Dual-action cephalosporins: cephalosporin 3'-quaternary ammonium quinolones.

abstract：:The structure of fenoterol, a beta2-adrenoceptor agonist used in therapy, has been joined with furoxan NO-donor moieties to give new NO-donor beta2-agonists. The furazan analogues, devoid of the property to release NO, were also synthesized for comparison. All the compounds retained beta2-agonistic activity at micromo...

journal_title：Journal of medicinal chemistry

authors： Buonsanti MF,Bertinaria M,Stilo AD,Cena C,Fruttero R,Gasco A

更新日期：2007-10-04 00:00:00

abstract：:For establishment of the structure-activity relationship, 19 heterobicycle-coumarin conjugated compounds with the -SCH(2)- linker were synthesized and found to possess significant antiviral activities. Prominent examples included imidazopyridine-coumarin 12c, purine-coumarin 12d, and benzoxazole-coumarin 14c, which in...

journal_title：Journal of medicinal chemistry

authors： Neyts J,De Clercq E,Singha R,Chang YH,Das AR,Chakraborty SK,Hong SC,Tsay SC,Hsu MH,Hwu JR

更新日期：2009-03-12 00:00:00

abstract：:A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-positi...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Du W,Hwang I,Rayl TJ,Kimball FS,Leung D,Hoover HS,Apodaca RL,Breitenbucher JG,Cravatt BF,Boger DL

更新日期：2007-03-08 00:00:00

abstract：:The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with...

journal_title：Journal of medicinal chemistry

authors： Matharu SS,Rowlands DA,Taylor JB,Westwood R

更新日期：1977-02-01 00:00:00

abstract：:We here report the synthesis of compounds structurally related to the high-affinity dopamine D(3) receptor ligand N-[4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl]-7-methoxy-2-benzofurancarboxamide (1). All compounds were specifically designed as potential PET radioligands for brain D(3) receptors visualization, havin...

journal_title：Journal of medicinal chemistry

authors： Leopoldo M,Lacivita E,De Giorgio P,Colabufo NA,Niso M,Berardi F,Perrone R

更新日期：2006-01-12 00:00:00

abstract：:Two new peptides, tailored after Ac-Thr-D-Trp(CHO)-Phe-NMeBzl (TRI), namely, Ac-Thr-D-Trp(CHO)-Phe-NMe alpha MeBzl (TRA) and Ac-Thr-D-Trp(CHO)-Oic-NMeBzl (TOI), in which Phe is replaced by (3aS, 7aS)-octahydroindole-2-carboxylic acid, proved more potent and selective NK1 antagonists. The conformational properties of a...

journal_title：Journal of medicinal chemistry

authors： Caliendo G,Grieco P,Perissutti E,Santagada V,Saviano G,Tancredi T,Temussi PA

更新日期：1997-02-14 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：:Structure-based methods were used to design a potent and highly selective group II p21-activated kinase (PAK) inhibitor with a novel binding mode, compound 17. Hydrophobic interactions within a lipophilic pocket past the methionine gatekeeper of group II PAKs approached by these type I 1/2 binders were found to be imp...

journal_title：Journal of medicinal chemistry

authors： Staben ST,Feng JA,Lyle K,Belvin M,Boggs J,Burch JD,Chua CC,Cui H,DiPasquale AG,Friedman LS,Heise C,Koeppen H,Kotey A,Mintzer R,Oh A,Roberts DA,Rouge L,Rudolph J,Tam C,Wang W,Xiao Y,Young A,Zhang Y,Hoeflich K

更新日期：2014-02-13 00:00:00

abstract：:The synthesis and CNS activity of a noval class of annelated 1,4-benzodiazepines, the aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepines, are described. An investigation of the structure--activity relationships in the series derived from 8-chloro-2,4-dihydro-2-dimethylaminomethylene-6-phenyl-1H-imidazo[1...

journal_title：Journal of medicinal chemistry

authors： Ager IR,Danswan GW,Harrison DR,Kay DP,Kennewell PD,Taylor JB

更新日期：1977-08-01 00:00:00

abstract：:Several N-2 substituted 1-methyl-1-(4-tolylsulfonyl)hydrazines were synthesized and evaluated for antineoplastic activity against the L1210 leukemia and the B16 melanoma. The most active compound to emerge from this study, 2-(methylsulfonyl)-1-methyl-1-(4-tolylsulfonyl)hydrazine, produced maximum percent T/C values wi...

