2,3-Disubstituted 1,8-naphthyridines as potential diuretic agents. 2. 5,7-Dimethyl derivatives.

abstract：:The NS2B/NS3 serine proteases of the Zika and Dengue flaviviruses are attractive targets for the development of antiviral drugs. We report the synthesis and evaluation of a new, proline-based compound class that displays allosteric inhibition of both proteases. The structural features relevant for protease binding and...

journal_title：Journal of medicinal chemistry

authors： Millies B,von Hammerstein F,Gellert A,Hammerschmidt S,Barthels F,Göppel U,Immerheiser M,Elgner F,Jung N,Basic M,Kersten C,Kiefer W,Bodem J,Hildt E,Windbergs M,Hellmich UA,Schirmeister T

更新日期：2019-12-26 00:00:00

abstract：:The synthesis of a series of N-phosphonalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lun...

journal_title：Journal of medicinal chemistry

authors： Bird J,De Mello RC,Harper GP,Hunter DJ,Karran EH,Markwell RE,Miles-Williams AJ,Rahman SS,Ward RW

更新日期：1994-01-07 00:00:00

abstract：:The first nonpeptidic, noncovalent inhibitors of the cysteine protease cathepsin S (CatS) are described. Electronic database searching using the program DOCK generated a screening set of potential CatS inhibitors from which two lead structures were identified as promising starting points for a drug discovery effort. L...

journal_title：Journal of medicinal chemistry

authors： Thurmond RL,Beavers MP,Cai H,Meduna SP,Gustin DJ,Sun S,Almond HJ,Karlsson L,Edwards JP

更新日期：2004-09-23 00:00:00

abstract：:The enantiomers of the leukotriene D4 antagonist 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (L-660,711)(MK-571) have been prepared, their absolute stereochemistry has been assigned as S for (+)-1 and R for (-)-1 by X-ray analysis of a synthetic...

journal_title：Journal of medicinal chemistry

authors： Gauthier JY,Jones T,Champion E,Charette L,Dehaven R,Ford-Hutchinson AW,Hoogsteen K,Lord A,Masson P,Piechuta H

更新日期：1990-10-01 00:00:00

abstract：:A series of (substituted amino)-1,2,4-benzothiadiazine 1-oxides has been synthesized and most members of the series have been shown to have blood pressure lowering effects in normotensive rabbits and in spontaneously hypertensive rats. The most active member of the series was 3-[4-(2-furoyl)-1-piperazinyl]-6,7-dimetho...

journal_title：Journal of medicinal chemistry

authors： Dillard RD,Yen TT,Stark P,Pavey DE

更新日期：1980-07-01 00:00:00

abstract：:Biaryl ethers were recently reported as potent NNRTIs. Herein we disclose a detailed SAR study that led to the biaryl ether 6. This compound possessed excellent potency against WT RT and key clinically observed RT mutants and had an excellent pharmacokinetic profile in rats, dogs, and rhesus macaques. The compound als...

journal_title：Journal of medicinal chemistry

authors： Su DS,Lim JJ,Tinney E,Wan BL,Young MB,Anderson KD,Rudd D,Munshi V,Bahnck C,Felock PJ,Lu M,Lai MT,Touch S,Moyer G,DiStefano DJ,Flynn JA,Liang Y,Sanchez R,Perlow-Poehnelt R,Miller M,Vacca JP,Williams TM,Anthony

更新日期：2009-11-26 00:00:00

abstract：:The G protein-coupled chemokine receptors CXCR1 and CXCR2 play key roles in inflammatory diseases and carcinogenesis. In inflammation, they activate and recruit polymorphonuclear cells (PMNs) through binding of the chemokines CXCL1 (CXCR1) and CXCL8 (CXCR1 and CXCR2). Structure-activity studies that examined the effec...

journal_title：Journal of medicinal chemistry

authors： Maeda DY,Peck AM,Schuler AD,Quinn MT,Kirpotina LN,Wicomb WN,Fan GH,Zebala JA

更新日期：2014-10-23 00:00:00

abstract：:The labeling of proteins with ubiquitin/ubiquitin-like (Ubl) proteins is crucial for several physiological processes and in the onset of various diseases. Recently, targeting ubiquitin protein labeling has shifted toward the use of allosteric mechanisms over classical activity-based approaches. Allosteric enzyme regul...

journal_title：Journal of medicinal chemistry

authors： Paiva SL,da Silva SR,de Araujo ED,Gunning PT

更新日期：2018-01-25 00:00:00

abstract：:Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydr...

