当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Assessment of a potential dopaminergic prodrug moiety in several ring systems.

Assessment of a potential dopaminergic prodrug moiety in several ring systems.

Abstract：

:The ortho hydroxy/methyl, hydroxy/hydroxymethyl, hydroxy/formyl, and hydroxy/carboxy substitution patterns, some of which confer dopaminergic agonist effects upon 2-aminotetralin ring systems, have been incorporated into beta-phenethylamine, 2-aminoindan, and trans-octahydrobenzo[f]quinoline rings. Certain of the 2-aminoindan derivatives displayed pharmacologic properties consistent with their being dopaminergic agonists. The beta-phenethylamine derivative did not show any significant dopamine-like activity. The 7-hydroxy-8-methyloctahydrobenzo[f]quinoline derivative 4a was a moderately potent, short-acting DA2 receptor antagonist. All of the carboxylic acid derivatives were inert. Of the ortho hydroxy/methyl derivatives, only the 5-hydroxy-6-methyl-2-aminotetralin derivative displayed pharmacological properties consistent with its being a dopaminergic prodrug. It is concluded that 5-hydroxy-6-methyl-2-(di-n-propylamino)tetralin (1a) is structurally unique for a dopaminergic drug.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Cannon JG,Furlano DC,Dushin RG,Chang YA,Baird SR,Soliman LN,Flynn JR,Long JP,Bhatnagar RK

doi

10.1021/jm00160a036

subject

Has Abstract

pub_date

1986-10-01 00:00:00

pages

2016-20

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

29

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Design and syntheses of 1,6-naphthalene derivatives as selective HCMV protease inhibitors.

    abstract：:Through high throughput screening of various libraries, substituted styryl naphthalene 6 was identified as an HCMV protease inhibitor. Optimization of various regions of the lead molecule using parallel synthesis resulted in 1,6-substituted naphthalenes 19d-i. These compounds displayed good potency and were selective ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030540h

    authors： Gopalsamy A,Lim K,Ellingboe JW,Mitsner B,Nikitenko A,Upeslacis J,Mansour TS,Olson MW,Bebernitz GA,Grinberg D,Feld B,Moy FJ,O'Connell J

    更新日期：2004-04-08 00:00:00

  • Design, synthesis, and characterization of a dual modality positron emission tomography and fluorescence imaging agent for monoclonal antibody tumor-targeted imaging.

    abstract：:A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A' ') for sequestering radiometals (86Y or 111In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm070657w

    authors： Xu H,Baidoo K,Gunn AJ,Boswell CA,Milenic DE,Choyke PL,Brechbiel MW

    更新日期：2007-09-20 00:00:00

  • Inhibitors of cholesterol biosynthesis. 2. Hypocholesterolemic and antioxidant activities of benzopyran and tetrahydronaphthalene analogues of the tocotrienols.

    abstract：:Tocotrienols exhibit antioxidant and cholesterol-biosynthesis-inhibitory activities and may be of value as antiatherosclerotic agents. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase (HMGR) in a manner mimicking the action of putative non-sterol feedback inhibi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00030a012

    authors： Pearce BC,Parker RA,Deason ME,Dischino DD,Gillespie E,Qureshi AA,Volk K,Wright JJ

    更新日期：1994-02-18 00:00:00

  • Drug Induced Liver Injury (DILI). Mechanisms and Medicinal Chemistry Avoidance/Mitigation Strategies.

    abstract：:Adverse drug reactions (ADRs) are a common cause of attrition in drug discovery and development and drug-induced liver injury (DILI) is a leading cause of preclinical and clinical drug terminations. This perspective outlines many of the known DILI mechanisms and assessment methods used to evaluate and mitigate DILI ri...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.0c00524

    authors： Norman BH

    更新日期：2020-10-22 00:00:00

  • Structure-function correlation of chloroquine and analogues as transgene expression enhancers in nonviral gene delivery.

    abstract：:To understand how chloroquine (CQ) enhances transgene expression in polycation-based, nonviral gene delivery systems, a number of CQ analogues with variations in the aliphatic amino side chain or in the aromatic ring are synthesized and investigated. Our studies indicate that the aliphatic amino moiety of CQ is essent...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060736s

    authors： Cheng J,Zeidan R,Mishra S,Liu A,Pun SH,Kulkarni RP,Jensen GS,Bellocq NC,Davis ME