journal_title：Journal of medicinal chemistry

authors： Hrubiec RT,Shyam K,Cosby LA,Furubayashi R,Sartorelli AC

更新日期：1986-07-01 00:00:00

abstract：:The dengue virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development of dual-acting therapeutics against these arboviral pathogens. We present the synthesis and extensive biological evaluation of inhibitors that contain benzyl ethers of 4-hydroxyphenylglycine as non-natural p...

journal_title：Journal of medicinal chemistry

authors： Behnam MA,Graf D,Bartenschlager R,Zlotos DP,Klein CD

更新日期：2015-12-10 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：:Reaction of 3'-acetylthymidine with phosphorus oxychloride in trimethyl phosphate yielded the phosphorodichloridate 5, which was subsequently reacted with aziridine, or 2,2-dimethylaziridine to give compounds 6 and 7, respectively. The 2,2-dimethylaziridine derivative 7 was considerably more active than 6 against leuk...

journal_title：Journal of medicinal chemistry

authors： Hsiao LY,Bardos TJ

更新日期：1981-07-01 00:00:00

abstract：:From the whole plant of Euphorbia peplus L., five new diterpenes based on a jatrophane skeleton (pepluanins A-E, 1-5) were isolated, together with two known analogues (6 and 7), which served to divulge in detail the structure-activity relationships within this class of P-glycoprotein inhibitors. The results revealed t...

journal_title：Journal of medicinal chemistry

authors： Corea G,Fattorusso E,Lanzotti V,Motti R,Simon PN,Dumontet C,Di Pietro A

更新日期：2004-02-12 00:00:00

abstract：:Tumor suppressor protein, p53, is an intracellular protein that is critical within the biochemical cascade that leads to cell death via apoptosis. Recent studies identified the tetrahydrobenzothiazole analogue, pifithrin-alpha (2), as a p53 inhibitor that was effective in protecting neuronal cells against a variety of...

journal_title：Journal of medicinal chemistry

authors： Zhu X,Yu QS,Cutler RG,Culmsee CW,Holloway HW,Lahiri DK,Mattson MP,Greig NH

更新日期：2002-11-07 00:00:00

abstract：:A conformationally defined retinoic acid analog (1) which contains a dimethylene bridge to maintain the 6-s-trans orientation for two terminal double bonds in the polyene chain was synthesized. A Reformatsky reaction was utilized to extend the polyene chain of the starting enone, which provided exclusively the 9Z-conf...

journal_title：Journal of medicinal chemistry

authors： Vaezi MF,Alam M,Sani BP,Rogers TS,Simpson-Herren L,Wille JJ,Hill DL,Doran TI,Brouillette WJ,Muccio DD

更新日期：1994-12-23 00:00:00

abstract：:We have synthesized a library of thiosemicarbazones and screened them against three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and against the respective parasite sources of these three proteases, Trypanosoma cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified compounds...

journal_title：Journal of medicinal chemistry

authors： Greenbaum DC,Mackey Z,Hansell E,Doyle P,Gut J,Caffrey CR,Lehrman J,Rosenthal PJ,McKerrow JH,Chibale K

更新日期：2004-06-03 00:00:00

abstract：:The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized ...

journal_title：Journal of medicinal chemistry

authors： Smith LH,Tucker H

更新日期：1977-12-01 00:00:00

abstract：:The oxazolidinones are a new class of synthetic antibacterials effective against a broad range of pathogenic Gram-positive bacteria, including multi-drug-resistant strains. Linezolid is the first drug from this class to reach the market and has become an important new option for the treatment of serious infections, pa...

journal_title：Journal of medicinal chemistry

authors： Renslo AR,Jaishankar P,Venkatachalam R,Hackbarth C,Lopez S,Patel DV,Gordeev MF