journal_title：Journal of medicinal chemistry

authors： Murugesan N,Gu Z,Stein PD,Bisaha S,Spergel S,Girotra R,Lee VG,Lloyd J,Misra RN,Schmidt J,Mathur A,Stratton L,Kelly YF,Bird E,Waldron T,Liu EC,Zhang R,Lee H,Serafino R,Abboa-Offei B,Mathers P,Giancarli M,Seymou

更新日期：1998-12-17 00:00:00

abstract：:Fragment based drug discovery (FBDD) is a widely used tool for discovering novel therapeutics. NMR is a powerful means for implementing FBDD, and several approaches have been proposed utilizing (1)H-(15)N heteronuclear single quantum coherence (HSQC) as well as one-dimensional (1)H and (19)F NMR to screen compound mix...

journal_title：Journal of medicinal chemistry

authors： Jordan JB,Poppe L,Xia X,Cheng AC,Sun Y,Michelsen K,Eastwood H,Schnier PD,Nixey T,Zhong W

更新日期：2012-01-26 00:00:00

abstract：:We explore the significance of pi-cation interactions in the binding of ligands to nicotinic acetylcholine receptors. Specifically, the Austin method of semiempirical molecular orbital theory is utilized to estimate the interaction of aromatic amino acid side chains with the cation-containing heterocyclic ring fragmen...

journal_title：Journal of medicinal chemistry

authors： Schmitt JD,Sharples CG,Caldwell WS

更新日期：1999-08-12 00:00:00

abstract：:The synthesis and in vitro antiplatelet activity significant data of coumarin derivatives 5i-x and quinolin-2(1H)-one derivatives 22a,b, as well as the corresponding structure-activity relationships are described. The recently reported 8-methyl-4-(1-piperazinyl)-7-(3-pyridylmethoxy)coumarin 5f and its potent 7-(2-morp...

journal_title：Journal of medicinal chemistry

authors： Roma G,Di Braccio M,Grossi G,Piras D,Leoncini G,Bruzzese D,Signorello MG,Fossa P,Mosti L

更新日期：2007-06-14 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：:Aberrant activation of S6 kinase 1 (S6K1) is found in many diseases, including diabetes, aging, and cancer. We developed ATP competitive organometallic kinase inhibitors, EM5 and FL772, which are inspired by the structure of the pan-kinase inhibitor staurosporine, to specifically inhibit S6K1 using a strategy previous...

journal_title：Journal of medicinal chemistry

authors： Qin J,Rajaratnam R,Feng L,Salami J,Barber-Rotenberg JS,Domsic J,Reyes-Uribe P,Liu H,Dang W,Berger SL,Villanueva J,Meggers E,Marmorstein R

更新日期：2015-01-08 00:00:00

abstract：:Previously reported 2-(hydroxymethyl)indoloquinones, prepared as their acetates or carbamates, were less active than 2-methyl analogues in bacterial cultures and they had no activity in mice, despite functionality appropriate for DNA cross-linking. On the basis of the hypothesis that these compounds might have been to...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Remers WA,Catino JJ

更新日期：1989-08-01 00:00:00

abstract：:The synthesis and biological evaluation of three classes of chain-modified derivatives of (+)-EHNA are described. Among the 5', 6'-unsaturated derivatives, the Z-isomer was the most potent inhibitor of adenosine deaminase (ADA) but 3-fold less active than (+)-EHNA. Several 9-aralkyladenines (ARADs) have been prepared,...

journal_title：Journal of medicinal chemistry

authors： Pragnacharyulu PV,Varkhedkar V,Curtis MA,Chang IF,Abushanab E

更新日期：2000-11-30 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：:Glycosylation of 2-fluoroadenine with the appropriate protected thioglycoside derivatives, followed by deprotection and anomer separation, produced the alpha- and beta-anomers of 2',5'-dideoxy-2-fluoroadenosine (1), 2',5'-dideoxy-2,5'-difluoroadenosine (2), and 2'-deoxy-2-fluoroadenosine (3). These were examined as P-...

journal_title：Journal of medicinal chemistry

authors： Ye S,Rezende MM,Deng WP,Herbert B,Daly JW,Johnson RA,Kirk KL

更新日期：2004-02-26 00:00:00

abstract：:Tocotrienols are farnesylated benzopyran natural products that exhibit hypocholesterolemic activity in vitro and in vivo. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase by a process distinct from other known inhibitors of cholesterol biosynthesis. An efficient...

journal_title：Journal of medicinal chemistry

authors： Pearce BC,Parker RA,Deason ME,Qureshi AA,Wright JJ

更新日期：1992-10-02 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：:A select series of methyl ether derivatives of vancomcyin aglycon were prepared and examined for antimicrobial activity against vancomycin-sensitive Staphylococcus aureus and vancomycin-resistant Enterococci faecalis as well as their binding affinity for D-Ala-D-Ala and D-Ala-D-Lac. The intent of the study was to eluc...

