Studies on new acidic azoles as glucose-lowering agents in obese, diabetic db/db mice.

abstract：:Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides...

journal_title：Journal of medicinal chemistry

authors： Souto JA,Vaz E,Lepore I,Pöppler AC,Franci G,Alvarez R,Altucci L,de Lera AR

更新日期：2010-06-24 00:00:00

abstract：:2,9beta-Dimethyl-2'-hydroxy-6,7-benzomorphan (18) has been synthesized from m-methoxyphenylacetone (6a) or m-methoxyphenylacetonitrile (1) via bromo-alpha-tetralone (10). Isomeric bromo-alpha-tetralone 9, instead of undergoing cyclization to a 6,7-benzomorphan, gave aromatization product 12. The structures and stereoc...

journal_title：Journal of medicinal chemistry

authors： Inoue H,O-ishi T,May EL

更新日期：1975-08-01 00:00:00

abstract：:Seven 3-N-substituted derivatives of 3-amino-beta-carboline were synthesized and their affinities for the benzodiazepine receptor were assessed in vitro. Two compounds, 3-(ethylamino)-beta-carboline and 3-[(methoxycarbonyl)amino]-beta-carboline (beta-CMC), showing IC50 values of 460 and 71 nM, respectively, were selec...

journal_title：Journal of medicinal chemistry

authors： Dodd RH,Ouannès C,de Carvalho LP,Valin A,Venault P,Chapouthier G,Rossier J,Potier P

更新日期：1985-06-01 00:00:00

abstract：:9,11-Secoestradiol (9) and 11-hydroxy-9,11-secoestradiol (12) have been synthesized starting from 17-acetoxyestradiol 3-methyl ether (1) and found to possess significant antifertility activity in rats. 3-Methoxy-9,11-seco-9-oxo-17beta-acetoxyestra-1,3,5(10)-trien-11-oic acid (2), prepared by CrO3 oxidation of 1, on h...

journal_title：Journal of medicinal chemistry

authors： Kole P,Ray S,Kamboj VP,Anand N

更新日期：1975-07-01 00:00:00

abstract：:New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cycl...

journal_title：Journal of medicinal chemistry

authors： Ashton WT,Cantone CL,Tolman RL,Greenlee WJ,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

更新日期：1992-07-24 00:00:00

abstract：:Four subtypes of adenosine receptors are currently known, that is, A(1), A(2A), A(2B), and A(3) receptors. Interestingly, quite substantial species differences exist especially between human and rat A(3) receptors. As a result, ligands such as CCPA, which are very selective for the rat A(1) receptor versus the human A...

journal_title：Journal of medicinal chemistry

authors： Beukers MW,Wanner MJ,Von Frijtag Drabbe Künzel JK,Klaasse EC,IJzerman AP,Koomen GJ

更新日期：2003-04-10 00:00:00

abstract：:Four new 2-(2-piperidinoethyl)benzocycloalkanone derivatives, 20-23, were prepared and evaluated as potential antipsychotic agents in receptor binding assays for dopamine (DA) and 5-HT2A receptors and in functional and behavioral screens. Their affinities for D2 receptors (Ki's in the nanomolar range: 46.7-70.7) and D...

journal_title：Journal of medicinal chemistry

authors： Fontenla JA,Osuna J,Rosa E,Castro ME,G-Ferreiro T,Loza-García I,Calleja JM,Sanz F,Rodríguez J,Raviña E

更新日期：1994-08-05 00:00:00

abstract：:G-protein coupled receptor (GPCR) GPR109a is a molecular target for nicotinic acid and is expressed in adipocytes, spleen, and immune cells. Nicotinic acid has long been used for the treatment of dyslipidemia due to its capacity to positively affect serum lipids to a greater extent than other currently marketed drugs....

journal_title：Journal of medicinal chemistry

authors： Boatman PD,Lauring B,Schrader TO,Kasem M,Johnson BR,Skinner P,Jung JK,Xu J,Cherrier MC,Webb PJ,Semple G,Sage CR,Knudsen J,Chen R,Luo WL,Caro L,Cote J,Lai E,Wagner J,Taggart AK,Carballo-Jane E,Hammond M,Collett

更新日期：2012-04-26 00:00:00

abstract：:Chlamydia pneumoniae is an intracellular bacterium that responds poorly to antibiotic treatment. Insufficient antibiotic usage leads to chronic infection, which is linked to disease processes of asthma, atherosclerosis, and Alzheimer's disease. The Chlamydia research lacks genetic tools exploited by other antimicrobia...

