 1 (MLL1) and histone 3 peptides to WD repeat domain 5 (WDR5) for the design of inhibitors of the MLL1-WDR5 interaction.

    abstract：:MLL1 is a histone 3 lysine 4 (H3K4) methyltransferase and a promising new cancer therapeutic target. The catalytic activity of MLL1 is regulated by the formation of a core complex consisting of MLL1, WDR5, RbBP5, and Ash2L. The interaction between WDR5 and MLL1 plays an essential role in regulation of the H3K4 methylt...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100139b

    authors： Karatas H,Townsend EC,Bernard D,Dou Y,Wang S

    更新日期：2010-07-22 00:00:00

  • Synthesis of 5-substituted 2'-deoxyuridines.

    abstract：:A series of thymidylate synthetase inhibitors was synthesized, some of which were potential irreversible inhibitors. 5-Formyl-2'-deoxyuridine (9) and its dithiolane derivative 11 were prepared by condensation of the bis(trimethylsilyl) derivative of 5-formyluracil dimethyl acetal and the protected chloro sugar followe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00229a010

    authors： Kampf A,Pillar CJ,Woodford WJ,Mertes MP

    更新日期：1976-07-01 00:00:00

  • Design of rat renin inhibitory peptides.

    abstract：:Because several well-studied strains of rats manifest spontaneous hypertension, we set out to design a renin inhibitor suitable for use in this species. On the basis of the sequence of the renin substrate, a series of substrate analogue inhibitory peptides were synthesized by systematically modifying the P5, P3, P2, P...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00117a003

    authors： Hui KY,Holtzman EJ,Quinones MA,Hollenberg NK,Haber E

    更新日期：1988-09-01 00:00:00

  • Topography and conformational preferences of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6- ylamin e. A rationale for the dopaminergic inactivity.

    abstract：:In an attempt to rationalize the inability of phenolic benzocycloheptenylamines to activate dopamine (DA) D2 receptors, we have studied the conformational preferences and topography of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6-++ +ylamine (1). Preferred conformations of 1 have been defined by use...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00124a007

    authors： Karlén A,Helander A,Kenne L,Hacksell U

    更新日期：1989-04-01 00:00:00

  • Structure-activity relationships of 2'-fluoro-2',3'-unsaturated D-nucleosides as anti-HIV-1 agents.

    abstract：:We studied the structure-activity relationships of a series of 2'-fluoro-2',3'-unsaturated D-nucleosides against HIV-1 in human peripheral blood mononuclear (PBM) cells. The target compounds 10-21 and 28-33 were prepared by N-glycosylation of the acetate 4, which was readily prepared from 2,3-O-isopropylidene-D-glycer...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm010418n

    authors： Lee K,Choi Y,Gumina G,Zhou W,Schinazi RF,Chu CK

    更新日期：2002-03-14 00:00:00

  • Potent and selective conformationally restricted neuronal nitric oxide synthase inhibitors.

    abstract：:Selective inhibition of the isoforms of nitric oxide synthase (NOS) in pathologically elevated synthesis of nitric oxide has great therapeutic potential. We previously reported nitroarginine-containing dipeptide amides and some peptidomimetic analogues as potent and selective inhibitors of neuronal NOS (nNOS). Here we...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030297m

    authors： Gómez-Vidal JA,Martásek P,Roman LJ,Silverman RB

    更新日期：2004-01-29 00:00:00

  • Salicylanilide Analog Minimizes Relapse of Clostridioides difficile Infection in Mice.

    abstract：:Clostridioides difficile infection (CDI) causes serious and sometimes fatal symptoms like diarrhea and pseudomembranous colitis. Although antibiotics for CDI exist, they are either expensive or cause recurrence of the infection due to their altering the colonic microbiota, which is necessary to suppress the infection....

