当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Structurally simple trichostatin A-like straight chain hydroxamates as potent histone deacetylase inhibitors.

Structurally simple trichostatin A-like straight chain hydroxamates as potent histone deacetylase inhibitors.

Abstract：

:A series of new, structurally simple trichostatin A (TSA)-like straight chain hydroxamates were prepared and evaluated for their ability to inhibit partially purified human histone deacetylase 1 (HDAC-1). Some of these compounds such as 8m, 8n, 12, and 15b exhibited potent HDAC inhibitory activity with low nanomolar IC(50) values, comparable to natural TSA. These compounds induce hyperacetylation of histones in T24 human cancer cells and significantly inhibit proliferation in various human cancer cells. They also induce expression of p21 and cause cell cycle blocks in human cancer cells. In this paper, we describe the synthesis of these new compounds as well as structure-activity relationship results from enzyme inhibition and alterations in cellular function.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Woo SH,Frechette S,Abou Khalil E,Bouchain G,Vaisburg A,Bernstein N,Moradei O,Leit S,Allan M,Fournel M,Trachy-Bourget MC,Li Z,Besterman JM,Delorme D

doi

10.1021/jm020154k

keywords:

subject

Has Abstract

pub_date

2002-06-20 00:00:00

pages

2877-85

issue

13

eissn

0022-2623

issn

1520-4804

pii

jm020154k

journal_volume

45

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Structure-based design and synthesis of macroheterocyclic peptidomimetic inhibitors of the aspartic protease beta-site amyloid precursor protein cleaving enzyme (BACE).

    abstract：:Based on the X-ray cocrystal structure of the Tang-Ghosh heptapeptide inhibitor 1 (OM00-3), a series of macroheterocyclic analogues were designed and synthesized. Analogues containing dithia, dioxa, oxathia, and carbathia macrocycles were synthesized by methods relying on ring-closing olefin metathesis for the dioxa a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060154a

    authors： Hanessian S,Yang G,Rondeau JM,Neumann U,Betschart C,Tintelnot-Blomley M

    更新日期：2006-07-27 00:00:00

  • Synthesis and evaluation of selected key methyl ether derivatives of vancomycin aglycon.

    abstract：:A select series of methyl ether derivatives of vancomcyin aglycon were prepared and examined for antimicrobial activity against vancomycin-sensitive Staphylococcus aureus and vancomycin-resistant Enterococci faecalis as well as their binding affinity for D-Ala-D-Ala and D-Ala-D-Lac. The intent of the study was to eluc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100946e

    authors： Crane CM,Pierce JG,Leung SS,Tirado-Rives J,Jorgensen WL,Boger DL

    更新日期：2010-10-14 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

  • Fluorinated retinoic acids and their analogues. 1. Synthesis and Biological activity of (4-methoxy-2,3,6-trimethylphenyl)nonatetraenoic acid analogues.

    abstract：:(4-Methoyx-2,3,6-trimethylphenyl)nonatetraenoic acids, esters, and amides (analogues of retinoic acid) bearing a fluorine atom(s) or a trifluoromethyl group on the polyene side chain were synthesized. The biological activities of these compounds and of 10-, 12-, and 14-fluororetinoic acid esters were evaluated in vivo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00195a010

    authors： Pawson BA,Chan KK,DeNoble J,Han RJ,Piermattie V,Specian AC,Srisethnil S,Trown PW,Bohoslawec O,Machlin LJ,Gabriel E

    更新日期：1979-09-01 00:00:00

  • Structure-activity relationships of cyclic opioid peptide analogues containing a phenylalanine residue in the 3-position.

    abstract：:Ten analogues of the highly mu-receptor selective cyclic opioid peptide H-Tyr-D-Orn-Phe-Asp-NH2 (1) were synthesized by the solid phase method and were characterized in vitro in mu- and delta-receptor representative binding assays and bioassays. These cyclic analogues are structurally related to the linear opioid pept...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00394a027

    authors： Schiller PW,Nguyen TM,Maziak LA,Wilkes BC,Lemieux C

    更新日期：1987-11-01 00:00:00

  • Second generation "peptoid" CCK-B receptor antagonists: identification and development of N-(adamantyloxycarbonyl)-alpha-methyl-(R)-tryptophan derivative (CI-1015) with an improved pharmacokinetic profile.

    abstract：:We have previously described the design and development of CI-988, a peptoid analogue of CCK-4 with excellent binding affinity and selectivity for the CCK-B receptor. Due to its anxiolytic profile in animal models of anxiety, this compound was developed as a clinical candidate. However, during its development, it was ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970065l

    authors： Trivedi BK,Padia JK,Holmes A,Rose S,Wright DS,Hinton JP,Pritchard MC,Eden JM,Kneen C,Webdale L,Suman-Chauhan N,Boden P,Singh L,Field MJ,Hill D

