Alkyl esters of 3-adenin-9-yl-2-hydroxypropanoic acid: a new class of broad-spectrum antiviral agents.

abstract：:The development of pharmacotherapeutic treatments of psychostimulant abuse has remained a challenge, despite significant efforts made toward relevant mechanistic targets, such as the dopamine transporter (DAT). The atypical DAT inhibitors have received attention due to their promising pharmacological profiles in anima...

journal_title：Journal of medicinal chemistry

authors： Cao J,Slack RD,Bakare OM,Burzynski C,Rais R,Slusher BS,Kopajtic T,Bonifazi A,Ellenberger MP,Yano H,He Y,Bi GH,Xi ZX,Loland CJ,Newman AH

更新日期：2016-12-08 00:00:00

abstract：:Inhibitor of secreted frizzled related protein-1 (sFRP-1) would be a novel potential osteogenic agent, since loss of sFRP-1 affects osteoblast proliferation, differentiation, and activity, resulting in improved bone mineral density, quality, and strength. We have identified small molecule diarylsulfone sulfonamide der...

journal_title：Journal of medicinal chemistry

authors： Gopalsamy A,Shi M,Stauffer B,Bahat R,Billiard J,Ponce-de-Leon H,Seestaller-Wehr L,Fukayama S,Mangine A,Moran R,Krishnamurthy G,Bodine P

更新日期：2008-12-25 00:00:00

abstract：:Analogues of the anticonvulsant agent milacemide (1,2-(n-pentylamino)acetamide), in which the carboxamide group is changed to a nitrile (2), a carbethoxy group (3), a carboxylic acid (4), a cyanomethyl group (5), and a trifluoromethyl group (6), were synthesized and tested as substrates and inactivators of monoamine o...

journal_title：Journal of medicinal chemistry

authors： Nishimura K,Lu X,Silverman RB

更新日期：1993-02-19 00:00:00

abstract：:The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carbox yli c acid (1) in the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of an (arylamino)methylene moiety into position 9 of the pyridopyrimidine ring. Compound 34, (+)-6(S)-methyl-9-[...

journal_title：Journal of medicinal chemistry

authors： Hermecz I,Horváth A,Mészáros Z,De Vos C,Rodriguez L

更新日期：1984-10-01 00:00:00

abstract：:The synthesis, characterization, inhibitory activity against topoisomerase I, and biological evaluation of a series of oligopeptide-substituted bisindolylmaleimides 7-12 are described. Compounds 7-9, which contain a basic C-terminus function such as (dimethylamino)propyl and bind to DNA with C(50) values of 200, 160, ...

journal_title：Journal of medicinal chemistry

authors： Xie G,Gupta R,Atchison K,Lown JW

更新日期：1996-03-01 00:00:00

abstract：:There is reported the first four members of heteroarotinoids, the names of which are ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b), ethyl (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoate (1c), ethyl (E)-p-[2-(4,4-dimethyl-1-oxothiochroman-6-yl)propenyl]benzoate (1d), and (E)-p-[2-(4,4-dimethy...

journal_title：Journal of medicinal chemistry

authors： Waugh KM,Berlin KD,Ford WT,Holt EM,Carrol JP,Schomber PR,Thompson MD,Schiff LJ

更新日期：1985-01-01 00:00:00

abstract：:In a previously described chimeric peptide, we reported that the multifunctional opioid/neuropeptide FF (NPFF) receptor agonist 0 (BN-9) produced antinociception for 1.5 h after supraspinal administration. Herein, four cyclic disulfide analogs containing l- and/or d-type cysteine at positions 2 and 5 were synthesized....

journal_title：Journal of medicinal chemistry

authors： Zhang M,Xu B,Li N,Liu H,Shi X,Zhang Q,Shi Y,Xu K,Xiao J,Chen D,Zhu H,Sun Y,Zhang T,Zhang R,Fang Q

更新日期：2020-12-24 00:00:00

abstract：:A class of new pyrimidinyl peptidomimetic agents (compounds 1-6) were synthesized, and their in vitro antimalarial activities against Plasmodium falciparum were evaluated. The core structure of the new agents consists of a substituted 5-aminopyrimidone ring and a Michael acceptor side chain methyl 2-hydroxymethyl-but-...

journal_title：Journal of medicinal chemistry

authors： Zhu S,Hudson TH,Kyle DE,Lin AJ

更新日期：2002-08-01 00:00:00

abstract：:A novel series of 3,4-dihydroxychalcones was synthesized to evaluate their effects against 5-lipoxygenase and cyclooxygenase. Almost all compounds exhibited potent inhibitory effects on 5-lipoxygenase with antioxidative effects, and some also inhibited cyclooxygenase. The 2',5'-disubstituted 3,4-dihydroxychalcones wit...