更新日期：2005-07-28 00:00:00

abstract：:Three new dimeric analogues of ethidium cation in which the monomeric moieties are linked at the 3' positions by alpha,omega-diethers of varying length and composition have been synthesized. The circular dichroism spectra of all three compounds indicate that they double intercalate, and their effects on the thermal he...

journal_title：Journal of medicinal chemistry

authors： Kuhlmann KF,Mosher CW

更新日期：1981-11-01 00:00:00

abstract：:Cancer cells generally possess higher levels of reactive oxygen species than normal cells, and this can serve as a possible therapeutic target. In this proof-of-concept study, an antioxidant-inspired drug discovery strategy was evaluated using a hydroxycinnamic acid derivative. The processing of oxidized mixtures of p...

journal_title：Journal of medicinal chemistry

authors： Fási L,Di Meo F,Kuo CY,Stojkovic Buric S,Martins A,Kúsz N,Béni Z,Dékány M,Balogh GT,Pesic M,Wang HC,Trouillas P,Hunyadi A

更新日期：2019-02-14 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：:Carbonates containing an iodinated aromatic ring on one side of the carbonate linkage and an alkyl group on the other were prepared. The aromatic side consisted of p-iodophenyl, p-iodobenzyl, m-iodobenzyl, 3,5-diiodobenzyl, m-amino-2,4,6-triiodobenzyl, m-acetamido-2,4,6-triiodobenzyl, p-iodophenethyl, p-iodo-sec-phene...

journal_title：Journal of medicinal chemistry

authors： Newton BN

更新日期：1976-12-01 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：:Despite a myriad of available pharmacotherapies for the treatment of type 2 diabetes (T2D), challenges still exist in achieving glycemic control. Several novel glucose-lowering strategies are currently under clinical investigation, highlighting the need for more robust treatments. Previously, we have shown that suppre...

journal_title：Journal of medicinal chemistry

authors： Lin H,Sharabi K,Lin L,Ruiz C,Zhu D,Cameron MD,Novick SJ,Griffin PR,Puigserver P,Kamenecka TM

更新日期：2021-01-28 00:00:00

abstract：:PAC1 receptor is abundant in the CNS and plays an important role in neuronal survival. To identify the molecular determinants and the conformational components responsible for the activation of the PAC1 receptor, we performed a SAR study focusing on the N-terminal domain of its endogenous ligand, PACAP. This approach ...

journal_title：Journal of medicinal chemistry

authors： Bourgault S,Vaudry D,Ségalas-Milazzo I,Guilhaudis L,Couvineau A,Laburthe M,Vaudry H,Fournier A

更新日期：2009-05-28 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：:Partition properties, that is partition coefficients and enthalpies (delta Hp degree) and entropies (delta Sp degree) of partition, have been measured for 50 benzoic acids in the 1-octanol/water system, and their role in QSAR (quantitative structure-activity relationship) analysis examined. The novel hydrophobic param...

journal_title：Journal of medicinal chemistry

authors： Da YZ,Ito K,Fujiwara H

更新日期：1992-09-04 00:00:00

abstract：:(N)-Methanocarba nucleosides containing bicyclo[3.1.0]hexane replacement of the ribose ring previously demonstrated selectivity as A(3) adenosine receptor (AR) agonists (5'-uronamides) or antagonists (5'-truncated). Here, these two series were modified in parallel at the adenine C2 position. N(6)-3-Chlorobenzyl-5'-N-m...

journal_title：Journal of medicinal chemistry

authors： Tosh DK,Chinn M,Ivanov AA,Klutz AM,Gao ZG,Jacobson KA

更新日期：2009-12-10 00:00:00

abstract：:2-Hydroxy-5-(3,4-dichlorophenyl)-6,7-bis(hydroxymethyl)-2,3-dihydro-1H- pyrrolizine bis(2-propylcarbamate) (11) was prepared in a multistep synthesis. The 2-hydroxy group was used to prepare ester prodrugs 14 and 15, and the antineoplastic activities of 11, 14, and 15a were compared to 1 (the 2-deoxy analogue of 11) i...

journal_title：Journal of medicinal chemistry

authors： Anderson WK,Chang CP,McPherson HL Jr

更新日期：1983-09-01 00:00:00