Synergy and antagonism of promiscuous inhibition in multiple-compound mixtures.

abstract：:We investigated the pharmacological profile of a novel series of quinoxaline-based 5-HT(3) receptor ligands bearing an extra basic moiety on the piperazine N-4. High affinity and selectivity were dependent on the electronic properties of the substituents, and at cardiac level 3a and 3c modulated chronotropy but not in...

journal_title：Journal of medicinal chemistry

authors： Butini S,Budriesi R,Hamon M,Morelli E,Gemma S,Brindisi M,Borrelli G,Novellino E,Fiorini I,Ioan P,Chiarini A,Cagnotto A,Mennini T,Fracasso C,Caccia S,Campiani G

更新日期：2009-11-12 00:00:00

abstract：:The synthesis of a series of orally active, phosphinyloxyacyl proline inhibitors of angiotensin converting enzyme (ACE) is described. The in vitro and in vivo ACE inhibitory activities are reported for each compound. The structure-activity relationship for this series of compounds in relation to the carboxyalkyl dipep...

journal_title：Journal of medicinal chemistry

authors： Karanewsky DS,Badia MC,Cushman DW,DeForrest JM,Dejneka T,Loots MJ,Perri MG,Petrillo EW Jr,Powell JR

更新日期：1988-01-01 00:00:00

abstract：:Two isomeric 6-endo- and 6-exo-(3',4'-dihydroxyphenyl) derivatives (1 and 2) of 2-azabicyclo[2.2.2]octane were synthesized as semirigid analogues of dopamine (DA) to help evaluate the preferred conformation of dopamine at the uptake site of the presynaptic nerve terminal and at the DA receptor. Against the uptake of 0...

journal_title：Journal of medicinal chemistry

authors： Law SJ,Morgan JM,Masten LW,Borne RF,Arana GW,Kula NS,Baldessarini RJ

更新日期：1982-03-01 00:00:00

abstract：:There is growing interest in using tumor associated antigens presented by class I major histocompatibility complex (MHC-I) proteins as cancer vaccines. As native peptides are poorly stable in biological fluids, researchers have sought to engineer synthetic peptidomimetics with greater biostability. Here, we demonstrat...

journal_title：Journal of medicinal chemistry

authors： Douat-Casassus C,Borbulevych O,Tarbe M,Gervois N,Jotereau F,Baker BM,Quideau S

更新日期：2010-10-14 00:00:00

abstract：:Twenty-three acrylonitriles, substituted at position 2 with either triazoles or benzimidazoles and at position 3 with various substituted furan, thiophene, or phenyl rings, were prepared by Knoevenagel condensation and tested for in vitro cytotoxic potency on 11 human cancer cell lines. X-ray crystal analysis of two r...

journal_title：Journal of medicinal chemistry

authors： Saczewski F,Reszka P,Gdaniec M,Grünert R,Bednarski PJ

更新日期：2004-06-17 00:00:00

abstract：:A series of 3-thioindolamidines (and 3-indolamidines) related to mixidine (1) was studied for cardiac-slowing properties, following the discovery of activity for prototype thioindole 2. Structure-activity relationships were explored, leading to many potent antitachycardiac agents (6-9, 12, 13, 15-17, 20, 23, 24, 30, 3...

journal_title：Journal of medicinal chemistry

authors： Zelesko MJ,McComsey DF,Hageman WE,Nortey SO,Baker CA,Maryanoff BE

更新日期：1983-02-01 00:00:00

abstract：:A representative series of 5-(4-hydroxyphenyl)-2-azabicyclo[3.2.1]octanes was synthesized and evaluated in vitro, as well as in vivo, as potential analgetic agents. In general, moderate to good activity (19 twice as active as morphine) was observed in the phenylquinone writhing assay (PQW), while only marginal activit...

journal_title：Journal of medicinal chemistry

authors： Ong HH,Anderson VB,Wilker JC,Spaulding TC,Meyerson LR

更新日期：1980-07-01 00:00:00

abstract：:In order to investigate the structural requirements for gastroprotective activity in 6-[[1(S)-(3(S),4-dihydro-8- hydroxy-1-oxo-1H-2-benzopyran-3-yl)-3-methylbutyl]amino]-4(S),5(S)-dihydroxy 6-oxo-3(S)-ammoniohexanoate [AI-77-B, 1], a product of Bacillus pumilus AI-77, nine derivatives were prepared and then tested for...

journal_title：Journal of medicinal chemistry

authors： Shimojima Y,Hayashi H

更新日期：1983-10-01 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

abstract：:A novel cytochrome P450, CYP53A15, was identified in the pathogenic filamentous ascomycete Cochliobolus lunatus. The protein, classified into the CYP53 family, was capable of para hydroxylation of benzoate. Benzoate is a key intermediate in the metabolism of aromatic compounds in fungi and yet basically toxic to the o...

