Discovery of boronic acids as novel and potent inhibitors of fatty acid amide hydrolase.

abstract：:A series of 2-guanidino-4-oxoimidazoline (deoxo-IZ) derivatives was prepared and showed potent antimalarial activities in rodent and Rhesus models. Compound 8e, the most potent analogues of this series, is the first non-8-aminoqinoline antimalarial that demonstrated radical curative activity in non-human primate by or...

journal_title：Journal of medicinal chemistry

authors： Liu X,Wang X,Li Q,Kozar MP,Melendez V,O'Neil MT,Lin AJ

更新日期：2011-07-14 00:00:00

abstract：:A series of Ala and Aoc analogues of (-)-ternatin were prepared, and their bioactivities were assessed by a fat-accumulation inhibition assay using 3T3-L1 adipocytes, which led to the discovery of key structure-activity relationships (SAR). ...

journal_title：Journal of medicinal chemistry

authors： Shimokawa K,Iwase Y,Miwa R,Yamada K,Uemura D

更新日期：2008-10-09 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：:Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and are attractive targets for therapy against inflammation, neurodegeneration, ischemia, and cancer. Many caspase structures are known, but most involve either peptide or protein inhibitors, unatt...

journal_title：Journal of medicinal chemistry

authors： Becker JW,Rotonda J,Soisson SM,Aspiotis R,Bayly C,Francoeur S,Gallant M,Garcia-Calvo M,Giroux A,Grimm E,Han Y,McKay D,Nicholson DW,Peterson E,Renaud J,Roy S,Thornberry N,Zamboni R

更新日期：2004-05-06 00:00:00

abstract：:Enantiomerically pure (+)- and (-)-carbocyclic thymidine, (-)-carbocyclic 3'-epi-thymidine, (+)-carbocyclic 3'-deoxy-3'-azidothymidine, (+)-carbocyclic 2,3'-O-anhydrothymidine, (+)-carbocyclic 3'-O,6'-methylenethymidine, and (+)-(6'S)-carbocyclic 6'-methylthymidine were synthesized in a stereospecific manner from comm...

journal_title：Journal of medicinal chemistry

authors： Béres J,Sági G,Tömösközi I,Gruber L,Baitz-Gács E,Otvös L,De Clercq E

更新日期：1990-05-01 00:00:00

abstract：:Inhibition of embryonic ectoderm development (EED) is a new cancer therapeutic strategy. Herein, we report our discovery of EEDi-5285 as an exceptionally potent, efficacious, and orally active EED inhibitor. EEDi-5285 binds to the EED protein with an IC50 value of 0.2 nM and inhibits cell growth with IC50 values of 20...

journal_title：Journal of medicinal chemistry

authors： Rej RK,Wang C,Lu J,Wang M,Petrunak E,Zawacki KP,McEachern D,Fernandez-Salas E,Yang CY,Wang L,Li R,Chinnaswamy K,Wen B,Sun D,Stuckey J,Zhou Y,Chen J,Tang G,Wang S

更新日期：2020-07-09 00:00:00

abstract：:A series of 3-descladinosyl-2,3-anhydro-6-O-methylerythromycin A 11, 12-carbamate analogues have been synthesized and evaluated for antibacterial activity. These compounds were found to be potent antibacterial agents against Gram-positive organisms in vitro, many having MIC values below 1 microg/mL for the macrolide-s...

journal_title：Journal of medicinal chemistry

authors： Elliott RL,Pireh D,Griesgraber G,Nilius AM,Ewing PJ,Bui MH,Raney PM,Flamm RK,Kim K,Henry RF,Chu DT,Plattner JJ,Or YS

更新日期：1998-05-07 00:00:00

abstract：:The synthesis of analogues of the antipsychotic drug butaclamol bearing chloro substituents on the benzene rings is described. On the basis of a perceived topographical similarity of a putative chlorophenylethylamine pharmacophore present in these analogues and in VUFB-10032 and doclothepin, agents related to octoclot...

journal_title：Journal of medicinal chemistry

authors： Humber LG,Sideridis N,Asselin AA,Bruderlein FT,Voith K

更新日期：1978-12-01 00:00:00

abstract：:Podophyllotoxin has been extensively used as a lead agent in the development of new anticancer drugs. On the basis of the previously reported simplified 4-aza-2,3-didehydro podophyllotoxin analogues, we implemented a bioisosteric replacement of the methylenedioxybenzene subunit with a pyrazole moiety to afford tetracy...

journal_title：Journal of medicinal chemistry

authors： Magedov IV,Manpadi M,Slambrouck SV,Steelant WF,Rozhkova E,Przheval'skii NM,Rogelj S,Kornienko A

更新日期：2007-10-18 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：: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

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

abstract：:A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thi...

