Structure-activity relationships of kadsurenone analogues.


:Kadsurenone, a specific receptor antagonist of platelet-activating factor (PAF), and its analogues were prepared from derivatives of cinnamyl alcohol and (allyloxy)phenol. Racemic kadsurenone, resolvable by a Chiralpak column at low temperatures, has an IC50 value of 2 X 10(-7) M, which is about 50% of the activity of the natural product (IC50 = 1 X 10(-7) M). The structural specificity of kadsurenone was further demonstrated by the low PAF-receptor-blocking activities of denudatin B, mirandin A, desallylkadsurenone, and the 2-epimer of kadsurenone.


J Med Chem


Ponpipom MM,Bugianesi RL,Brooker DR,Yue BZ,Hwang SB,Shen TY




Has Abstract


1987-01-01 00:00:00












  • Anti-HIV activities of precisely defined, semirigid, carboxylated alternating copolymers.

    abstract::Di-tert-butyl (E)-4,4'-stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Savage AM,Li Y,Matolyak LE,Doncel GF,Turner SR,Gandour RD

    更新日期:2014-08-14 00:00:00

  • Preparation, DNA binding, and in vitro cytotoxicity of a pair of enantiomeric platinum(II) complexes, [(R)- and (S)-3-aminohexahydroazepine]dichloroplatinum(II). Crystal structure of the S enantiomer.

    abstract::A pair of enantiomeric Pt(II) complexes, [Pt(R-ahaz)Cl2] and [Pt(S-ahaz)Cl2] (ahaz = 3-aminohexahydroazepine), has been investigated for their ability to bind enantioselectively to DNA. Improved synthetic procedures were developed for preparing both the ligands and the Pt complexes. The structure of the complex of the...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Fenton RR,Easdale WJ,Er HM,O'Mara SM,McKeage MJ,Russell PJ,Hambley TW

    更新日期:1997-03-28 00:00:00

  • Design, synthesis, and proposed active site binding analysis of monocyclic 2-azetidinone inhibitors of prostate specific antigen.

    abstract::A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC(50) = 8.98 +/- 0.90 microM) which was used as a lead compo...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Adlington RM,Baldwin JE,Becker GW,Chen B,Cheng L,Cooper SL,Hermann RB,Howe TJ,McCoull W,McNulty AM,Neubauer BL,Pritchard GJ

    更新日期:2001-05-10 00:00:00

  • PRO_LIGAND: an approach to de novo molecular design. 2. Design of novel molecules from molecular field analysis (MFA) models and pharmacophores.

    abstract::A computational approach for molecular design, PRO_LIGAND, has been developed within the PROMETHEUS molecular design and simulation system in order to provide a unified framework for the de novo generation of diverse molecules which are either similar or complementary to a specified target. In this instance, the targe...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Waszkowycz B,Clark DE,Frenkel D,Li J,Murray CW,Robson B,Westhead DR

    更新日期:1994-11-11 00:00:00

  • 1-[[(3-hydroxy-1-adamantyl)amino]acetyl]-2-cyano-(S)-pyrrolidine: a potent, selective, and orally bioavailable dipeptidyl peptidase IV inhibitor with antihyperglycemic properties.

    abstract::Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Villhauer EB,Brinkman JA,Naderi GB,Burkey BF,Dunning BE,Prasad K,Mangold BL,Russell ME,Hughes TE

    更新日期:2003-06-19 00:00:00

  • 5-Benzylidene 1,2-dihydrochromeno[3,4-f]quinolines, a novel class of nonsteroidal human progesterone receptor agonists.

    abstract::A novel series of nonsteroidal progestins, 5-benzylidene-1, 2-dihydrochromeno[3,4-f]quinolines (2), was discovered, and a preliminary structure-activity relationship study around the 5-benzylidene ring generated several potent human progesterone receptor agonists (compounds 8, 16). These new progestins showed biologic...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Tegley CM,Zhi L,Marschke KB,Gottardis MM,Yang Q,Jones TK

    更新日期:1998-10-22 00:00:00

  • Potent, Plasmodium-selective farnesyltransferase inhibitors that arrest the growth of malaria parasites: structure-activity relationships of ethylenediamine-analogue scaffolds and homology model validation.