journal_title：Journal of medicinal chemistry

authors： Podobnik B,Stojan J,Lah L,Krasevec N,Seliskar M,Rizner TL,Rozman D,Komel R

更新日期：2008-06-26 00:00:00

abstract：:GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as a...

journal_title：Journal of medicinal chemistry

authors： Wang C,Zhang YF,Guo S,Zhao Q,Zeng Y,Xie Z,Xie X,Lu B,Hu Y

更新日期：2021-01-28 00:00:00

abstract：:A new series of N'-(pyridinioacetyl)alkanoic and -benzoic acid hydrazides, as chloride salts, and some cyclic analogues produced ring closure have been synthesize and tested in a search for more effective germicides. Physicochemical parameters, such as surface tension, critical micelle concentration, and thermodynamic...

journal_title：Journal of medicinal chemistry

authors： Sicardi SM,Vega CM,Cimijotti EB

更新日期：1980-10-01 00:00:00

abstract：:A range of cis- and trans-3-substituted 1-aminocyclobutane-1-carboxylic acids has been synthesized and evaluated for antagonism at excitatory amino acid receptor sites and for anticonvulsant activity. Potent and selective antagonist activity at N-methyl-D-aspartate (NMDA) receptor sites in neonatal rat motoneurones wa...

journal_title：Journal of medicinal chemistry

authors： Gaoni Y,Chapman AG,Parvez N,Pook PC,Jane DE,Watkins JC

更新日期：1994-12-09 00:00:00

abstract：:We present the first report of the application of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to hydroxy-containing drug derivatives. In particular, we applied this strategy to the highly lipophilic antiviral drug family of bicyclic furanopyrimidine nucleoside analogues (BCNA) in order to improve t...

journal_title：Journal of medicinal chemistry

authors： Diez-Torrubia A,Balzarini J,Andrei G,Snoeck R,De Meester I,Camarasa MJ,Velázquez S

更新日期：2011-03-24 00:00:00

abstract：:The title compounds were prepared to investigate their potential as thromboxane synthetase inhibitors as well as antihypertensive agents. Imidazoles VIII and triazoles X were prepared to examine the effects of aromatic substitution, chain length, and heterocycle substitution upon biological activity. Imidazoles VIII a...

journal_title：Journal of medicinal chemistry

authors： Wright WB Jr,Press JB,Chan PS,Marsico JW,Haug MF,Lucas J,Tauber J,Tomcufcik AS

更新日期：1986-04-01 00:00:00

abstract：:We recently described a novel series of CA(1)A(2)X peptidomimetics as farnesyl transferase inhibitors (FTIs). These compounds possess an N-(4-piperidinyl)benzamide scaffold mimicking A(1)A(2) residue. Extensive exploration of structure--activity relationships revealed that replacement of cysteine by substituted benzyl...

journal_title：Journal of medicinal chemistry

authors： Millet R,Domarkas J,Houssin R,Gilleron P,Goossens JF,Chavatte P,Logé C,Pommery N,Pommery J,Hénichart JP

更新日期：2004-12-30 00:00:00

abstract：:The S-adenosylmethionine (AdoMet) analogue S-(5'-deoxy-5'-adenosyl)-1-aminoxy-4-(methylsulfonio)-2-cycl opentene (AdoMao) was synthesized in two of its four possible diastereomeric forms using a facile chemoenzymatic route. The trans-1R,4R- and trans-1S,4S-diastereomers of AdoMao, as well as the corresponding diastere...

journal_title：Journal of medicinal chemistry

authors： Guo J,Wu YQ,Rattendi D,Bacchi CJ,Woster PM

更新日期：1995-05-12 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 syntheses of three new cyclosporin A (CsA) analogues that contain novel MeBmt derivatives in the 1-position are described. The MeBmt analogue that contains an additional methyl group on C4, (2S,3R,6E)-4,4-dimethyl-3-hydroxy-2-(N-methylamino)-6-octenoic acid (MeBm2t), was synthesized in four steps beginning with th...

journal_title：Journal of medicinal chemistry

authors： Aebi JD,Deyo DT,Sun CQ,Guillaume D,Dunlap B,Rich DH

更新日期：1990-03-01 00:00:00

abstract：:Derivatives of N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide bearing a wide variety of different groups at the 5-position (and for comparative purposes at the 7-position) have been prepared, and their physicochemical properties and biological activities have been determined. Although both 5- and 7-substitut...

journal_title：Journal of medicinal chemistry

authors： Denny WA,Atwell GJ,Rewcastle GW,Baguley BC

更新日期：1987-04-01 00:00:00

abstract：:Antagonizing the robust stimulation of food intake by neuropeptide Y represents a new potential therapeutic approach for the treatment of obesity. Earlier pharmacological studies have pointed to the Y1 and Y5 receptors as the most likely mediators of the NPY orexigenic response. In this paper, we describe a new series...