    更新日期：2006-11-02 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

  • Synthesis and biological evaluations of certain 2-halo-2'-substituted derivatives of 9-beta-D-arabinofuranosyladenine.

    abstract：:The synthesis of a series of 2-chloro- or 2-fluoro-9-(2-substituted-2-deoxy-beta-D-arabinofuranosyl)adenines (4g-n) is described. New compounds were prepared from either 2-chloroadenosine or 2-fluoroadenosine by first blocking the 3'- and 5'-hydroxyls as the tetraisopropyldisiloxane derivatives. Activation of O-2' by ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00397a024

    authors： Secrist JA 3rd,Shortnacy AT,Montgomery JA

    更新日期：1988-02-01 00:00:00

  • N- versus C-domain selectivity of catalytic inactivation of human angiotensin converting enzyme by lisinopril-coupled transition metal chelates.

    abstract：:The N- and C-terminal domains of human somatic angiotensin I converting enzyme (sACE-1) demonstrate distinct physiological functions, with resulting interest in the development of domain-selective inhibitors for specific therapeutic applications. Herein, the activity of lisinopril-coupled transition metal chelates was...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm4009345

    authors： Hocharoen L,Joyner JC,Cowan JA

    更新日期：2013-12-27 00:00:00

  • Antitumor activity and toxicity of novel nitroheterocyclic phosphoramidates.

    abstract：:A series of novel nitroheterocyclic phosphoramidates has been evaluated for antitumor activity in murine and xenograft tumor models and for toxicity in mice. Significant increases in lifespan and long-term survivors were noted in L1210 leukemia and B16 melanoma models, and both complete and partial tumor regressions w...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000359y

    authors： Borch RF,Liu J,Joswig C,Baggs RB,Dexter DL,Mangold GL

    更新日期：2001-01-04 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

  • An integrated computational approach to the phenomenon of potent and selective inhibition of aurora kinases B and C by a series of 7-substituted indirubins.

    abstract：:A variation of the bromine substitution from 6- to 7-position converts the glycogen synthase kinase-3alpha/beta-(GSK-3-alpha/beta) selective inhibitor 6-bromoindirubin-3'-oxime (6BIO) to a potent inhibitor of Aurora B and C kinases. The novel indirubin analogue 7-bromoindirubin-3'-oxime (7BIO) demonstrated unexpected ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm070077z

    authors： Myrianthopoulos V,Magiatis P,Ferandin Y,Skaltsounis AL,Meijer L,Mikros E

    更新日期：2007-08-23 00:00:00

  • Design, synthesis, and biological evaluation of ellipticine-estradiol conjugates.

    abstract：:Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) pos...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9602930

    authors： Devraj R,Barrett JF,Fernandez JA,Katzenellenbogen JA,Cushman M

    更新日期：1996-08-16 00:00:00

  • Toward general methods of targeted library design: topomer shape similarity searching with diverse structures as queries.

    abstract：:A promising strategy for selecting synthetic targets is similarity-based searching of very large "virtual libraries", which comprise all structures accessible by linking two or three commercially available building blocks with combinatorial syntheses. To assess the general applicability of this strategy, leading struc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000003m

    authors： Andrews KM,Cramer RD

    更新日期：2000-05-04 00:00:00

  • Substituted 1,4-naphthoquinones vs. the ascitic sarcoma 180 of mice.

    abstract：:Twelve 1,4-naphthoquinones have been tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis shows that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials. Although the toxicities of the compounds...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00358a021

    authors： Hodnett EM,Wongwiechintana C,Dunn WJ 3rd,Marrs P

    更新日期：1983-04-01 00:00:00

  • Structure-activity relationships of substituted 1-pyridyl-2-phenyl-1,2-ethanediones: potent, selective carboxylesterase inhibitors.

    abstract：:Inhibition of intestinal carboxylesterases may allow modification of the pharmacokinetics/pharmacodynamic profile of existing drugs by altering half-life or toxicity. Since previously identified diarylethane-1,2-dione inhibitors are decidedly hydrophobic, a modified dione scaffold was designed and elaborated into a >3...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm101101q

    authors： Young BM,Hyatt JL,Bouck DC,Chen T,Hanumesh P,Price J,Boyd VA,Potter PM,Webb TR

