当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > 2-(oxadiazolyl)- and 2-(thiazolyl)imidazo[1,2-a]pyrimidines as agonists and inverse agonists at benzodiazepine receptors.

2-(oxadiazolyl)- and 2-(thiazolyl)imidazo[1,2-a]pyrimidines as agonists and inverse agonists at benzodiazepine receptors.

Abstract：

:Oxadiazoles, like the benzoyl group in a series of imidazo[1,2-a]pyrimidines, have been found to be metabolically stable alternatives to ester groups in benzodiazepine-receptor ligands. This change has lead to a number of compounds which bind to the receptors and which exhibit potent agonist activity in a food-motivated conflict test thought to predict anxiolytic properties. Compounds 4, 5, and 13 were equipotent with chlordiazepoxide but showed little or no myorelaxant effects. Replacing the oxadiazole group by thiazole gave compounds such as 23 which binds to the benzodiazepine receptor but exhibits the intrinsic activity of a partial inverse agonist in vivo.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Tully WR,Gardner CR,Gillespie RJ,Westwood R

doi

10.1021/jm00111a021

keywords:

subject

Has Abstract

pub_date

1991-07-01 00:00:00

pages

2060-7

issue

7

eissn

0022-2623

issn

1520-4804

journal_volume

34

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Potent in vitro and in vivo inhibitors of platelet aggregation based upon the Arg-Gly-Asp-Phe sequence of fibrinogen. A proposal on the nature of the binding interaction between the Arg-guanidine of RGDX mimetics and the platelet GP IIb-IIIa receptor.

    abstract：:Peptide mimetics of the RGDF sequence in which Arg-Gly has been replaced with 5-(4-amidinophenyl)pentanoyl mimetic has led to a 1000-fold increase in inhibitory potency over the natural RGDF ligand. The guanidine residue of the arginine may be involved in a reinforced ionic interaction with a carboxylate of the recept...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00065a003

    authors： Zablocki JA,Miyano M,Garland RB,Pireh D,Schretzman L,Rao SN,Lindmark RJ,Panzer-Knodle SG,Nicholson NS,Taite BB

    更新日期：1993-06-25 00:00:00

  • Lead-like Drugs: A Perspective.

    abstract：:Lead-like drugs, or drugs below molecular weight 300, are an important and sometimes overlooked component of the current pharmacopeia and contemporary medicinal chemistry practice. To examine the recent state-of-the-art in lead-like drug discovery, we surveyed recent drug approvals from 2011 to 2017 and top 200 prescr...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.8b00407

    authors： Raymer B,Bhattacharya SK

    更新日期：2018-12-13 00:00:00

  • Crystal structure and anti herpes simplex virus activity of 2,2'-anhydro-1-beta-D-arabinofuranosylthymine.

    abstract：:1-beta-D-Arabinofuranosylthymine (aThy; ara-T) is a potent selective anti herpes simplex virus drug. Its anhydro analogue, 2,2'-anhydro-aThy, was shown to be 9-fold less active and at least 3-fold less toxic than aThy. This compound was relatively stable at physiological pH and in strong acid but was rapidly hydrolyze...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00354a025

    authors： Harrison DH,Schinazi RF,Rubin BH

    更新日期：1982-12-01 00:00:00

  • Synthesis and evaluation of keto-glutamine analogues as potent inhibitors of severe acute respiratory syndrome 3CLpro.

    abstract：:The 3C-like proteinase (3CL(pro)) of severe acute respiratory syndrome (SARS) coronavirus is a key target for structure-based drug design against this viral infection. The enzyme recognizes peptide substrates with a glutamine residue at the P1 site. A series of keto-glutamine analogues with a phthalhydrazido group at ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0494873

    authors： Jain RP,Pettersson HI,Zhang J,Aull KD,Fortin PD,Huitema C,Eltis LD,Parrish JC,James MN,Wishart DS,Vederas JC

    更新日期：2004-12-02 00:00:00

  • Discovery of new inhibitors of Cdc25B dual specificity phosphatases by structure-based virtual screening.

    abstract：:Cell division cycle 25 (Cdc25) proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent attractive drug targets for anticancer therapies. To discover more potent and diverse inhibitors of Cdc25 biological activity, virtual screening was performed by docking 2.1 m...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm201624h

    authors： Lavecchia A,Di Giovanni C,Pesapane A,Montuori N,Ragno P,Martucci NM,Masullo M,De Vendittis E,Novellino E

    更新日期：2012-05-10 00:00:00

  • Nucleoside Derived Antibiotics to Fight Microbial Drug Resistance: New Utilities for an Established Class of Drugs?

