Antineoplastic agents. 291. Isolation and synthesis of combretastatins A-4, A-5, and A-6(1a)

abstract：:A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavio...

journal_title：Journal of medicinal chemistry

authors： Mortensen DS,Rodriguez AL,Carlson KE,Sun J,Katzenellenbogen BS,Katzenellenbogen JA

更新日期：2001-11-08 00:00:00

abstract：:(3-Phenyl-7-flavonoxy)propanolamines have been shown to exhibit antihypertensive activity in spontaneously hypertensive rats. Although they are structurally similar to classical beta-adrenergic blocking compounds, their activity is not due to inhibition of beta-adrenoceptors. In the present study, a series of simple f...

journal_title：Journal of medicinal chemistry

authors： Wu ES,Cole TE,Davidson TA,Dailey MA,Doring KG,Fedorchuk M,Loch JT 3rd,Thomas TL,Blosser JC,Borrelli AR

更新日期：1989-01-01 00:00:00

abstract：:We have developed a fast and robust computational method for prediction of antiviral activity in automated de novo design of HIV-1 reverse transcriptase inhibitors. This is a structure-based approach that uses a linear relation between activity and interaction energy with discrete orientation sampling and with localiz...

journal_title：Journal of medicinal chemistry

authors： de Jonge MR,Koymans LM,Vinkers HM,Daeyaert FF,Heeres J,Lewi PJ,Janssen PA

更新日期：2005-03-24 00:00:00

abstract：:The serotonin transporter (SERT) is the primary target for antidepressant drugs. The existence of a high affinity primary orthosteric binding site (S1) and a low affinity secondary site (S2) has been described, and their relation to antidepressant pharmacology has been debated. Herein, structural modifications to the ...

journal_title：Journal of medicinal chemistry

authors： Banala AK,Zhang P,Plenge P,Cyriac G,Kopajtic T,Katz JL,Loland CJ,Newman AH

更新日期：2013-12-12 00:00:00

abstract：:Coactivator-associated arginine methyltransferase 1 (CARM1) represents a valuable target for hormone-dependent tumors such as prostate and breast cancers. Here we report the enzyme and cellular characterization of the 1-benzyl-3,5-bis(3-bromo-4-hydroxybenzylidene)piperidin-4-one (7g) and its analogues 8a-l. Among them...

journal_title：Journal of medicinal chemistry

authors： Cheng D,Valente S,Castellano S,Sbardella G,Di Santo R,Costi R,Bedford MT,Mai A

更新日期：2011-07-14 00:00:00

abstract：:Peptidyl alpha-keto amides have been synthesized and tested as inhibitors of the cysteine protease calpain. A stereospecific synthesis was devised in which Cbz-dipeptidyl-alpha-hydroxy amides were oxidized with TEMPO/hypochlorite to the corresponding alpha-keto amides. This oxidation was accomplished in good yields an...

journal_title：Journal of medicinal chemistry

authors： Harbeson SL,Abelleira SM,Akiyama A,Barrett R 3rd,Carroll RM,Straub JA,Tkacz JN,Wu C,Musso GF

更新日期：1994-09-02 00:00:00

abstract：:Detailed molecular models of the free C1B domain of protein kinase C-gamma (PKC-gamma) and the C1B domain with its activator phorbol-12-myristate-13-acetate (PMA) in water solution and in the presence of dipalmitoylphosphatidylcholine (DPPC) bilayer are presented. Molecular dynamics of the free C1B domain reveals hydr...

journal_title：Journal of medicinal chemistry

authors： Hritz J,Ulicny J,Laaksonen A,Jancura D,Miskovsky P

更新日期：2004-12-16 00:00:00

abstract：:Cytochrome P450 aromatase catalyzes the conversion of androgen substrates into estrogens. Aromatase inhibitors (AIs) have been used as first-line drugs in the treatment of estrogen-dependent breast cancer in postmenopausal women. However, the search for new, more potent, and selective AIs still remains necessary to av...

journal_title：Journal of medicinal chemistry

authors： Caporuscio F,Rastelli G,Imbriano C,Del Rio A

更新日期：2011-06-23 00:00:00

abstract：:The interesting bronchodilator activity of certain dl-11-deoxy-3-thiaprostaglandins and their preparation by the conjugate addition of appropriately substituted (E)-1-alkenyllithio cuprate reagents to requisite cyclopentenones are described. ...