    更新日期：2010-12-23 00:00:00

  • Nitric oxide synthases activation and inhibition by metallacarborane-cluster-based isoform-specific affectors.

    abstract：:A small library of boron-cluster- and metallacarborane-cluster-based ligands was designed, prepared, and tested for isoform-selective activation or inhibition of the three nitric oxide synthase isoforms. On the basis of the concept of creating a hydrophobic analogue of a natural substrate, a stable and nontoxic basic ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm300805x

    authors： Kaplánek R,Martásek P,Grüner B,Panda S,Rak J,Masters BS,Král V,Roman LJ

    更新日期：2012-11-26 00:00:00

  • Characterization of potent and selective antagonists at postsynaptic 5-HT1A receptors in a series of N4-substituted arylpiperazines.

    abstract：:Benzocycloalkyl and benzocycloalkenyl moities linked, directly or via an alkyl chain, to oxygen-bearing heteroarylpiperazines were synthesized, in an attempt to obtain potent and selective antagonists at postsynaptic 5-HT1A receptors. From the numerous arylpiperazines described in the literature, 1-(2,3-dihydro-1,4-be...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00020a020

    authors： Peglion JL,Canton H,Bervoets K,Audinot V,Brocco M,Gobert A,Le Marouille-Girardon S,Millan MJ

    更新日期：1995-09-29 00:00:00

  • Benzodiazepine receptor binding and anticonflict activity in a series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines devoid of anticonvulsant properties.

    abstract：:A series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines were synthesized and tested for their ability to inhibit the binding of [3H]diazepam to rat brain receptors in vitro. Compounds bearing a phenyl, 4-methoxyphenyl, or methyl group at position 3 and a dialkylamino group at position 6 showed the highest affinit...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00147a034

    authors： Toja E,Tarzia G,Barone D,Luzzani F,Gallico L

    更新日期：1985-09-01 00:00:00

  • Structure-activity relationships of analogues of thapsigargin modified at O-11 and O-12.

    abstract：:A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed s...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00002a009

    authors： Nielsen SF,Thastrup O,Pedersen R,Olsen CE,Christensen SB

    更新日期：1995-01-20 00:00:00

  • Phosphate Chemical Probes Designed for Location Specific Inhibition of Intracellular Carbonic Anhydrases.

    abstract：:Chemical probes are small molecules designed to bind to a specific protein and disrupt the proteins function. Although many inhibitors are reported for human carbonic anhydrase (CA) enzymes, few may be considered useful as chemical probes as they exhibit broad action against the 12 catalytically active CA isozymes. In...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b01228

    authors： Rankin GM,Vullo D,Supuran CT,Poulsen SA

    更新日期：2015-09-24 00:00:00

  • Design of triazole-stapled BCL9 α-helical peptides to target the β-catenin/B-cell CLL/lymphoma 9 (BCL9) protein-protein interaction.

    abstract：:The interaction between β-catenin and B-cell CLL/lymphoma 9 (BCL9), critical for the transcriptional activity of β-catenin, is mediated by a helical segment from BCL9 and a large binding groove in β-catenin. Design of potent, metabolically stable BCL9 peptides represents an attractive approach to inhibit the activity ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm201125d

    authors： Kawamoto SA,Coleska A,Ran X,Yi H,Yang CY,Wang S

    更新日期：2012-02-09 00:00:00

  • Synthesis of 1-(2-aminophenyl)isoquinolines and the biological activity of their cis-dichloro platinum(II) complexes.

    abstract：:The broad biological effects of isoquinolines prompted us to use them as chelating, nonleaving ligands in cis-platinum(II) antitumor complexes. The synthesis of several 1-(2-aminophenyl)isoquinoline derivatives with different levels of hydrogenation and varying substitution of the phenyl ring is reported. These compou...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm980434t

    authors： von Nussbaum F,Miller B,Wild S,Hilger CS,Schumann S,Zorbas H,Beck W,Steglich W

    更新日期：1999-09-09 00:00:00

  • Synthesis and pharmacokinetics of valopicitabine (NM283), an efficient prodrug of the potent anti-HCV agent 2'-C-methylcytidine.