    abstract::New chemotherapeutics are urgently needed to combat malaria. We previously reported on a novel series of antimalarial, ethylenediamine-based inhibitors of protein farnesyltransferase (PFT). In the current study, we designed and synthesized a series of second generation inhibitors, wherein the core ethylenediamine scaf...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Fletcher S,Cummings CG,Rivas K,Katt WP,Hornéy C,Buckner FS,Chakrabarti D,Sebti SM,Gelb MH,Van Voorhis WC,Hamilton AD

    更新日期:2008-09-11 00:00:00

  • Computer-aided design of selective COX-2 inhibitors: comparative molecular field analysis, comparative molecular similarity indices analysis, and docking studies of some 1,2-diarylimidazole derivatives.

    abstract::Comparative molecular field analysis and comparative molecular similarity indices analysis were performed on 114 analogues of 1,2-diarylimidazole to optimize their cyclooxygenase-2 (COX-2) selective antiinflammatory activities. These studies produced models with high correlation coefficients and good predictive abilit...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Desiraju GR,Gopalakrishnan B,Jetti RK,Nagaraju A,Raveendra D,Sarma JA,Sobhia ME,Thilagavathi R

    更新日期:2002-10-24 00:00:00

  • Novel orally active antimalarial thiazoles.

    abstract::An aminomethylthiazole pyrazole carboxamide lead 3 with good in vitro antiplasmodial activity [IC(50): 0.08 μM (K1, chloroquine and multidrug resistant strain) and 0.07 μM (NF54, chloroquine sensitive strain)] and microsomal metabolic stability was identified from whole cell screening of a SoftFocus kinase library. Co...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: González Cabrera D,Douelle F,Feng TS,Nchinda AT,Younis Y,White KL,Wu Q,Ryan E,Burrows JN,Waterson D,Witty MJ,Wittlin S,Charman SA,Chibale K

    更新日期:2011-11-10 00:00:00

  • 4-Benzyloxy-gamma-sultone derivatives: discovery of a novel family of non-nucleoside inhibitors of human cytomegalovirus and varicella zoster virus.

    abstract::We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the 4-keto-1,2-oxathiole-2,2-dioxide (beta-keto-gamma-sultone) heterocyclic system. Several 4- and 5-substituted-5H-1,2-oxathiole-2,2-dioxide derivatives were found to have a selective inhibitory activity against ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: De Castro S,García-Aparicio C,Andrei G,Snoeck R,Balzarini J,Camarasa MJ,Velázquez S

    更新日期:2009-03-26 00:00:00

  • 2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors.

    abstract::Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and a phenyl ring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX-2). The selectivity for COX-2 over COX-1 is dramatically improved by substituting the 2-phenyl group with halogens in the meta position or by replacing the...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Black WC,Brideau C,Chan CC,Charleson S,Chauret N,Claveau D,Ethier D,Gordon R,Greig G,Guay J,Hughes G,Jolicoeur P,Leblanc Y,Nicoll-Griffith D,Ouimet N,Riendeau D,Visco D,Wang Z,Xu L,Prasit P

    更新日期:1999-04-08 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


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

    更新日期:2007-08-23 00:00:00

  • Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity.

    abstract::The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute corona...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Chackalamannil S,Wang Y,Greenlee WJ,Hu Z,Xia Y,Ahn HS,Boykow G,Hsieh Y,Palamanda J,Agans-Fantuzzi J,Kurowski S,Graziano M,Chintala M

    更新日期:2008-06-12 00:00:00

  • Direct NMR Probing of Hydration Shells of Protein Ligand Interfaces and Its Application to Drug Design.

    abstract::Fragment-based drug design exploits initial screening of low molecular weight compounds and their concomitant affinity improvement. The multitude of possible chemical modifications highlights the necessity to obtain structural information about the binding mode of a fragment. Herein we describe a novel NMR methodology...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Geist L,Mayer M,Cockcroft XL,Wolkerstorfer B,Kessler D,Engelhardt H,McConnell DB,Konrat R

    更新日期:2017-11-09 00:00:00

  • Derivatives of the triazoloquinazoline adenosine antagonist (CGS15943) are selective for the human A3 receptor subtype.

    abstract::The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) binds to human A3 receptors with high affinity (Ki = 14 nM), while it lacks affinity at rat A3 receptors. Acylated derivatives of the 5-amino group and other modifications were prepared in an effort to provide A3 subtype...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kim YC,Ji XD,Jacobson KA

    更新日期:1996-10-11 00:00:00

  • Benzodiazepine receptor binding activity of 6,9-disubstituted purines.

