Hydrochalarones: a novel endohedral metallofullerene platform for enhancing magnetic resonance imaging contrast.

abstract：:Selective inhibition of the isoforms of nitric oxide synthase (NOS) in pathologically elevated synthesis of nitric oxide has great therapeutic potential. We previously reported nitroarginine-containing dipeptide amides and some peptidomimetic analogues as potent and selective inhibitors of neuronal NOS (nNOS). Here we...

journal_title：Journal of medicinal chemistry

authors： Gómez-Vidal JA,Martásek P,Roman LJ,Silverman RB

更新日期：2004-01-29 00:00:00

abstract：:Previous SAR studies (Part 1: Mai, A.; et al. J. Med. Chem. 2003, 46, 512-524) performed on some portions (pyrrole-C4, pyrrole-N1, and hydroxamate group) of 3-(4-benzoyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide (1a) highlighted its 4-phenylacetyl (1b) and 4-cynnamoyl (1c) analogues as more potent compounds in ...

journal_title：Journal of medicinal chemistry

authors： Mai A,Massa S,Cerbara I,Valente S,Ragno R,Bottoni P,Scatena R,Loidl P,Brosch G

更新日期：2004-02-26 00:00:00

abstract：:New potent and selective KISS1R agonists were designed using a combination of rational chemical modifications of the endogenous neuropeptide kisspeptin 10 (KP10). Improved resistance to degradation and presumably reduced renal clearance were obtained by introducing a 1,4-disubstituted 1,2,3-triazole as a proteolysis-r...

journal_title：Journal of medicinal chemistry

authors： Beltramo M,Robert V,Galibert M,Madinier JB,Marceau P,Dardente H,Decourt C,De Roux N,Lomet D,Delmas AF,Caraty A,Aucagne V

更新日期：2015-04-23 00:00:00

abstract：:Fluorescence spectrometry data by Tyulmenkov and Klinge (Arch. Biochem. Biophys. 2000, 381, 135-142) suggest the presence of a second binding site in both subtypes ER alpha and ER beta of the estrogen receptor (ER). A cavity previously described as a solvent channel was located in close proximity to the steroid bindin...

journal_title：Journal of medicinal chemistry

authors： van Hoorn WP

更新日期：2002-01-31 00:00:00

abstract：:On the basis of the remarkable biological similarities between hycanthone and oxamniquine and as a sequel to our finding that some esters of hycanthone are active against hycanthone-resistant schistosomes, we prepared oxamniquine acetate, oxamniquine N-methylcarbamate, and four substituted phenylsulfonohydrazones of o...

journal_title：Journal of medicinal chemistry

authors： el-Hamouly W,Pica-Mattoccia L,Cioli D,Schwartz HM,Archer S

更新日期：1988-08-01 00:00:00

abstract：:A series of novel thiazolo[4,5- d]pyrimidin-7(6 H)-ones (3aa-3eq) were designed, synthesized, and evaluated as the type I positive allosteric modulators of human α7 nAChR expressed in Xenopus ooctyes by a two-electrode voltage clamp. The structure-activity relationship analysis identified the compound 3ea as a potent ...

journal_title：Journal of medicinal chemistry

authors： Li Y,Sun L,Yang T,Jiao W,Tang J,Huang X,Huang Z,Meng Y,Luo L,Wang X,Bian X,Zhang F,Wang K,Sun Q

更新日期：2019-01-10 00:00:00

abstract：:The first nonpeptidic, noncovalent inhibitors of the cysteine protease cathepsin S (CatS) are described. Electronic database searching using the program DOCK generated a screening set of potential CatS inhibitors from which two lead structures were identified as promising starting points for a drug discovery effort. L...

journal_title：Journal of medicinal chemistry

authors： Thurmond RL,Beavers MP,Cai H,Meduna SP,Gustin DJ,Sun S,Almond HJ,Karlsson L,Edwards JP

更新日期：2004-09-23 00:00:00

abstract：:Nalfurafine, a κ-selective opioid receptor agonist, unexpectedly showed a selective antagonist activity toward the orexin 1 receptor (OX1R) (Ki = 250 nM). Modification of the 17-amino side chain of the opioid ligand to an arylsulfonyl group and the 6-furan acrylamide chain to 2-pyridyl acrylamide led to compound 71 wi...

journal_title：Journal of medicinal chemistry

authors： Nagase H,Yamamoto N,Yata M,Ohrui S,Okada T,Saitoh T,Kutsumura N,Nagumo Y,Irukayama-Tomobe Y,Ishikawa Y,Ogawa Y,Hirayama S,Kuroda D,Watanabe Y,Gouda H,Yanagisawa M

更新日期：2017-02-09 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：:We recently described a number of inhibitors of P450(17 alpha), the key enzyme of androgen biosynthesis. Here, we report the synthesis and activity of novel 17-imidazolyl, pyrazolyl, and isoxazolyl androstene derivatives as potential agents for the treatment of prostatic cancer. A number of 17-(4'-Imidazolyl) derivati...

