Substituted (pyrroloamino)pyridines: potential agents for the treatment of Alzheimer's disease.

abstract：:Regioselective syntheses of substituted 2-chloroquinoxalines and derived 2-(1-piperazinyl)quinoxalines are described. Selectivity in regards to serotonin reuptake blocking and serotoninmimetic activities of the piperazinylquinoxalines is reported. In general, introduction of a 6-substituent into the piperazinylquinoxa...

journal_title：Journal of medicinal chemistry

authors： Lumma WC Jr,Hartman RD,Saari WS,Engelhardt EL,Lotti VJ,Stone CA

更新日期：1981-01-01 00:00:00

abstract：:Monophenolic (2-(dipropylamino)indans and related compounds have been synthesized and tested for central dopamine-receptor stimulating activity, using biochemical and behavioral tests in rats and emesis tests in dogs. The active compounds possess similar relative potencies in eliciting the three different dopamine-rec...

journal_title：Journal of medicinal chemistry

authors： Hacksell U,Arvidsson LE,Svensson U,Nilsson JL,Wikström H,Lindberg P,Sanchez D,Hjorth S,Carlsson A,Paalzow L

更新日期：1981-04-01 00:00:00

abstract：:The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and...

journal_title：Journal of medicinal chemistry

authors： Pommery N,Taverne T,Telliez A,Goossens L,Charlier C,Pommery J,Goossens JF,Houssin R,Durant F,Hénichart JP

更新日期：2004-12-02 00:00:00

abstract：:(R,S)-2-Amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid ((R,S)-APPA) is the only partial agonist at the (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) subtype of excitatory amino acid receptors so far described. In light of the pharmacological interest in partial agonists, we have now a...

journal_title：Journal of medicinal chemistry

authors： Ebert B,Lenz S,Brehm L,Bregnedal P,Hansen JJ,Frederiksen K,Bøgesø KP,Krogsgaard-Larsen P

更新日期：1994-04-01 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：:The parasitic trypanosomes Trypanosoma brucei and T. cruzi are responsible for significant human suffering in the form of human African trypanosomiasis (HAT) and Chagas disease. Drugs currently available to treat these neglected diseases leave much to be desired. Herein we report optimization of a novel class of N-(2-...

journal_title：Journal of medicinal chemistry

authors： Russell S,Rahmani R,Jones AJ,Newson HL,Neilde K,Cotillo I,Rahmani Khajouei M,Ferrins L,Qureishi S,Nguyen N,Martinez-Martinez MS,Weaver DF,Kaiser M,Riley J,Thomas J,De Rycker M,Read KD,Flematti GR,Ryan E,Tanghe S,R

更新日期：2016-11-10 00:00:00

abstract：:The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great ...

journal_title：Journal of medicinal chemistry

authors： Soubhye J,Chikh Alard I,Aldib I,Prévost M,Gelbcke M,De Carvalho A,Furtmüller PG,Obinger C,Flemmig J,Tadrent S,Meyer F,Rousseau A,Nève J,Mathieu V,Zouaoui Boudjeltia K,Dufrasne F,Van Antwerpen P

更新日期：2017-08-10 00:00:00

abstract：:Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that co...

journal_title：Journal of medicinal chemistry

authors： Shi J,Van de Water R,Hong K,Lamer RB,Weichert KW,Sandoval CM,Kasibhatla SR,Boehm MF,Chao J,Lundgren K,Timple N,Lough R,Ibanez G,Boykin C,Burrows FJ,Kehry MR,Yun TJ,Harning EK,Ambrose C,Thompson J,Bixler SA,Dunah

更新日期：2012-09-13 00:00:00

abstract：:Attempts to develop new (aryloxy)acetic acids with a better profile of diuretic and uricosuric activities as well as with fewer side effects have produced a series of compounds in which the ring system has been varied. Diuretic screening of these analogues in rats indicated that the great difference in the activity be...

journal_title：Journal of medicinal chemistry

authors： Koga H,Sato H,Dan T,Aoki B

更新日期：1991-09-01 00:00:00

abstract：:A novel and highly efficient flexible docking approach is presented where the conformations (internal degrees of freedom) and orientations (external degrees of freedom) of the ligands are successively considered. This hybrid method takes advantage of the synergistic effects of structure-based and ligand-based drug des...

journal_title：Journal of medicinal chemistry

authors： Moitessier N,Henry C,Maigret B,Chapleur Y

更新日期：2004-08-12 00:00:00

abstract：:The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationsh...

