Inhibitors of acyl CoA:cholesterol acyltransferase.

abstract：:A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency. Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentratio...

journal_title：Journal of medicinal chemistry

authors： de Zwart MA,Bastiaans HM,van der Goot H,Timmerman H

更新日期：1991-03-01 00:00:00

abstract：:Adverse drug reactions (ADRs) are a common cause of attrition in drug discovery and development and drug-induced liver injury (DILI) is a leading cause of preclinical and clinical drug terminations. This perspective outlines many of the known DILI mechanisms and assessment methods used to evaluate and mitigate DILI ri...

journal_title：Journal of medicinal chemistry

authors： Norman BH

更新日期：2020-10-22 00:00:00

abstract：:The ever-growing risk of bacterial resistance is a critical concern. Among the various antimicrobial resistant bacterial strains, methicillin and vancomycin resistant Staphylococcus aureus are among the most dreadful, causing serious complications. On the basis of the hypothesis that microbes have reduced ability to d...

journal_title：Journal of medicinal chemistry

authors： Singla P,Dalal P,Kaur M,Arya G,Nimesh S,Singh R,Salunke DB

更新日期：2018-11-21 00:00:00

abstract：:Analogues of [Leu10]NKA4-10 were synthesized in which each of the amide bonds was sequentially replaced with the reduced amide psi (CH2NH) bond to determine the effect of this structural modification on the antagonism of NKA binding to the HUB NK2 receptor. [psi (CH2-NH)9,Leu10]NKA4-10 (6) retained significant affinit...

journal_title：Journal of medicinal chemistry

authors： Harbeson SL,Shatzer SA,Le TB,Buck SH

更新日期：1992-10-16 00:00:00

abstract：:Gamma9delta2T cells represent the most abundant population of human blood gammadeltaT lymphocytes. They produce and promote strong cytotoxic activity against many pathogens that are implicated in several human infectious diseases. Their activation requires their exposure to small phosphorus-containing antigens in the ...

journal_title：Journal of medicinal chemistry

authors： Zgani I,Menut C,Seman M,Gallois V,Laffont V,Liautard J,Liautard JP,Criton M,Montero JL

更新日期：2004-08-26 00:00:00

abstract：:Here, we report the synthesis of a designed multi-pharmacophore ligand derived from the linkage of a delta selective peptide antagonist (Dmt-Tic) and a mu/kappa morphinan agonist butorphan (MCL 101) through a two methylene spacer. The new compound MCL 450 maintains the same characteristics as those the two reference c...

journal_title：Journal of medicinal chemistry

authors： Neumeyer JL,Peng X,Knapp BI,Bidlack JM,Lazarus LH,Salvadori S,Trapella C,Balboni G

更新日期：2006-09-07 00:00:00

abstract：:Study of surface representations of the inhibitor-bound thrombin P-1 pocket revealed a lipophilic recess in this pocket which is not occupied by any known inhibitor. Solid-phase synthesis was used to generate benzylamides of D-diphenylAlaPro by aminolysis of Boc dipeptide Kaiser resin. The resulting amides inhibited t...

journal_title：Journal of medicinal chemistry

authors： Lumma WC Jr,Witherup KM,Tucker TJ,Brady SF,Sisko JT,Naylor-Olsen AM,Lewis SD,Lucas BJ,Vacca JP

更新日期：1998-03-26 00:00:00

abstract：:In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis, aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to re...

journal_title：Journal of medicinal chemistry

authors： Mellini P,Kokkola T,Suuronen T,Salo HS,Tolvanen L,Mai A,Lahtela-Kakkonen M,Jarho EM

更新日期：2013-09-12 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：:A novel series of aryl 1-but-3-ynyl-4-phenyl-1,2,3,6-tetrahydropyridines with dopaminergic activity is described. The structure-activity relationships of this series were studied by synthesis of analogs and evaluation of their affinities for the dopamine (DA) D2 receptor and inhibition of locomotor activity (LMA) in r...

journal_title：Journal of medicinal chemistry

authors： Glase SA,Akunne HC,Heffner TG,Jaen JC,MacKenzie RG,Meltzer LT,Pugsley TA,Smith SJ,Wise LD

