Structure-carcinogenic activity relationships in the Benz [a] anthracene series.

abstract：:Peroxisome proliferator-activated receptor alpha (PPARα) is expressed in retinal Müller cells, endothelial cells, and in retinal pigment epithelium; agonism of PPARα with genetic or pharmacological tools ameliorates inflammation, vascular leakage, neurodegeneration, and neovascularization associated with retinal disea...

journal_title：Journal of medicinal chemistry

authors： Dou X,Nath D,Shin H,Nurmemmedov E,Bourne PC,Ma JX,Duerfeldt AS

更新日期：2020-03-26 00:00:00

abstract：:The interaction between leukocyte function-associated antigen-1 (LFA-1) and intracellular adhesion molecule-1 (ICAM-1) has been implicated in inflammatory and immune diseases. Recently, a novel series of p-arylthio cinnamides has been described as potent antagonists of the LFA-1/ICAM-1 interaction. These compounds wer...

journal_title：Journal of medicinal chemistry

authors： Liu G,Huth JR,Olejniczak ET,Mendoza R,DeVries P,Leitza S,Reilly EB,Okasinski GF,Fesik SW,von Geldern TW

更新日期：2001-04-12 00:00:00

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

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

abstract：:Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P(1) ligand resulted in compounds with improved selectivity for factor Xa relative to trypsin and plasma kallikrein. Further optimization of the P(4) moiety led to compounds with enhanced permeability and reduced prot...

journal_title：Journal of medicinal chemistry

authors： Quan ML,Lam PY,Han Q,Pinto DJ,He MY,Li R,Ellis CD,Clark CG,Teleha CA,Sun JH,Alexander RS,Bai S,Luettgen JM,Knabb RM,Wong PC,Wexler RR

更新日期：2005-03-24 00:00:00

abstract：:Serotonin N-acetyltransferase, also called the melatonin rhythm enzyme, is thought to play an important regulatory role in circadian rhythm in animals and people. A series of analogues were synthesized in which indole and coenzyme A were linked via ketone tethers as designed inhibitors of this enzyme. These compounds ...

journal_title：Journal of medicinal chemistry

authors： Kim CM,Cole PA

更新日期：2001-07-19 00:00:00

abstract：:A series of novel β-carboline-based N-heterocyclic carbenes was prepared via Mannich reaction between methyl 1-(dimethoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate, formaldehyde, and primary amines. All compounds were evaluated for their antiproliferative activity using human breast cancer and lung cancer cell lines...

journal_title：Journal of medicinal chemistry

authors： Dighe SU,Khan S,Soni I,Jain P,Shukla S,Yadav R,Sen P,Meeran SM,Batra S

更新日期：2015-04-23 00:00:00

abstract：:We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-L-tyrosine derivatives which are potent, selective PPARgamma agonists. Through the use of in vitro PPARgamma binding and functional assays (2S)-3-(4-(benzyloxy)phenyl)-2-((1-methyl-3-oxo-3-phenylpropenyl)+ ++amin o)propionic acid (2) was identified ...

journal_title：Journal of medicinal chemistry

authors： Henke BR,Blanchard SG,Brackeen MF,Brown KK,Cobb JE,Collins JL,Harrington WW Jr,Hashim MA,Hull-Ryde EA,Kaldor I,Kliewer SA,Lake DH,Leesnitzer LM,Lehmann JM,Lenhard JM,Orband-Miller LA,Miller JF,Mook RA Jr,Noble SA,Ol

更新日期：1998-12-03 00:00:00

abstract：:Enantiostructure-activity studies of chlorophenoxybutyric and propionic acids have provided evidence for the dissociation of serum cholesterol lowering and platelet antiaggregatory activities from the adverse chloride ion channel mediated myotonic effects of these compounds. R-(+) propionic and butyric acid enantiomer...

journal_title：Journal of medicinal chemistry

authors： Feller DR,Kamanna VS,Newman HA,Romstedt KJ,Witiak DT,Bettoni G,Bryant SH,Conte-Camerino D,Loiodice F,Tortorella V

更新日期：1987-08-01 00:00:00

abstract：:The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Rep...

journal_title：Journal of medicinal chemistry

authors： Allen MC,Fuhrer W,Tuck B,Wade R,Wood JM

更新日期：1989-07-01 00:00:00

abstract：:A series of 5-substituted tetrahydroisoquinolines was synthesized via a 10-step linear synthesis to assess whether replacement of noscapine's southern isobenzofuranone with other moieties resulted in retained cytotoxic activity. One such molecule, 18g, bearing a para-methoxybenzyl functionality with N-ethylcarbamoyl s...

journal_title：Journal of medicinal chemistry

authors： Devine SM,Yong C,Amenuvegbe D,Aurelio L,Muthiah D,Pouton C,Callaghan R,Capuano B,Scammells PJ

更新日期：2018-09-27 00:00:00

abstract：:Symmetrical and asymmetrical fluorinated phenyltriazolyl-thiodigalactoside derivatives have been synthesized and evaluated as inhibitors of galectin-1 and galectin-3. Systematic tuning of the phenyltriazolyl-thiodigalactosides' fluoro-interactions with galectin-3 led to the discovery of inhibitors with exceptional aff...