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c00123

    authors： Blake S,Thanissery R,Rivera AJ,Hixon MS,Lin M,Theriot CM,Janda KD

    更新日期：2020-07-09 00:00:00

  • Development of potent glucagon-like peptide-1 agonists with high enzyme stability via introduction of multiple lactam bridges.

    abstract：:Glucagon-like peptide-1 (GLP-1) has the ability to lower the blood glucose level, and its regulatory functions make it an attractive therapeutic agent for the treatment of type 2 diabetes. However, its rapid degradation by enzymes like dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely com...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100602m

    authors： Murage EN,Gao G,Bisello A,Ahn JM

    更新日期：2010-09-09 00:00:00

  • 1H-2-benzopyran-1-one derivatives, microbial products with pharmacological activity. Relationship between structure and activity in 6-[[1(S)-(3(S),4- dihydro-8-hydroxy-1-oxo-1H-2-benzopyran-3-yl)-3-methylbutyl]-amino]-4(S), 5(S)-dihydroxy-6-oxo-3(S)-ammon

    abstract：:In order to investigate the structural requirements for gastroprotective activity in 6-[[1(S)-(3(S),4-dihydro-8- hydroxy-1-oxo-1H-2-benzopyran-3-yl)-3-methylbutyl]amino]-4(S),5(S)-dihydroxy 6-oxo-3(S)-ammoniohexanoate [AI-77-B, 1], a product of Bacillus pumilus AI-77, nine derivatives were prepared and then tested for...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00364a007

    authors： Shimojima Y,Hayashi H

    更新日期：1983-10-01 00:00:00

  • pH-Activatable Singlet Oxygen-Generating Boron-dipyrromethenes (BODIPYs) for Photodynamic Therapy and Bioimaging.

    abstract：:Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired dam...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01873

    authors： Radunz S,Wedepohl S,Röhr M,Calderón M,Tschiche HR,Resch-Genger U

    更新日期：2020-02-27 00:00:00

  • Adenosine deaminase inhibitors. Synthesis and biological evaluation of C1' and nor-C1' derivatives of (+)-erythro-9-(2(S)-hydroxy-3(R)-nonyl)adenine.

    abstract：:The synthesis of various chiral derivatives of (+)-erythro-9-(2-hydroxy-3-nonyl)adenine, (+)-EHNA, from (2S,3R)-3-amino-1,2-O-isopropylidene-1,2-nonanediol by condensation with 5-amino-4,6-dichloropyrimidine is described. The compounds synthesized were C1'- and nor-C1'-(+)-EHNA derivatives. When tested with calf splee...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00100a025

    authors： Harriman GC,Poirot AF,Abushanab E,Midgett RM,Stoeckler JD

    更新日期：1992-10-30 00:00:00

  • Design and development of water-soluble curcumin conjugates as potential anticancer agents.

    abstract：:Conjugates of curcumin to two differently sized poly(ethylene glycol) molecules were synthesized in an attempt to overcome the low aqueous solubility of this natural product with cytotoxic activity against some human cancer cell lines. The soluble conjugates exhibited enhanced cytotoxicity as compared to that of the p...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm700988f

    authors： Safavy A,Raisch KP,Mantena S,Sanford LL,Sham SW,Krishna NR,Bonner JA

    更新日期：2007-11-29 00:00:00

  • Probing the subpockets of factor Xa reveals two binding modes for inhibitors based on a 2-carboxyindole scaffold: a study combining structure-activity relationship and X-ray crystallography.

    abstract：:Structure-activity relationships within a series of highly potent 2-carboxyindole-based factor Xa inhibitors incorporating a neutral P1 ligand are described with particular emphasis on the structural requirements for addressing subpockets of the factor Xa enzyme. Interactions with the subpockets were probed by systema...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0490540

    authors： Nazaré M,Will DW,Matter H,Schreuder H,Ritter K,Urmann M,Essrich M,Bauer A,Wagner M,Czech J,Lorenz M,Laux V,Wehner V