journal_title：Journal of medicinal chemistry

authors： Azevedo CM,Watterson KR,Wargent ET,Hansen SV,Hudson BD,Kępczyńska MA,Dunlop J,Shimpukade B,Christiansen E,Milligan G,Stocker CJ,Ulven T

更新日期：2016-10-13 00:00:00

abstract：:Sixteen long-chain arylpiperazines bearing the fluorescent moiety 2-phenylimidazo[1,2-a]pyridine were synthesized as fluorescent dopamine D3 receptors ligands (385 nM < Ki < 0.72 nM). The most potent D3 compounds 15a and 19a (Ki = 1.6 and 0.72 nM, respectively) showed good Stokes shift and high quantum yield in ethano...

journal_title：Journal of medicinal chemistry

authors： Leopoldo M,Lacivita E,Passafiume E,Contino M,Colabufo NA,Berardi F,Perrone R

更新日期：2007-10-04 00:00:00

abstract：:Cyclic and acyclic nitroaryl phosphoramide mustard analogues were activated by E. coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4-nitrobenzyl phosphoramide mustard (7) showed 167 500x selective cytotoxicity toward nitroreductase-expressing V79 cells with an IC(50) as low as 0.4 nM. This is ...

journal_title：Journal of medicinal chemistry

authors： Hu L,Yu C,Jiang Y,Han J,Li Z,Browne P,Race PR,Knox RJ,Searle PF,Hyde EI

更新日期：2003-11-06 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：:Water soluble analogues of the lipophilic immunostimulant, octadecyl D-alanyl-L-glutamine, BCH-527, were synthesized and evaluated for the ability to stimulate natural killer (NK) cells. One of these compounds in which the octadecyl chain of BCH-527 was replaced with a shorter chain alcohol, 6-(D-alanyl-L-glutaminylam...

journal_title：Journal of medicinal chemistry

authors： Abbott SD,Gagnon L,Lagraoui M,Kadhim S,Attardo G,Zacharie B,Penney CL

更新日期：1998-05-21 00:00:00

abstract：:A new series of 11-[(aminoalkyl)carbonyl] derivatives of 6,11-dihydrodibenzo[c,f][1,2,5]thiadiazepine 5,5-dioxide (10-39) were synthesized and evaluated for potential antidepressant activity in the apomorphine-induced hypothermia (Apo 16) test. Effects on reserpine-induced hypothermia and toxicity for the most potent ...

journal_title：Journal of medicinal chemistry

authors： Giannotti D,Viti G,Sbraci P,Pestellini V,Volterra G,Borsini F,Lecci A,Meli A,Dapporto P,Paoli P

更新日期：1991-04-01 00:00:00

abstract：:The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]q...

journal_title：Journal of medicinal chemistry

authors： Wadsworth HJ,Jenkins SM,Orlek BS,Cassidy F,Clark MS,Brown F,Riley GJ,Graves D,Hawkins J,Naylor CB

更新日期：1992-04-03 00:00:00

abstract：:The effect of substitution in the acyclic structure of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds. Preparation of 1-[(2-alkyloxyethoxy)methyl]-6- (phenylthio)thymine (2-4) derivatives was carried out ...

journal_title：Journal of medicinal chemistry

authors： Tanaka H,Takashima H,Ubasawa M,Sekiya K,Nitta I,Baba M,Shigeta S,Walker RT,De Clercq E,Miyasaka T

更新日期：1992-12-11 00:00:00

abstract：:Iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu A analogues 2. In some cases, however, the corresponding cyclic ethers 5 were formed competitively with the cyclic peroxides 2, the ratios of these two products being a marked function of the structure of the starting ma...

journal_title：Journal of medicinal chemistry

authors： Kim HS,Begum K,Ogura N,Wataya Y,Tokuyasu T,Masuyama A,Nojima M,McCullough KJ

更新日期：2002-10-10 00:00:00

abstract：:It is now plausible to dock libraries of 10 million molecules against targets over several days or weeks. When the molecules screened are commercially available, they may be rapidly tested to find new leads. Although docking retains important liabilities (it cannot calculate affinities accurately nor even reliably ran...

journal_title：Journal of medicinal chemistry

authors： Irwin JJ,Shoichet BK

更新日期：2016-05-12 00:00:00

abstract：:In a previous study, we described affinity labeling of the lamb uterine estrogen receptor by 17 alpha-[(bromoacetoxy)alkyl/alkynyl]estradiols. However, the intrinsic receptor-alkylating activities of these compounds were probably very hampered by their poor hydrolytic stability in estrogen receptor-containing tissue e...