journal_title：Journal of medicinal chemistry

authors： Kim YZ,Lim JC,Yeo JH,Bang CS,Kim WS,Kim SS,Woo YM,Yang DH,Oh H,Nahm K

更新日期：1994-10-28 00:00:00

abstract：:AM1 semiempirical molecular orbital calculations have been used to probe the complexation sites for naked and hydrated magnesium ions to the different conformations and protonation states of tetracycline. The calculations reveal a wealth of possible magnesium complexation sites within a small energy range, but also in...

journal_title：Journal of medicinal chemistry

authors： Othersen OG,Lanig H,Clark T

更新日期：2003-12-18 00:00:00

abstract：:A group of compounds, structurally related to metoprolol, in which the aromatic nucleus is formally moved stepwise away from the ethanolamine side chain, has been studied as adrenergic agonists and antagonists. All the compounds were active on the adrenergic receptors and showed similar affinity for the receptor regar...

journal_title：Journal of medicinal chemistry

authors： Lövgren K,Hedberg A,Nilsson JL

更新日期：1981-04-01 00:00:00

abstract：:Recently, our group identified that harmine is able to induce β-cell proliferation both in vitro and in vivo, mediated via the DYRK1A-NFAT pathway. Since, harmine suffers from a lack of selectivity, both against other kinases and CNS off-targets, we therefore sought to expand structure-activity relationships for harmi...

journal_title：Journal of medicinal chemistry

authors： Kumar K,Wang P,Wilson J,Zlatanic V,Berrouet C,Khamrui S,Secor C,Swartz EA,Lazarus M,Sanchez R,Stewart AF,Garcia-Ocana A,DeVita RJ

更新日期：2020-03-26 00:00:00

abstract：:A series of 3-aryloxindole derivatives were synthesized and evaluated as activators of the cloned maxi-K channel mSlo expressed in Xenopus laevis oocytes using electrophysiological methods. The most promising maxi-K openers to emerge from this study were (+/-)-3-(5-chloro-2-hydroxyphenyl)-1,3-dihydro-3-hydroxy-6-(trif...

journal_title：Journal of medicinal chemistry

authors： Hewawasam P,Erway M,Moon SL,Knipe J,Weiner H,Boissard CG,Post-Munson DJ,Gao Q,Huang S,Gribkoff VK,Meanwell NA

更新日期：2002-03-28 00:00:00

abstract：:Certain derivatives containing the 1,2-dihydropyrido[3,4-b]pyrazine (1-deaza-7,8-dihydropteridine) ring system are active against experimental neoplasms in mice. The mechanism of action of these agents has been attributed to the accumulation of cells at mitosis. Identification of the structural features that are neces...

journal_title：Journal of medicinal chemistry

authors： Temple C Jr,Wheeler GP,Elliott RD,Rose JD,Comber RN,Montgomery JA

更新日期：1983-01-01 00:00:00

abstract：:Certain phenylalkylamine derivatives have been considered to bind selectively at 5-HT2 serotonin receptors. It is now recognized that the most widely used derivatives, i.e., 1-(2,5-dimethoxy-4-X-phenyl)-2-aminopropanes where X = Me (DOM), Br (DOB), and I (DOI) (1-3, respectively) also bind at the more recently identif...

journal_title：Journal of medicinal chemistry

authors： Glennon RA,Raghupathi R,Bartyzel P,Teitler M,Leonhardt S

更新日期：1992-02-21 00:00:00

abstract：:In this Perspective, recent advances and challenges in the development of GPR119 agonists as new oral antidiabetic drugs will be discussed. Such agonists are expected to exhibit a low risk to induce hypoglycemia as well as to have a beneficial impact on body weight. Many pharmaceutical companies have been active in th...

journal_title：Journal of medicinal chemistry

authors： Ritter K,Buning C,Halland N,Pöverlein C,Schwink L

更新日期：2016-04-28 00:00:00

abstract：:Dual-acting kappa opioid receptor (KOR) agonist and mu opioid receptor (MOR) partial agonist ligands have been put forward as potential treatment agents for cocaine and other psychostimulant abuse. Members of the orvinol series of ligands are known for their high binding affinity to both KOR and MOR, but efficacy at t...

journal_title：Journal of medicinal chemistry

authors： Greedy BM,Bradbury F,Thomas MP,Grivas K,Cami-Kobeci G,Archambeau A,Bosse K,Clark MJ,Aceto M,Lewis JW,Traynor JR,Husbands SM

更新日期：2013-04-25 00:00:00

abstract：:A series of 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl)methyl]tropane analogues were synthesized and evaluated as cocaine binding site ligands at the dopamine transporter (DAT). The in vitro affinity (Ki) for the DAT of the 6-alkyl-3 beta-benzyl-2-[(methoxycarbonyl) methyl]tropane analogues was determined by inhibition...