    abstract：:Novel antibiotics are urgently needed to combat the rise of infections due to drug-resistant microorganisms. Numerous natural nucleosides and their synthetically modified analogues have been reported to have moderate to good antibiotic activity against different bacterial and fungal strains. Nucleoside-based compounds...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.6b00325

    authors： Serpi M,Ferrari V,Pertusati F

    更新日期：2016-12-08 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

  • Novel 4-(4-aryl)cyclohexyl-1-(2-pyridyl)piperazines as Delta(8)-Delta(7) sterol isomerase (emopamil binding protein) selective ligands with antiproliferative activity.

    abstract：:To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some sigma receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH(3), CH(3)O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-py...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm800965b

    authors： Berardi F,Abate C,Ferorelli S,de Robertis AF,Leopoldo M,Colabufo NA,Niso M,Perrone R

    更新日期：2008-12-11 00:00:00

  • Synthesis and in vitro and in vivo functional studies of ortho-substituted phenylpiperazine and N-substituted 4-N-(o-methoxyphenyl)aminopiperidine analogues of WAY100635.

    abstract：:WAY100635 (2), N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide, is a silent serotonin 5-HT(1A) antagonist, which is now widely used to study the 5-HT(1A) receptor both in vivo and in vitro. In this paper, we describe the synthesis and in vitro (5-HT(1A) affinity and pA(2) values a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm991088y

    authors： Mensonides-Harsema MM,Liao Y,Böttcher H,Bartoszyk GD,Greiner HE,Harting J,de Boer P,Wikström HV

    更新日期：2000-02-10 00:00:00

  • Synthesis and carbonic anhydrase isoenzymes I, II, IX, and XII inhibitory effects of dimethoxybromophenol derivatives incorporating cyclopropane moieties.

    abstract：:Cyclopropylcarboxylic acids and esters and cyclopropylmethanols incorporating bromophenol moieties were investigated as inhibitors of the carbonic anhydrase enzyme (CA; EC 4.2.1.1). The cis- and trans-esters 5 and 6 were obtained from the reaction of 4-allyl-1,2-dimethoxybenzene (4) with ethyl diazoacetate, which afte...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm501573b

    authors： Boztaş M,Çetinkaya Y,Topal M,Gülçin İ,Menzek A,Şahin E,Tanc M,Supuran CT

    更新日期：2015-01-22 00:00:00

  • Regression analysis of the relationship between physical properties and the in vitro inhibition of monoamine oxidase by propynylamines.

    abstract：:Regression analysis of the potency of inhibition of monoamine oxidase by 47 propynylamines revealed that there are three determinants of inhibitory potency: (1) the smallest substituent on the nitrogen must be methyl or hydrogen in order for any activity to be observed; (2) potency is parabolically related to pKa-the ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00243a004

    authors： Martin YC,Martin WB,Taylor JD

    更新日期：1975-09-01 00:00:00

  • Optimization of brain penetrant 11β-hydroxysteroid dehydrogenase type I inhibitors and in vivo testing in diet-induced obese mice.

    abstract：:11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine comp...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm4016729

    authors： Goldberg FW,Dossetter AG,Scott JS,Robb GR,Boyd S,Groombridge SD,Kemmitt PD,Sjögren T,Gutierrez PM,deSchoolmeester J,Swales JG,Turnbull AV,Wild MJ

    更新日期：2014-02-13 00:00:00

  • Biased ligand modulation of seven transmembrane receptors (7TMRs): functional implications for drug discovery.

    abstract：:Seven transmembrane receptors (7TMRs), also known as G-protein-coupled receptors (GPCRs), have proven to be valuable targets for the development of therapeutics. The expansion of our understanding of 7TMR downstream signaling pathways beyond G-proteins has broadened our appreciation of the versatility of these cell su...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm401677g

    authors： Correll CC,McKittrick BA

    更新日期：2014-08-28 00:00:00

  • Alkylating nucleosides. 2. Synthesis and cytostatic activity of bromomethylpyrazole and pyrazole nitrogen mustard nucleosides.

    abstract：:Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucle...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00193a011

    authors： García-López MT,Herranz R,Alonso G

    更新日期：1979-07-01 00:00:00

  • Molecular and conformational determinants of pituitary adenylate cyclase-activating polypeptide (PACAP) for activation of the PAC1 receptor.

