当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Conformational effects on retinoid receptor selectivity. 2. Effects of retinoid bridging group on retinoid X receptor activity and selectivity.

Conformational effects on retinoid receptor selectivity. 2. Effects of retinoid bridging group on retinoid X receptor activity and selectivity.

Abstract：

:The natural retinoid 9-cis-retinoic acid is an activating ligand for both the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs), which are members of the retinoid/thyroid hormone/steroid hormone family of nuclear receptor proteins that activate gene transcription through specific response elements. The pharmacophoric groups necessary to confer RXR selectivity were established by evaluating the ability of 21 conformationally restricted retinoids to activate the TREpal retinoic acid receptor response element for gene transcription in the presence of one of the three RAR subtypes or RXR alpha. In contrast to those retinoids selective for the RARs, these RXR-selective retinoids have one less atom in the bridge linking the hydrophobic and carboxylic acid termini of the retinoid skeleton. Therefore, a one-carbon bridge replaces the 19-methyl group and 9E-double bond of 9-cis-retinoic acid and is further functionalized by inclusion in an isopropylidene group, a dioxolane ring, or a cyclopropane ring for optimal RXR alpha activity and selectivity. In addition, the beta-geranylidene and 20-methyl-(11E,13E)-dienoic acid groups of 9-cis-retinoic acid are replaced by a 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl ring and a 4-carboxylphenyl ring, respectively, for optimal activation and selectivity. RXR alpha selectivity is reduced on replacement of the 4-carboxylphenyl group by a 2-carboxyl-5-thienyl group or the 9-cis-retinoic acid methylpentadienoic acid terminus.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Dawson MI,Jong L,Hobbs PD,Cameron JF,Chao WR,Pfahl M,Lee MO,Shroot B,Pfahl M

doi

10.1021/jm00017a021

subject

Has Abstract

pub_date

1995-08-18 00:00:00

pages

3368-83

issue

17

eissn

0022-2623

issn

1520-4804

journal_volume

38

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Hydroxamate-Based Selective Macrophage Elastase (MMP-12) Inhibitors and Radiotracers for Molecular Imaging.

    abstract：:Macrophage elastase [matrix metalloproteinase (MMP)-12] is the most upregulated MMP in abdominal aortic aneurysm (AAA) and, hence, MMP-12-targeted imaging may predict AAA progression and rupture risk. Here, we report the design, synthesis, and evaluation of three novel hydroxamate-based selective MMP-12 inhibitors (CG...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c01514

    authors： Gona K,Toczek J,Ye Y,Sanzida N,Golbazi A,Boodagh P,Salarian M,Jung JJ,Rajendran S,Kukreja G,Wu TL,Devel L,Sadeghi MM

    更新日期：2020-12-10 00:00:00

  • Conformations and "nictinic" activites of cyclic analogues of choline aryl ether.

    abstract：:The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the min...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00227a022

    authors： Clark ER,Hughes IE,Smith CF

    更新日期：1976-05-01 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

  • Localizing antithrombotic and vasodilatory activity with a novel, ultrafast nitric oxide donor.

    abstract：:Reaction of nitric oxide (NO) with L-proline in methanolic sodium methoxide yields a diazeniumdiolate product, C5H7N3O4Na2.CH3OH (PROLI/NO), that can be stabilized in basic solution but that dissociates to proline (1 mol) and NO (2 mol) with a half-life of only 1.8 s at pH 7.4 and 37 degrees C. This kinetic behavior h...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960616s

    authors： Saavedra JE,Southan GJ,Davies KM,Lundell A,Markou C,Hanson SR,Adrie C,Hurford WE,Zapol WM,Keefer LK

    更新日期：1996-10-25 00:00:00

  • Toward development of targeted nonsteroidal antiandrogen-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-gadolinium complex for prostate cancer diagnostics.

    abstract：:Androgen receptors are present in most advanced prostate cancer specimens, having a critical role in development of this type of cancer. For correct prognosis of patient conditions and treatment monitoring, noninvasive imaging techniques have great advantages over surgical procedures. We developed synthetic methodolog...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100289b

    authors： Marom H,Miller K,Bechor-Bar Y,Tsarfaty G,Satchi-Fainaro R,Gozin M

    更新日期：2010-09-09 00:00:00

  • Nonsymmetrical bipiperidyls as inhibitors of vesicular acetylcholine storage.