journal_title：Journal of medicinal chemistry

authors： Peterson K,Kumar R,Stenström O,Verma P,Verma PR,Håkansson M,Kahl-Knutsson B,Zetterberg F,Leffler H,Akke M,Logan DT,Nilsson UJ

更新日期：2018-02-08 00:00:00

abstract：:Extension of the structure-activity relationship studies that led to the discovery of the nonsedating potent muscle relaxant, antiinflammatory, and analgesic agent (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 1, has given rise to (E)-2-(4-chloro-6-fluoro-1-indanylidene)-N-methylacetamide, 2. Compound 2 is a potent an...

journal_title：Journal of medicinal chemistry

authors： Musso DL,Orr GF,Cochran FR,Kelley JL,Selph JL,Rigdon GC,Cooper BR,Jones ML

更新日期：2003-01-30 00:00:00

abstract：:Variation of the bridge linking the heterocyclic ring and p-aminobenzoyl-L-glutamate portions of our previously described classical 2,4-diaminofuro[2,3-d]pyrimidines 1 and 2 are reported as inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) and as antitumor agents. Specifically -CH2CH2- and -CH...

journal_title：Journal of medicinal chemistry

authors： Gangjee A,Devraj R,McGuire JJ,Kisliuk RL

更新日期：1995-09-15 00:00:00

abstract：:Small-molecule fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has gained increasing interest in clinical application. Till now, very few studies have been exploited in the small-molecule fluorophores with both excitation and emission in the NIR-II window. Inspired by the indocyanine gre...

journal_title：Journal of medicinal chemistry

authors： Ding B,Xiao Y,Zhou H,Zhang X,Qu C,Xu F,Deng Z,Cheng Z,Hong X

更新日期：2019-02-28 00:00:00

abstract：:Thalidomide, 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, has been shown to inhibit angiogenesis, the formation of new blood vessels from existing vasculature. As a result, there is renewed interest in this drug as a potential therapy for solid tumors. Thalidomide forms a number of metabolites and has been ...

journal_title：Journal of medicinal chemistry

authors： Lepper ER,Ng SS,Gütschow M,Weiss M,Hauschildt S,Hecker TK,Luzzio FA,Eger K,Figg WD

更新日期：2004-04-22 00:00:00

abstract：:Novel 5-[(alkylamino)methyl]thieno[2,3-b]furan-2-sulfonamides were prepared and evaluated in vitro for inhibition of human carbonic anhydrase II (CA II) and ex vivo for their ability to inhibit Ca II in the albino rabbit eye after topical administration. Compound 11a was found to lower intraocular pressure (IOP) in bo...

journal_title：Journal of medicinal chemistry

authors： Hartman GD,Halczenko W,Prugh JD,Smith RL,Sugrue MF,Mallorga P,Michelson SR,Randall WC,Schwam H,Sondey JM

更新日期：1992-08-07 00:00:00

abstract：:4,4-Ditritio-(-)-nicotine (5) of high specific activity (4.7 Ci/mmol) has been synthesized from (-)-nicotine via the readily prepared 4,4-dibromocotinine (3). Scatchard analysis of the binding of 5 to the crude mitochondrial fraction of whole rat brain revealed a Ka of 4.7 X 10(6) M-1 and 13 fmol of binding sites/mg o...

journal_title：Journal of medicinal chemistry

authors： Vincek WC,Martin BR,Aceto MD,Bowman ER

更新日期：1980-08-01 00:00:00

abstract：:A series of 1-methyl-1H-pyrazole-5-carboxamides were synthesized as potent inhibitors of the parasitic nematode of sheep, Haemonchus contortus. These compounds did not show overt cytotoxicity to a range of mammalian cell lines under standard in vitro culture conditions, had high selectivity indices, and were progresse...

journal_title：Journal of medicinal chemistry

authors： Preston S,Garcia-Bustos J,Hall LG,Martin SD,Le TG,Kundu A,Ghoshal A,Nguyen NH,Jiao Y,Ruan B,Xue L,Huang F,Chang BCH,McGee SL,Wells TNC,Palmer MJ,Jabbar A,Gasser RB,Baell JB

更新日期：2021-01-14 00:00:00

abstract：:Analogues of the antimycotic allylamine terbinafine were prepared in which the naphthalene and the tert-butyl-acetylene moieties were preserved, but the spacer between these two groups was varied, and the antifungal activity of the new compounds was evaluated. All modifications of the original spacer such as reduction...

journal_title：Journal of medicinal chemistry

authors： Nussbaumer P,Leitner I,Stütz A

更新日期：1994-03-04 00:00:00

abstract：:Three ellipticine-estradiol conjugates were synthesized in an effort to target the cytotoxicity of ellipticine to estrogen-receptor positive cells. The three conjugates were prepared with linker chains extending from the 17 alpha position of the estradiol to N-2 (compound 3), N-6 (compound 4), and C-9 (compound 5) pos...