    abstract：:PAC1 receptor is abundant in the CNS and plays an important role in neuronal survival. To identify the molecular determinants and the conformational components responsible for the activation of the PAC1 receptor, we performed a SAR study focusing on the N-terminal domain of its endogenous ligand, PACAP. This approach ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900291j

    authors： Bourgault S,Vaudry D,Ségalas-Milazzo I,Guilhaudis L,Couvineau A,Laburthe M,Vaudry H,Fournier A

    更新日期：2009-05-28 00:00:00

  • Structure and dynamics of the full-length lipid-modified H-Ras protein in a 1,2-dimyristoylglycero-3-phosphocholine bilayer.

    abstract：:Ras proteins regulate signal transduction processes that control cell growth and proliferation. Their disregulation is a common cause of human tumors. Atomic level structural and dynamical information in a membrane environment is crucial for understanding signaling specificity among Ras isoforms and for the design of ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm061053f

    authors： Gorfe AA,Hanzal-Bayer M,Abankwa D,Hancock JF,McCammon JA

    更新日期：2007-02-22 00:00:00

  • Conformational analysis of ketolide, conformations of RU 004 in solution and bound to bacterial ribosomes.

    abstract：:A new structurally distinct class of 14-membered-ring macrolides is characterized by a keto-function instead of the cladinose sugar, well-known for its fragility even in weakly acidic media. This new class called ketolides is endowed with remarkable antibacterial activity against macrolide-resistant strains. A complet...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970852i

    authors： Bertho G,Gharbi-Benarous J,Delaforge M,Lang C,Parent A,Girault JP

    更新日期：1998-08-27 00:00:00

  • Synthesis and Characterization of Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Antibacterial Activity against Gram-Negative Bacteria.

    abstract：:There is an urgent unmet medical need for novel antibiotics that are effective against a broad range of bacterial species, especially multidrug resistant ones. Tetrahydropyran-based inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) display potent activity against Gram-positive pathogens ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01831

    authors： Surivet JP,Zumbrunn C,Bruyère T,Bur D,Kohl C,Locher HH,Seiler P,Ertel EA,Hess P,Enderlin-Paput M,Enderlin-Paput S,Gauvin JC,Mirre A,Hubschwerlen C,Ritz D,Rueedi G

    更新日期：2017-05-11 00:00:00

  • 7-Methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indolo[2,3-g]azecine: a new heterocyclic system and a new lead compound for dopamine receptor antagonists.

    abstract：:Partially hydrogenated derivatives of the new heterocyclic ring systems benz[d]indolo[2,3-g]azecine and bisindolo[3,2-d][2, 3-g]azecine were synthesized starting from lactones and amines via the described synthetic methods. In binding assays with rat striatal receptors, 7-methyl-6,7,8,9,14,15-hexahydro-5H-benz[d]indol...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9911478

    authors： Witt T,Hock FJ,Lehmann J

    更新日期：2000-05-18 00:00:00

  • The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors.

    abstract：:Coumarins constitute a general and totally new class of inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), binding at the entrance of the active site cavity. We report here that the coumarin-binding site in CAs may interact with diverse compounds, such as the antiepileptic drug lacosamide, which inhibi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm901524f

    authors： Temperini C,Innocenti A,Scozzafava A,Parkkila S,Supuran CT

    更新日期：2010-01-28 00:00:00

  • New series of morpholine and 1,4-oxazepane derivatives as dopamine D4 receptor ligands: synthesis and 3D-QSAR model.

    abstract：:Since the identification of the dopamine D(4) receptor subtype and speculations about its possible involvement in schizophrenia, much work has been put into development of selective D(4) ligands. These selective ligands may be effective antipsychotics without extrapyramidal side effects. This work describes the synthe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm031111m

    authors： Audouze K,Nielsen EØ,Peters D

    更新日期：2004-06-03 00:00:00

  • Tailoring of integrin ligands: probing the charge capability of the metal ion-dependent adhesion site.

    abstract：:Intervention in integrin-mediated cell adhesion and integrin signaling pathways is an ongoing area of research in medicinal chemistry and drug development. One key element in integrin-ligand interaction is the coordination of the bivalent cation at the metal ion-dependent adhesion site (MIDAS) by a carboxylic acid fun...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm2013826

    authors： Bollinger M,Manzenrieder F,Kolb R,Bochen A,Neubauer S,Marinelli L,Limongelli V,Novellino E,Moessmer G,Pell R,Lindner W,Fanous J,Hoffman A,Kessler H

    更新日期：2012-01-26 00:00:00

  • Analgesic and tranquilizing activity of 5,8-disubstituted 2-aminomethyl-3,4-dihydronaphthalenes.

