Regio- and stereochemical studies on the alpha-carbon oxidation of (S)-nicotine by cytochrome P-450 model systems.

abstract：:The incidence of malignant melanoma is rising faster than that of any other cancer in the United States. Because of its high expression on the surface of melanomas, MC1R has been investigated as a target for selective imaging and therapeutic agents against melanoma. Eight ligands were screened against cell lines engin...

journal_title：Journal of medicinal chemistry

authors： Barkey NM,Tafreshi NK,Josan JS,De Silva CR,Sill KN,Hruby VJ,Gillies RJ,Morse DL,Vagner J

更新日期：2011-12-08 00:00:00

abstract：:Toward improving pharmacokinetics, in vivo efficacy, and selectivity over hERG, structure-activity relationship studies around the central core of antimalarial imidazopyridazines were conducted. This study led to the identification of potent pyrazolopyridines, which showed good in vivo efficacy and pharmacokinetics pr...

journal_title：Journal of medicinal chemistry

authors： Le Manach C,Paquet T,Brunschwig C,Njoroge M,Han Z,Gonzàlez Cabrera D,Bashyam S,Dhinakaran R,Taylor D,Reader J,Botha M,Churchyard A,Lauterbach S,Coetzer TL,Birkholtz LM,Meister S,Winzeler EA,Waterson D,Witty MJ,Wittl

更新日期：2015-11-12 00:00:00

abstract：:Carbamate derivatives of bile acids were synthesized with the aim of systematically exploring the potential for farnesoid X receptor (FXR) modulation endowed with occupancy of the receptor's back door, localized between loops H1-H2 and H4-H5. Since it was previously shown that bile acids bind to FXR by projecting the ...

journal_title：Journal of medicinal chemistry

authors： Pellicciari R,Gioiello A,Costantino G,Sadeghpour BM,Rizzo G,Meyer U,Parks DJ,Entrena-Guadix A,Fiorucci S

更新日期：2006-07-13 00:00:00

abstract：:Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervention at different life-cycle stages of the parasite, including th...

journal_title：Journal of medicinal chemistry

authors： Ressurreição AS,Gonçalves D,Sitoe AR,Albuquerque IS,Gut J,Góis A,Gonçalves LM,Bronze MR,Hanscheid T,Biagini GA,Rosenthal PJ,Prudêncio M,O'Neill P,Mota MM,Lopes F,Moreira R

更新日期：2013-10-10 00:00:00

abstract：:Models for predicting oral drug absorption kinetics were developed by correlating absorption rate constants in humans (K(a)) with computational molecular descriptors. The K(a) values of a set of 22 passively absorbed drugs were derived from human plasma time-concentration profiles using a deconvolution approach. The K...

journal_title：Journal of medicinal chemistry

authors： Linnankoski J,Mäkelä JM,Ranta VP,Urtti A,Yliperttula M

更新日期：2006-06-15 00:00:00

abstract：:The design, synthesis, and biological evaluation of a new class of inhibitors of thymidylate synthase (TS) is described. The molecular design was carried out by a repetitive crystallographic analysis of protein-ligand structures. At the onset of this project, we focused on the folate cofactor binding site of a high-re...

journal_title：Journal of medicinal chemistry

authors： Webber SE,Bleckman TM,Attard J,Deal JG,Kathardekar V,Welsh KM,Webber S,Janson CA,Matthews DA,Smith WW

更新日期：1993-03-19 00:00:00

abstract：:A series of new, structurally simple trichostatin A (TSA)-like straight chain hydroxamates were prepared and evaluated for their ability to inhibit partially purified human histone deacetylase 1 (HDAC-1). Some of these compounds such as 8m, 8n, 12, and 15b exhibited potent HDAC inhibitory activity with low nanomolar I...

journal_title：Journal of medicinal chemistry

authors： Woo SH,Frechette S,Abou Khalil E,Bouchain G,Vaisburg A,Bernstein N,Moradei O,Leit S,Allan M,Fournel M,Trachy-Bourget MC,Li Z,Besterman JM,Delorme D