journal_title：Journal of medicinal chemistry

authors： Ling YZ,Li JS,Liu Y,Kato K,Klus GT,Brodie A

更新日期：1997-09-26 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：:N-(5,5-Diacetoxypent-1-yl)doxorubicin (1b) is an intensely cytotoxic doxorubicin analogue that retains full potency against tumor cells that express elevated levels of P-glycoprotein and are resistant to doxorubicin. 1b was designed to be hydrolyzed in the presence of carboxylate esterases to N-(5-oxypent-1-yl)doxorub...

journal_title：Journal of medicinal chemistry

authors： Farquhar D,Cherif A,Bakina E,Nelson JA

更新日期：1998-03-12 00:00:00

abstract：:Three [5-t-BuPro(7)]oxytocin analogues were synthesized by substituting (2S,5R)-5-tert-butylproline for proline in oxytocin, [Mpa(1)]oxytocin, and [dPen(1)]oxytocin. Relative to oxytocin, [5-t-BuPro(7)]oxytocin and [Mpa(1),5-t-BuPro(7)]oxytocin exhibited strongly reduced binding affinity to the receptor; however, both...

journal_title：Journal of medicinal chemistry

authors： Bélec L,Slaninova J,Lubell WD

更新日期：2000-04-20 00:00:00

abstract：:The perceived and actual burden of false positives in high-throughput screening has received considerable attention; however, few studies exist on the contributions of distinct mechanisms of nonspecific effects like chemical reactivity, assay signal interference, and colloidal aggregation. Here, we analyze the outcome...

journal_title：Journal of medicinal chemistry

authors： Jadhav A,Ferreira RS,Klumpp C,Mott BT,Austin CP,Inglese J,Thomas CJ,Maloney DJ,Shoichet BK,Simeonov A

更新日期：2010-01-14 00:00:00

abstract：:The structural features of a new class of non-nucleoside HIV-1 reverse transcriptase inhibitors (3) are presented. Comparison of the structural and electronic properties with those of TIBO (1) and Nevirapine (2) yields a common three-dimensional model. This model permits the improvement of the lead compound 3 by chemi...

journal_title：Journal of medicinal chemistry

authors： Schäfer W,Friebe WG,Leinert H,Mertens A,Poll T,von der Saal W,Zilch H,Nuber B,Ziegler ML

更新日期：1993-03-19 00:00:00

abstract：:We present Fleksy, a new approach to consider both ligand and receptor flexibility in small molecule docking. Pivotal to our method is the use of a receptor ensemble to describe protein flexibility. To construct these ensembles, we use a backbone-dependent rotamer library and implement the concept of interaction sampl...

journal_title：Journal of medicinal chemistry

authors： Nabuurs SB,Wagener M,de Vlieg J

更新日期：2007-12-27 00:00:00

abstract：:The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]q...

journal_title：Journal of medicinal chemistry

authors： Wadsworth HJ,Jenkins SM,Orlek BS,Cassidy F,Clark MS,Brown F,Riley GJ,Graves D,Hawkins J,Naylor CB

更新日期：1992-04-03 00:00:00

abstract：:We describe the synthesis of gramine derivatives and their pharmacological evaluation as multipotent drugs for the treatment of Alzheimer's disease. An innovative multitarget approach is presented, targeting both voltage-gated Ca(2+) channels, classically studied for neurodegenerative diseases, and Ser/Thr phosphatase...

journal_title：Journal of medicinal chemistry

authors： Lajarín-Cuesta R,Nanclares C,Arranz-Tagarro JA,González-Lafuente L,Arribas RL,Araujo de Brito M,Gandía L,de Los Ríos C

更新日期：2016-07-14 00:00:00

abstract：:The imidazoquinoline (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine [(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and ox...

journal_title：Journal of medicinal chemistry

authors： Heier RF,Dolak LA,Duncan JN,Hyslop DK,Lipton MF,Martin IJ,Mauragis MA,Piercey MF,Nichols NF,Schreur PJ,Smith MW,Moon MW

更新日期：1997-02-28 00:00:00

abstract：:The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a no...

journal_title：Journal of medicinal chemistry

authors： Kerwin JF Jr,Wagenaar F,Kopecka H,Lin CW,Miller T,Witte D,Stashko M,Nadzan AM

更新日期：1991-12-01 00:00:00

abstract：:In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic...

journal_title：Journal of medicinal chemistry

authors： Talamas FX,Abbot SC,Anand S,Brameld KA,Carter DS,Chen J,Davis D,de Vicente J,Fung AD,Gong L,Harris SF,Inbar P,Labadie SS,Lee EK,Lemoine R,Le Pogam S,Leveque V,Li J,McIntosh J,Nájera I,Park J,Railkar A,Rajyagur

