Design, synthesis, and preliminary pharmacological evaluation of N-acyl-3-aminoglutarimides as broad-spectrum chemokine inhibitors in vitro and anti-inflammatory agents in vivo.

abstract：:The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of 14 camptothecin derivatives of polypyrrolecarboxamide (lexitropsin) conjugates of two structural classes: (A) camptothecin-NHCO-lexitropsin 44-51 and (B) camptothecin-CONH-lexitropsin 38-43 are descri...

journal_title：Journal of medicinal chemistry

authors： Zhao R,al-Said NH,Sternbach DL,Lown JW

更新日期：1997-01-17 00:00:00

abstract：:Benzodiazepines (BZ) exert their effects through GABAA receptors, which belong to the superfamily of ligand-gated ion channels. Coexpression of recombinant alpha, beta, and gamma subunits in a cell culture system mimics the BZ binding sites. The alpha variants largely determine the nature of the BZ binding site in suc...

journal_title：Journal of medicinal chemistry

authors： Wieland HA,Lüddens H

更新日期：1994-12-23 00:00:00

abstract：:A series of four structurally related carbocyclic nucleosides (6a, 6b, 10a, and 10b) were synthesized and evaluated for their ability to inhibit tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) production from human primary macrophages. These compounds had little effect...

journal_title：Journal of medicinal chemistry

authors： Borcherding DR,Peet NP,Munson HR,Zhang H,Hoffman PF,Bowlin TL,Edwards CK 3rd

更新日期：1996-06-21 00:00:00

abstract：:We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitr...

journal_title：Journal of medicinal chemistry

authors： Rai D,Johar M,Manning T,Agrawal B,Kunimoto DY,Kumar R

更新日期：2005-11-03 00:00:00

abstract：:A dihydropyridine-pyridine type redox pro-drug system was developed for delivering quaternary pyridinium salts through biological membranes. As a first application, the dihydropyridine derivative of N-methylpyridinium-2-carbaldoxime chloride (2-PAM) was synthesized using a reduction-addition-elimination sequence. The ...

journal_title：Journal of medicinal chemistry

authors： Bodor N,Shek E,Higuchi T

更新日期：1976-01-01 00:00:00

abstract：: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...

journal_title：Journal of medicinal chemistry

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

更新日期：1987-01-01 00:00:00

abstract：:Colony stimulation factor-1 receptor (CSF-1R), which is also known as FMS kinase, plays an important role in initiating inflammatory, cancer, and bone disorders when it is overstimulated by its ligand, CSF-1. Innate immunity, as well as macrophage differentiation and survival, are regulated by the stimulation of the C...

journal_title：Journal of medicinal chemistry

authors： El-Gamal MI,Al-Ameen SK,Al-Koumi DM,Hamad MG,Jalal NA,Oh CH

更新日期：2018-07-12 00:00:00

abstract：:Benzofuran, indan and tetrahydronaphthalene analogs of 3,4-(methylenedioxy)amphetamine (MDA) were prepared in order to examine the role of the dioxole ring oxygen atoms of MDA in interacting with the serotonin and catecholamine uptake carriers. The series of compounds was evaluated for discriminative stimulus effects ...

journal_title：Journal of medicinal chemistry

authors： Monte AP,Marona-Lewicka D,Cozzi NV,Nichols DE

更新日期：1993-11-12 00:00:00

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

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

abstract：:A set of 4-quinolone-3-carboxylic acids bearing different substituents on the condensed benzene ring was designed and synthesized as potential HIV-1 integrase inhibitors structurally related to elvitegravir. Some of the new compounds proved to be able to inhibit the strand transfer step of the virus integration proces...

journal_title：Journal of medicinal chemistry

authors： Pasquini S,Mugnaini C,Tintori C,Botta M,Trejos A,Arvela RK,Larhed M,Witvrouw M,Michiels M,Christ F,Debyser Z,Corelli F

更新日期：2008-08-28 00:00:00

abstract：:alpha-Ethynyl- and alpha-vinylornithine were designed and synthesized as potential enzyme-activated inhibitors of mammalian ornithine decarboxylase. These two new inhibitors produce both immediate and time-dependent inhibition of rat liver ornithine decarboxylase in vitro. The inhibitions exhibition saturation kinetic...

journal_title：Journal of medicinal chemistry

authors： Danzin C,Casara P,Claverie N,Metcalf BW

更新日期：1981-01-01 00:00:00

abstract：:Quantitative structure-activity studies were carried out on a series of N-isopropylaryl hydrazides which inhibits monoamine oxidase (MAO). The inhibitory potencies of these compounds of MAO were found to correlate with the electron-withdrawing capacity of the aryl ring substituents as estimated by both empirical Hamme...

journal_title：Journal of medicinal chemistry

authors： Johnson CL

更新日期：1976-05-01 00:00:00

abstract：:Real-time, noninvasive assessment of glomerular filtration rate (GFR) is essential not only for monitoring critically ill patients at the bedside, but also for staging and monitoring patients with chronic kidney disease. In our pursuit to develop exogenous luminescent probes for dynamic optical monitoring of GFR, we h...

