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












  • New dibenzothiadiazepine derivatives with antidepressant activities.

    abstract::A new series of 11-[(aminoalkyl)carbonyl] derivatives of 6,11-dihydrodibenzo[c,f][1,2,5]thiadiazepine 5,5-dioxide (10-39) were synthesized and evaluated for potential antidepressant activity in the apomorphine-induced hypothermia (Apo 16) test. Effects on reserpine-induced hypothermia and toxicity for the most potent ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Giannotti D,Viti G,Sbraci P,Pestellini V,Volterra G,Borsini F,Lecci A,Meli A,Dapporto P,Paoli P

    更新日期:1991-04-01 00:00:00

  • Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit.

    abstract::We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the alpha(3) receptor subtype with 5-fold selectivity in binding affinity over alpha(1). This paper describes a detailed investigation of the substituents on this core structure at bot...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Russell MG,Carling RW,Atack JR,Bromidge FA,Cook SM,Hunt P,Isted C,Lucas M,McKernan RM,Mitchinson A,Moore KW,Narquizian R,Macaulay AJ,Thomas D,Thompson SA,Wafford KA,Castro JL

    更新日期:2005-03-10 00:00:00

  • Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2.

    abstract::Dysregulation of translation initiation factor 4E (eIF4E) activity occurs in various cancers. Mitogen-activated protein kinase (MAPK) interacting kinases 1 and 2 (MNK1 and MNK2) play a fundamental role in activation of eIF4E. Structure-activity relationship-driven expansion of a fragment hit led to discovery of dual M...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kwiatkowski J,Liu B,Pang S,Ahmad NHB,Wang G,Poulsen A,Yang H,Poh YR,Tee DHY,Ong E,Retna P,Dinie N,Kwek P,Wee JLK,Manoharan V,Low CB,Seah PG,Pendharkar V,Sangthongpitag K,Joy J,Baburajendran N,Jansson AE,Nacro

    更新日期:2020-01-23 00:00:00

  • Structure-activity relationships of (arylalkyl)imidazole anticonvulsants: comparison of the (fluorenylalkyl)imidazoles with nafimidone and denzimol.

    abstract::A recently discovered and structurally distinct class of antiepileptic drugs is the (arylalkyl)imidazoles. Two independently discovered representatives of this class, denzimol (alpha-[4-(2-phenylethyl)phenyl]-1H-imidazole-1-ethanol) and nafimidone (2-(1H-imidazol-1-yl)-1-(2-naphthalenyl)ethanone), are undergoing clini...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Robertson DW,Krushinski JH,Beedle EE,Leander JD,Wong DT,Rathbun RC

    更新日期:1986-09-01 00:00:00

  • Preparation and biological evaluation of indole, benzimidazole, and thienopyrrole piperazine carboxamides: potent human histamine h(4) antagonists.

    abstract::Three series of H(4) receptor ligands, derived from indoly-2-yl-(4-methyl-piperazin-1-yl)-methanones, have been synthesized and their structure-activity relationships evaluated for activity at the H(4) receptor in competitive binding and functional assays. In all cases, substitution of small lipophilic groups in the 4...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Venable JD,Cai H,Chai W,Dvorak CA,Grice CA,Jablonowski JA,Shah CR,Kwok AK,Ly KS,Pio B,Wei J,Desai PJ,Jiang W,Nguyen S,Ling P,Wilson SJ,Dunford PJ,Thurmond RL,Lovenberg TW,Karlsson L,Carruthers NI,Edwards JP

    更新日期:2005-12-29 00:00:00

  • Synthesis and antiinflammatory activity of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11-oxodibenzo[b,e]thiepinacetic and -oxepinacetic acids.

    abstract::A series of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11- oxodibenzo[b,e]thiepinacetic acids (6-9) and -oxepinacetic acids (10-13) were prepared and their antiinflammatory activity was examined in the rat carrageenan hind paw edema test. The antiinflammatory activity of these compounds depended on their stereochem...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kurokawa M,Uno H,Nakamura H,Sato F,Naruto S

    更新日期:1990-02-01 00:00:00

  • Novel trisubstituted benzimidazoles, targeting Mtb FtsZ, as a new class of antitubercular agents.