journal_title：Journal of medicinal chemistry

authors： Blum CA,Zheng X,De Lombaert S

更新日期：2004-04-22 00:00:00

abstract：:3alpha-(diphenylmethoxy)tropane (benztropine) and its analogues are tropane ring-containing dopamine uptake inhibitors that display binding and behavioral profiles that are distinct from cocaine. We previously prepared a benztropine-based photoaffinity label [125I]-(N-[4-(4'-azido-3'-iodophenyl)butyl]-3alpha-[bis(4'-f...

journal_title：Journal of medicinal chemistry

authors： Zou MF,Kopajtic T,Katz JL,Wirtz S,Justice JB Jr,Newman AH

更新日期：2001-12-06 00:00:00

abstract：:Glucuronidation and transporter-mediated efflux into bile are important in the elimination of xeno- and endobiotics, including the natural biladienone pigment bilirubin. The mechanisms of these processes and the structural factors that dictate whether cholephilic compounds are excreted directly in bile or require prio...

journal_title：Journal of medicinal chemistry

authors： McDonagh AF,Lightner DA

更新日期：2007-02-08 00:00:00

abstract：:We have designed and synthesized eight compounds 2-9 which incorporate various amino acid residues in positions 17, 18, and 21 of the glucagon molecule: 2, [Lys17]glucagon amide; 3, [Lys18]glucagon amide; 4, [Nle17,Lys18,Glu21]glucagon amide; 5, [Orn17,18, Glu21]glucagon amide; 6, [d-Arg17]glucagon; 7, [d-Arg18]glucag...

journal_title：Journal of medicinal chemistry

authors： Sturm NS,Lin Y,Burley SK,Krstenansky JL,Ahn JM,Azizeh BY,Trivedi D,Hruby VJ

更新日期：1998-07-16 00:00:00

abstract：:The atypical chemokine receptor 3 (ACKR3)/CXC chemokine receptor 7 (CXCR7) recognizes stromal cell-derived factor 1 (SDF-1)/CXCL12 and is involved in a number of physiological and pathological processes. Here, we investigated the SAR of the component amino acids in an ACKR3-selective ligand, FC313 [ cyclo(-d-Tyr-l-Arg...

journal_title：Journal of medicinal chemistry

authors： Sekiguchi H,Kuroyanagi T,Rhainds D,Kobayashi K,Kobayashi Y,Ohno H,Heveker N,Akaji K,Fujii N,Oishi S

更新日期：2018-04-26 00:00:00

abstract：:The inhibition of chicken liver dihydrofolate reductase by a series of substituted benzylpyrimidines has been investigated. From the inhibition constants a quantitative structure-activity relationship has been formulated. This mathematical model is compared with molecular graphics models constructed from the X-ray cry...

journal_title：Journal of medicinal chemistry

authors： Selassie CD,Fang ZX,Li RL,Hansch C,Klein T,Langridge R,Kaufman BT

更新日期：1986-05-01 00:00:00

abstract：:Twenty-six episilon-rhodomycinone glycosides have been synthesized. These include the episilon-rhodomycinone glycosides of 2-deoxy-L-fucose, 2-deoxy-L-rhamnose, and 2-deoxy-D-ribose as well as their 2-hydroxyl derivatives. NMR spectroscopy showed that all the glycosides prepared had the saccharide residues linked to p...

journal_title：Journal of medicinal chemistry

authors： Khadem HS,Swartz DL,Cermak RC

更新日期：1977-07-01 00:00:00

abstract：:We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more p...

journal_title：Journal of medicinal chemistry

authors： Koh JJ,Zou H,Lin S,Lin H,Soh RT,Lim FH,Koh WL,Li J,Lakshminarayanan R,Verma C,Tan DT,Cao D,Beuerman RW,Liu S

更新日期：2016-01-14 00:00:00

abstract：:LTX 109 is a synthetic antimicrobial peptidomimetic (SAMP) currently in clinical phase II trials for topical treatment of infections of multiresistant bacterial strains. All possible eight stereoisomers of the peptidomimetic have been synthesized and tested for antimicrobial effect, hemolysis, and hydrophobicity, reve...

journal_title：Journal of medicinal chemistry

authors： Isaksson J,Brandsdal BO,Engqvist M,Flaten GE,Svendsen JS,Stensen W

更新日期：2011-08-25 00:00:00

abstract：:N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both P...

journal_title：Journal of medicinal chemistry

authors： Rackham MD,Brannigan JA,Rangachari K,Meister S,Wilkinson AJ,Holder AA,Leatherbarrow RJ,Tate EW

更新日期：2014-03-27 00:00:00