    更新日期：1998-01-01 00:00:00

  • Additivity of molecular fields: CoMFA study on dual activators of PPARalpha and PPARgamma.

    abstract：:Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm049383s

    authors： Khanna S,Sobhia ME,Bharatam PV

    更新日期：2005-04-21 00:00:00

  • Metal-dependent inhibition of HIV-1 integrase.

    abstract：:Human immunodeficiency virus type 1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Therefore, IN inhibitors are being sought for chemotherapy against AIDS. We had previously identified a series of salicylhydrazides as potent inhibitors of IN in vitro (Neamati, N.; et al. J. Med. Chem. 199...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0201417

    authors： Neamati N,Lin Z,Karki RG,Orr A,Cowansage K,Strumberg D,Pais GC,Voigt JH,Nicklaus MC,Winslow HE,Zhao H,Turpin JA,Yi J,Skalka AM,Burke TR Jr,Pommier Y

    更新日期：2002-12-19 00:00:00

  • Glucosamine-glycerophospholipids that activate cell-matrix adhesion and migration.

    abstract：:Two new analogues derived from the platelet activating factor (PAF), containing glucosamine instead of the acetyl group, were synthesized, and their effect on the human keratinocyte cell line HaCaT was evaluated with respect to cytotoxicity, proliferation, adhesion, and migration. Starting with (R)-1,2-isopropylideneg...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm050558n

    authors： Bartolmäs T,Heyn T,Mickeleit M,Fischer A,Reutter W,Danker K

    更新日期：2005-10-20 00:00:00

  • Synthesis and biological characterization of pyridohomotropanes. Structure-activity relationships of conformationally restricted nicotinoids.

    abstract：:The recently discovered nicotinic agonist pyrido[3,4-b]norhomotropane [corrected] (PHT) as well as its N-methyl and 2'-methyl derivatives (syntheses reported herein) were compared with nicotine, nornicotine, and anatoxin a in a series of in vitro and in vivo assays. The results reveal that PHT possesses activity compa...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00398a004

    authors： Kanne DB,Abood LG

    更新日期：1988-03-01 00:00:00

  • A Dipolar Cycloaddition Reaction To Access 6-Methyl-4,5,6,7-tetrahydro-1H-[1,2,3]triazolo[4,5-c]pyridines Enables the Discovery Synthesis and Preclinical Profiling of a P2X7 Antagonist Clinical Candidate.

    abstract：:A single pot dipolar cycloaddition reaction/Cope elimination sequence was developed to access novel 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridine P2X7 antagonists that contain a synthetically challenging chiral center. The structure-activity relationships of the new compounds are described. Two of these compoun...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b01279

    authors： Chrovian CC,Soyode-Johnson A,Peterson AA,Gelin CF,Deng X,Dvorak CA,Carruthers NI,Lord B,Fraser I,Aluisio L,Coe KJ,Scott B,Koudriakova T,Schoetens F,Sepassi K,Gallacher DJ,Bhattacharya A,Letavic MA

    更新日期：2018-01-11 00:00:00

  • Ester prodrugs of cyclic 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine: synthesis and antiviral activity.

    abstract：:Reaction of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (1) with dicyclohexylcarbodiimide and N,N,-dicyclohexyl-4-morpholinocarboxamidine in dimethylformamide at elevated temperature afforded the corresponding cyclic phosphonate 2, that is, 1-{[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-5...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0707166

    authors： Krecmerová M,Holý A,Pohl R,Masojídková M,Andrei G,Naesens L,Neyts J,Balzarini J,De Clercq E,Snoeck R

    更新日期：2007-11-15 00:00:00

  • Structure-activity relationships in potentially hallucinogenic N,N-dialkyltryptamines substituted in the benzene moiety.

    abstract：:A series of N,N-dialkyltryptamines with methylthio or methylenedioxy substituents in the 4, 5, and 6 positions and methyl or isopropyl on the side-chain nitrogen has been synthesized. The behavioral pharmacology of these compounds showed them to possess Bovet-Gatti profiles characteristic of hallucinogens, and the 5-m...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00350a005

    authors： Kline TB,Benington F,Morin RD,Beaton JM

    更新日期：1982-08-01 00:00:00

  • Mineralocorticoid properties of potential metabolites of 18-hydroxydeoxycorticosterone and 18-hydroxyprogesterone.

    abstract：:The high secretion rate of 18-hydroxydeoxycorticosterone in hypertensives and the steroids implication as a mineralocorticoid has led to the synthesis of potential di-, tetra-, and hexahydro metabolites of it and 18-hydroxy-progesterone. These potential metabolites have been synthesized by reduction of the double bond...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00380a014

    authors： Weet JF,Lenz GR

    更新日期：1985-02-01 00:00:00

  • Structure-activity analysis of a class of orally active hydroxamic acid inhibitors of leukotriene biosynthesis.