    abstract::Libraries of novel trisubstituted benzimidazoles were created through rational drug design. A good number of these benzimidazoles exhibited promising MIC values in the range of 0.5-6 μg/mL (2-15 μM) for their antibacterial activity against Mtb H37Rv strain. Moreover, five of the lead compounds also exhibited excellent...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kumar K,Awasthi D,Lee SY,Zanardi I,Ruzsicska B,Knudson S,Tonge PJ,Slayden RA,Ojima I

    更新日期:2011-01-13 00:00:00

  • Scaffold-Hopping Approach To Discover Potent, Selective, and Efficacious Inhibitors of NF-κB Inducing Kinase.

    abstract::NF-κB-inducing kinase (NIK) is a protein kinase central to the noncanonical NF-κB pathway downstream from multiple TNF receptor family members, including BAFF, which has been associated with B cell survival and maturation, dendritic cell activation, secondary lymphoid organ development, and bone metabolism. We report ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Blaquiere N,Castanedo GM,Burch JD,Berezhkovskiy LM,Brightbill H,Brown S,Chan C,Chiang PC,Crawford JJ,Dong T,Fan P,Feng J,Ghilardi N,Godemann R,Gogol E,Grabbe A,Hole AJ,Hu B,Hymowitz SG,Alaoui Ismaili MH,Le H,Lee

    更新日期:2018-08-09 00:00:00

  • Tetramisole analogues as inhibitors of alkaline phosphatase, an enzyme involved in the resistance of neoplastic cells to 6-thiopurines.

    abstract::A series of tetramisole derivatives was synthesized and tested for inhibitory activity against alkaline phosphatase which was partially purified from a murine ascitic neoplasm resistant to 6-thiopurines (Sarcoma 180/TG). These agents included derivatives substituted with halogens, CH3, or NO2 groups at either the meta...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Bhargava KK,Lee MH,Huang Y,Cunningham LS,Agrawal KC,Sartorelli AC

    更新日期:1977-04-01 00:00:00

  • Nitro and amino derivatives of lucanthone as antitumor agents.

    abstract::A group of nitro and amino derivatives of lucanthone was prepared and tested for antitumor activity. Reaction of 1-chloro-4-methyl-7-nitrothioxanthenone and N,N-diethylethylenediamine gave the 7-amino analogue (11) directly, accompanied by 7-amino-1-chloro-4-methylthioxanthenone. The antitumor activity of 11 was infer...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Archer S,Rej R

    更新日期:1982-03-01 00:00:00

  • Acrylamide derivatives as antiallergic agents. 2. Synthesis and structure-activity relationships of N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(3-pyridyl)acryl amides.

    abstract::A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compound 1a [(E)-N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3- ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Nishikawa Y,Shindo T,Ishii K,Nakamura H,Kon T,Uno H

    更新日期:1989-03-01 00:00:00

  • Ligand-Based Design of Allosteric Retinoic Acid Receptor-Related Orphan Receptor γt (RORγt) Inverse Agonists.

    abstract::Retinoic acid receptor-related orphan receptor γt (RORγt) is a nuclear receptor associated with the pathogenesis of autoimmune diseases. Allosteric inhibition of RORγt is conceptually new, unique for this specific nuclear receptor, and offers advantages over traditional orthosteric inhibition. Here, we report a highly...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Meijer FA,Doveston RG,de Vries RMJM,Vos GM,Vos AAA,Leysen S,Scheepstra M,Ottmann C,Milroy LG,Brunsveld L

    更新日期:2020-01-09 00:00:00

  • Nucleoside analogs. 14. The synthesis of antitumor activity in mice of molecular combinations of 5-fluorouracil and N-(2-Chloroethyl)-N-nitrosourea moieties separated by a three-carbon chain.

    abstract::5-fluorouracil (5-FU) seco-nucleosdies having as the "sugar" moiety a two-carbon (C2) side chain carrying a N-(2-chloroethyl)-N-nitrosourea group were designed as molecular combinations of antimetabolite and alkylating agent, but hydrolytic release of free 5-FU was not fast enough for significant contribution to the h...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: McElhinney RS,McCormick JE,Bibby MC,Double JA,Radacic M,Dumont P

    更新日期:1996-03-29 00:00:00

  • Structure-based design of flavonoid compounds as a new class of small-molecule inhibitors of the anti-apoptotic Bcl-2 proteins.