    abstract：:Introduction of a nitrogen atom into the cyclohexane ring of 2-(4-phenylpiperidinyl)cyclohexanol (vesamicol, AH5183) yielded two positional isomers, 5-azavesamicol (5, prezamicol) and 4-azavesamicol (6, trozamicol). As inhibitors of vesicular acetylcholine transport, 5 and 6 were found to be 147 and 85 times less pote...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00060a005

    authors： Efange SM,Khare A,Parsons SM,Bau R,Metzenthin T

    更新日期：1993-04-16 00:00:00

  • A Drosophila model to identify polyamine-drug conjugates that target the polyamine transporter in an intact epithelium.

    abstract：:Polyamine transport is elevated in many tumor types, suggesting that toxic polyamine-drug conjugates could be targeted to cancer cells via the polyamine transporter (PAT). We have previously reported the use of Chinese hamster ovary (CHO) cells and its PAT-deficient mutant cell line, CHO-MG, to screen anthracene-polya...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701198s

    authors： Tsen C,Iltis M,Kaur N,Bayer C,Delcros JG,von Kalm L,Phanstiel O 4th

    更新日期：2008-01-24 00:00:00

  • Dual-action cephalosporins: cephalosporin 3'-quinolone carbamates.

    abstract：:A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibac...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00113a026

    authors： Albrecht HA,Beskid G,Christenson JG,Georgopapadakou NH,Keith DD,Konzelmann FM,Pruess DL,Rossman PL,Wei CC

    更新日期：1991-09-01 00:00:00

  • Biospectra analysis: model proteome characterizations for linking molecular structure and biological response.

    abstract：:Establishing quantitative relationships between molecular structure and broad biological effects has been a long-standing goal in drug discovery. Evaluation of the capacity of molecules to modulate protein functions is a prerequisite for understanding the relationship between molecular structure and in vivo biological...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm050494g

    authors： Fliri AF,Loging WT,Thadeio PF,Volkmann RA

    更新日期：2005-11-03 00:00:00

  • Synthesis, characterization, and comparative in vitro cytotoxicity studies of platinum(II), palladium(II), and gold(III) methylsarcosinedithiocarbamate complexes.

    abstract：:This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049191x

    authors： Giovagnini L,Ronconi L,Aldinucci D,Lorenzon D,Sitran S,Fregona D

    更新日期：2005-03-10 00:00:00

  • Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis.

    abstract：:Farnesoid X receptor (FXR) agonists are emerging as important potential therapeutics for the treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multiple aspects of the disease. FXR agonists reduce lipid accumulation in the liver, hepatocellular inflammation, hepatic injury, an...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01621

    authors： Chianelli D,Rucker PV,Roland J,Tully DC,Nelson J,Liu X,Bursulaya B,Hernandez ED,Wu J,Prashad M,Schlama T,Liu Y,Chu A,Schmeits J,Huang DJ,Hill R,Bao D,Zoll J,Kim Y,Groessl T,McNamara P,Liu B,Richmond W,Sancho

    更新日期：2020-04-23 00:00:00

  • Antimalarial activity of yingzhaosu A analogues.

    abstract：:Iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu A analogues 2. In some cases, however, the corresponding cyclic ethers 5 were formed competitively with the cyclic peroxides 2, the ratios of these two products being a marked function of the structure of the starting ma...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020208q

    authors： Kim HS,Begum K,Ogura N,Wataya Y,Tokuyasu T,Masuyama A,Nojima M,McCullough KJ

    更新日期：2002-10-10 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

  • 3'-Fluoro-2',3'-dideoxy-5-chlorouridine: most selective anti-HIV-1 agent among a series of new 2'- and 3'-fluorinated 2',3'-dideoxynucleoside analogues.

    abstract：:A series of 2'- and 3'-fluorinated 2',3'-dideoxynucleosides and 3'-azido-2',3'-dideoxynucleosides were synthesized and evaluated for their inhibitory activity against human immunodeficiency virus-1 (HIV-1) replication in MT-4 cells. Neither conversion of 3'-fluoro- or 3'-azido-2',3'-dideoxyadenosine to the correspondi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00128a013

    authors： Van Aerschot A,Herdewijn P,Balzarini J,Pauwels R,De Clercq E

    更新日期：1989-08-01 00:00:00

  • Nintedanib: from discovery to the clinic.