更新日期：2002-06-20 00:00:00

abstract：:A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM(-1) s(-1)) of the complex compare well with those of s...

journal_title：Journal of medicinal chemistry

authors： Kim HK,Kang MK,Jung KH,Kang SH,Kim YH,Jung JC,Lee GH,Chang Y,Kim TJ

更新日期：2013-10-24 00:00:00

abstract：:From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silic...

journal_title：Journal of medicinal chemistry

authors： Smits RA,de Esch IJ,Zuiderveld OP,Broeker J,Sansuk K,Guaita E,Coruzzi G,Adami M,Haaksma E,Leurs R

更新日期：2008-12-25 00:00:00

abstract：:The optimization of a series of aminooxazoline xanthene inhibitors of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is described. An early lead compound showed robust Aβ lowering activity in a rat pharmacodynamic model, but advancement was precluded by a low therapeutic window to QTc prolongation in cardi...

journal_title：Journal of medicinal chemistry

authors： Epstein O,Bryan MC,Cheng AC,Derakhchan K,Dineen TA,Hickman D,Hua Z,Human JB,Kreiman C,Marx IE,Weiss MM,Wahl RC,Wen PH,Whittington DA,Wood S,Zheng XM,Fremeau RT Jr,White RD,Patel VF

更新日期：2014-12-11 00:00:00

abstract：:Four highly charged, water soluble platinum-acridine bisintercalating agents have been synthesized. Depending on the cis/trans isomerism of the metal and the nature of the acridine side chains, bisintercalation induces/stabilizes the classical Watson-Crick B-form or a non-B-form. Circular dichroism spectra and chemica...

journal_title：Journal of medicinal chemistry

authors： Choudhury JR,Guddneppanavar R,Saluta G,Kucera GL,Bierbach U

更新日期：2008-06-12 00:00:00

abstract：:Novel N,N-disubstituted indol-3-ylglyoxylamides (1-56), bearing different combinations of substituents R 1-R 5, were synthesized and evaluated as ligands of the translocator protein (TSPO), the 18 kDa protein representing the minimal functional unit of the "peripheral-type benzodiazepine receptor" (PBR). Most of the n...

journal_title：Journal of medicinal chemistry

authors： Da Settimo F,Simorini F,Taliani S,La Motta C,Marini AM,Salerno S,Bellandi M,Novellino E,Greco G,Cosimelli B,Da Pozzo E,Costa B,Simola N,Morelli M,Martini C

更新日期：2008-09-25 00:00:00

abstract：:The synthesis of 19 (5-nitro-2,3-dihydro-1H-benzo[e]indol-1-yl)methyl sulfonate prodrugs containing sulfonate leaving groups and 7-substituted electron-withdrawing groups is reported. These were designed to undergo hypoxia-selective metabolism to form potent DNA minor groove-alkylating agents. Analogues 17 and 24, con...

journal_title：Journal of medicinal chemistry

authors： Stevenson RJ,Denny WA,Tercel M,Pruijn FB,Ashoorzadeh A

更新日期：2012-03-22 00:00:00

abstract：:Continuing our search for vitamin D analogues, we explored the modification of the steroidal side chain and inserted a methylene moiety in position C-22 together with either lengthening the side chain or introducing a ring at the terminal end. Our conformational studies confirmed that the presence of a methylene group...

journal_title：Journal of medicinal chemistry

authors： Sibilska-Kaminski IK,Sicinski RR,Plum LA,DeLuca HF

更新日期：2020-07-09 00:00:00

abstract：:The sea anemone peptide APETx2 is a potent and selective blocker of acid-sensing ion channel 3 (ASIC3). APETx2 is analgesic in a variety of rodent pain models, but the lack of knowledge of its pharmacophore and binding site on ASIC3 has impeded development of improved analogues. Here we present a detailed structure-ac...

