Synthesis, chemistry, and antineoplastic activity of alpha-halopyridinium salts: potential pyridone prodrugs of acylated vinylogous carbinolamine tumor inhibitors.

abstract：:Liver-fatty acid binding protein (L-FABP) is found in high levels in enterocytes and is involved in the cytosolic solubilization of fatty acids during fat absorption. In the current studies, the interaction of L-FABP with a range of lipophilic drugs has been evaluated to explore the potential for L-FABP to provide an ...

journal_title：Journal of medicinal chemistry

authors： Chuang S,Velkov T,Horne J,Porter CJ,Scanlon MJ

更新日期：2008-07-10 00:00:00

abstract：:New carboxyalkyl compounds derived from Phe-Leu and Phe-Ala were synthesized and checked as inhibitors of "enkephalinase", a metalloendopeptidase cleaving the Gly3-Phe4 bond of enkephalins from mouse striatal membranes. Differential recognition of both brain enkephalinase and angiotensin-converting enzyme (ACE) cataly...

journal_title：Journal of medicinal chemistry

authors： Fournié-Zaluski MC,Chaillet P,Soroca-Lucas E,Marçais-Collado H,Costentin J,Roques BP

更新日期：1983-01-01 00:00:00

abstract：:The cancer research community has begun to address the in silico modeling approaches, such as quantitative structure-activity relationships (QSAR), as an important alternative tool for screening potential anticancer drugs. With the compilation of a large dataset of nucleosides synthesized in our laboratories, or elsew...

journal_title：Journal of medicinal chemistry

authors： Helguera AM,Rodríguez-Borges JE,García-Mera X,Fernández F,Cordeiro MN

更新日期：2007-04-05 00:00:00

abstract：:The antimicrobial and cytotoxic properties of a series of 9,10-dihydrophenanthrenes structurally related to juncusol (1a), a postulated phytoalexin with confirmed cytotoxic properties, are detailed. Two simple 9,10-dihydrophenanthrenes, 2,7-dihydroxy-3,8-dimethyl-9,10-dihydrophenanthrene (2h, desvinyljuncusol) and 2-h...

journal_title：Journal of medicinal chemistry

authors： Boger DL,Mitscher LA,Mullican MD,Drake SD,Kitos P

更新日期：1985-10-01 00:00:00

abstract：:Treatment of a methanolic solution of 4-hydroxy-1-beta-D-ribofuranosyl-2-pyridinone (3-deazauridine, 1) with diazomethane gave 2-methoxy-1-beta-D-ribofuranosyl-4-pyridinone (2) and 4-methoxy-1-beta-D-ribofuranosyl-2-pyridinone (3a) in an approximate ratio of 1:2. Analogous treatment of 1 with diazomethane in the prese...

journal_title：Journal of medicinal chemistry

authors： Robins MJ,Lee AS

更新日期：1975-11-01 00:00:00

abstract：:A series of renin inhibitors were designed to examine the topography of the contiguous binding pocket of renin that is normally occupied by the P1 and P3 side chains. Molecular modeling suggested that extending the P1 hydrophobic side chain into the adjacent hydrophobic S3 enzyme pocket was feasible. Novel transition ...

journal_title：Journal of medicinal chemistry

authors： Plummer MS,Shahripour A,Kaltenbronn JS,Lunney EA,Steinbaugh BA,Hamby JM,Hamilton HW,Sawyer TK,Humblet C,Doherty AM

更新日期：1995-07-21 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 series of novel benzoheterocyclic [(methoxyphenyl)amino]oxoalkanoic acid esters has been prepared. These compounds were tested as inhibitors of rat polymorphonuclear leukocyte 5-lipoxgenase (LO) in vitro and as inhibitors of leukotriene D4 (LTD4) and ovalbumin (OA) induced bronchospasm in the guinea pig (GP) in vivo...

journal_title：Journal of medicinal chemistry

authors： Musser JH,Kubrak DM,Chang J,DiZio SM,Hite M,Hand JM,Lewis AJ

更新日期：1987-02-01 00:00:00

abstract：:Recently, FXIIa was highlighted as an original attractive target for the development of new anticoagulant drugs with low rates of therapy-related hemorrhages. In this work, we describe the development of a new series of 3-carboxamide-coumarins that are the first potent and selective nonpeptidic inhibitors of FXIIa. ...

journal_title：Journal of medicinal chemistry

authors： Robert S,Bertolla C,Masereel B,Dogné JM,Pochet L

更新日期：2008-06-12 00:00:00

abstract：:In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma w...

journal_title：Journal of medicinal chemistry

authors： Liu LQ,Hong PX,Song XH,Zhou CC,Ling R,Kang Y,Qi QR,Yang J

更新日期：2020-07-23 00:00:00

abstract：:Naturally occurring N(ω)-hydroxy-l-arginine (NOHA, 1) is the best substrate of NO synthases (NOS). The development of stable and bioavailable prodrugs would provide a pharmacologically valuable strategy for the treatment of cardiovascular diseases that are associated with endothelial dysfunction. To improve NOHAs drug...

