当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > 2-Phenylindoles. Effect of N-benzylation on estrogen receptor affinity, estrogenic properties, and mammary tumor inhibiting activity.

2-Phenylindoles. Effect of N-benzylation on estrogen receptor affinity, estrogenic properties, and mammary tumor inhibiting activity.

Abstract：

:Hydroxy-2-phenylindoles carrying substituted benzyl groups and similar substituents at the nitrogen were synthesized and tested for their ability to displace estradiol from its receptor. All of the derivatives tested exhibited high binding affinities for the calf uterine estrogen receptor, with RBA values ranging from 0.55 to 16 (estradiol 100). The mouse uterine weight tested revealed only low estrogenicity for this class of compounds. Several derivatives showed antiestrogenic activity with a maximum inhibition of estrone-stimulated uterine growth of 40%. Two of the compounds (6c, 21c) were tested for antitumor activity in dimethylbenanthracene- (DMBA-) induced estrogen-dependent rat mammary tumors. Only the 4-cyanobenzyl derivative 21c was active. After 4 weeks of treatment with 12 mg/kg (6 times/week), the average tumor area was decreased by 57% (control +204%). In vitro, an inhibitory effect of 21b was only observed with hormone-sensitive MCF-7 breast cancer cells but not with hormone-independent MDA-MB 231 cells. These results make a mode of action involving the estrogen receptor system likely.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

von Angerer E,Strohmeier J

doi

10.1021/jm00384a022

subject

Has Abstract

pub_date

1987-01-01 00:00:00

pages

131-6

issue

1

eissn

0022-2623

issn

1520-4804

journal_volume

30

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • 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

  • alpha-Methylproline-containing renin inhibitory peptides: in vivo evaluation in an anesthetized, ganglion-blocked, hog renin infused rat model.

    abstract：:A structure-activity analysis of peptides containing backbone C alpha-methyl modification at the P4 site of the angiotensinogen sequence led to the discovery of potent renin inhibitors with apparent in vitro metabolic stability. Boc-alpha-MePro-Phe-His-Leu psi[CHOHCH2]Val-Ile-Amp dicitrate (Va) is a potent inhibitor o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00386a016

    authors： Thaisrivongs S,Pals DT,Lawson JA,Turner SR,Harris DW

    更新日期：1987-03-01 00:00:00

  • New opioid designed multiple ligand from Dmt-Tic and morphinan pharmacophores.

    abstract：:Here, we report the synthesis of a designed multi-pharmacophore ligand derived from the linkage of a delta selective peptide antagonist (Dmt-Tic) and a mu/kappa morphinan agonist butorphan (MCL 101) through a two methylene spacer. The new compound MCL 450 maintains the same characteristics as those the two reference c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0605785

    authors： Neumeyer JL,Peng X,Knapp BI,Bidlack JM,Lazarus LH,Salvadori S,Trapella C,Balboni G

    更新日期：2006-09-07 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

  • A novel approach for heavy metal poisoning treatment, a model. Mercury poisoning by means of chelating microspheres: hemoperfusion and oral administration.

    abstract：:The chelating drugs BAL (2,3-dimercaptopropanol), EDTA (ethylenediaminetetraacetic acid), and penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), which are used for metal poisoning, are toxic and there is a real need for alternatives, especially for severe cases. A novel approach for treatment of heavy-metal poi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00142a028

    authors： Margel S

    更新日期：1981-10-01 00:00:00

  • Synthesis of steroidal nitrosoureas with antitumor activity.

    abstract：:Four steroidal nitrosoureas with structures which may permit specific binding to estrogen receptor were synthesized. Inhibitory activity was observed against the growth of the DMBA-induced transplantable rat mammary tumor 13762. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00188a015

    authors： Lam HY,Begleiter A,Goldenberg GJ,Wong CM

    更新日期：1979-02-01 00:00:00

  • Prazosin-related compounds. Effect of transforming the piperazinylquinazoline moiety into an aminomethyltetrahydroacridine system on the affinity for alpha1-adrenoreceptors.

    abstract：:In a search for structurally new alpha(1)-adrenoreceptor (alpha(1)-AR) antagonists, prazosin (1)-related compounds 2-11 were synthesized and their affinity profiles were assessed by functional experiments in isolated rat vas deferens (alpha(1A)), spleen (alpha(1B)), and aorta (alpha(1D)) and by binding assays in CHO c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030952q

    authors： Rosini M,Antonello A,Cavalli A,Bolognesi ML,Minarini A,Marucci G,Poggesi E,Leonardi A,Melchiorre C