    abstract：:Nintedanib (BIBF1120) is a potent, oral, small-molecule tyrosine kinase inhibitor, also known as a triple angiokinase inhibitor, inhibiting three major signaling pathways involved in angiogenesis. Nintedanib targets proangiogenic and pro-fibrotic pathways mediated by the VEGFR family, the fibroblast growth factor rece...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/jm501562a

    authors： Roth GJ,Binder R,Colbatzky F,Dallinger C,Schlenker-Herceg R,Hilberg F,Wollin SL,Kaiser R

    更新日期：2015-02-12 00:00:00

  • Synthesis and antiviral activity of 5-[(cyanomethylene)oxy]-2'-deoxyuridine.

    abstract：:To study the influence of substitution of CN for C identical to CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-[(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated produ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00136a007

    authors： Huang GF,Okada M,De Clercq E,Torrence PF

    更新日期：1981-04-01 00:00:00

  • Synthesis and preliminary biological studies of 4- and 5-[2-hydroxy-3-(isopropylamino)propoxy]benzimidazoles: selective beta2 adrenergic blocking agents.

    abstract：:Benzimidazoles carrying the 2-hydroxy-3-(isopropylamino)propoxy side chain at either the C-4 or C-5 ring positions were synthesized and investigated for beta-adrenergic blocking activity. Both compounds demonstrated beta2 selectivity when evaluated in guinea pig atrial and tracheal preparations. The C-4 isomer was 17 ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00188a019

    authors： Crooks CR,Wright J,Callery PS,Moreton JE

    更新日期：1979-02-01 00:00:00

  • Probing the cysteine-34 position of endogenous serum albumin with thiol-binding doxorubicin derivatives. Improved efficacy of an acid-sensitive doxorubicin derivative with specific albumin-binding properties compared to that of the parent compound.

    abstract：:We have recently proposed a macromolecular prodrug strategy for improved cancer chemotherapy based on two features (Kratz, F.; et al. J. Med. Chem 2000, 43, 1253-1256.): (a) rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration and (b)...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020276c

    authors： Kratz F,Warnecke A,Scheuermann K,Stockmar C,Schwab J,Lazar P,Drückes P,Esser N,Drevs J,Rognan D,Bissantz C,Hinderling C,Folkers G,Fichtner I,Unger C

    更新日期：2002-12-05 00:00:00

  • Potential antitumor agents. 31. Quantitative structure-activity relationships for the antileukemic bis(guanylhydrazones).

    abstract：:Certain L1210-active bis(guanylhydrazones) have structural and biological properties in common with the DNA minor groove binding, antileukemic, bisquaternary ammonium heterocycles. Monitoring of the DNA binding of the bis(guanylhydrazones), by fluorimetric quantitation of drug displacement of DNA-bound ethidium, shows...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00196a016

    authors： Denny WA,Cain BF

    更新日期：1979-10-01 00:00:00

  • Selective inhibitors of monoamine oxidase. 2. Arylamide SAR.

    abstract：:Monoamine oxidase (MAO) exists in two forms distinguishable by substrate specificity. Inhibition of MAO A is believed to be responsible for the antidepressant activity of MAO inhibitors. A group of N-arylacetamides are highly specific inhibitors of MAO A, some with IC50 values in the 10-100 nM range. The requirements ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00039a021

    authors： Harfenist M,Joyner CT,Mize PD,White HL

    更新日期：1994-06-24 00:00:00

  • Drug Discovery Targeting Anaplastic Lymphoma Kinase (ALK).

    abstract：:As a receptor tyrosine kinase of insulin receptor (IR) subfamily, anaplastic lymphoma kinase (ALK) has been validated to play important roles in various cancers, especially anaplastic large cell lymphoma (ALCL), nonsmall cell lung cancer (NSCLC), and neuroblastomas. Currently, five small-molecule inhibitors of ALK, in...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.9b00446

    authors： Kong X,Pan P,Sun H,Xia H,Wang X,Li Y,Hou T

    更新日期：2019-12-26 00:00:00

  • Structure-Based Discovery and Development of a Series of Potent and Selective Bromodomain and Extra-Terminal Protein Inhibitors.