    更新日期：2005-07-14 00:00:00

  • Discovery of a Novel Class of Negative Allosteric Modulator of the Dopamine D2 Receptor Through Fragmentation of a Bitopic Ligand.

    abstract：:Recently, we have demonstrated that N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652) (1) adopts a bitopic pose at one protomer of a dopamine D2 receptor (D2R) dimer to negatively modulate the binding of dopamine at the other protomer. The 1H-indole-2-carboxa...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00585

    authors： Mistry SN,Shonberg J,Draper-Joyce CJ,Klein Herenbrink C,Michino M,Shi L,Christopoulos A,Capuano B,Scammells PJ,Lane JR

    更新日期：2015-09-10 00:00:00

  • Design, synthesis and biological evaluation of novel arachidonic acid derivatives as highly potent and selective endocannabinoid transporter inhibitors.

    abstract：:In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm015545y

    authors： López-Rodríguez ML,Viso A,Ortega-Gutiérrez S,Lastres-Becker I,González S,Fernández-Ruiz J,Ramos JA

    更新日期：2001-12-20 00:00:00

  • Bis-pyranobenzoquinones as a new family of reversal agents of the multidrug resistance phenotype mediated by P-glycoprotein in mammalian cells and the protozoan parasite Leishmania.

    abstract：:We have synthesized a set of bis-pyranobenzoquinones through a direct and highly efficient approach based on a double intramolecular domino Knoevenagel hetero Diels-Alder reaction. These bis-pyranobenzoquinone derivatives are compounds whose skeletons have similarities to those of some anticancerous and leishmanicidal...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm800403b

    authors： Jiménez-Alonso S,Pérez-Lomas AL,Estévez-Braun A,Muñoz Martinez F,Chávez Orellana H,Ravelo AG,Gamarro F,Castanys S,López M

    更新日期：2008-11-27 00:00:00

  • Jatrophane diterpenes as modulators of multidrug resistance. Advances of structure-activity relationships and discovery of the potent lead pepluanin A.

    abstract：:From the whole plant of Euphorbia peplus L., five new diterpenes based on a jatrophane skeleton (pepluanins A-E, 1-5) were isolated, together with two known analogues (6 and 7), which served to divulge in detail the structure-activity relationships within this class of P-glycoprotein inhibitors. The results revealed t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030951y

    authors： Corea G,Fattorusso E,Lanzotti V,Motti R,Simon PN,Dumontet C,Di Pietro A

    更新日期：2004-02-12 00:00:00

  • 8-Azatetracyclines: synthesis and evaluation of a novel class of tetracycline antibacterial agents.

    abstract：:A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds w...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm1015389

    authors： Clark RB,He M,Fyfe C,Lofland D,O'Brien WJ,Plamondon L,Sutcliffe JA,Xiao XY

    更新日期：2011-03-10 00:00:00

  • Annulated heterocyclic bioisosteres of norarecoline. Synthesis and molecular pharmacology at five recombinant human muscarinic acetylcholine receptors.

    abstract：:A series of O-alkylated analogs of 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-3-ol (THAO) were synthesized and characterized as ligands for muscarinic acetylcholine receptors (mAChRs). O-Methyl-THAO (4a), O-ethyl-THAO (4b), O-isopropyl-THAO (4c), and O-propargyl-THAO (4d) were shown to be potent inhibitors of the bi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00012a019

    authors： Bräuner-Osborne H,Ebert B,Brann MR,Falch E,Krogsgaard-Larsen P

    更新日期：1995-06-09 00:00:00

  • Structure-based optimization of protein tyrosine phosphatase 1B inhibitors: from the active site to the second phosphotyrosine binding site.