journal_title：Journal of medicinal chemistry

authors： Sogawa S,Nihro Y,Ueda H,Izumi A,Miki T,Matsumoto H,Satoh T

更新日期：1993-11-26 00:00:00

abstract：:Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of he...

journal_title：Journal of medicinal chemistry

authors： Weiss JT,Dawson JC,Fraser C,Rybski W,Torres-Sánchez C,Bradley M,Patton EE,Carragher NO,Unciti-Broceta A

更新日期：2014-06-26 00:00:00

abstract：:In order to expand the structure-activity relationship of tetramic acid molecules with structural similarity to the antibiotic reutericyclin, 22 compounds were synthesized and tested against a panel of clinically relevant bacteria. Key structural changes on the tetramic acid core affected antibacterial activity. Vario...

journal_title：Journal of medicinal chemistry

authors： Yendapally R,Hurdle JG,Carson EI,Lee RB,Lee RE

更新日期：2008-03-13 00:00:00

abstract：:By applying a novel cell- and caspase-based HTS assay, 2-amino-3-cyano-7-(dimethylamino)-4-(3-methoxy-4,5-methylenedioxyphenyl)-4H-chromene (1a) has been identified as a potent apoptosis inducer. Compound 1a was found to induce nuclear fragmentation and PARP cleavage, as well as to arrest cells at the G(2)/M stage and...

journal_title：Journal of medicinal chemistry

authors： Kemnitzer W,Drewe J,Jiang S,Zhang H,Wang Y,Zhao J,Jia S,Herich J,Labreque D,Storer R,Meerovitch K,Bouffard D,Rej R,Denis R,Blais C,Lamothe S,Attardo G,Gourdeau H,Tseng B,Kasibhatla S,Cai SX

更新日期：2004-12-02 00:00:00

abstract：:1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the ...

journal_title：Journal of medicinal chemistry

authors： Batra S,Srivastava P,Roy K,Pandey VC,Bhaduri AP

更新日期：2000-09-07 00:00:00

abstract：:A novel water-soluble paclitaxel prodrug, isotaxel 2, that realizes a higher water-solubility and the formation of paclitaxel through a simple pH-dependent chemical mechanism via the O-N acyl migration was synthesized and showed promising results in water-solubility and kinetics. This prodrug, a 2'-O-benzoyl isoform o...

journal_title：Journal of medicinal chemistry

authors： Hayashi Y,Skwarczynski M,Hamada Y,Sohma Y,Kimura T,Kiso Y

更新日期：2003-08-28 00:00:00

abstract：:In an effort to identify selective ligands for the estrogen receptor subtype ERbeta, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assays in HeLa and SH-SY5Y cells, compounds were characterized as ERbeta-selective agonists. By targeting ERbeta in the brain, these com...

journal_title：Journal of medicinal chemistry

authors： Schopfer U,Schoeffter P,Bischoff SF,Nozulak J,Feuerbach D,Floersheim P

更新日期：2002-03-28 00:00:00

abstract：:Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary b...

journal_title：Journal of medicinal chemistry

authors： Morrell A,Placzek M,Parmley S,Grella B,Antony S,Pommier Y,Cushman M

更新日期：2007-09-06 00:00:00

abstract：:A variety of 2,3-disubstituted 5,7-dimethyl-1,8-naphthyridines was synthesized and tested in saline-loaded rats for their diuretic properties. The 2-amino-3-carbomethoxy and four 2-amino-3-N-alkylcarbamoyl compounds exhibited significant activity as measured by volume output; however, they were generally less potent t...

journal_title：Journal of medicinal chemistry

authors： Hawes EM,Gorecki DK,Gedir RG

更新日期：1977-06-01 00:00:00

abstract：:A variety of nonsteroidal systems can function as ligands for the estrogen receptor (ER), in some cases showing selectivity for one of the two ER subtypes, ER alpha or ER beta. We have prepared a series of heterocycle-based (furans, thiophenes, and pyrroles) ligands for the estrogen receptor and assessed their behavio...

journal_title：Journal of medicinal chemistry

authors： Mortensen DS,Rodriguez AL,Carlson KE,Sun J,Katzenellenbogen BS,Katzenellenbogen JA

更新日期：2001-11-08 00:00:00

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：:Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent p...

journal_title：Journal of medicinal chemistry

authors： Hudkins RL,DeHaven-Hudkins DL,Stubbins JF

更新日期：1991-10-01 00:00:00

abstract：:A conceptionally new 3D molecular descriptor type and methodology are deduced by simple statistical thermodynamic reasoning, based on the free energy change encountered during a transformation of a conformational ensemble of the ligand to an active conformation. The performance of the descriptor was first tested on 37...