journal_title：Journal of medicinal chemistry

authors： Chinen LK,Galen KP,Kuan KT,Dyszlewski ME,Ozaki H,Sawai H,Pandurangi RS,Jacobs FG,Dorshow RB,Rajagopalan R

更新日期：2008-02-28 00:00:00

abstract：:Thirteen newly synthesized or resynthesized diamine-platinum(II) complexes were characterized, and their cytotoxic activities (IC50) were tested on parental and resistant ovarian cancer cell lines. They represent models of conjugates between biologically active vectors and cytotoxic Pt(II) moieties within the "drug ta...

journal_title：Journal of medicinal chemistry

authors： Monti E,Gariboldi M,Maiocchi A,Marengo E,Cassino C,Gabano E,Osella D

更新日期：2005-02-10 00:00:00

abstract：:We have synthesized and evaluated azaquinoxalinediones 3a-c for their activity in inhibiting [3H]AMPA binding from rat whole brain. It was found that the azaquinoxalinedione nucleus functions as a bioisostere for quinoxalinedione in AMPA receptor binding. The detailed structure-activity relationships of 6- and/or 7-su...

journal_title：Journal of medicinal chemistry

authors： Ohmori J,Kubota H,Shimizu-Sasamata M,Okada M,Sakamoto S

更新日期：1996-03-15 00:00:00

abstract：:Our previous publication (Eur. J. Pharmacol. 1995, 294, 411-422) reported preliminary chemical and biological studies of some 2,3-benzodiazepines, analogues of 1-(4-aminophenyl)-4-methyl-7,8-(methylenedioxy)-5H-2,3-benzodiazepine (1, GYKI 52466), which have been shown to possess significant anticonvulsant activity. Th...

journal_title：Journal of medicinal chemistry

authors： Chimirri A,De Sarro G,De Sarro A,Gitto R,Grasso S,Quartarone S,Zappalà M,Giusti P,Libri V,Constanti A,Chapman AG

更新日期：1997-04-11 00:00:00

abstract：:A small series of compounds is described in which a narrow SAR has identified N,N-dimethyl-3,4-diphenyl-1H-pyrazole-1-propanamine, 3, as a potential antidepressant with reduced side effects. The isomeric N,N-dimethyl-4,5-diphenyl-1H-pyrazole-1-propanamine was completely inactive in the primary antidepressant screens. ...

journal_title：Journal of medicinal chemistry

authors： Bailey DM,Hansen PE,Hlavac AG,Baizman ER,Pearl J,DeFelice AF,Feigenson ME

更新日期：1985-02-01 00:00:00

abstract：:Upon the basis of The Cancer Genome Atlas (TCGA) data set, we identified that several autophagy-related proteins such as AMP-activated protein kinase (AMPK) were remarkably downregulated in breast cancer. Combined with coimmunoprecipitation assay, we demonstrated that BRD4 might interact with AMPK. After analyses of t...

journal_title：Journal of medicinal chemistry

authors： Ouyang L,Zhang L,Liu J,Fu L,Yao D,Zhao Y,Zhang S,Wang G,He G,Liu B

更新日期：2017-12-28 00:00:00

abstract：:Compound 3 is a potent aminobenzimidazole urea with broad-spectrum Gram-positive antibacterial activity resulting from dual inhibition of bacterial gyrase (GyrB) and topoisomerase IV (ParE), and it demonstrates efficacy in rodent models of bacterial infection. Preclinical in vitro and in vivo studies showed that compo...

journal_title：Journal of medicinal chemistry

authors： Grillot AL,Le Tiran A,Shannon D,Krueger E,Liao Y,O'Dowd H,Tang Q,Ronkin S,Wang T,Waal N,Li P,Lauffer D,Sizensky E,Tanoury J,Perola E,Grossman TH,Doyle T,Hanzelka B,Jones S,Dixit V,Ewing N,Liao S,Boucher B,Ja

更新日期：2014-11-13 00:00:00

abstract：:A number of novel alpha-melanotropin (alpha-MSH) analogues have been designed, synthesized, and assayed for bioactivity at the melanocortin-1 (MC1) receptor from Xenopus frog skin, and selected potent analogues were examined at recombinant human MC1, MC3, and MC4 receptors expressed in human embryonic kidney (HEK) cel...

journal_title：Journal of medicinal chemistry

authors： Han G,Quillan JM,Carlson K,Sadée W,Hruby VJ

更新日期：2003-02-27 00:00:00

abstract：:Alkylation-elimination of adenine and 2-amino-6-chloropurine with gem-difluorocyclopropane dibromide 10 gave E- and Z-methylene-gem-difluorocyclopropanes 11a, 11b, 12a, and 12b and gem-difluorocyclopropenes 13a and 13b. Debenzylation of intermediates 11a, 11b, 12a, and 12b afforded E- and Z-methylenecyclopropanes 4a, ...