更新日期：2014-03-13 00:00:00

abstract：:Various 2',3'-dideoxy-L-cytidine,2',3'-dideoxy-L-uridine, and 3'-deoxy-L-thymidine analogues have been synthesized and evaluated in vitro as potential anti-HIV and anti-HBV agents. Coupling of 1-O-acetyl-5-O-(tert-butyldimethylsilyl)-2,3-dideoxy-L-ribofuranose (1) with silylated derivatives of 5-fluorocytosine, cytosi...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Luo MZ,Liu MC,Pai SB,Dutschman GE,Cheng YC

更新日期：1994-03-18 00:00:00

abstract：:Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A(1) and A(3) adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5'-uronamides consistently lost affinity at A(1)/A(2A)ARs and gained at A(3)AR. Among 9-riboside deri...

journal_title：Journal of medicinal chemistry

authors： Jacobson KA,Gao ZG,Tchilibon S,Duong HT,Joshi BV,Sonin D,Liang BT

更新日期：2005-12-29 00:00:00

abstract：:A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thi...

journal_title：Journal of medicinal chemistry

authors： Kim YZ,Lim JC,Yeo JH,Bang CS,Kim WS,Kim SS,Woo YM,Yang DH,Oh H,Nahm K

更新日期：1994-10-28 00:00:00

abstract：:Structure-activity relationship studies of substituted arylsulfoanilides as antiproliferatives, which are mediated by the partial depletion of intracellular Ca(2+) stores, resulted in the identification of compounds with micromolar activity against lung cancer cells in a growth inhibition assay. Incorporating the subs...

journal_title：Journal of medicinal chemistry

authors： Natarajan A,Guo Y,Harbinski F,Fan YH,Chen H,Luus L,Diercks J,Aktas H,Chorev M,Halperin JA

更新日期：2004-10-07 00:00:00

abstract：:Pharmacophore, two-dimensional (2D), and three-dimensional (3D) quantitative structure-activity relationship (QSAR) modeling techniques were used to develop and test models capable of rationalizing and predicting human UDP-glucuronosyltransferase 1A4 (UGT1A4) substrate selectivity and binding affinity (as K(m,app)). T...

journal_title：Journal of medicinal chemistry

authors： Smith PA,Sorich MJ,McKinnon RA,Miners JO

更新日期：2003-04-24 00:00:00

abstract：:With a view to identify novel and biocompatible neuroprotectants, we designed nucleoside 5'-thiophosphate analogues, 6-11. We identified 2-SMe-ADP(α-S), 7A, as a most promising neuroprotectant. 7A reduced ROS production in PC12 cells under oxidizing conditions, IC50 of 0.08 vs 21 μM for ADP. Furthermore, 7A rescued pr...

journal_title：Journal of medicinal chemistry

authors： Azran S,Danino O,Förster D,Kenigsberg S,Reiser G,Dixit M,Singh V,Major DT,Fischer B

更新日期：2015-11-12 00:00:00

abstract：:Members of the JAK family of nonreceptor tyrosine kinases play a critical role in the growth and progression of many cancers and in inflammatory diseases. JAK2 has emerged as a leading therapeutic target for oncology, providing a rationale for the development of a selective JAK2 inhibitor. A program to optimize select...

journal_title：Journal of medicinal chemistry

authors： Dugan BJ,Gingrich DE,Mesaros EF,Milkiewicz KL,Curry MA,Zulli AL,Dobrzanski P,Serdikoff C,Jan M,Angeles TS,Albom MS,Mason JL,Aimone LD,Meyer SL,Huang Z,Wells-Knecht KJ,Ator MA,Ruggeri BA,Dorsey BD

更新日期：2012-06-14 00:00:00

abstract：:We report herein the discovery of the human immunodeficiency virus type-1 (HIV-1) integrase inhibitors dolutegravir (S/GSK1349572) (3) and S/GSK1265744 (4). These drugs stem from a series of carbamoyl pyridone analogues designed using a two-metal chelation model of the integrase catalytic active site. Structure-activi...

journal_title：Journal of medicinal chemistry

authors： Johns BA,Kawasuji T,Weatherhead JG,Taishi T,Temelkoff DP,Yoshida H,Akiyama T,Taoda Y,Murai H,Kiyama R,Fuji M,Tanimoto N,Jeffrey J,Foster SA,Yoshinaga T,Seki T,Kobayashi M,Sato A,Johnson MN,Garvey EP,Fujiwara T

更新日期：2013-07-25 00:00:00

abstract：:Seven 3-alkyl-4-aryl-1,5-dihydro-2H-pyrrol-2-ones were prepared as potential inhibitors of cardiac cAMP phosphodiesterase (PDE). The design of these compounds made use of rolipram, a known inhibitor of the brain cAMP PDE isozyme, as a lead structure and was guided by a model which describes the features required for p...

journal_title：Journal of medicinal chemistry

authors： Lampe JW,Chou YL,Hanna RG,Di Meo SV,Erhardt PW,Hagedorn AA 3rd,Ingebretsen WR,Cantor E

更新日期：1993-04-16 00:00:00