journal_title：Journal of medicinal chemistry

authors： Jensen JE,Cristofori-Armstrong B,Anangi R,Rosengren KJ,Lau CH,Mobli M,Brust A,Alewood PF,King GF,Rash LD

更新日期：2014-11-13 00:00:00

abstract：:A novel piperidine series of farnesyltransferase (FTase) inhibitors is described. Systematic medicinal chemistry studies starting with the lead compound, discovered from a 5-nitropiperidin-2-one combinatorial library, resulted in a potent series of novel FTase inhibitors. We found that all of four substituents of the ...

journal_title：Journal of medicinal chemistry

authors： Nara S,Tanaka R,Eishima J,Hara M,Takahashi Y,Otaki S,Foglesong RJ,Hughes PF,Turkington S,Kanda Y

更新日期：2003-06-05 00:00:00

abstract：:Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. Utilizing the hydrophobic scaffold of xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antimicrobials. Compoun...

journal_title：Journal of medicinal chemistry

authors： Koh JJ,Lin S,Aung TT,Lim F,Zou H,Bai Y,Li J,Lin H,Pang LM,Koh WL,Salleh SM,Lakshminarayanan R,Zhou L,Qiu S,Pervushin K,Verma C,Tan DT,Cao D,Liu S,Beuerman RW

更新日期：2015-01-22 00:00:00

abstract：:The scaffold concept was applied to systematically determine, analyze, and compare core structures of kinase inhibitors. From publicly available inhibitors of the human kinome, scaffolds and cyclic skeletons were systematically extracted and organized taking activity data, structural relationships, and retrosynthetic ...

journal_title：Journal of medicinal chemistry

authors： Hu Y,Bajorath J

更新日期：2015-01-08 00:00:00

abstract：:A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H 3 receptor inverse agonists. 2-Methyl-3-(4-[[3-(1-pyrrolidinyl)propyl]oxy]phenyl)-5-(trifluoromethyl)-4(3 H)-quinazolinone ( 1) was identified as a promising derivative for further evaluation following optimization of key paramet...

journal_title：Journal of medicinal chemistry

authors： Nagase T,Mizutani T,Ishikawa S,Sekino E,Sasaki T,Fujimura T,Ito S,Mitobe Y,Miyamoto Y,Yoshimoto R,Tanaka T,Ishihara A,Takenaga N,Tokita S,Fukami T,Sato N

更新日期：2008-08-14 00:00:00

abstract：:A new approach to generating information on ligand receptor interactions within the binding pocket of G protein-coupled receptors has been developed, called Biophysical Mapping (BPM). Starting from a stabilized receptor (StaR), minimally engineered for thermostability, additional single mutations are then added at pos...

journal_title：Journal of medicinal chemistry

authors： Zhukov A,Andrews SP,Errey JC,Robertson N,Tehan B,Mason JS,Marshall FH,Weir M,Congreve M

更新日期：2011-07-14 00:00:00

abstract：:The synthesis and testing of potential multisubstrate inhibitors of tyrosine-specific protein kinases are described. One of the substrates, ATP, was mimicked by the known kinase inhibitor 5'-[4-(fluorosulfonyl)benzoyl]adenosine, which was covalently linked via the sulfonyl moiety to tyrosine mimics. The resulting mult...

journal_title：Journal of medicinal chemistry

authors： Kruse CH,Holden KG,Pritchard ML,Feild JA,Rieman DJ,Greig RG,Poste G

更新日期：1988-09-01 00:00:00

abstract：:Translocator protein (18 kDa), known as TSPO, is a recognized biomarker of neuroinflammation. Radioligands with PET accurately quantify TSPO in neuroinflammatory conditions. However, the existence of three human TSPO genotypes that show differential affinity to almost all useful TSPO PET radioligands hampers such stud...

journal_title：Journal of medicinal chemistry

authors： Brouwer C,Jenko K,Zoghbi SS,Innis RB,Pike VW

更新日期：2014-07-24 00:00:00

abstract：:A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obt...