journal_title：Journal of medicinal chemistry

authors： Skotnicki JS,Schaub RE,Weiss MJ,Dessy F

更新日期：1977-12-01 00:00:00

abstract：:A new computational method for the in situ generation of small molecules within the binding site of a protein is described. The method has been evaluated using two well-studied systems, dihydrofolate reductase and thymidylate synthase. The method has also been used to guide improvements to inhibitors of HIV-1 protease...

journal_title：Journal of medicinal chemistry

authors： Gehlhaar DK,Moerder KE,Zichi D,Sherman CJ,Ogden RC,Freer ST

更新日期：1995-02-03 00:00:00

abstract：:A unique, dual-function, photoactivatable anticancer prodrug, RuEuL, has been tailored that features a ruthenium(II) complex linked to a cyclen-europium chelate via a π-conjugated bridge. Under irradiation at 488 nm, the dark-inactive prodrug undergoes photodissociation, releasing the DNA-damaging ruthenium species. U...

journal_title：Journal of medicinal chemistry

authors： Li H,Xie C,Lan R,Zha S,Chan CF,Wong WY,Ho KL,Chan BD,Luo Y,Zhang JX,Law GL,Tai WCS,Bünzli JG,Wong KL

更新日期：2017-11-09 00:00:00

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

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

更新日期：1994-06-24 00:00:00

abstract：:In the present study, L-prolyl-L-leucyl-glycinamide (1) peptidomimetics 3a-3d and 4a-4d were synthesized utilizing alpha, alpha-disubstituted amino acids. These analogues were designed to explore the conformational effects of constraints at the phi3 and psi3 torsion angles. Constrained conformations were verified by t...

journal_title：Journal of medicinal chemistry

authors： Evans MC,Pradhan A,Venkatraman S,Ojala WH,Gleason WB,Mishra RK,Johnson RL

更新日期：1999-04-22 00:00:00

abstract：:Recently, we reported the identification of a novel class of pregnane-X-receptor (PXR) agonists, solomonsterols A and B, isolated from the marine sponge Theonella swinhoei. Preliminary pharmacological studies demonstrated that these natural compounds are potential leads for the treatment of human disorders characteriz...

journal_title：Journal of medicinal chemistry

authors： Sepe V,Ummarino R,D'Auria MV,Mencarelli A,D'Amore C,Renga B,Zampella A,Fiorucci S

更新日期：2011-07-14 00:00:00

abstract：:Syntheses of several tripeptide analogues of leupeptin containing C-terminal argininal, lysinal, or ornithinal units are presented. The synthetic analogues were tested as inhibitors of trypsin, plasmin, and kallikrein. (Benzyloxycarbonyl)-L-leucyl-L-leucyl-L-argininal (2a) was significantly less effective as an inhibi...

journal_title：Journal of medicinal chemistry

authors： McConnell RM,Barnes GE,Hoyng CF,Gunn JM

更新日期：1990-01-01 00:00:00

abstract：:A series of balanol analogs in which the perhydroazepine ring and the p-hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to low-nanomolar inhibitors of the alpha, beta I, be...

journal_title：Journal of medicinal chemistry

authors： Defauw JM,Murphy MM,Jagdmann GE Jr,Hu H,Lampe JW,Hollinshead SP,Mitchell TJ,Crane HM,Heerding JM,Mendoza JS,Davis JE,Darges JW,Hubbard FR,Hall SE

更新日期：1996-12-20 00:00:00

abstract：:A series of 3-fluoromethyl-1,2,3,4-tetrahydroisoquinolines (3-fluoromethyl-THIQs) was proposed, and their phenylethanolamine N-methyltransferase (PNMT) and alpha(2)-adrenoceptor affinities were predicted through the use of comparative molecular field analysis (CoMFA) models. These compounds were synthesized and evalua...

journal_title：Journal of medicinal chemistry

authors： Grunewald GL,Caldwell TM,Li Q,Slavica M,Criscione KR,Borchardt RT,Wang W

更新日期：1999-09-09 00:00:00

abstract：:Multidrug resistance-associated protein 1 (MRP1) is a drug efflux transporter that has been implicated in the pathology of several neurological diseases and is associated with development of multidrug resistance. To enable measurement of MRP1 function in the living brain, a series of 6-halopurines decorated with fluor...

journal_title：Journal of medicinal chemistry

authors： Galante E,Okamura T,Sander K,Kikuchi T,Okada M,Zhang MR,Robson M,Badar A,Lythgoe M,Koepp M,Årstad E