    abstract：:The nature of the carbonyl and nitrogen substituents of hydroxamic acids has a major influence on the biological profile of these compounds. Hydroxamates with small groups such as methyl appended to the carbonyl and relatively large nitrogen substituents generally have longer duration in vivo, produce greater plasma c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00118a016

    authors： Summers JB,Gunn BP,Martin JG,Martin MB,Mazdiyasni H,Stewart AO,Young PR,Bouska JB,Goetze AM,Dyer RD

    更新日期：1988-10-01 00:00:00

  • Structure-function studies on positions 17, 18, and 21 replacement analogues of glucagon: the importance of charged residues and salt bridges in glucagon biological activity.

    abstract：:We have designed and synthesized eight compounds 2-9 which incorporate various amino acid residues in positions 17, 18, and 21 of the glucagon molecule: 2, [Lys17]glucagon amide; 3, [Lys18]glucagon amide; 4, [Nle17,Lys18,Glu21]glucagon amide; 5, [Orn17,18, Glu21]glucagon amide; 6, [d-Arg17]glucagon; 7, [d-Arg18]glucag...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm980084a

    authors： Sturm NS,Lin Y,Burley SK,Krstenansky JL,Ahn JM,Azizeh BY,Trivedi D,Hruby VJ

    更新日期：1998-07-16 00:00:00

  • Molecular Basis for Multiple Omapatrilat Binding Sites within the ACE C-Domain: Implications for Drug Design.

    abstract：:Omapatrilat was designed as a vasopeptidase inhibitor with dual activity against the zinc metallopeptidases angiotensin-1 converting enzyme (ACE) and neprilysin (NEP). ACE has two homologous catalytic domains (nACE and cACE), which exhibit different substrate specificities. Here, we report high-resolution crystal stru...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b01309

    authors： Cozier GE,Arendse LB,Schwager SL,Sturrock ED,Acharya KR

    更新日期：2018-11-21 00:00:00

  • N-cycloalkyl derivatives of adenosine and 1-deazaadenosine as agonists and partial agonists of the A(1) adenosine receptor.

    abstract：:A number of cycloalkyl substituents (from C-3 to C-8) have been introduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guano...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9911231

    authors： Vittori S,Lorenzen A,Stannek C,Costanzi S,Volpini R,IJzerman AP,Kunzel JK,Cristalli G

    更新日期：2000-01-27 00:00:00

  • Potential antitumor agents: synthesis and biological properties of aliphatic amino acid 9-hydroxyellipticinium derivatives.

    abstract：:Aliphatic amino acids glycine, alanine, valine, and leucine were conjugated to the antitumor drug N2-methyl-9-hydroxyellipticinium (NMHE) through a peroxidase-catalyzed oxidation reaction. NMR studies of the adducts so obtained have indicated (i) that the amino acids were linked to NMHE between the nitrogen of their p...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00375a013

    authors： Auclair C,Voisin E,Banoun H,Paoletti C,Bernadou J,Meunier B

    更新日期：1984-09-01 00:00:00

  • CNS Physicochemical Property Space Shaped by a Diverse Set of Molecules with Experimentally Determined Exposure in the Mouse Brain.

    abstract：:Understanding the "limits and boundaries" of the central nervous system (CNS) property space is a critical aspect of modern CNS drug design. Medicinal chemists are often guided by the physicochemical properties of marketed CNS drugs, which are heavily biased toward "traditional" aminergic targets and commonly describe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,收录出版

    doi：10.1021/acs.jmedchem.6b01469

    authors： Rankovic Z

    更新日期：2017-07-27 00:00:00

  • Potential modes of interaction of 9-aminomethyl-9,10-dihydroanthracene (AMDA) derivatives with the 5-HT2A receptor: a ligand structure-affinity relationship, receptor mutagenesis and receptor modeling investigation.

    abstract：:The effects of 3-position substitution of 9-aminomethyl-9,10-dihydroanthracene (AMDA) on 5-HT 2A receptor affinity were determined and compared to a parallel series of DOB-like 1-(2,5-dimethoxyphenyl)-2-aminopropanes substituted at the 4-position. The results were interpreted within the context of 5-HT 2A receptor mod...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm800771x

    authors： Runyon SP,Mosier PD,Roth BL,Glennon RA,Westkaemper RB

    更新日期：2008-11-13 00:00:00

  • Novel 3-carboxamide-coumarins as potent and selective FXIIa inhibitors.