    abstract::Structure-based strategy was employed to design flavonoid compounds to mimic the Bim BH3 peptide as a new class of inhibitors of the anti-apoptotic Bcl-2 proteins. The most potent compound, 4 (BI-33), binds to Bcl-2 and Mcl-1 with Ki values of 17 and 18 nM, respectively. Compound 4 inhibits cell growth in the MDA-MB-2...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Tang G,Ding K,Nikolovska-Coleska Z,Yang CY,Qiu S,Shangary S,Wang R,Guo J,Gao W,Meagher J,Stuckey J,Krajewski K,Jiang S,Roller PP,Wang S

    更新日期:2007-07-12 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

  • A dynamic G-quadruplex region regulates the HIV-1 long terminal repeat promoter.

    abstract::G-Quadruplexes, noncanonical nucleic acid structures, act as silencers in the promoter regions of human genes; putative G-quadruplex forming sequences are also present in promoters of other mammals, yeasts, and prokaryotes. Here we show that also the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional re...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Perrone R,Nadai M,Frasson I,Poe JA,Butovskaya E,Smithgall TE,Palumbo M,Palù G,Richter SN

    更新日期:2013-08-22 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


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

    更新日期:1988-02-01 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

  • Crystal structures of HLA-A*0201 complexed with Melan-A/MART-1(26(27L)-35) peptidomimetics reveal conformational heterogeneity and highlight degeneracy of T cell recognition.

    abstract::There is growing interest in using tumor associated antigens presented by class I major histocompatibility complex (MHC-I) proteins as cancer vaccines. As native peptides are poorly stable in biological fluids, researchers have sought to engineer synthetic peptidomimetics with greater biostability. Here, we demonstrat...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Douat-Casassus C,Borbulevych O,Tarbe M,Gervois N,Jotereau F,Baker BM,Quideau S

    更新日期:2010-10-14 00:00:00

  • Synthesis and radioprotective activity of new cysteamine and cystamine derivatives.

    abstract::A variety of N-(aminoalkanoyl)-S-acylcysteamine and N,N'-bis(aminoalkanoyl)cystamine salt derivatives were synthesized. Toxicity and radioprotective activity (as the dose reduction factor DRF) were determined in vivo on mice and compared to WR 2721 and S-acetylcysteamine hydrochloride. One of the most interesting comp...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Oiry J,Pue JY,Imbach JL,Fatome M,Sentenac-Roumanou H,Lion C

    更新日期:1986-11-01 00:00:00

  • Peptide sweeteners. 4. Hydroxy and methoxy substitution of the aromatic ring in L-aspartyl-L-phenylalanine methyl ester. Structure-taste relationships.

    abstract::A series of analogues of the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester having hydroxy and/or methoxy substitution on the aromatic ring was synthesized and tasted. The introduction of a methoxy group in the para position of the aromatic ring of the peptide sweetener is crucial to the reduction or dest...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Kawai M,Chorev M,Marin-Rose J,Goodman M

    更新日期:1980-04-01 00:00:00

  • 2-Aryl-3-methyloctahydrophenanthrene-2,3,7-triols as potent dissociated glucocorticoid receptor agonists.

    abstract::A significant improvement in agonist activity of the previously described 2-aryloctahydrophenanthrene-2,3,7-triol series of dissociated glucocorticoid receptor agonists (DAGRs) was achieved by modifying the substitution at C3 from (S)-3-hydroxy to (R)-3-hydroxy-3-methyl. The IC50 of the prototype 13 in the efficacy as...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Chantigny YA,Murray JC,Kleinman EF,Robinson RP,Plotkin MA,Reese MR,Buckbinder L,McNiff PA,Millham ML,Schaefer JF,Abramov YA,Bordner J

    更新日期:2015-03-26 00:00:00

  • Design, synthesis, and structure--activity relationship studies for a new imidazole series of J774 macrophage specific acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors.

    abstract::Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme involved in intracellular cholesterol esterification. Arterial wall infiltration by macrophages and subsequent uncontrolled esterification of cholesterol leading to foam cell formation is believed to be an important process which leads to the developmen...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Maduskuie TP Jr,Wilde RG,Billheimer JT,Cromley DA,Germain S,Gillies PJ,Higley CA,Johnson AL,Pennev P,Shimshick EJ