    更新日期：2003-11-06 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

  • 1-Aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones: novel AMPA receptor antagonists.

    abstract：:Our previous publication (Eur. J. Pharmacol. 1995, 294, 411-422) reported preliminary chemical and biological studies of some 2,3-benzodiazepines, analogues of 1-(4-aminophenyl)-4-methyl-7,8-(methylenedioxy)-5H-2,3-benzodiazepine (1, GYKI 52466), which have been shown to possess significant anticonvulsant activity. Th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960506l

    authors： Chimirri A,De Sarro G,De Sarro A,Gitto R,Grasso S,Quartarone S,Zappalà M,Giusti P,Libri V,Constanti A,Chapman AG

    更新日期：1997-04-11 00:00:00

  • Dopaminergic pharmacophore of ergoline and its analogues. A molecular electrostatic potential study.

    abstract：:Spatial correspondence between apomorphine, a prototype dopaminergic (DA) drug, and ergoline and some of its (partial) analogues were derived by matching their molecular electrostatic potential (MEP) patterns surrounding the aromatic moieties with respect to the coincident aliphatic N atoms. The MEP patterns were calc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00158a017

    authors： Kocjan D,Hodoscek M,Hadzi D

    更新日期：1986-08-01 00:00:00

  • A Kinome-Wide Selective Radiolabeled TrkB/C Inhibitor for in Vitro and in Vivo Neuroimaging: Synthesis, Preclinical Evaluation, and First-in-Human.

    abstract：:The proto-oncogenes NTRK1/2/3 encode the tropomyosin receptor kinases TrkA/B/C which play pivotal roles in neurobiology and cancer. We describe herein the discovery of [11C]-(R)-3 ([11C]-(R)-IPMICF16), a first-in-class positron emission tomography (PET) TrkB/C-targeting radiolabeled kinase inhibitor lead. Relying on e...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b00396

    authors： Bernard-Gauthier V,Bailey JJ,Mossine AV,Lindner S,Vomacka L,Aliaga A,Shao X,Quesada CA,Sherman P,Mahringer A,Kostikov A,Grand'Maison M,Rosa-Neto P,Soucy JP,Thiel A,Kaplan DR,Fricker G,Wängler B,Bartenstein P,Schirrm

    更新日期：2017-08-24 00:00:00

  • Novel [(diazomethyl)carbonyl]-1,2,3,4-tetrahydronaphthalene derivatives as potential photoaffinity ligands for the 5-HT1A receptor.

    abstract：:The photolabile (diazomethyl)carbonyl function was introduced into the 8-position of 2-(N,N-di-n-propyl-amino)-1,2,3,4-tetrahydronaphthalene in three ways, resulting in the ether 8-[[(diazomethyl)carbonyl]methoxy]-2-(N,N-di-n-propylamino)-1,2,3,4- tetrahydronaphthalene (2), the ester 8-(diazoacetoxy)-2-(N,N-di-n-propy...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00165a011

    authors： Kline TB,Nelson DL,Namboodiri K

    更新日期：1990-03-01 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

  • Rational approach to discover multipotent anti-Alzheimer drugs.

    abstract：:The coupling of two different pharmacophores, each endowed with different biological properties, afforded the hybrid compound lipocrine (7), whose biological profile was markedly improved relative to those of prototypes tacrine and lipoic acid. Lipocrine is the first compound that inhibits the catalytic activity of AC...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049112h

    authors： Rosini M,Andrisano V,Bartolini M,Bolognesi ML,Hrelia P,Minarini A,Tarozzi A,Melchiorre C

    更新日期：2005-01-27 00:00:00

  • 3-Pyrroline N-oxide bis(carbamate) tumor inhibitors as analogues of indicine N-oxide.

    abstract：:The 2,3-bis[[(N-methylcarbamoyl)oxy]methyl]-3-pyrroline 1-oxide 5 was synthesized and tested in the murine P388 lymphocytic leukemia model. The compound showed significant reproducible activity and was more potent than indicine N-oxide. 1-Methyl-2-phenyl-3,4-bis[[(N-2- propylcarbamoyl)oxy]methyl]-3-pyrroline N-oxide (...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00394a036

    authors： Anderson WK,Milowsky AS

    更新日期：1987-11-01 00:00:00

  • Reactions of artemisinin and arteether with acid: implications for stability and mode of antimalarial action.