journal_title：Journal of medicinal chemistry

authors： Litty FA,Gudd J,Girreser U,Clement B,Schade D

更新日期：2016-09-08 00:00:00

abstract：:Cancer cells generally generate higher amounts of reactive oxygen species than normal cells. On the basis of this difference, prodrugs have been developed (e.g., hydroxyferrocifen), which remain inactive in normal cells, but become activated in cancer cells. In this work we describe novel aminoferrocene-based prodrugs...

journal_title：Journal of medicinal chemistry

authors： Hagen H,Marzenell P,Jentzsch E,Wenz F,Veldwijk MR,Mokhir A

更新日期：2012-01-26 00:00:00

abstract：:3,4-Dihydro-2(1H)-quinolones, evolved from 2-carboxy-1,2,3,4,- tetrahydroquinolines and 3-carboxy-4-hydroxy-2(1H)-quinolones, have been synthesized and evaluated in vitro for antagonist activity at the glycine site on the NMDA receptor and for AMPA [(RS)-alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid] antag...

journal_title：Journal of medicinal chemistry

authors： Carling RW,Leeson PD,Moore KW,Smith JD,Moyes CR,Mawer IM,Thomas S,Chan T,Baker R,Foster AC

更新日期：1993-10-29 00:00:00

abstract：:A series of novel, disulfide-constrained human beta-melanocyte stimulating hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food in...

journal_title：Journal of medicinal chemistry

authors： Mayer JP,Hsiung HM,Flora DB,Edwards P,Smith DP,Zhang XY,Gadski RA,Heiman ML,Hertel JL,Emmerson PJ,Husain S,O'brien TP,Kahl SD,Smiley DL,Zhang L,Dimarchi RD,Yan LZ

更新日期：2005-05-05 00:00:00

abstract：:Every week, articles disclosing new antifungal leads reported as promising starting points for optimization projects are published. In many cases, the mechanism that accounts for their antifungal activity has not been fully elucidated. More significantly, the detrimental impact that could result from certain embedded ...

journal_title：Journal of medicinal chemistry

authors： Pouliot M,Jeanmart S

更新日期：2016-01-28 00:00:00

abstract：:On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenocepto...

journal_title：Journal of medicinal chemistry

authors： Macchia B,Balsamo A,Lapucci A,Martinelli A,Macchia F,Breschi MC,Fantoni B,Martinotti E

更新日期：1985-02-01 00:00:00

abstract：:Synthesis of four arabinofuranosyl derivatives of the antitumor agent 3-deazaguanine is described. By the use of 13C and 1H nuclear magnetic resonance spectroscopy, the structures of these nucleosides were established to be alpha and beta pairs of N-7 and N-9 arabinosides of 3-deazaguanine. In contrast to 3-deazaguani...

journal_title：Journal of medicinal chemistry

authors： Poonian MS,McComas WW,Kramer MJ

更新日期：1979-08-01 00:00:00

abstract：:Since the discovery of the serotonin 4 receptor (5-HT(4)R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazol...

journal_title：Journal of medicinal chemistry

authors： Furlotti G,Alisi MA,Apicella C,Capezzone de Joannon A,Cazzolla N,Costi R,Cuzzucoli Crucitti G,Garrone B,Iacovo A,Magarò G,Mangano G,Miele G,Ombrato R,Pescatori L,Polenzani L,Rosi F,Vitiello M,Di Santo R

更新日期：2012-11-26 00:00:00

abstract：:Thymidine phosphorylase plays an important role in angiogenesis, which is an attractive target for therapy of cancer and other diseases. In our continuous effort to develop novel inhibitors of thymidine phosphorylase, we have discovered that 6-halouracils substituted at position C5 by certain hydrophobic groups exhibi...

journal_title：Journal of medicinal chemistry

authors： Nencka R,Votruba I,Hrebabecký H,Jansa P,Tloust'ová E,Horská K,Masojídková M,Holý A

更新日期：2007-11-29 00:00:00

abstract：:In an intensive study of South American medicinal plants, herein we report the isolation, structure elucidation and biological activity of fourteen new and five known dihydro-beta-agarofuran sesquiterpenes from the leaves of Zinowiewia costaricensis (1-19). Their structures were determined by means of (1)H and (13)C N...

journal_title：Journal of medicinal chemistry

authors： Muñoz-Martínez F,Mendoza CR,Bazzocchi IL,Castanys S,Jiménez IA,Gamarro F