journal_title：Journal of medicinal chemistry

authors： Podlogar BL,Leo GC,McDonnell PA,Loughney DA,Caldwell GW,Barrett JF

更新日期：1997-10-10 00:00:00

abstract：:Nicotine binds to nicotinic acetylcholine receptors (nAChR), which can exist as many different subtypes. The α4β2 nAChR is the most prevalent subtype in the brain and possesses the most evidence linking it to nicotine seeking behavior. Herein we report the use of mixture based combinatorial libraries for the rapid dis...

journal_title：Journal of medicinal chemistry

authors： Wu J,Zhang Y,Maida LE,Santos RG,Welmaker GS,LaVoi TM,Nefzi A,Yu Y,Houghten RA,Toll L,Giulianotti MA

更新日期：2013-12-27 00:00:00

abstract：:The synthesis of several 8-carboxy-6-sulfamyldibenz[b,f][1,4]oxazepines and -thiazepines is described. The results of diuretic screening lend support to the thesis that activity is strongly dependent on the conformational mobility of 4-substituents in the 3-amino-5-sulfamylbenzoic acids. ...

journal_title：Journal of medicinal chemistry

authors： Allen RC,Reitano PA,Urbach H

更新日期：1978-08-01 00:00:00

abstract：:The preparation and testing of the two racemic diastereoisomers and the four optically active enantiomers of the title compound in in vitro and in vivo models for determining potential antipsychotic activity are described. Both racemic diastereoisomers and two of the four chiral enantiomers are potent and long-acting ...

journal_title：Journal of medicinal chemistry

authors： Welch WM,Ewing FE,Harbert CA,Weissman A,Koe BK

更新日期：1980-08-01 00:00:00

abstract：:The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8- amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted th...

journal_title：Journal of medicinal chemistry

authors： Stjernlöf P,Gullme M,Elebring T,Andersson B,Wikström H,Lagerquist S,Svensson K,Ekman A,Carlsson A,Sundell S

更新日期：1993-07-23 00:00:00

abstract：:Alpha-galactoglycosphingolipids (alpha-GalGSLs) are unique immunostimulatory glycosphingolipids from marine sponges. Analysis of the glycosphingolipid composition of the marine sponge Axinella damicornis revealed the presence of a new alpha-GalGSL, damicoside (3a), which is the first alpha-GalGSL with a glycosylated g...

journal_title：Journal of medicinal chemistry

authors： Costantino V,D'Esposito M,Fattorusso E,Mangoni A,Basilico N,Parapini S,Taramelli D

更新日期：2005-11-17 00:00:00

abstract：:Long chain fatty acid elongase 6 (ELOVL6) catalyzes the elongation of long chain fatty acyl-CoAs and is a potential target for the treatment of metabolic disorders. The ultrahigh throughput screen of our corporate chemical collections resulted in the identification of a novel 3-sulfonyl-8-azabicyclo[3.2.1]octane class...

journal_title：Journal of medicinal chemistry

authors： Nagase T,Takahashi T,Sasaki T,Nagumo A,Shimamura K,Miyamoto Y,Kitazawa H,Kanesaka M,Yoshimoto R,Aragane K,Tokita S,Sato N

更新日期：2009-07-23 00:00:00

abstract：:Mining of an in-house collection of angiotensin II type 1 receptor antagonists to identify compounds with activity at the peroxisome proliferator-activated receptor-γ (PPARγ) revealed a new series of imidazo[4,5-b]pyridines 2 possessing activity at these two receptors. Early availability of the crystal structure of th...

journal_title：Journal of medicinal chemistry

authors： Casimiro-Garcia A,Filzen GF,Flynn D,Bigge CF,Chen J,Davis JA,Dudley DA,Edmunds JJ,Esmaeil N,Geyer A,Heemstra RJ,Jalaie M,Ohren JF,Ostroski R,Ellis T,Schaum RP,Stoner C

更新日期：2011-06-23 00:00:00