更新日期：1996-08-02 00:00:00

abstract：:Malaria is still a leading cause of mortality among children in the developing world, and despite the immense progress made in reducing the global burden, further efforts are needed if eradication is to be achieved. In this context, targeting transmission is widely recognized as a necessary intervention toward that go...

journal_title：Journal of medicinal chemistry

authors： Rueda-Zubiaurre A,Yahiya S,Fischer OJ,Hu X,Saunders CN,Sharma S,Straschil U,Shen J,Tate EW,Delves MJ,Baum J,Barnard A,Fuchter MJ

更新日期：2020-03-12 00:00:00

abstract：:Little is known of the conformation of peptide hormones as they interact with their receptors for a number of reasons: peptide hormones are notoriously flexible in solution, their receptors are particularly complex, and there is strong evidence that receptor-ligand interaction leading to activation is a dynamic proces...

journal_title：Journal of medicinal chemistry

authors： Koerber SC,Rizo J,Struthers RS,Rivier JE

更新日期：2000-03-09 00:00:00

abstract：:The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized ...

journal_title：Journal of medicinal chemistry

authors： Smith LH,Tucker H

更新日期：1977-12-01 00:00:00

abstract：:The polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized in our laboratory and established as potent and selective inhibitors of human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behav...

journal_title：Journal of medicinal chemistry

authors： Zhu Z,Lippa B,Drach JC,Townsend LB

更新日期：2000-06-15 00:00:00

abstract：:To design and synthesize new potent and selective antagonists of the human A(3) adenosine receptor, pharmacophoric hypotheses were generated with the software Catalyst for a comprehensive set of compounds retrieved from previous literature. Three of these pharmacophores were used to drive the optimization of a molecul...

journal_title：Journal of medicinal chemistry

authors： Tafi A,Bernardini C,Botta M,Corelli F,Andreini M,Martinelli A,Ortore G,Baraldi PG,Fruttarolo F,Borea PA,Tuccinardi T

更新日期：2006-07-13 00:00:00

abstract：:The resurgence of tuberculosis (TB), the incidence of drug-resistant strains of Mycobacterium tuberculosis (MTB), and the coinfection between TB and HIV have led to serious infections, high mortality, and a global health threat, resulting in the urgent search for new classes of antimycobacterial agents. Herein, we rep...

journal_title：Journal of medicinal chemistry

authors： Guo S,Song Y,Huang Q,Yuan H,Wan B,Wang Y,He R,Beconi MG,Franzblau SG,Kozikowski AP

更新日期：2010-01-28 00:00:00

abstract：:A series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives targeting the allosteric lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractive target for antiviral chemotherapy, was prepared and screened for activity against HIV-1 infection in cell culture. Small molecules t...

journal_title：Journal of medicinal chemistry

authors： Peese KM,Allard CW,Connolly T,Johnson BL,Li C,Patel M,Sorensen ME,Walker MA,Meanwell NA,McAuliffe B,Minassian B,Krystal M,Parker DD,Lewis HA,Kish K,Zhang P,Nolte RT,Simmermacher J,Jenkins S,Cianci C,Naidu BN

更新日期：2019-02-14 00:00:00

abstract：:The discovery of the (acryloylaryloxy)acetic acids as a new class of potent diuretics prompted the investigation of related bicyclic compounds. Annelated analogues of the parent series, the (2-alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids, were the subjects of this study. Those compounds, unlike the monocycli...

journal_title：Journal of medicinal chemistry

authors： Woltersdorf OW Jr,deSolms SJ,Schultz EM,Cragoe EJ Jr

更新日期：1977-11-01 00:00:00

abstract：:CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus ...

journal_title：Journal of medicinal chemistry

authors： Li B,Ni S,Mao F,Chen F,Liu Y,Wei H,Chen W,Zhu J,Lan L,Li J

更新日期：2018-01-11 00:00:00

abstract：:The synthesis of a series of novel, potent angiotensin converting enzyme (ACE) inhibitors containing saturated bicyclic amino acids in place of proline is described. Octahydroindole-2-carboxylic acid, octahydroisoindole-1-carboxylic acid, and octahydro-3-oxoisoindole-1-carboxylic acid can replace proline in both sulfh...