journal_title：Journal of medicinal chemistry

authors： Keurulainen L,Salin O,Siiskonen A,Kern JM,Alvesalo J,Kiuru P,Maass M,Yli-Kauhaluoma J,Vuorela P

更新日期：2010-11-11 00:00:00

abstract：:The proteasome plays a crucial role in degradation of normal proteins that happen to be constitutively or inducibly unstable, and in this capacity it plays a regulatory role. Additionally, it degrades abnormal/damaged/mutant/misfolded proteins, which serves a quality-control function. Inhibitors of the proteasome have...

journal_title：Journal of medicinal chemistry

authors： Perez C,Li J,Parlati F,Rouffet M,Ma Y,Mackinnon AL,Chou TF,Deshaies RJ,Cohen SM

更新日期：2017-02-23 00:00:00

abstract：:Details of the interaction between HIV-1 reverse transcriptase and non-nucleoside inhibitors (NNRTIs) have been elucidated using a biosensor-based approach. This initial study was performed with HIV-1 reverse transcriptase mutant K103N, the phenethylthioazolylthiourea compound (PETT) MIV-150, and the three NNRTIs lice...

journal_title：Journal of medicinal chemistry

authors： Geitmann M,Unge T,Danielson UH

更新日期：2006-04-20 00:00:00

abstract：:Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity ( 7, 18- 20) ...

journal_title：Journal of medicinal chemistry

authors： Wen X,Sun H,Liu J,Cheng K,Zhang P,Zhang L,Hao J,Zhang L,Ni P,Zographos SE,Leonidas DD,Alexacou KM,Gimisis T,Hayes JM,Oikonomakos NG

更新日期：2008-06-26 00:00:00

abstract：:Twenty-two structural derivatives of clonidine [2-(2,6-dichlorophenylimino)imidazolidine] have been synthesized and their main physicochemical parameters (log P, deltaRM, pKa) determined. Quantitative correlations between the peripheral alpha-mimetic action (pithed rats) and physicochemical parameters pointed out the ...

journal_title：Journal of medicinal chemistry

authors： Rouot B,Leclerc G,Wermuth CG

更新日期：1976-08-01 00:00:00

abstract：:We previously have reported four possible binding conformation of dynorphin A (Dyn A) for the central kappa opioid receptors, induced by the address sequence, using a molecular mechanics energy minimization approach. The lowest energy conformation was found to exhibit an alpha-helical conformation in the cyclized addr...

journal_title：Journal of medicinal chemistry

authors： Lung FD,Collins N,Stropova D,Davis P,Yamamura HI,Porreca F,Hruby VJ

更新日期：1996-03-01 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：:The discovery and synthesis of a new series of pyrimidines as potent sigma-1 receptor (σ1R) antagonists, associated with pharmacological antineuropathic pain activity, are the focus of this article. The new compounds were evaluated in vitro in σ-1 and σ-2 receptor binding assays. The nature of the pyrimidine scaffold ...

journal_title：Journal of medicinal chemistry

authors： Lan Y,Chen Y,Cao X,Zhang J,Wang J,Xu X,Qiu Y,Zhang T,Liu X,Liu BF,Zhang G

更新日期：2014-12-26 00:00:00

abstract：:Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5alpha-reductase isozymes 1 and 2. The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC(50) values in the nanomolar range. The phe...

journal_title：Journal of medicinal chemistry

authors： Salem OI,Frotscher M,Scherer C,Neugebauer A,Biemel K,Streiber M,Maas R,Hartmann RW

更新日期：2006-01-26 00:00:00

abstract：:The four stereoisomers of the muscarinic agonist 7 have been synthesized from enantiomerically pure exo-azanorbornane esters (13a,b). The esters were obtained in optically active form by separation of the carboxamide diastereomers 12a,b, formed from the borane complex of exo-azanorbornane-3-carboxylate 10 and a chiral...

journal_title：Journal of medicinal chemistry

authors： Showell GA,Baker R,Davis J,Hargreaves R,Freedman SB,Hoogsteen K,Patel S,Snow RJ

更新日期：1992-03-06 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：: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：:A series of C7-O- and C20-O-amidated 2,3-dehydrosilybin (DHS) derivatives ((+/-)-1a-f and (+/-)-2), as well as a set of alkenylated DHS analogues ((+/-)-4a-f), were designed and de novo synthesized. A diesteric derivative of DHS ((+/-)-3) and two C23 esterified DHS analogues ((+/-)-5a and (+/-)-5b) were also prepared ...

