Synthesis and blood pressure lowering activity of 3-(substituted-amino)-1,2,4-benzothiadiazine 1-oxide derivatives.

abstract：:Three [5-t-BuPro(7)]oxytocin analogues were synthesized by substituting (2S,5R)-5-tert-butylproline for proline in oxytocin, [Mpa(1)]oxytocin, and [dPen(1)]oxytocin. Relative to oxytocin, [5-t-BuPro(7)]oxytocin and [Mpa(1),5-t-BuPro(7)]oxytocin exhibited strongly reduced binding affinity to the receptor; however, both...

journal_title：Journal of medicinal chemistry

authors： Bélec L,Slaninova J,Lubell WD

更新日期：2000-04-20 00:00:00

abstract：:CC-chemokine receptor 5 (CCR5) is an attractive target for preventing the entry of human immunodeficiency virus 1 (HIV-1) into human host cells. Maraviroc is the only CCR5 antagonist, and it was marketed in 2007. To overcome the shortcomings of maraviroc, structure-based drug design was performed to minimize CYP450 in...

journal_title：Journal of medicinal chemistry

authors： Peng P,Chen H,Zhu Y,Wang Z,Li J,Luo RH,Wang J,Chen L,Yang LM,Jiang H,Xie X,Wu B,Zheng YT,Liu H

更新日期：2018-11-08 00:00:00

abstract：:A series of analogues of the dipeptide sweetener L-aspartyl-L-phenylalanine methyl ester having hydroxy and/or methoxy substitution on the aromatic ring was synthesized and tasted. The introduction of a methoxy group in the para position of the aromatic ring of the peptide sweetener is crucial to the reduction or dest...

journal_title：Journal of medicinal chemistry

authors： Kawai M,Chorev M,Marin-Rose J,Goodman M

更新日期：1980-04-01 00:00:00

abstract：:The limited efficacy and considerable side effects of currently available therapies for the treatment of hepatitis C virus (HCV) infection have prompted significant efforts toward the development of safe and effective new therapeutics. The pentapeptide alpha-ketoamides of type 1 were weak HCV inhibitors with a binding...

journal_title：Journal of medicinal chemistry

authors： Chen KX,Njoroge FG,Pichardo J,Prongay A,Butkiewicz N,Yao N,Madison V,Girijavallabhan V

更新日期：2005-10-06 00:00:00

abstract：:A primary goal of lead optimization is to identify compounds with improved absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. A number of reports have linked computed molecular properties to desirable in vivo ADMET outcomes, but a significant limitation of these analyses is the failure t...

journal_title：Journal of medicinal chemistry

authors： Sutherland JJ,Raymond JW,Stevens JL,Baker TK,Watson DE

更新日期：2012-07-26 00:00:00

abstract：:Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligo...

journal_title：Journal of medicinal chemistry

authors： Serby MD,Zhao H,Szczepankiewicz BG,Kosogof C,Xin Z,Liu B,Liu M,Nelson LT,Kaszubska W,Falls HD,Schaefer V,Bush EN,Shapiro R,Droz BA,Knourek-Segel VE,Fey TA,Brune ME,Beno DW,Turner TM,Collins CA,Jacobson PB,Sham H

更新日期：2006-04-20 00:00:00

abstract：:The construction of bioactive peptides using β-amino acid-containing sequence patterns is a very promising strategy to obtain analogues that exhibit properties of high interest for medicinal chemistry applications. β-Amino acids have been shown to modulate the conformation, dynamics, and proteolytic susceptibility of ...

journal_title：Journal of medicinal chemistry

authors： Cabrele C,Martinek TA,Reiser O,Berlicki Ł

更新日期：2014-12-11 00:00:00

abstract：:Exposure of dopamine to an excess of linoleic acid 13-hydroperoxide (13-hydroperoxyoctadecadienoic acid) in the presence of ferrous ions in Tris buffer, pH 7.4, resulted in a relatively fast, oxygen-independent reaction exhibiting first-order kinetics with respect to both catecholamine and metal concentrations. Produc...

journal_title：Journal of medicinal chemistry

authors： Pezzella A,d'Ischia M,Napolitano A,Misuraca G,Prota G

更新日期：1997-07-04 00:00:00

abstract：:New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-r...

journal_title：Journal of medicinal chemistry

authors： Beltramo M,Robert V,Galibert M,Madinier JB,Marceau P,Dardente H,Decourt C,De Roux N,Lomet D,Delmas AF,Caraty A,Aucagne V

更新日期：2015-04-23 00:00:00

abstract：:An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to unders...

journal_title：Journal of medicinal chemistry

authors： Snow RJ,Cardozo MG,Morwick TM,Busacca CA,Dong Y,Eckner RJ,Jacober S,Jakes S,Kapadia S,Lukas S,Panzenbeck M,Peet GW,Peterson JD,Prokopowicz AS 3rd,Sellati R,Tolbert RM,Tschantz MA,Moss N