journal_title：Journal of medicinal chemistry

authors： Devraj R,Barrett JF,Fernandez JA,Katzenellenbogen JA,Cushman M

更新日期：1996-08-16 00:00:00

abstract：:Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compo...

journal_title：Journal of medicinal chemistry

authors： Graham SL,Hoffman JM,Gautheron P,Michelson SR,Scholz TH,Schwam H,Shepard KL,Smith AM,Smith RL,Sondey JM

更新日期：1990-02-01 00:00:00

abstract：:Conjugating a siderophore to an antibiotic is a promising strategy to overcome the permeability-mediated resistance of Gram-negative pathogens. On the basis of the structure of BAL30072, novel pyridone-conjugated monosulfactams incorporating diverse substituents into the methylene linker between the 1,3-dihydroxypyrid...

journal_title：Journal of medicinal chemistry

authors： Tan L,Tao Y,Wang T,Zou F,Zhang S,Kou Q,Niu A,Chen Q,Chu W,Chen X,Wang H,Yang Y

更新日期：2017-04-13 00:00:00

abstract：:Novel pyridine- and pyrimidine-based allosteric inhibitors are reported that achieve PDE4D subtype selectivity through recognition of a single amino acid difference on a key regulatory domain, known as UCR2, that opens and closes over the catalytic site for cAMP hydrolysis. The design and optimization of lead compound...

journal_title：Journal of medicinal chemistry

authors： Gurney ME,Nugent RA,Mo X,Sindac JA,Hagen TJ,Fox D 3rd,O'Donnell JM,Zhang C,Xu Y,Zhang HT,Groppi VE,Bailie M,White RE,Romero DL,Vellekoop AS,Walker JR,Surman MD,Zhu L,Campbell RF

更新日期：2019-05-23 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：:A three-dimensional common feature pharmacophore model was developed using the X-ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs were designed and synthesized, having the benzimidazol-2-one system as a sca...

journal_title：Journal of medicinal chemistry

authors： Barreca ML,Rao A,De Luca L,Zappalà M,Monforte AM,Maga G,Pannecouque C,Balzarini J,De Clercq E,Chimirri A,Monforte P

更新日期：2005-05-05 00:00:00

abstract：:Rexinoids are ligands for the retinoid X receptor (RXR) that have great promise for both the prevention and treatment of cancer and metabolic diseases. In this regard, synthetic, functional, and structural investigations into the structure-activity relationships of derivatives of the potent RXR agonist (E)-3-[3-(3,5,5...

journal_title：Journal of medicinal chemistry

authors： Pérez Santín E,Germain P,Quillard F,Khanwalkar H,Rodríguez-Barrios F,Gronemeyer H,de Lera AR,Bourguet W

更新日期：2009-05-28 00:00:00

abstract：:In this article we introduce a molecular docking algorithm called MolDock. MolDock is based on a new heuristic search algorithm that combines differential evolution with a cavity prediction algorithm. The docking scoring function of MolDock is an extension of the piecewise linear potential (PLP) including new hydrogen...

journal_title：Journal of medicinal chemistry

authors： Thomsen R,Christensen MH

更新日期：2006-06-01 00:00:00

abstract：:Orally bioavailable SERDs may offer greater systemic drug exposure, improved clinical efficacy, and more durable treatment outcome for patients with ER-positive endocrine-resistant breast cancer. We report the design and synthesis of a boronic acid modified fulvestrant (5, ZB716), which binds to ERα competitively (IC5...

journal_title：Journal of medicinal chemistry

authors： Liu J,Zheng S,Akerstrom VL,Yuan C,Ma Y,Zhong Q,Zhang C,Zhang Q,Guo S,Ma P,Skripnikova EV,Bratton MR,Pannuti A,Miele L,Wiese TE,Wang G

更新日期：2016-09-08 00:00:00

abstract：:The chemokine receptor CXCR4 is a critical regulator of inflammation and immune surveillance, and it is specifically implicated in cancer metastasis and HIV-1 infection. On the basis of the observation that several of the known antagonists remarkably share a C(2) symmetry element, we constructed symmetric dimers with ...

journal_title：Journal of medicinal chemistry

authors： Demmer O,Dijkgraaf I,Schumacher U,Marinelli L,Cosconati S,Gourni E,Wester HJ,Kessler H

更新日期：2011-11-10 00:00:00

abstract：:Structural modifications requiring novel synthetic chemistry were made to the morpholine acetal human neurokinin-1 (hNK-1) receptor antagonist 4, and this resulted in the discovery of 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4-(3-ox o-1 ,2,4-triazol-5-yl)methyl morpholine (17). This m...

journal_title：Journal of medicinal chemistry

authors： Hale JJ,Mills SG,MacCoss M,Finke PE,Cascieri MA,Sadowski S,Ber E,Chicchi GG,Kurtz M,Metzger J,Eiermann G,Tsou NN,Tattersall FD,Rupniak NM,Williams AR,Rycroft W,Hargreaves R,MacIntyre DE

更新日期：1998-11-05 00:00:00