    abstract：:BRD4 has recently emerged as a promising drug target. Therefore, identifying novel inhibitors with distinct properties could enrich their use in anticancer treatment. Guided by the cocrystal structure of hit compound 4 harboring a five-membered-ring linker motif, we quickly identified lead compound 7, which exhibited ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01094

    authors： Hu J,Tian CQ,Damaneh MS,Li Y,Cao D,Lv K,Yu T,Meng T,Chen D,Wang X,Chen L,Li J,Song SS,Huan XJ,Qin L,Shen J,Wang YQ,Miao ZH,Xiong B

    更新日期：2019-09-26 00:00:00

  • Development of an Orally Available and Central Nervous System (CNS) Penetrant Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1) Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity for the Treatment of Toxoplasmosis.

    abstract：:New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite Toxoplasma gondii. To this end, we previously developed a potent and selective inhibitor (compound 1) of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) that possesses antitoxoplasmosis activ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00760

    authors： Vidadala RS,Rivas KL,Ojo KK,Hulverson MA,Zambriski JA,Bruzual I,Schultz TL,Huang W,Zhang Z,Scheele S,DeRocher AE,Choi R,Barrett LK,Siddaramaiah LK,Hol WG,Fan E,Merritt EA,Parsons M,Freiberg G,Marsh K,Kempf DJ,Ca

    更新日期：2016-07-14 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

  • Structure-based design and synthesis of non-nucleoside, potent, and orally bioavailable adenosine deaminase inhibitors.

    abstract：:We disclose optimization efforts based on the novel non-nucleoside adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based drug design utilizing the crystal structure of the 4/ADA complex led to discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from metabolic considerations, we discovered t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0499559

    authors： Terasaka T,Okumura H,Tsuji K,Kato T,Nakanishi I,Kinoshita T,Kato Y,Kuno M,Seki N,Naoe Y,Inoue T,Tanaka K,Nakamura K

    更新日期：2004-05-20 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

  • Design, Multicomponent Synthesis, and Anticancer Activity of a Focused Histone Deacetylase (HDAC) Inhibitor Library with Peptoid-Based Cap Groups.

    abstract：:In this work, we report the multicomponent synthesis of a focused histone deacetylase (HDAC) inhibitor library with peptoid-based cap groups and different zinc-binding groups. All synthesized compounds were tested in a cellular HDAC inhibition assay and an MTT assay for cytotoxicity. On the basis of their noteworthy a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b00197

    authors： Krieger V,Hamacher A,Gertzen CGW,Senger J,Zwinderman MRH,Marek M,Romier C,Dekker FJ,Kurz T,Jung M,Gohlke H,Kassack MU,Hansen FK

    更新日期：2017-07-13 00:00:00

  • Toward the design of chemical libraries for mass screening biased against mutagenic compounds.

    abstract：:The ability to develop a chemical into a drug depends on multiple factors. Beyond potency and selectivity, ADME/PK and the toxicological profile of the compound play a significant role in its evaluation as a candidate for development. Those factors are being brought into bear earlier in the discovery process and even ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0004594

    authors： Llorens O,Perez JJ,Villar HO

    更新日期：2001-08-16 00:00:00

  • Analogs of camptothecin.

    abstract：:Several compounds having portions of the camptothecin ring system were prepared. These compounds were screened against L1210 lymphoid leukemia with negative results. Two of the analogs which contained the pyridine and hydroxylactone D and E rings were also screened for inhibition of DNA and RNA syntheses in HeLa cells...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00239a024

    authors： Horwitz SB,Bristol JA,Comins DL,Davenport RW,Kane MJ,Lyle RE,Maloney JR,Portlock DE

    更新日期：1975-05-01 00:00:00

  • Structure-activity studies of reduced-size gonadotropin-releasing hormone agonists derived from the sequence of an endothelin antagonist.

    abstract：:We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (Ki = 1.9 microM) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm990432o

    authors： Yahalom D,Rahimipour S,Koch Y,Ben-Aroya N,Fridkin M

    更新日期：2000-07-27 00:00:00