journal_title：Journal of medicinal chemistry

authors： Lomenzo SA,Izenwasser S,Katz JL,Terry PD,Zhu N,Klein CL,Trudell ML

更新日期：1997-12-19 00:00:00

abstract：:We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected E. coli strains. One of the most interesting candidates, compound 86, was shown to inhibit specifically bacterial LPS heptosylation on efflux pum...

journal_title：Journal of medicinal chemistry

authors： Desroy N,Denis A,Oliveira C,Atamanyuk D,Briet S,Faivre F,LeFralliec G,Bonvin Y,Oxoby M,Escaich S,Floquet S,Drocourt E,Vongsouthi V,Durant L,Moreau F,Verhey TB,Lee TW,Junop MS,Gerusz V

更新日期：2013-02-28 00:00:00

abstract：:H(3) receptor antagonists based on a 2-aminoethylbenzofuran skeleton have been discovered, which are potent in vitro at human and rat H(3) receptors, with K(i) values of 0.1-5.8 nM. Analogues were discovered with potent (0.01-1 mg/kg) cognition and attention enhancing properties in animal models. One compound in parti...

journal_title：Journal of medicinal chemistry

authors： Cowart M,Faghih R,Curtis MP,Gfesser GA,Bennani YL,Black LA,Pan L,Marsh KC,Sullivan JP,Esbenshade TA,Fox GB,Hancock AA

更新日期：2005-01-13 00:00:00

abstract：:A series of N7-substituted 7-aminoactinomycin D analogues with alkyl, aralkyl, and heteroaralkyl substituents was synthesized and their biological properties were studied. All of these analogues proved to be 22- to 28-fold less toxic than actinomycin D when tested against human lymphoblastic leukemia cells (CCRF-CEM) ...

journal_title：Journal of medicinal chemistry

authors： Madhavarao MS,Chaykovsky M,Sengupta SK

更新日期：1978-09-01 00:00:00

abstract：:A novel series of pyridazinone-functionalized phenylalanine analogues was prepared and evaluated for inhibition of cellular adhesion mediated by alpha4beta1/VCAM-1 and alpha4beta7/MAdCAM-1 interactions. Concise syntheses were developed and applied for exploration of structure-activity relationships pertaining to the p...

journal_title：Journal of medicinal chemistry

authors： Gong Y,Barbay JK,Dyatkin AB,Miskowski TA,Kimball ES,Prouty SM,Fisher MC,Santulli RJ,Schneider CR,Wallace NH,Ballentine SA,Hageman WE,Masucci JA,Maryanoff BE,Damiano BP,Andrade-Gordon P,Hlasta DJ,Hornby PJ,He W

更新日期：2006-06-01 00:00:00

abstract：:A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital. ...

journal_title：Journal of medicinal chemistry

authors： Aeberli P,Gogerty JH,Houlihan WJ,Iorio LC

更新日期：1976-03-01 00:00:00

abstract：:Very few nonpeptide oxytocin agonists have currently been reported, and none of them seem suitable for the in vivo investigation of the oxytocin mediated functions. In an attempt to rationalize the design of better tools, we have systematically studied the structural determinants of the affinity and efficacy of repres...

journal_title：Journal of medicinal chemistry

authors： Frantz MC,Rodrigo J,Boudier L,Durroux T,Mouillac B,Hibert M

更新日期：2010-02-25 00:00:00

abstract：:Membrane transport of nucleosides or nucleobases is mediated by transporters including the equilibrative nucleoside transporters (ENTs), and resistance to antitumor antimetabolite drugs may arise via salvage of exogenous purine or pyrimidine nucleosides or nucleobases by ENT transporters. The therapeutic utility of di...

journal_title：Journal of medicinal chemistry

authors： Saravanan K,Barlow HC,Barton M,Calvert AH,Golding BT,Newell DR,Northen JS,Curtin NJ,Thomas HD,Griffin RJ

更新日期：2011-03-24 00:00:00

abstract：:A series of substituted benzenedisulfonamide carbonic anhydrase inhibitors is described and their anticonvulsant activities are listed. One compound, 4-(4-methoxypiperidinosulfonyl)-2-chlorobenzenesulfonamide (19, UK-12130), was found to have anticonvulsant activity in animals at a dose level that gave only a minimal ...

journal_title：Journal of medicinal chemistry

authors： Cross PE,Gadsby B

更新日期：1978-09-01 00:00:00

abstract：:Molecular docking studies of carbohydrate derivatives in protein binding sites are often challenging because of water-mediated interactions and the inherent flexibility of the many terminal hydroxyl groups. Using the recognition process between heat-labile enterotoxin from Escherichia coli and ganglioside GM1 as a par...

journal_title：Journal of medicinal chemistry

authors： Minke WE,Diller DJ,Hol WG,Verlinde CL

更新日期：1999-05-20 00:00:00