journal_title：Journal of medicinal chemistry

authors： Yang LX,Huang KX,Li HB,Gong JX,Wang F,Feng YB,Tao QF,Wu YH,Li XK,Wu XM,Zeng S,Spencer S,Zhao Y,Qu J

更新日期：2009-12-10 00:00:00

abstract：:The high secretion rate of 18-hydroxydeoxycorticosterone in hypertensives and the steroids implication as a mineralocorticoid has led to the synthesis of potential di-, tetra-, and hexahydro metabolites of it and 18-hydroxy-progesterone. These potential metabolites have been synthesized by reduction of the double bond...

journal_title：Journal of medicinal chemistry

authors： Weet JF,Lenz GR

更新日期：1985-02-01 00:00:00

abstract：:Reverse hydroxamate-based inhibitors of IspC, a key enzyme of the non-mevalonate pathway of isoprenoid biosynthesis and a validated antimalarial target, were synthesized and biologically evaluated. The binding mode of one derivative in complex with EcIspC and a divalent metal ion was clarified by X-ray analysis. Pilot...

journal_title：Journal of medicinal chemistry

authors： Behrendt CT,Kunfermann A,Illarionova V,Matheeussen A,Pein MK,Gräwert T,Kaiser J,Bacher A,Eisenreich W,Illarionov B,Fischer M,Maes L,Groll M,Kurz T

更新日期：2011-10-13 00:00:00

abstract：:Since the discovery of 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil (L-FMAU) as a potent anti-HBV and anti-EBV agent, we have studied the structure-activity relationships of 2'-deoxy-2'-fluoro-beta-L-arabinofuranosylpyrimidine nucleosides as anti-HBV agents. Therefore it is rational to extend this study to the pur...

journal_title：Journal of medicinal chemistry

authors： Ma T,Lin JS,Newton MG,Cheng YC,Chu CK

更新日期：1997-08-15 00:00:00

abstract：:Isocitrate dehydrogenases 1 and 2 (IDH1/2) are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid cycle. However, mutant IDH1/2 (mIDH1/2) reduces α-KG to the oncometabolite 2-hydroxyglutarate (2-HG). High levels of 2-HG competitively inhibit the α-KG-depe...

journal_title：Journal of medicinal chemistry

authors： Ma T,Zou F,Pusch S,Xu Y,von Deimling A,Zha X

更新日期：2018-10-25 00:00:00

abstract：:A series of structurally different Gd(III) conjugates incorporating a bile acid moiety have been prepared. Polyaminopolycarboxylic ligands such as diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetracetic acid (DOTA) have been selected as chelating subunit for the Gd(III) ion. Ch...

journal_title：Journal of medicinal chemistry

authors： Anelli PL,Lattuada L,Lorusso V,Lux G,Morisetti A,Morosini P,Serleti M,Uggeri F

更新日期：2004-07-01 00:00:00

abstract：:A series of 3-substituted [1,2,4]triazino[4,3-c]benzimidazoles V were prepared and tested at the central benzodiazepine receptor (BzR). These compounds were designed as rigid analogues of the previously described N-benzylindolylglyoxylylamide derivatives IV. The title compounds V showed an affinity which depended dire...

journal_title：Journal of medicinal chemistry

authors： Primofiore G,Da Settimo F,Taliani S,Marini AM,La Motta C,Novellino E,Greco G,Gesi M,Trincavelli L,Martini C

更新日期：2000-01-13 00:00:00

abstract：:The sodium ion site is an allosteric site conserved among many G protein-coupled receptors (GPCRs). Amiloride 1 and 5-(N,N-hexamethylene)amiloride 2 (HMA) supposedly bind in this sodium ion site and can influence orthosteric ligand binding. The availability of a high-resolution X-ray crystal structure of the human ade...

journal_title：Journal of medicinal chemistry

authors： Massink A,Louvel J,Adlere I,van Veen C,Huisman BJ,Dijksteel GS,Guo D,Lenselink EB,Buckley BJ,Matthews H,Ranson M,Kelso M,IJzerman AP

更新日期：2016-05-26 00:00:00

abstract：:In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) models are important tools in combating late-stage attrition in the drug discovery process. This work shows how ADMET models can be combined to tailor predictions depending on one's needs. We demonstrate how the judicious use of data and c...

journal_title：Journal of medicinal chemistry

authors： O'Brien SE,de Groot MJ

更新日期：2005-02-24 00:00:00

abstract：:A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaborati...

journal_title：Journal of medicinal chemistry

authors： Monn JA,Thurkauf A,Mattson MV,Jacobson AE,Rice KC

更新日期：1990-03-01 00:00:00