    abstract::A series of 6,9-disubstituted purines were tested for their ability to bind to the benzodiazepine receptor in rat brain tissue. One of the most active compounds was 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (44) with an IC50 = 0.9 microM, which was only 4.5-fold higher than the IC50 for chlordiazepoxide. Substitut...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kelley JL,McLean EW,Ferris RM,Howard JL

    更新日期:1989-05-01 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


    authors: Correll CC,McKittrick BA

    更新日期:2014-08-28 00:00:00

  • Carboxylated, heteroaryl-substituted chalcones as inhibitors of vascular cell adhesion molecule-1 expression for use in chronic inflammatory diseases.

    abstract::Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Correlations between lipophilicity determined by calculated logP val...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Meng CQ,Ni L,Worsencroft KJ,Ye Z,Weingarten MD,Simpson JE,Skudlarek JW,Marino EM,Suen KL,Kunsch C,Souder A,Howard RB,Sundell CL,Wasserman MA,Sikorski JA

    更新日期:2007-03-22 00:00:00

  • Potential inhibitors of L-asparagine biosynthesis. 2. Chemistry and biological activity of beta-hydroxyaspartic acid and its derivatives.

    abstract::Several derivatives of erythro-beta-hydroxy-DL-aspartic acid (1) were prepared as a potential inhibitors of L-asparagine synthetase (ASase) from rat Novikoff hepatoma. Benzylation of 1 gave the dibenzyl ester 2 which upon coupling with carbobenzoxyglycine afforded the blocked dipeptide 3. Deblocking of 3 gave glycl-er...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Mokotoff M,Bagaglio JF,Parikh BS

    更新日期:1975-04-01 00:00:00

  • Synthesis and analgesic activity of some 14 beta-substituted analogues of morphine.

    abstract::Treatment of 14 beta-nitrocodeinone with sodium borohydride gave the codeine derivative which was reduced with zinc dust in acetic anhydride-acetic acid solution to give 14 beta-acetamidocodeine 6-acetate. 14 beta-Thiocyanatocodeinone was obtained from the reaction of thebaine with thiocyanogen and was reduced to 14 b...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Osei-Gyimah P,Archer S

    更新日期:1980-02-01 00:00:00

  • Synthesis and siderophore and antibacterial activity of N5-acetyl-N5-hydroxy-L-ornithine-derived siderophore-beta-lactam conjugates: iron-transport-mediated drug delivery.

    abstract::N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl-N5-acety l- N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a "carrier" substructure into both carbacephalosporin and oxamazin type beta-lactam antibiotics. The previously synthe...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Dolence EK,Minnick AA,Lin CE,Miller MJ,Payne SM

    更新日期:1991-03-01 00:00:00

  • Synthesis, protein kinase inhibitory potencies, and in vitro antiproliferative activities of meridianin derivatives.

    abstract::The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as w...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Giraud F,Alves G,Debiton E,Nauton L,Théry V,Durieu E,Ferandin Y,Lozach O,Meijer L,Anizon F,Pereira E,Moreau P

    更新日期:2011-07-14 00:00:00

  • Azaindolylsulfonamides, with a more selective inhibitory effect on histone deacetylase 6 activity, exhibit antitumor activity in colorectal cancer HCT116 cells.

    abstract::A series of indolylsulfonylcinnamic hydroxamates has been synthesized. Compound 12, (E)-3-(3-((1H-pyrrolo[2,3-b]pyridin-1-yl)sulfonyl)phenyl)-N-hydroxyacrylamide, which has a 7-azaindole core cap, was shown to have antiproliferative activity against KB, H460, PC3, HSC-3, HONE-1, A549, MCF-7, TSGH, MKN45, HT29, and HCT...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lee HY,Tsai AC,Chen MC,Shen PJ,Cheng YC,Kuo CC,Pan SL,Liu YM,Liu JF,Yeh TK,Wang JC,Chang CY,Chang JY,Liou JP

    更新日期:2014-05-22 00:00:00

  • Kojic amine--a novel gamma-aminobutyric acid analogue.

    abstract::A series of compounds containing the 3-hydroxy-4H-pyran-4-one nucleus has been synthesized and tested as potential skeletal muscle relaxants. Reduction of 2-(azidomethyl)-5-hydroxy-4H-pyran-4-one (4) with HBr in HOAc--phenol yielded 2-(aminomethyl)-5-hydroxy-4H-pyran-4-one (kojic amine, 3) in 81% yield. Reaction of 2-...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Atkinson JG,Girard Y,Rokach J,Rooney CS,McFarlane CS,Rackham A,Share NN