    abstract：:Interesting analgesic activity approaching that of meperidine and codeine was observed in standard animal models for 8-chloro-3,4-dihydro-5-methoxy-2-pyrrolidinomethylnaphthalene (compound 7). This compound was orally effective and its analgesic activity was not reversed by the opiate antagonist, naloxone. A limited n...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00201a004

    authors： Welch WM,Plattner JJ,Stratten WP,Harbert CA

    更新日期：1978-03-01 00:00:00

  • Affinity-Guided Design of Caveolin-1 Ligands for Deoligomerization.

    abstract：:Caveolin-1 is a target for academic and pharmaceutical research due to its many cellular roles and associated diseases. We report peptide WL47 (1), a small, high-affinity, selective disrupter of caveolin-1 oligomers. Developed and optimized through screening and analysis of synthetic peptide libraries, ligand 1 has 75...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b01536

    authors： Gilliam AJ,Smith JN,Flather D,Johnston KM,Gansmiller AM,Fishman DA,Edgar JM,Balk M,Majumdar S,Weiss GA

    更新日期：2016-04-28 00:00:00

  • Design, synthesis, and DNA-binding of N-alkyl(anilino)quinazoline derivatives.

    abstract：:New N-alkylanilinoquinazoline derivatives 5, 12, 20, and 22 have been prepared from 4-chloro-6,7-dimethoxyquinazoline 3, 4-chloro-6,7-methylenedioxyquinazoline 19, and commercially available anilines. Differents classes of compounds substituted by an aryloxygroup (6a-c, 16a,b, and 17a,b), (aminophenyl)ureas (12a,b and...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm1009605

    authors： Garofalo A,Goossens L,Baldeyrou B,Lemoine A,Ravez S,Six P,David-Cordonnier MH,Bonte JP,Depreux P,Lansiaux A,Goossens JF

    更新日期：2010-11-25 00:00:00

  • Effect of aromatic nitro compounds on oxidative metabolism by cytochrome P-450 dependent enzymes.

    abstract：:The effect of aromatic nitro compounds on the oxidative metabolism of representative type I (hexobarbital and aminopyrene) and type II (aniline and zoxazolamine) substrates by cytochrome P-450 dependent liver enzymes was studied. Nitro compounds (nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene) ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00223a034

    authors： Sternson LA,Gammans RE

    更新日期：1976-01-01 00:00:00

  • 2-Methyl-1,3-dioxaazaspiro[4.5]decanes as novel muscarinic cholinergic agonists.

    abstract：:Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve. The current paper describes the synthesis and biochemical asse...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00397a039

    authors： Saunders J,Showell GA,Snow RJ,Baker R,Harley EA,Freedman SB

    更新日期：1988-02-01 00:00:00

  • Synthesis and preliminary biological evaluation of high-drug-load paclitaxel-antibody conjugates for tumor-targeted chemotherapy.

    abstract：:The goal of this study was to design paclitaxel (PTX)-monoclonal antibody (mAb) prodrug conjugates (PTXMAbs) with the ability to deliver therapeutically significant doses of the drug to the tumor while avoiding the previously observed solubility limitations of conjugates with PTX:mAb molar ratios of >3. New PTX conjug...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900899g

    authors： Quiles S,Raisch KP,Sanford LL,Bonner JA,Safavy A

    更新日期：2010-01-28 00:00:00

  • Discovery of hepatitis C virus NS3-4A protease inhibitors with improved barrier to resistance and favorable liver distribution.

    abstract：:Given the emergence of resistance observed for the current clinical-stage hepatitis C virus (HCV) NS3 protease inhibitors, there is a need for new inhibitors with a higher barrier to resistance. We recently reported our rational approach to the discovery of macrocyclic acylsulfonamides as HCV protease inhibitors addre...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm400121t

    authors： Moreau B,O'Meara JA,Bordeleau J,Garneau M,Godbout C,Gorys V,Leblanc M,Villemure E,White PW,Llinàs-Brunet M

    更新日期：2014-03-13 00:00:00

  • Identification of non-peptide malignant brain tumor (MBT) repeat antagonists by virtual screening of commercially available compounds.

    abstract：:The malignant brain tumor (MBT) repeat is an important epigenetic-code "reader" and is functionally associated with differentiation, gene silencing, and tumor suppression. (1-3) Small molecule probes of MBT domains should enable a systematic study of MBT-containing proteins and potentially reveal novel druggable targe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm1007374

    authors： Kireev D,Wigle TJ,Norris-Drouin J,Herold JM,Janzen WP,Frye SV

    更新日期：2010-11-11 00:00:00