journal_title：Journal of medicinal chemistry

authors： Blankley CJ,Kaltenbronn JS,DeJohn DE,Werner A,Bennett LR,Bobowski G,Krolls U,Johnson DR,Pearlman WM,Hoefle ML

更新日期：1987-06-01 00:00:00

abstract：:In tissue engineering, survival of larger constructs remains challenging due to limited supply of oxygen caused by a lack of early vascularization. Controlled release of oxygen from small organic molecules represents a possible strategy to prevent cell death under anoxic conditions. A comprehensive study of methylated...

journal_title：Journal of medicinal chemistry

authors： Benz S,Nötzli S,Siegel JS,Eberli D,Jessen HJ

更新日期：2013-12-27 00:00:00

abstract：:We have previously reported a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands to serve as potential nonaddictive opioid analgesics. These ligands have been shown to be active in vivo, do not manifest withdrawal syndromes or reward behavior in conditioned-place preference assays in ...

journal_title：Journal of medicinal chemistry

authors： Henry SP,Fernandez TJ,Anand JP,Griggs NW,Traynor JR,Mosberg HI

更新日期：2019-04-25 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：:5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated ...

journal_title：Journal of medicinal chemistry

authors： De Croos PZ,Sangdee P,Stockwell BL,Kar L,Thompson EB,Johnson ME,Currie BL

更新日期：1990-12-01 00:00:00

abstract：:A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cycli...

journal_title：Journal of medicinal chemistry

authors： Kim HS,Shibata Y,Wataya Y,Tsuchiya K,Masuyama A,Nojima M

更新日期：1999-07-15 00:00:00

abstract：:Aberrant activation of the MAPK pathway drives cell proliferation in multiple cancers. Inhibitors of BRAF and MEK kinases are approved for the treatment of BRAF mutant melanoma, but resistance frequently emerges, often mediated by increased signaling through ERK1/2. Here, we describe the fragment-based generation of E...

journal_title：Journal of medicinal chemistry

authors： Heightman TD,Berdini V,Braithwaite H,Buck IM,Cassidy M,Castro J,Courtin A,Day JEH,East C,Fazal L,Graham B,Griffiths-Jones CM,Lyons JF,Martins V,Muench S,Munck JM,Norton D,O'Reilly M,Palmer N,Pathuri P,Reader M,R

更新日期：2018-06-14 00:00:00

abstract：:Modulation of sphingosine 1-phosphate (S1P) signaling represents a solid opportunity for multiple sclerosis (MS) treatment. In this issue, a team at Novartis reports on the identification of the first direct S1P lyase (S1PL) inhibitors as new MS agents. One of the most potent inhibitors reported in their work was demo...

journal_title：Journal of medicinal chemistry

authors： Cosconati S,Novellino E

更新日期：2014-06-26 00:00:00

abstract：:2-[[(2-Pyridyl)methyl]thio]-1H-benzimidazoles (2, sulfides) exhibit antibacterial properties that are selective for Helicobacter spp., but they also have an inherent susceptibility to metabolic oxidation to furnish 2-[[(2-pyridyl)methyl]sulfinyl]-1H-benzimidazoles (1), which act as proton pump inhibitors (PPIs). We ha...

journal_title：Journal of medicinal chemistry

authors： Kühler TC,Swanson M,Christenson B,Klintenberg AC,Lamm B,Fägerhag J,Gatti R,Olwegård-Halvarsson M,Shcherbuchin V,Elebring T,Sjöström JE

更新日期：2002-09-12 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：:As a mitotic-specific target widely deregulated in various human cancers, polo-like kinase 1 (Plk1) has been extensively explored for anticancer activity and drug discovery. Although multiple catalytic domain inhibitors were tested in preclinical and clinical studies, their efficacies are limited by dose-limiting cyto...

journal_title：Journal of medicinal chemistry

authors： Alverez CN,Park JE,Toti KS,Xia Y,Krausz KW,Rai G,Bang JK,Gonzalez FJ,Jacobson KA,Lee KS

更新日期：2020-11-25 00:00:00