更新日期：2002-08-01 00:00:00

abstract：:An essential step in the HIV life cycle is integration of the viral DNA into the host chromosome. This step is catalyzed by a 32-kDa viral enzyme HIV integrase (IN). HIV-1 IN is an important and validated target, and the drugs that selectively inhibit this enzyme, when used in combination with reverse transcriptase (R...

journal_title：Journal of medicinal chemistry

authors： Kuo CL,Assefa H,Kamath S,Brzozowski Z,Slawinski J,Saczewski F,Buolamwini JK,Neamati N

更新日期：2004-01-15 00:00:00

abstract：:Structure for the adduct of carbonic anhydrase II with 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate, a membrane-impermeant antitumor sulfonamide, is reported. The phenylethyl moiety fills the active site, making van der Waals interactions with side chains of Gln192, Val121, Phe131, Leu198, Thr20...

journal_title：Journal of medicinal chemistry

authors： Menchise V,De Simone G,Alterio V,Di Fiore A,Pedone C,Scozzafava A,Supuran CT

更新日期：2005-09-08 00:00:00

abstract：:Computational ADME (absorption, distribution, metabolism, and excretion) models may be used early in the drug discovery process in order to flag drug candidates with potentially problematic ADME profiles. We report the development, validation, and application of quantitative structure-property relationship (QSPR) mode...

journal_title：Journal of medicinal chemistry

authors： Shen M,Xiao Y,Golbraikh A,Gombar VK,Tropsha A

更新日期：2003-07-03 00:00:00

abstract：:The medicinal chemistry community has directed considerable efforts toward the discovery of selective inhibitors of interleukin-2 inducible T-cell kinase (ITK), given its role in T-cell signaling downstream of the T-cell receptor (TCR) and the implications of this target for inflammatory disorders such as asthma. We h...

journal_title：Journal of medicinal chemistry

authors： Burch JD,Barrett K,Chen Y,DeVoss J,Eigenbrot C,Goldsmith R,Ismaili MH,Lau K,Lin Z,Ortwine DF,Zarrin AA,McEwan PA,Barker JJ,Ellebrandt C,Kordt D,Stein DB,Wang X,Chen Y,Hu B,Xu X,Yuen PW,Zhang Y,Pei Z

更新日期：2015-05-14 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：:A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging...

journal_title：Journal of medicinal chemistry

authors： Barrow JC,Stauffer SR,Rittle KE,Ngo PL,Yang Z,Selnick HG,Graham SL,Munshi S,McGaughey GB,Holloway MK,Simon AJ,Price EA,Sankaranarayanan S,Colussi D,Tugusheva K,Lai MT,Espeseth AS,Xu M,Huang Q,Wolfe A,Pietrak B,Z

更新日期：2008-10-23 00:00:00

abstract：:Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of α4β2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techn...

journal_title：Journal of medicinal chemistry

authors： German N,Kim JS,Jain A,Dukat M,Pandya A,Ma Y,Weltzin M,Schulte MK,Glennon RA

更新日期：2011-10-27 00:00:00

abstract：:A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [3H]-GABA uptake in rat synaptos...

journal_title：Journal of medicinal chemistry

authors： Andersen KE,Braestrup C,Grønwald FC,Jørgensen AS,Nielsen EB,Sonnewald U,Sørensen PO,Suzdak PD,Knutsen LJ

更新日期：1993-06-11 00:00:00

abstract：:Class A-class C mechanism-based beta-lactamase inhibitors were designed on the basis of the intermediacy of an oxycarbenium species capable of cross-linking with amino acids residues in the active site. Penams 24 and 27 were very potent against AmpC in vitro. The MIC values of 24 in combination with piperacillin again...

journal_title：Journal of medicinal chemistry

authors： Sandanayaka VP,Prashad AS,Yang Y,Williamson RT,Lin YI,Mansour TS

更新日期：2003-06-19 00:00:00

abstract：:Aromatic side-chain analogues (arocalciferols 6-9) of the steroid hormone 1 alpha,25-dihydroxyvitamin D3 (1) were synthesized and biologically evaluated. The analogues were prepared by coupling the vitamin D A-ring enyne 14 with the appropriate enol triflate of a modified CD steroid fragment of the type 22. The result...

journal_title：Journal of medicinal chemistry

authors： Figadère B,Norman AW,Henry HL,Koeffler HP,Zhou JY,Okamura WH

更新日期：1991-08-01 00:00:00

abstract：:Botulinum neurotoxins (BoNT) are the most potent toxins known and a significant bioterrorist threat. Few small molecule compounds have been identified that are active in cell-based or animal models, potentially due to toxin enzyme plasticity. Here we screened commercially available quinolinols, as well as synthesized ...