    abstract：:Recently, FXIIa was highlighted as an original attractive target for the development of new anticoagulant drugs with low rates of therapy-related hemorrhages. In this work, we describe the development of a new series of 3-carboxamide-coumarins that are the first potent and selective nonpeptidic inhibitors of FXIIa. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm8002697

    authors： Robert S,Bertolla C,Masereel B,Dogné JM,Pochet L

    更新日期：2008-06-12 00:00:00

  • Avermectin acyl derivatives with anthelmintic activity.

    abstract：:Avermectins A2a, B1a, and B2a (1, 2, and 3) were acetylated to give 4"- and 23-acetates 4 and 5 and 4",23-diacetate 6 from 1, the 4"-and 5-acetates 7 and 8 and 4",5-diacetate 9 from 2, and triacetate 10 from 3. Structure proof by 300-MHz 1H NMR and mass spectral fragmentation is discussed for 10. Forcing acetylation c...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00348a010

    authors： Mrozik H,Eskola P,Fisher MH,Egerton JR,Cifelli S,Ostlind DA

    更新日期：1982-06-01 00:00:00

  • Potent fibrinolysis inhibitor discovered by shape and electrostatic complementarity to the drug tranexamic acid.

    abstract：:Protein-protein interfaces provide an important class of drug targets currently receiving increased attention. The typical design strategy to inhibit protein-protein interactions usually involves large molecules such as peptides and macrocycles. One exception is tranexamic acid (TXA), which, as a lysine mimetic, inhib...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm301818g

    authors： Boström J,Grant JA,Fjellström O,Thelin A,Gustafsson D

    更新日期：2013-04-25 00:00:00

  • Designing allosteric inhibitors of factor XIa. Lessons from the interactions of sulfated pentagalloylglucopyranosides.

    abstract：:We recently introduced sulfated pentagalloylglucopyranoside (SPGG) as an allosteric inhibitor of factor XIa (FXIa) (Al-Horani et al., J. Med Chem. 2013, 56, 867-878). To better understand the SPGG-FXIa interaction, we utilized eight SPGG variants and a range of biochemical techniques. The results reveal that SPGG's su...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500311e

    authors： Al-Horani RA,Desai UR

    更新日期：2014-06-12 00:00:00

  • Oral absorption of cephalosporin antibiotics. 3. Synthesis and biological properties of 7 alpha-methoxy-7 beta-(arylacetamido)-3-chloro-3-cephem-4- carboxylic acids.

    abstract：:A series of 7 alpha-methoxy-7 beta-amido-3-chloro-3-cephem-4-carboxylic acids was prepared and evaluated for biological activity. When compared with the parent 7-non-methoxy analogues, these new 7 alpha-methoxy-3-chloro cephalosporins displayed diminished antimicrobial activity. ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00118a024

    authors： Pfeil-Doyle J,Kukolja S

    更新日期：1988-10-01 00:00:00

  • Preparation and pharmacological evaluation of enantiomers of certain nonoxygenated aporphines: (+)- and (-)-aporphine and (+)- and (-)-10-methylaporphine.

    abstract：:The subject compounds were prepared as a part of a continuing structure-activity study of the contrasting actions (agonism-antagonism) of (+)- and (-)-11-hydroxy-10-methylaporphine at serotonin (5-HT1A) receptors. None of the targeted nonoxygenated aporphine derivatives demonstrated significant activity in assays for ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00062a002

    authors： Cannon JG,Raghupathi R,Moe ST,Johnson AK,Long JP

    更新日期：1993-05-14 00:00:00

  • Design, Synthesis, and Biological Evaluation of Substituted 4,6-Dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione Analogues as Potent NS4B Inhibitors for the Treatment of Dengue Virus Infection.

    abstract：:A series of substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione analogues were synthesized and evaluated as potent dengue virus inhibitors. Throughout a structure-activity relationship exploration on the amide of the indolone moiety, a wide range of substitutions were found to be ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b00698

    authors： Xu J,Xie X,Ye N,Zou J,Chen H,White MA,Shi PY,Zhou J

    更新日期：2019-09-12 00:00:00

  • Synthesis and in vitro evaluation of N-substituted maleimide derivatives as selective monoglyceride lipase inhibitors.

    abstract：:The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900461w

    authors： Matuszak N,Muccioli GG,Labar G,Lambert DM

    更新日期：2009-12-10 00:00:00

  • Discovery and SAR of methylated tetrahydropyranyl derivatives as inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT).

    abstract：:A series of tetrahydropyranyl (THP) derivatives has been developed as potent inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT) for use as anticancer agents. Structural modification of the submicromolar hit compound 3 led to the potent 3-methoxy substituted analogue 27. Further SAR development around th...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200249a

    authors： Judd WR,Slattum PM,Hoang KC,Bhoite L,Valppu L,Alberts G,Brown B,Roth B,Ostanin K,Huang L,Wettstein D,Richards B,Willardsen JA

    更新日期：2011-07-28 00:00:00