    abstract：:In our search for new therapeutic agents against chronic hepatitis C, a ribonucleoside analogue, 2'-C-methylcytidine, was discovered to be a potent and selective inhibitor in cell culture of a number of RNA viruses, including the pestivirus bovine viral diarrhea virus, a surrogate model for hepatitis C virus (HCV), an...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0603623

    authors： Pierra C,Amador A,Benzaria S,Cretton-Scott E,D'Amours M,Mao J,Mathieu S,Moussa A,Bridges EG,Standring DN,Sommadossi JP,Storer R,Gosselin G

    更新日期：2006-11-02 00:00:00

  • Synthesis, NMDA receptor antagonist activity, and anticonvulsant action of 1-aminocyclobutanecarboxylic acid derivatives.

    abstract：:A range of cis- and trans-3-substituted 1-aminocyclobutane-1-carboxylic acids has been synthesized and evaluated for antagonism at excitatory amino acid receptor sites and for anticonvulsant activity. Potent and selective antagonist activity at N-methyl-D-aspartate (NMDA) receptor sites in neonatal rat motoneurones wa...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00051a005

    authors： Gaoni Y,Chapman AG,Parvez N,Pook PC,Jane DE,Watkins JC

    更新日期：1994-12-09 00:00:00

  • Amidate Prodrugs of Deoxythreosyl Nucleoside Phosphonates as Dual Inhibitors of HIV and HBV Replication.

    abstract：:The synthesis of four l-2'-deoxy-threose nucleoside phosphonates with the natural nucleobases adenine, thymine, cytosine, and guanosine has been performed. Especially the adenine containing analogue (PMDTA) was endowed with potent antiviral activity displaying an EC50 of 4.69 μM against HIV-1 and an EC50 value of 0.5 ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01260

    authors： Liu C,Dumbre SG,Pannecouque C,Huang C,Ptak RG,Murray MG,De Jonghe S,Herdewijn P

    更新日期：2016-10-27 00:00:00

  • Allosteric modulation of the dopamine D2 receptor by Pro-Leu-Gly-NH2 peptidomimetics constrained in either a polyproline II helix or a type II beta-turn conformation.

    abstract：:Type II beta-turn mimics and polyproline II helix mimics based upon diastereoisomeric 5.6.5 spiro bicyclic scaffolds have provided two pairs of Pro-Leu-Gly-NH(2) (PLG) peptidomimetics with contrasting dopamine receptor modulating activities. Compounds 1a and 3a were found to be positive allosteric modulators of the do...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm801575w

    authors： Raghavan B,Skoblenick KJ,Bhagwanth S,Argintaru N,Mishra RK,Johnson RL

    更新日期：2009-04-09 00:00:00

  • Comparative structure-activity relationships of antifolate triazines inhibiting murine tumor cells sensitive and resistant to methotrexate.

    abstract：:The inhibitory effect of 108 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines on murine L5178Y tumor cells, resistant and sensitive to methotrexate (MTX), has been studied. From the pI50 values, quantitative structure-activity relationships have been formulated which show that the lipophilic tri...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00369a019

    authors： Selassie CD,Hansch C,Khwaja TA,Dias CB,Pentecost S

    更新日期：1984-03-01 00:00:00

  • Synthesis of peptide analogues of prothrombin precursor sequence 5-9. Substrate specificity of vitamin K dependent carboxylase.

    abstract：:Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase. Carboxylation of substrate was determined by measuring the incorporation of carbon-24 labeled bic...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00138a013

    authors： Rich DH,Lehrman SR,Kawai M,Goodman HL,Suttie JW

    更新日期：1981-06-01 00:00:00

  • Discovery of 5-substituted-6-chlorouracils as efficient inhibitors of human thymidine phosphorylase.

    abstract：:Thymidine phosphorylase plays an important role in angiogenesis, which is an attractive target for therapy of cancer and other diseases. In our continuous effort to develop novel inhibitors of thymidine phosphorylase, we have discovered that 6-halouracils substituted at position C5 by certain hydrophobic groups exhibi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm070644i

    authors： Nencka R,Votruba I,Hrebabecký H,Jansa P,Tloust'ová E,Horská K,Masojídková M,Holý A

    更新日期：2007-11-29 00:00:00

  • 2-Phenylpyrroles as conformationally restricted benzamide analogues. A new class of potential antipsychotics. 1.

    abstract：:2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00394a028

    authors： van Wijngaarden I,Kruse CG,van Hes R,van der Heyden JA,Tulp MT

    更新日期：1987-11-01 00:00:00