journal_title：Journal of medicinal chemistry

authors： Caglič D,Krutein MC,Bompiani KM,Barlow DJ,Benoni G,Pelletier JC,Reitz AB,Lairson LL,Houseknecht KL,Smith GR,Dickerson TJ

更新日期：2014-02-13 00:00:00

abstract：:The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of li...

journal_title：Journal of medicinal chemistry

authors： Ding L,Etemad-Moghadam G,Cros S,Auclair C,Meunier B

更新日期：1991-03-01 00:00:00

abstract：:Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codepe...

journal_title：Journal of medicinal chemistry

authors： Tremont SJ,Lee LF,Huang HC,Keller BT,Banerjee SC,Both SR,Carpenter AJ,Wang CC,Garland DJ,Huang W,Jones C,Koeller KJ,Kolodziej SA,Li J,Manning RE,Mahoney MW,Miller RE,Mischke DA,Rath NP,Fletcher T,Reinhard EJ,Tol

更新日期：2005-09-08 00:00:00

abstract：:The synthesis and the biological and pharmacological evaluation of several 14-phenylpropoxy analogues of 14-methoxymetopon are described. Most of the new compounds were nonselective and exhibited binding affinities in the subnanomolar or low nanomolar range at opioid receptors mu, kappa, delta), with 14-phenylpropoxym...

journal_title：Journal of medicinal chemistry

authors： Schütz J,Spetea M,Koch M,Aceto MD,Harris LS,Coop A,Schmidhammer H

更新日期：2003-09-11 00:00:00

abstract：:Since the discovery of the serotonin 4 receptor (5-HT(4)R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazol...

journal_title：Journal of medicinal chemistry

authors： Furlotti G,Alisi MA,Apicella C,Capezzone de Joannon A,Cazzolla N,Costi R,Cuzzucoli Crucitti G,Garrone B,Iacovo A,Magarò G,Mangano G,Miele G,Ombrato R,Pescatori L,Polenzani L,Rosi F,Vitiello M,Di Santo R

更新日期：2012-11-26 00:00:00

abstract：:9-acridinyl derivatives of 1,6-hexanediamine, 1,8-octanediamine, bis(3-aminopropyl)amine, N,N'-bis(3-amino-propyl)piperazine, and N-ethyl-1,6-hexanediamine in the form of their hydrochlorides were prepared in high yields and converted into potential hetero bis DNA intercalating diacridines. The corresponding potential...

journal_title：Journal of medicinal chemistry

authors： Hansen JB,Langvad E,Frandsen F,Buchardt O

更新日期：1983-10-01 00:00:00

abstract：:A series of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11- oxodibenzo[b,e]thiepinacetic acids (6-9) and -oxepinacetic acids (10-13) were prepared and their antiinflammatory activity was examined in the rat carrageenan hind paw edema test. The antiinflammatory activity of these compounds depended on their stereochem...

journal_title：Journal of medicinal chemistry

authors： Kurokawa M,Uno H,Nakamura H,Sato F,Naruto S

更新日期：1990-02-01 00:00:00

abstract：:The dipeptide D-alanyl-D-alanine is an essential precursor of bacterial peptidoglycan; thus, blocking its formation is a possible target for the design of novel antibacterial agents. The synthesis of this dipeptide by bacterial D-alanine:D-alanine ligase requires ATP. In analogy with glutamine synthetase, we hypothesi...

journal_title：Journal of medicinal chemistry

authors： Chakravarty PK,Greenlee WJ,Parsons WH,Patchett AA,Combs P,Roth A,Busch RD,Mellin TN

更新日期：1989-08-01 00:00:00

abstract：:Coactivator-associated arginine methyltransferase 1 (CARM1) represents a valuable target for hormone-dependent tumors such as prostate and breast cancers. Here we report the enzyme and cellular characterization of the 1-benzyl-3,5-bis(3-bromo-4-hydroxybenzylidene)piperidin-4-one (7g) and its analogues 8a-l. Among them...

journal_title：Journal of medicinal chemistry

authors： Cheng D,Valente S,Castellano S,Sbardella G,Di Santo R,Costi R,Bedford MT,Mai A

更新日期：2011-07-14 00:00:00

abstract：:We describe the preparation and evaluation of a novel series of glycine transporter 1 (GlyT1) inhibitors derived from a high-throughput screening hit. The SAR studies resulted in the discovery of 3-biphenyl-4-yl-4-(2-fluorophenyl)-5-isopropyl-4H-1,2,4-triazole (6p). A pharmacokinetic study was also conducted and revea...

journal_title：Journal of medicinal chemistry

authors： Sugane T,Tobe T,Hamaguchi W,Shimada I,Maeno K,Miyata J,Suzuki T,Kimizuka T,Kohara A,Morita T,Doihara H,Saita K,Aota M,Furutani M,Shimada Y,Hamada N,Sakamoto S,Tsukamoto S

更新日期：2011-01-13 00:00:00