    更新日期:1979-01-01 00:00:00

  • Development of Potent and Selective Pyrazolopyrimidine IRAK4 Inhibitors.

    abstract::A series of pyrazolopyrimidine inhibitors of IRAK4 were developed from a high-throughput screen (HTS). Modification of an HTS hit led to a series of bicyclic heterocycles with improved potency and kinase selectivity but lacking sufficient solubility to progress in vivo. Structure-based drug design, informed by cocryst...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Bryan MC,Drobnick J,Gobbi A,Kolesnikov A,Chen Y,Rajapaksa N,Ndubaku C,Feng J,Chang W,Francis R,Yu C,Choo EF,DeMent K,Ran Y,An L,Emson C,Huang Z,Sujatha-Bhaskar S,Brightbill H,DiPasquale A,Maher J,Wai J,McKenzi

    更新日期:2019-07-11 00:00:00

  • Structure-activity relationships for NAMI-A-type complexes (HL)[trans-RuCl4L(S-dmso)ruthenate(III)] (L = imidazole, indazole, 1,2,4-triazole, 4-amino-1,2,4-triazole, and 1-methyl-1,2,4-triazole): aquation, redox properties, protein binding, and antiprolif

    abstract::Imidazolium [trans-tetrachloro(1H-imidazole)(S-dimethylsulfoxide)ruthenate(III)] (NAMI-A) and indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019) are the most promising ruthenium complexes for anticancer chemotherapy. In this study, the azole ligand of NAMI-A was systematically varied (from imidazole...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Groessl M,Reisner E,Hartinger CG,Eichinger R,Semenova O,Timerbaev AR,Jakupec MA,Arion VB,Keppler BK

    更新日期:2007-05-03 00:00:00

  • Ketanserin analogues: structure-affinity relationships for 5-HT2 and 5-HT1C serotonin receptor binding.

    abstract::Ketanserin is the prototypic 5-HT2 serotonin antagonist; although it has been an important tool for the study of serotonin pharmacology, it has had relatively little impact on drug design because remarkably little is known about its structure-affinity relationships. Furthermore, ketanserin also binds at 5-HT1C recepto...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Herndon JL,Ismaiel A,Ingher SP,Teitler M,Glennon RA

    更新日期:1992-12-25 00:00:00

  • Metabolism-directed design of oxetane-containing arylsulfonamide derivatives as γ-secretase inhibitors.

    abstract::A metabolism-based approach toward the optimization of a series of N-arylsulfonamide-based γ-secretase inhibitors is reported. The lead cyclohexyl analogue 6 suffered from extensive oxidation on the cycloalkyl motif by cytochrome P450 3A4, translating into poor human liver microsomal stability. Knowledge of the metabo...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Stepan AF,Karki K,McDonald WS,Dorff PH,Dutra JK,Dirico KJ,Won A,Subramanyam C,Efremov IV,O'Donnell CJ,Nolan CE,Becker SL,Pustilnik LR,Sneed B,Sun H,Lu Y,Robshaw AE,Riddell D,O'Sullivan TJ,Sibley E,Capetta S,Atch

    更新日期:2011-11-24 00:00:00

  • Design, synthesis, and biological activity of a family of novel ceramide analogues in chemoresistant breast cancer cells.

    abstract::Resistance to chemotherapy and endocrine therapy is a major cause of breast cancer treatment failure. We have synthesized six novel analogues using C8-ceramide as the lead analogue and studied their effect on hormone therapy resistant (MDA-MB-231) and chemoresistant (MCF-7TN-R) breast cancer cells. Pharmacologic inter...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Antoon JW,Liu J,Gestaut MM,Burow ME,Beckman BS,Foroozesh M

    更新日期:2009-09-24 00:00:00

  • Structure-Based Drug Design of Bisubstrate Inhibitors of Phenylethanolamine N-Methyltransferase Possessing Low Nanomolar Affinity at Both Substrate Binding Domains1.

    abstract::The enzyme phenylethanolamine N-methyltransferase (PNMT, EC catalyzes the final step in the biosynthesis of epinephrine and is a potential drug target, primarily for the control of hypertension. Unfortunately, many potent PNMT inhibitors also possess significant affinity for the a2-adrenoceptor, which compli...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Lu J,Bart AG,Wu Q,Criscione KR,McLeish MJ,Scott EE,Grunewald GL

    更新日期:2020-11-25 00:00:00