更新日期：2014-02-13 00:00:00

abstract：:Network theory provides one of the most potent analysis tools for the study of complex systems. In this paper, we illustrate the network-based perspective in drug research and how it is coherent with the new paradigm of drug discovery. We first present data sources from which networks are built, then show some example...

journal_title：Journal of medicinal chemistry

authors： Recanatini M,Cabrelle C

更新日期：2020-08-27 00:00:00

abstract：:The antimicrobial and cytotoxic properties of a series of 9,10-dihydrophenanthrenes structurally related to juncusol (1a), a postulated phytoalexin with confirmed cytotoxic properties, are detailed. Two simple 9,10-dihydrophenanthrenes, 2,7-dihydroxy-3,8-dimethyl-9,10-dihydrophenanthrene (2h, desvinyljuncusol) and 2-h...

journal_title：Journal of medicinal chemistry

authors： Boger DL,Mitscher LA,Mullican MD,Drake SD,Kitos P

更新日期：1985-10-01 00:00:00

abstract：:G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors and major targets for drug development. Herein, we sought to identify the regions of the human angiotensin II (AngII) type 1 (hAT(1)) receptor binding cleft that interact with all positions of the AngII using photoaffinity labeling. W...

journal_title：Journal of medicinal chemistry

authors： Fillion D,Lemieux G,Basambombo LL,Lavigne P,Guillemette G,Leduc R,Escher E

更新日期：2010-03-11 00:00:00

abstract：:A series of [(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids was synthesized and tested for diuretic activity in saline-loaded mice and in conscious, water-loaded dogs. The structural requirements for good diuretic activity in both mice and dogs were found to be very specific. In summary, the compounds with the best di...

journal_title：Journal of medicinal chemistry

authors： Shutske GM,Setescak LL,Allen RC,Davis L,Effland RC,Ranbom K,Kitzen JM,Wilker JC,Novick WJ Jr

更新日期：1982-01-01 00:00:00

abstract：:The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction...

journal_title：Journal of medicinal chemistry

authors： Green J,Cao J,Bandarage UK,Gao H,Court J,Marhefka C,Jacobs M,Taslimi P,Newsome D,Nakayama T,Shah S,Rodems S

更新日期：2015-06-25 00:00:00

abstract：:Herein we describe the development of a focused series of functionalized pyridazin-3(2 H)-one-based formyl peptide receptor (FPR) agonists that demonstrate high potency and biased agonism. The compounds described demonstrated biased activation of prosurvival signaling, ERK1/2 phosphorylation, through diminution of the...

journal_title：Journal of medicinal chemistry

authors： Deora GS,Qin CX,Vecchio EA,Debono AJ,Priebbenow DL,Brady RM,Beveridge J,Teguh SC,Deo M,May LT,Krippner G,Ritchie RH,Baell JB

更新日期：2019-05-23 00:00:00

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

authors： Clark ER,Hughes IE,Smith CF

更新日期：1976-05-01 00:00:00

abstract：:We recently described a number of inhibitors of P450(17 alpha), the key enzyme of androgen biosynthesis. Here, we report the synthesis and activity of novel 17-imidazolyl, pyrazolyl, and isoxazolyl androstene derivatives as potential agents for the treatment of prostatic cancer. A number of 17-(4'-Imidazolyl) derivati...

journal_title：Journal of medicinal chemistry

authors： Ling YZ,Li JS,Liu Y,Kato K,Klus GT,Brodie A

更新日期：1997-09-26 00:00:00

abstract：:Modern rational drug design not only deals with the search for ligands binding to interesting and promising validated targets but also aims to identify the function and ligands of yet uncharacterized proteins having impact on different diseases. Additionally, it contributes to the design of inhibitors with distinct se...

journal_title：Journal of medicinal chemistry

authors： Ehrt C,Brinkjost T,Koch O

更新日期：2016-05-12 00:00:00

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

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

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

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

abstract：:Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligo...

journal_title：Journal of medicinal chemistry

authors： Serby MD,Zhao H,Szczepankiewicz BG,Kosogof C,Xin Z,Liu B,Liu M,Nelson LT,Kaszubska W,Falls HD,Schaefer V,Bush EN,Shapiro R,Droz BA,Knourek-Segel VE,Fey TA,Brune ME,Beno DW,Turner TM,Collins CA,Jacobson PB,Sham H

更新日期：2006-04-20 00:00:00