    abstract：:Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. Starting with a high micromolar lead compound, structure-based optimization of novel PTP1B inhibitors by extension of the molecule from the enz...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0702478

    authors： Wilson DP,Wan ZK,Xu WX,Kirincich SJ,Follows BC,Joseph-McCarthy D,Foreman K,Moretto A,Wu J,Zhu M,Binnun E,Zhang YL,Tam M,Erbe DV,Tobin J,Xu X,Leung L,Shilling A,Tam SY,Mansour TS,Lee J

    更新日期：2007-09-20 00:00:00

  • 3-Aryl-[1,2,4]triazino[4,3-a]benzimidazol-4(10H)-ones: tricyclic heteroaromatic derivatives as a new class of benzodiazepine receptor ligands.

    abstract：:A series of 3-substituted [1,2,4]triazino[4,3-c]benzimidazoles V were prepared and tested at the central benzodiazepine receptor (BzR). These compounds were designed as rigid analogues of the previously described N-benzylindolylglyoxylylamide derivatives IV. The title compounds V showed an affinity which depended dire...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm991131h

    authors： Primofiore G,Da Settimo F,Taliani S,Marini AM,La Motta C,Novellino E,Greco G,Gesi M,Trincavelli L,Martini C

    更新日期：2000-01-13 00:00:00

  • Discovery and development of the novel potent orally active thrombin inhibitor N-(9-hydroxy-9-fluorenecarboxy)prolyl trans-4-aminocyclohexylmethyl amide (L-372,460): coapplication of structure-based design and rapid multiple analogue synthesis on solid su

    abstract：:Early studies in these laboratories of peptidomimetic structures containing a basic P1 moiety led to the highly potent and selective thrombin inhibitors 2 (Ki = 5.0 nM) and 3 (Ki = 0.1 nM). However, neither attains significant blood levels upon oral administration to rats and dogs. With the aim of improving pharmacoki...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9705014

    authors： Brady SF,Stauffer KJ,Lumma WC,Smith GM,Ramjit HG,Lewis SD,Lucas BJ,Gardell SJ,Lyle EA,Appleby SD,Cook JJ,Holahan MA,Stranieri MT,Lynch JJ Jr,Lin JH,Chen IW,Vastag K,Naylor-Olsen AM,Vacca JP

    更新日期：1998-01-29 00:00:00

  • Anhydrolide macrolides. 1. Synthesis and antibacterial activity of 2,3-anhydro-6-O-methyl 11,12-carbamate erythromycin A analogues.

    abstract：:A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-carbamate analogues have been synthesized and evaluated for antibacterial activity. These compounds were found to be potent antibacterial agents against Gram-positive organisms in vitro, many having MIC values below 1 microg/mL for the macrolide-s...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970547x

    authors： Elliott RL,Pireh D,Griesgraber G,Nilius AM,Ewing PJ,Bui MH,Raney PM,Flamm RK,Kim K,Henry RF,Chu DT,Plattner JJ,Or YS

    更新日期：1998-05-07 00:00:00

  • Synthesis and biological studies of different duocarmycin based glycosidic prodrugs for their use in the antibody-directed enzyme prodrug therapy.

    abstract：:The synthesis and biological evaluation of novel prodrugs for use in the antibody directed enzyme prodrug therapy (ADEPT) of cancer based on the cytotoxic antibiotic duocarmycin SA (1) are described. In this approach, we investigated the influence of the sugar moiety of the glycosidic prodrug on the QIC(50) values as ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm8009102

    authors： Tietze LF,Schuster HJ,Krewer B,Schuberth I

    更新日期：2009-01-22 00:00:00

  • Synthetic mimics of antimicrobial peptides from triaryl scaffolds.

    abstract：:In this report, we describe the synthesis of a new series of small amphiphilic aromatic compounds that mimic the essential properties of cationic antimicrobial peptides using Suzuki-Miyaura coupling. The new design allowed the easy tuning of the conformational restriction, controlled by introduction of intramolecular ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm101410t

    authors： Thaker HD,Sgolastra F,Clements D,Scott RW,Tew GN

    更新日期：2011-04-14 00:00:00