更新日期：2005-06-30 00:00:00

abstract：:In the framework of the design and development of TGR5 agonists, we reported that the introduction of a C(23)(S)-methyl group in the side chain of bile acids such as chenodeoxycholic acid (CDCA) and 6-ethylchenodeoxycholic acid (6-ECDCA, INT-747) affords selectivity for TGR5. Herein we report further lead optimization...

journal_title：Journal of medicinal chemistry

authors： Pellicciari R,Gioiello A,Macchiarulo A,Thomas C,Rosatelli E,Natalini B,Sardella R,Pruzanski M,Roda A,Pastorini E,Schoonjans K,Auwerx J

更新日期：2009-12-24 00:00:00

abstract：:Starting with 2,6-dichlorophenyl isothiocyanate, 1-(2-aminoethyl)-2-cyano-3-(2,6-dichlorophenyl)guanidine (2) was prepared in three steps. In contrast to the corresponding thiourea 1, this compound was essentially inactive as an antihypertensive agent. ...

journal_title：Journal of medicinal chemistry

authors： Tilley JW,Ramuz H,Hefti F,Gerold M

更新日期：1980-12-01 00:00:00

abstract：:Polymeric nanoparticles (PNPs) may efficiently deliver in vivo therapeutics to tumors when conjugated to specific targeting agents. Gint4.T aptamer specifically recognizes platelet-derived growth factor receptor β and can cross the blood-brain barrier (BBB). We synthesized Gint4.T-conjugated PNPs able of high uptake i...

journal_title：Journal of medicinal chemistry

authors： Monaco I,Camorani S,Colecchia D,Locatelli E,Calandro P,Oudin A,Niclou S,Arra C,Chiariello M,Cerchia L,Comes Franchini M

更新日期：2017-05-25 00:00:00

abstract：:Dysregulation of translation initiation factor 4E (eIF4E) activity occurs in various cancers. Mitogen-activated protein kinase (MAPK) interacting kinases 1 and 2 (MNK1 and MNK2) play a fundamental role in activation of eIF4E. Structure-activity relationship-driven expansion of a fragment hit led to discovery of dual M...

journal_title：Journal of medicinal chemistry

authors： Kwiatkowski J,Liu B,Pang S,Ahmad NHB,Wang G,Poulsen A,Yang H,Poh YR,Tee DHY,Ong E,Retna P,Dinie N,Kwek P,Wee JLK,Manoharan V,Low CB,Seah PG,Pendharkar V,Sangthongpitag K,Joy J,Baburajendran N,Jansson AE,Nacro

更新日期：2020-01-23 00:00:00

abstract：:Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems. There is now an emerging body of evidence to suggest that the blockade of S. aureus virulence gene expression significantly attenuates infection in ...

journal_title：Journal of medicinal chemistry

authors： Gordon CP,Williams P,Chan WC

更新日期：2013-02-28 00:00:00

abstract：:Two new long-acting hydrazone derivatives of 14-hydroxydihydromorphinones have been synthesized, oxymorphazone and naltrexazone. Both derivatives show high affinity for opiate binding sites in vitro, similar to naloxazone, the hydrazone analogue of naloxone. Sodium and manganese shifts imply that naltrexazone, like na...

journal_title：Journal of medicinal chemistry

authors： Pasternak GW,Hahn EF

更新日期：1980-06-01 00:00:00

abstract：:By use of the effectively cleaved beta-secretase (BACE) substrate (1), incorporation of a statine in P(1) resulted in a weak inhibitor 13 of the enzyme. Further substitution of P(1)'-Asp by P(1)'-Val in 13 results in a potent inhibitor 22 of BACE. Removal of the P(10)-P(5) residues on the N-terminal part of inhibitor ...

journal_title：Journal of medicinal chemistry

authors： Tung JS,Davis DL,Anderson JP,Walker DE,Mamo S,Jewett N,Hom RK,Sinha S,Thorsett ED,John V

更新日期：2002-01-17 00:00:00

abstract：:Five series of pyrrolo[3,2-d]pyrimidines were synthesized and evaluated with respect to potency and selectivity toward multidrug resistance-associated protein 1 (MRP1, ABCC1). This transport protein is a major target to overcome multidrug resistance in cancer patients. We investigated differently substituted pyrrolopy...

journal_title：Journal of medicinal chemistry

authors： Schmitt SM,Stefan K,Wiese M

更新日期：2016-04-14 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：:We report the activities of 62 bisphosphonates as inhibitors of the Leishmania major mevalonate/isoprene biosynthesis pathway enzyme, farnesyl pyrophosphate synthase. The compounds investigated exhibit activities (IC(50) values) ranging from approximately 100 nM to approximately 80 microM (corresponding to K(i) values...

journal_title：Journal of medicinal chemistry

authors： Sanders JM,Gómez AO,Mao J,Meints GA,Van Brussel EM,Burzynska A,Kafarski P,González-Pacanowska D,Oldfield E

更新日期：2003-11-20 00:00:00