journal_title：Journal of medicinal chemistry

authors： Crane CM,Pierce JG,Leung SS,Tirado-Rives J,Jorgensen WL,Boger DL

更新日期：2010-10-14 00:00:00

abstract：:Inspired by the previously reported superior gene transfer efficacies of amine headgroup-containing cationic lipids to their hydroxy counterparts, in the present structure-activity investigation we have compared the relative in vitro gene transfer efficacies of eight newly synthesized structural analogues of our previ...

journal_title：Journal of medicinal chemistry

authors： Majeti BK,Karmali PP,Reddy BS,Chaudhuri A

更新日期：2005-06-02 00:00:00

abstract：:A series of amide, urea, and carbamate analogues of the muscarinic (M1) ganglionic stimulant [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343; 1) was prepared. The C1-methyl-substituted carbamates 8-11 were resolved into the enantiomers. In order to investigate the ganglionic stimu...

journal_title：Journal of medicinal chemistry

authors： Nilsson BM,Vargas HM,Hacksell U

更新日期：1992-07-24 00:00:00

abstract：:There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo ...

journal_title：Journal of medicinal chemistry

authors： Schenkel LB,Olivieri PR,Boezio AA,Deak HL,Emkey R,Graceffa RF,Gunaydin H,Guzman-Perez A,Lee JH,Teffera Y,Wang W,Youngblood BD,Yu VL,Zhang M,Gavva NR,Lehto SG,Geuns-Meyer S

更新日期：2016-03-24 00:00:00

abstract：:N-Acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure, indicating that this pathway might be useful for treating obesity and associated...

journal_title：Journal of medicinal chemistry

authors： Lin H,Long JZ,Roche AM,Svensson KJ,Dou FY,Chang MR,Strutzenberg T,Ruiz C,Cameron MD,Novick SJ,Berdan CA,Louie SM,Nomura DK,Spiegelman BM,Griffin PR,Kamenecka TM

更新日期：2018-04-12 00:00:00

abstract：:Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays a major role in T-cell signaling downstream of the T-cell receptor (TCR), and considerable efforts have been directed toward discovery of ITK-selective inhibitors as potential treatments of inflammatory disorders such as...

journal_title：Journal of medicinal chemistry

authors： Burch JD,Lau K,Barker JJ,Brookfield F,Chen Y,Chen Y,Eigenbrot C,Ellebrandt C,Ismaili MH,Johnson A,Kordt D,MacKinnon CH,McEwan PA,Ortwine DF,Stein DB,Wang X,Winkler D,Yuen PW,Zhang Y,Zarrin AA,Pei Z

更新日期：2014-07-10 00:00:00

abstract：:One of the pattern recognition techniques, the SIMCA method, has been applied to structure-taste studies on L-aspartyl dipeptides (L-Asp-NH-R). The sweet and bitter taste class models of the peptides were obtained by using five structural descriptors, such as molar refractivity, and four kinds of STERIMOL parameters. ...

journal_title：Journal of medicinal chemistry

authors： Miyashita Y,Takahashi Y,Takayama C,Sumi K,Nakatsuka K,Ohkubo T,Abe H,Sasaki S

更新日期：1986-06-01 00:00:00

abstract：:The crystal structure of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in ternary complex with the coenzyme NADP (+) and the potent inhibitor 3,5-dichlorosalicylic acid was determined at a resolution of 1.8 A. The inhibitor is held in place by a network of hydrogen bonding interactions with the active site resid...

journal_title：Journal of medicinal chemistry

authors： Dhagat U,Endo S,Sumii R,Hara A,El-Kabbani O

更新日期：2008-08-14 00:00:00

abstract：:In order to define the role of the cholestane moiety in the anti-HIV agent cosalane, a series of cosalane analogs was synthesized in which the cholestane ring system was replaced by normal alkenyl and phosphodiester substituents having varied chain lengths and lipophilicities. The compounds containing simple alkenyl s...

journal_title：Journal of medicinal chemistry

authors： Keyes RF,Golebiewski WM,Cushman M

更新日期：1996-01-19 00:00:00

abstract：:A series of novel, disulfide-constrained human beta-melanocyte stimulating hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food in...

journal_title：Journal of medicinal chemistry

authors： Mayer JP,Hsiung HM,Flora DB,Edwards P,Smith DP,Zhang XY,Gadski RA,Heiman ML,Hertel JL,Emmerson PJ,Husain S,O'brien TP,Kahl SD,Smiley DL,Zhang L,Dimarchi RD,Yan LZ

更新日期：2005-05-05 00:00:00