journal_title：Journal of medicinal chemistry

authors： Wang R,Ksebati MB,Corbett TH,Kern ER,Drach JC,Zemlicka J

更新日期：2001-11-08 00:00:00

abstract：:This paper reports the synthesis of 4-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2) and 2-(3,4-dihydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)propylamine (3). The biological activity of these agents relative to that of trimetoquinol (1) in guinea pig atria and guinea pig trachea is reported. Th...

journal_title：Journal of medicinal chemistry

authors： Kador PF,Venkatraman R,Feller DR,Miller DD

更新日期：1977-07-01 00:00:00

abstract：:The Keap1 (Kelch-like ECH-associated protein 1)-Nrf2 (nuclear factor erythroid 2-related factor 2)-ARE (antioxidant response element) pathway is the major defending mechanism against oxidative stresses, and directly disrupting the Keap1-Nrf2 protein-protein interaction (PPI) has been an attractive strategy to target o...

journal_title：Journal of medicinal chemistry

authors： Zhou HS,Hu LB,Zhang H,Shan WX,Wang Y,Li X,Liu T,Zhao J,You QD,Jiang ZY

更新日期：2020-10-08 00:00:00

abstract：:Despite a myriad of available pharmacotherapies for the treatment of type 2 diabetes (T2D), challenges still exist in achieving glycemic control. Several novel glucose-lowering strategies are currently under clinical investigation, highlighting the need for more robust treatments. Previously, we have shown that suppre...

journal_title：Journal of medicinal chemistry

authors： Lin H,Sharabi K,Lin L,Ruiz C,Zhu D,Cameron MD,Novick SJ,Griffin PR,Puigserver P,Kamenecka TM

更新日期：2021-01-28 00:00:00

abstract：:Recruitment of suppressive CD4+ FOXP3+ regulatory T cells (Treg) to the tumor microenvironment (TME) has the potential to weaken the antitumor response in patients receiving treatment with immuno-oncology (IO) agents. Human Treg express CCR4 and can be recruited to the TME through the CC chemokine ligands CCL17 and CC...

journal_title：Journal of medicinal chemistry

authors： Jackson JJ,Ketcham JM,Younai A,Abraham B,Biannic B,Beck HP,Bui MHT,Chian D,Cutler G,Diokno R,Hu DX,Jacobson S,Karbarz E,Kassner PD,Marshall L,McKinnell J,Meleza C,Okal A,Pookot D,Reilly MK,Robles O,Shunatona HP

更新日期：2019-07-11 00:00:00

abstract：:A new class of acyclic adenosine analogues is described which exhibit broad-spectrum antiviral activity and are apparently targeted at S-adenosyl-L-homocysteine hydrolase. The compounds are all alkyl (i.e., methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl, tert-butyl, 1-pentyl, 3-methylbutyl, 1-octy...

journal_title：Journal of medicinal chemistry

authors： De Clercq E,Holý A

更新日期：1985-03-01 00:00:00

abstract：:Epigenetic regulators that exhibit aberrant enzymatic activities or expression profiles are potential therapeutic targets for cancers. Specifically, enzymes responsible for methylation at histone-3 lysine-9 (like G9a) and aberrant DNA hypermethylation (DNMTs) have been implicated in a number of cancers. Recently, mole...

journal_title：Journal of medicinal chemistry

authors： Rabal O,Sánchez-Arias JA,San José-Enériz E,Agirre X,de Miguel I,Garate L,Miranda E,Sáez E,Roa S,Martínez-Climent JA,Liu Y,Wu W,Xu M,Prosper F,Oyarzabal J

更新日期：2018-08-09 00:00:00

abstract：:We have recently proposed a macromolecular prodrug strategy for improved cancer chemotherapy based on two features (Kratz, F.; et al. J. Med. Chem 2000, 43, 1253-1256.): (a) rapid and selective binding of thiol-reactive prodrugs to the cysteine-34 position of endogenous albumin after intravenous administration and (b)...

journal_title：Journal of medicinal chemistry

authors： Kratz F,Warnecke A,Scheuermann K,Stockmar C,Schwab J,Lazar P,Drückes P,Esser N,Drevs J,Rognan D,Bissantz C,Hinderling C,Folkers G,Fichtner I,Unger C

更新日期：2002-12-05 00:00:00

abstract：:Targeting of DNA secondary structures, such as G-quadruplexes, is now considered an appealing opportunity for drug intervention in anticancer therapy. So far, efforts made in the discovery of chemotypes able to target G-quadruplexes mainly succeeded in the identification of a number of polyaromatic compounds featuring...

journal_title：Journal of medicinal chemistry

authors： Cosconati S,Rizzo A,Trotta R,Pagano B,Iachettini S,De Tito S,Lauri I,Fotticchia I,Giustiniano M,Marinelli L,Giancola C,Novellino E,Biroccio A,Randazzo A

更新日期：2012-11-26 00:00:00

abstract：:We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analogue and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese ha...

journal_title：Journal of medicinal chemistry

authors： Mitchell-Ryan S,Wang Y,Raghavan S,Ravindra MP,Hales E,Orr S,Cherian C,Hou Z,Matherly LH,Gangjee A

更新日期：2013-12-27 00:00:00