    更新日期:1995-03-31 00:00:00

  • Isotope effects in enzymatic N-demethylation of tertiary amines.

    abstract::The N-demethylation of 1-(N-methyl-N-trideuteriomethylamino)-3-phenylpropane (1) by rodent liver homogenates was studied. The ratio of 1-trideuteriomethylamino-3-phenylpropane (2)/1-methylamino-3-phenylpropane (3) was determined by gc-ms. The ratio of 2/3 in the product of N-demethylation of 1 by liver homogenate from...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Abdel-Monem MM

    更新日期:1975-04-01 00:00:00

  • Characterization of the interaction between human alpha-thrombin and methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carboxylate (LY806303) using electrospray mass spectrometry and tandem mass spectrometry.

    abstract::Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) have been used for the first time to study the interaction of human alpha-thrombin with methyl 3-(2-methyl-1-oxopropoxy)[1]benzothieno[3,2-b]furan-2-carbox ylate (LY806303; 1), a potent and selective inhibitor whose mechanism of ac...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Sall DJ,Kaiser RE Jr

    更新日期:1993-08-06 00:00:00

  • Activation of human telomerase reverse transcriptase expression by some new symmetrical bis-substituted derivatives of the anthraquinone.

    abstract::As a part of our program aimed at exploring the biological activity of symmetrical substitution of side chains into the anthracene-9,10-dione chromophore, we have synthesized a series of 1,5-bisthioanthraquinones 2 and 1,5-bisacyloxyanthraquinones 3 that are related to the antitumor agent mitoxantrone. Since the telom...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Huang HS,Chiou JF,Fong Y,Hou CC,Lu YC,Wang JY,Shih JW,Pan YR,Lin JJ

    更新日期:2003-07-17 00:00:00

  • Antiseizure activity of novel gamma-aminobutyric acid (A) receptor subtype-selective benzodiazepine analogues in mice and rat models.

    abstract::The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for alpha2beta3gamma2 and alpha3beta3gamma2 GABA(A)-receptors. Significant anticonvulsant activity with little or no motor impairment and therapeutic indexes (TI) of 2.8-44 (mice, i...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Rivas FM,Stables JP,Murphree L,Edwankar RV,Edwankar CR,Huang S,Jain HD,Zhou H,Majumder S,Sankar S,Roth BL,Ramerstorfer J,Furtmüller R,Sieghart W,Cook JM

    更新日期:2009-04-09 00:00:00

  • N-substituent modulation of opiate agonist/antagonist activity in resolved 3-methyl-3-(m-hydroxyphenyl)piperidines.

    abstract::A series of 3-methyl-3-(m-hydroxyphenyl)piperidines with N-substituent variations have been synthesized and resolved, and an X-ray crystal structure of one analogue was determined. The compounds have been characterized, pharmacologically, by detailed opiate receptor binding studies and determination of in vivo analges...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Cheng A,Uyeno E,Polgar W,Toll L,Lawson JA,DeGraw JI,Loew G,Camerman A,Camerman N

    更新日期:1986-04-01 00:00:00

  • Sterol 14α-Demethylase Structure-Based Optimization of Drug Candidates for Human Infections with the Protozoan Trypanosomatidae.

    abstract::Sterol 14α-demethylases (CYP51) are cytochrome P450 enzymes essential for sterol biosynthesis in eukaryotes and therapeutic targets for antifungal azoles. Multiple attempts to repurpose antifungals for treatment of human infections with protozoa (Trypanosomatidae) have been undertaken, yet so far none of them have rev...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Friggeri L,Hargrove TY,Rachakonda G,Blobaum AL,Fisher P,de Oliveira GM,da Silva CF,Soeiro MNC,Nes WD,Lindsley CW,Villalta F,Guengerich FP,Lepesheva GI

    更新日期:2018-12-13 00:00:00

  • (1-Amino-2-propenyl) phosphonic acid, an inhibitor of alanine racemase and D-alanine:D-alanine ligase.

    abstract::DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Stre...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章


    authors: Vo-Quang Y,Carniato D,Vo-Quang L,Lacoste AM,Neuzil E,Le Goffic F

    更新日期:1986-04-01 00:00:00