    abstract：:The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060673d

    authors： Drew MG,Metcalfe J,Dascombe MJ,Ismail FM

    更新日期：2006-10-05 00:00:00

  • Structure-activity relationships of a series of novel (piperazinylbutyl)thiazolidinone antipsychotic agents related to 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate.

    abstract：:HP-236 (3-[4-[4-(6-Fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate; P-9236) (54) displayed a pharmacological profile indicative of potential atypical antipsychotic activity. A series of piperazinyl butyl thiazolidinones structurally related to this compound were prepared and ev...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960268u

    authors： Hrib NJ,Jurcak JG,Bregna DE,Burgher KL,Hartman HB,Kafka S,Kerman LL,Kongsamut S,Roehr JE,Szewczak MR,Woods-Kettelberger AT,Corbett R

    更新日期：1996-09-27 00:00:00

  • Regio- and stereochemical studies on the alpha-carbon oxidation of (S)-nicotine by cytochrome P-450 model systems.

    abstract：:Results from previous studies indicate that rabbit liver microsomal cytochrome P-450 catalyzes the C-5' two-electron oxidation of (S)-nicotine stereoselectivity with preferential loss of the pro-(E)-hydrogen atom trans to the pyridine ring. We now have examined the regio- and stereochemical features of the oxidation o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00398a024

    authors： Peterson LA,Castagnoli N Jr

    更新日期：1988-03-01 00:00:00

  • Synthesis, characterization, and Ca2+ antagonistic activity of diltiazem metabolites.

    abstract：:Diltiazem is a calcium antagonist widely used in the treatment of angina and hypertension. The contributions of metabolites of diltiazem to the vasorelaxant effects of diltiazem were investigated. The synthesis and spectroscopic characterization of eight major cis-diltiazem metabolites are described. Three of the comp...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00095a022

    authors： Li R,Farmer PS,Xie M,Quilliam MA,Pleasance S,Howlett SE,Yeung PK

    更新日期：1992-08-21 00:00:00

  • 1,2-Dihydropyrido[3,4-b]pyrazines: structure-activity relationships.

    abstract：:Certain derivatives containing the 1,2-dihydropyrido[3,4-b]pyrazine (1-deaza-7,8-dihydropteridine) ring system are active against experimental neoplasms in mice. The mechanism of action of these agents has been attributed to the accumulation of cells at mitosis. Identification of the structural features that are neces...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00355a018

    authors： Temple C Jr,Wheeler GP,Elliott RD,Rose JD,Comber RN,Montgomery JA

    更新日期：1983-01-01 00:00:00

  • N- and 2-substituted N-(phenylsulfonyl)glycines as inhibitors of rat lens aldose reductase.

    abstract：:A variety of N-(phenylsulfonyl)-N-phenylglycines 5, N-(phenylsulfonyl)-2-phenylglycines 6, and N-(phenylsulfonyl)anthranilic acids 7 were prepared as analogues of the N-(phenylsulfonyl)glycine 1 aldose reductase inhibitors. In the rat lens assay, several derivatives of 5 display greater inhibitory activity than the co...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00121a027

    authors： DeRuiter J,Borne RF,Mayfield CA

    更新日期：1989-01-01 00:00:00

  • N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms.

    abstract：:In this study, we described a series of N-(pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine derivatives as selective JAK2 (Janus kinase 2) inhibitors. Systematic exploration of the structure-activity relationship though cyclization modification based on previously reported compound 18e led to the discovery of the...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c01488

    authors： Yang T,Hu M,Chen Y,Xiang M,Tang M,Qi W,Shi M,He J,Yuan X,Zhang C,Liu K,Li J,Yang Z,Chen L

    更新日期：2020-12-10 00:00:00

  • New neplanocin analogues. 1. Synthesis of 6'-modified neplanocin A derivatives as broad-spectrum antiviral agents.