journal_title：Journal of medicinal chemistry

authors： el Garrouj D,Aliau S,Aumelas A,Borgna JL

更新日期：1995-06-23 00:00:00

abstract：:The optimization of a class of indole cPLA 2 alpha inhibitors is described herein. The importance of the substituent at C3 and the substitution pattern of the phenylmethane sulfonamide region are highlighted. Optimization of these regions led to the discovery of 111 (efipladib) and 121 (WAY-196025), which are shown to...

journal_title：Journal of medicinal chemistry

authors： McKew JC,Lee KL,Shen MW,Thakker P,Foley MA,Behnke ML,Hu B,Sum FW,Tam S,Hu Y,Chen L,Kirincich SJ,Michalak R,Thomason J,Ipek M,Wu K,Wooder L,Ramarao MK,Murphy EA,Goodwin DG,Albert L,Xu X,Donahue F,Ku MS,Keit

更新日期：2008-06-26 00:00:00

abstract：:The aim of this work was to obtain photoactivatable nonpeptide antagonists of the angiotensin II AT(1) receptor. Based on structure-function relationships, two chemical structures as well as appropriate synthetic schemes were chosen as a frame for the design of radiolabeled azido probes. The feasibility of the strateg...

journal_title：Journal of medicinal chemistry

authors： Nouet S,Dodey PR,Bondoux MR,Pruneau D,Luccarini JM,Groblewski T,Larguier R,Lombard C,Marie J,Renaut PP,Leclerc G,Bonnafous JC

更新日期：1999-11-04 00:00:00

abstract：:We have previously described a cyclic tetrapeptide, 1, that displays μ opioid receptor (MOPr) agonist and δ opioid receptor (DOPr) antagonist activity, a profile associated with a reduced incidence of opioid tolerance and dependence. Like many peptides, 1 has poor bioavailability. We describe here an analogue of 1 wit...

journal_title：Journal of medicinal chemistry

authors： Mosberg HI,Yeomans L,Anand JP,Porter V,Sobczyk-Kojiro K,Traynor JR,Jutkiewicz EM

更新日期：2014-04-10 00:00:00

abstract：:A new 1,4-dihydropyridine 5a, containing a cyano group at the C3 position, was recently reported to possess excellent mineralocorticoid receptor (MR) antagonist in vitro potency and no calcium channel-blocker (CCB) activity. In the present study, we report the structure-activity relationships of this novel series of c...

journal_title：Journal of medicinal chemistry

authors： Arhancet GB,Woodard SS,Iyanar K,Case BL,Woerndle R,Dietz JD,Garland DJ,Collins JT,Payne MA,Blinn JR,Pomposiello SI,Hu X,Heron MI,Huang HC,Lee LF

更新日期：2010-08-26 00:00:00

abstract：:A series of nitrocoumarin and nitrochromene derivatives have been prepared and shown to inhibit the phosphatidylinositol-specific phospholipase C(PLC)(IC50 < 10 micrograms/mL) isolated from human melanoma. The inhibition of PLC by nitrocoumarin 4a was time-dependent and irreversible. The inhibition of PLC was shown to...

journal_title：Journal of medicinal chemistry

authors： Perrella FW,Chen SF,Behrens DL,Kaltenbach RF 3rd,Seitz SP

更新日期：1994-07-08 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：:Quantitative structure-activity relationship (QSAR) and comparative molecular field analysis (CoMFA) have been applied to elucidate the mechanisms of genotoxicity (SOSIP) of nitrofuran derivatives on Escherichia coli PQ37. The following equation was developed: log SOSIP = -33.1qc2 + 1.00 log P - 1.50Isat - 1.19MR - 0....

journal_title：Journal of medicinal chemistry

authors： Debnath AK,Hansch C,Kim KH,Martin YC

更新日期：1993-04-16 00:00:00

abstract：:A study of the effect of aromatic substitution on 5-HT2, D2, and alpha 1 receptor affinity in a subseries of new and previously synthesized 1-piperazino-3-phenylindans indicated that high 5-HT2 selectivity could be obtained in 5-substituted derivatives. Accordingly, a series of 5-substituted derivatives was synthesize...

journal_title：Journal of medicinal chemistry

authors： Bøgesø KP,Arnt J,Hyttel J,Pedersen H

更新日期：1993-09-17 00:00:00

abstract：:A theoretically rigorous and computationally tractable methodology for the prediction of the free energies of binding of protein-ligand complexes is presented. The method formulated involves developing molecular dynamics trajectories of the enzyme, the inhibitor, and the complex, followed by a free energy component an...

journal_title：Journal of medicinal chemistry

authors： Kalra P,Reddy TV,Jayaram B

更新日期：2001-12-06 00:00:00