journal_title：Journal of medicinal chemistry

authors： Martinek TA,Otvös F,Dervarics M,Tóth G,Fülöp F

更新日期：2005-05-05 00:00:00

abstract：:A series of 1-substituted mitosene analogues of the mitomycin antitumor antibiotics was prepared by total synthesis and screened for activity against P388 leukemia in mice. In general, analogues with moderately good leaving groups (mostly esters) at the 1 position were active, whereas analogues without such substituen...

journal_title：Journal of medicinal chemistry

authors： Hodges JC,Remers WA,Bradner WT

更新日期：1981-10-01 00:00:00

abstract：:Inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a novel and attractive approach to reduce the local levels of the active estrogen 17β-estradiol in patients with estrogen-dependent diseases like breast cancer or endometriosis. With the aim of optimizing the biological profile of 17β-HSD1 inhibitors ...

journal_title：Journal of medicinal chemistry

authors： Marchais-Oberwinkler S,Wetzel M,Ziegler E,Kruchten P,Werth R,Henn C,Hartmann RW,Frotscher M

更新日期：2011-01-27 00:00:00

abstract：:The coordination complex cyclo-tetrakis[bis(1-phenyl-3-methyl-4-benzoylpyrazolon-5-ato++ +)mu-o xotitanium(IV)] has been synthesized and characterized with IR and NMR spectroscopies and X-ray diffraction. The core of this species consists of an eight-membered Ti-mu-oxo ring with alternate short-long Ti-O bond lengths....

journal_title：Journal of medicinal chemistry

authors： Caruso F,Rossi M,Tanski J,Sartori R,Sariego R,Moya S,Diez S,Navarrete E,Cingolani A,Marchetti F,Pettinari C

更新日期：2000-10-05 00:00:00

abstract：:Previously, vibsanin B (ViB) was found to preferentially target HSP90β compared to HSP90α. In this study, multiple experiments, including pull-down assays of biotin-ViB with recombinant HSP90β-NTD, MD, CTD, and full-length HSP90β, molecular docking of ViB and its derivatives to the HSP90 CTD, and a inhibition assay of...

journal_title：Journal of medicinal chemistry

authors： Shao LD,Su J,Ye B,Liu JX,Zuo ZL,Li Y,Wang YY,Xia C,Zhao QS

更新日期：2017-11-09 00:00:00

abstract：:The crystal structure of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in ternary complex with the coenzyme NADP (+) and the potent inhibitor 3,5-dichlorosalicylic acid was determined at a resolution of 1.8 A. The inhibitor is held in place by a network of hydrogen bonding interactions with the active site resid...

journal_title：Journal of medicinal chemistry

authors： Dhagat U,Endo S,Sumii R,Hara A,El-Kabbani O

更新日期：2008-08-14 00:00:00

abstract：:A number of pyridazinone derivatives bearing an arylpiperazinylalkyl chain were synthesized and tested icv in a model of acute nociception induced by thermal stimuli in mice (tail flick). The most interesting and potent compound in this series was 6a, which showed an ED(50) = 3.5 microg, a value about 3-fold higher wi...

journal_title：Journal of medicinal chemistry

authors： Biancalani C,Giovannoni MP,Pieretti S,Cesari N,Graziano A,Vergelli C,Cilibrizzi A,Di Gianuario A,Colucci M,Mangano G,Garrone B,Polenzani L,Dal Piaz V

更新日期：2009-12-10 00:00:00

abstract：:Six new analogues of 1α,25-dihydroxy-19-norvitamin D(3) (3a-4b, 5, and 6) were prepared by a convergent synthesis applying the Wittig-Horner reaction as a key step. The influence of methyl groups at C-22 on their biological activity was examined. It was established that both in vitro and in vivo activity is strongly d...

journal_title：Journal of medicinal chemistry

authors： Flores A,Sicinski RR,Grzywacz P,Thoden JB,Plum LA,Clagett-Dame M,DeLuca HF

更新日期：2012-05-10 00:00:00

abstract：:In only four chemical steps from naturally occurring artemisinin (1), trioxane dimers 6 and 7 were prepared on a multigram scale in overall 32-44% yields. In mice, both isonicotinate N-oxide dimer 6 and isobutyric acid dimer 7 were considerably more antimalarially efficacious than clinically used sodium artesunate (2)...

journal_title：Journal of medicinal chemistry

authors： Posner GH,McRiner AJ,Paik IH,Sur S,Borstnik K,Xie S,Shapiro TA,Alagbala A,Foster B

更新日期：2004-02-26 00:00:00

abstract：:Fragment-based docking was used to select a conformation for virtual screening from a molecular dynamics trajectory of the West Nile virus nonstructural 3 protease. This conformation was chosen from an ensemble of 100 molecular dynamics snapshots because it optimally accommodates benzene, the most common ring in known...

journal_title：Journal of medicinal chemistry

authors： Ekonomiuk D,Su XC,Ozawa K,Bodenreider C,Lim SP,Otting G,Huang D,Caflisch A

更新日期：2009-08-13 00:00:00