    abstract：:Novel neplanocin A analogues modified at the 6'-position, i.e., 6'-deoxy analogues (2, 3, 6, 9, 20), 6'-O-methylneplanocin A (15), and 6'-C-methylneplanocin A's (22a and 22b) have been synthesized and evaluated for their antiviral activity in a wide variety of DNA and RNA virus systems. These compounds showed an activ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00080a018

    authors： Shuto S,Obara T,Toriya M,Hosoya M,Snoeck R,Andrei G,Balzarini J,De Clercq E

    更新日期：1992-01-24 00:00:00

  • Ergot alkaloids. Synthesis of nitrosourea derivatives of ergolines as potential anticancer agents.

    abstract：:Nitrosourea derivatives of ergolines have been synthesized for the purpose of obtaining agents with both prolactin-and tumor-inhibitory activity. Two derivatives of 8-amino-6-methylergoline (3), 8-[3-(2-chloroethyl)-3-nitrosoureido]-1-nitroso-6-methylergoline (5c) and 8-[3-2-chloroethyl)-3-nitrosoureido]-6-methylergol...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00187a008

    authors： Crider AM,Lu CK,Floss HG,Cassady JM,Clemens JA

    更新日期：1979-01-01 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

  • 3-substituted indole inhibitors against Francisella tularensis FabI identified by structure-based virtual screening.

    abstract：:In this study, we describe novel inhibitors against Francisella tularensis SchuS4 FabI identified from structure-based in silico screening with integrated molecular dynamics simulations to account for induced fit of a flexible loop crucial for inhibitor binding. Two 3-substituted indoles, 54 and 57, preferentially bou...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm4001242

    authors： Hu X,Compton JR,Abdulhameed MD,Marchand CL,Robertson KL,Leary DH,Jadhav A,Hershfield JR,Wallqvist A,Friedlander AM,Legler PM

    更新日期：2013-07-11 00:00:00

  • Orally potent human renin inhibitors derived from angiotensinogen transition state: design, synthesis, and mode of interaction.

    abstract：:A three-dimensional structure of the complex of human renin and the scissile site P4 Pro to P1' Val of angiotensinogen was deduced in order to design potent human renin inhibitors rationally. On the basis of this structure, an orally potent human renin inhibitor (1a) was designed from the angiotensinogen transition st...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00172a005

    authors： Iizuka K,Kamijo T,Harada H,Akahane K,Kubota T,Umeyama H,Ishida T,Kiso Y

    更新日期：1990-10-01 00:00:00

  • Structure-Based Optimization of Nonquaternary Reactivators of Acetylcholinesterase Inhibited by Organophosphorus Nerve Agents.

    abstract：:Acetylcholinesterase (AChE), a key enzyme in the central and peripheral nervous systems, is the principal target of organophosphorus nerve agents. Quaternary oximes can regenerate AChE activity by displacing the phosphyl group of the nerve agent from the active site, but they are poorly distributed in the central nerv...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b00592

    authors： Santoni G,de Sousa J,de la Mora E,Dias J,Jean L,Sussman JL,Silman I,Renard PY,Brown RCD,Weik M,Baati R,Nachon F

    更新日期：2018-09-13 00:00:00

  • Zwitterionic 3'-O-acyl derivatives of thymidine 5'-phosphate as potential sources of intracellular thymidine 5'-phosphate in cells in culture.

    abstract：:A convenient route is described for attachment of acyl groups CO(CH2)nN(Et)2(CH2)mNH(Et)2 (n = 3, m = 2; n = 4, m = 2-4), CO(CH2)nN(Et)2(CH2)mNEt3 (n = 4, m = 2-4), or CO(CH2)4N(CH2CH2)3N(CH2)nCH3 (n = 1 or 9) to O-3' of thymidine 5'-phosphate (TMP). The compounds are prototypes of 5'-nucleotide derivatives in which t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00155a033

    authors： Chawla RR,Freed JJ,Kappler F,Hampton A

    更新日期：1986-05-01 00:00:00

  • SAR Exploration of Tight-Binding Inhibitors of Influenza Virus PA Endonuclease.

    abstract：:Significant efforts have been reported on the development of influenza antivirals including inhibitors of the RNA-dependent RNA polymerase PA N-terminal (PAN) endonuclease. Based on recently identified, highly active metal-binding pharmacophores (MBPs) for PAN endonuclease inhibition, a fragment-based drug development...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00747

    authors： Credille CV,Morrison CN,Stokes RW,Dick BL,Feng Y,Sun J,Chen Y,Cohen SM

    更新日期：2019-11-14 00:00:00