Bis-pyranobenzoquinones as a new family of reversal agents of the multidrug resistance phenotype mediated by P-glycoprotein in mammalian cells and the protozoan parasite Leishmania.

abstract：:Intervention in integrin-mediated cell adhesion and integrin signaling pathways is an ongoing area of research in medicinal chemistry and drug development. One key element in integrin-ligand interaction is the coordination of the bivalent cation at the metal ion-dependent adhesion site (MIDAS) by a carboxylic acid fun...

journal_title：Journal of medicinal chemistry

authors： Bollinger M,Manzenrieder F,Kolb R,Bochen A,Neubauer S,Marinelli L,Limongelli V,Novellino E,Moessmer G,Pell R,Lindner W,Fanous J,Hoffman A,Kessler H

更新日期：2012-01-26 00:00:00

abstract：:Identification of a selective inhibitor for a particular protein kinase without inhibition of other kinases is critical for use as a biological tool or drug. However, this is very difficult because there are hundreds of homologous kinases and their kinase domains including the ATP binding pocket have a common folding ...

journal_title：Journal of medicinal chemistry

authors： Honma T,Yoshizumi T,Hashimoto N,Hayashi K,Kawanishi N,Fukasawa K,Takaki T,Ikeura C,Ikuta M,Suzuki-Takahashi I,Hayama T,Nishimura S,Morishima H

更新日期：2001-12-20 00:00:00

abstract：:In the course of studies on tranquilizers, new non-benzodiazepine-like compounds were synthesized. These are 1-(3,4,5-trimethoxyphenoxy)-3-[4-(2-methoxyphenyl)piperazinyl]prop an-2-ol (INN: enciprazine) and derivatives thereof which were screened pharmacologically in order to evaluate their central nervous system acti...

journal_title：Journal of medicinal chemistry

authors： Engel J,Fleischhauer I,Jakovlev V,Kleemann A,Kutscher B,Nickel B,Rauer H,Werner U,Szelenyi I,Johanson CE

更新日期：1990-11-01 00:00:00

abstract：:In the present paper, we described the design, synthesis, SAR, and biological profile of a novel spirocyclic sulfone series of γ-secretase inhibitors (GSIs) related to MRK-560. We utilized an additional spirocyclic ring system to stabilize the active chair conformation of the parent γ-secretase inhibitors. The resulti...

journal_title：Journal of medicinal chemistry

authors： Zhao Z,Pissarnitski DA,Josien HB,Wu WL,Xu R,Li H,Clader JW,Burnett DA,Terracina G,Hyde L,Lee J,Song L,Zhang L,Parker EM

更新日期：2015-11-25 00:00:00

abstract：:A series of next in class small-molecule hepatitis C virus (HCV) NS5A inhibitors with picomolar potency containing 2-pyrrolidin-2-yl-5-{4-[4-(2-pyrrolidin-2-yl-1H-imidazol-5-yl)buta-1,3-diynyl]phenyl}-1H-imidazole cores was designed based on the SAR studies available for the reported NS5A inhibitors. Compound 13a (AV4...

journal_title：Journal of medicinal chemistry

authors： Ivachtchenko AV,Mitkin OD,Yamanushkin PM,Kuznetsova IV,Bulanova EA,Shevkun NA,Koryakova AG,Karapetian RN,Bichko VV,Trifelenkov AS,Kravchenko DV,Vostokova NV,Veselov MS,Chufarova NV,Ivanenkov YA

更新日期：2014-09-25 00:00:00

abstract：:Bromodomains (BD) are readers of lysine acetylation marks present in numerous proteins associated with chromatin. Here we describe a dual inhibitor of the bromodomain and PHD finger (BRPF) family member BRPF2 and the TATA box binding protein-associated factors TAF1 and TAF1L. These proteins are found in large chromati...

journal_title：Journal of medicinal chemistry

authors： Bouché L,Christ CD,Siegel S,Fernández-Montalván AE,Holton SJ,Fedorov O,Ter Laak A,Sugawara T,Stöckigt D,Tallant C,Bennett J,Monteiro O,Díaz-Sáez L,Siejka P,Meier J,Pütter V,Weiske J,Müller S,Huber KVM,Hartung IV,H

更新日期：2017-05-11 00:00:00

abstract：:A procedure for analyzing and classifying publicly available crystal structures has been developed. It has been used to identify high-resolution protein-ligand complexes that can be assessed by reconstructing the electron density for the ligand using the deposited structure factors. The complexes have been clustered a...

journal_title：Journal of medicinal chemistry

authors： Hartshorn MJ,Verdonk ML,Chessari G,Brewerton SC,Mooij WT,Mortenson PN,Murray CW

更新日期：2007-02-22 00:00:00

abstract：:In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane prepar...

journal_title：Journal of medicinal chemistry

authors： Chumpradit S,Kung MP,Panyachotipun C,Prapansiri V,Foulon C,Brooks BP,Szabo SA,Tejani-Butt S,Frazer A,Kung HF

更新日期：1992-11-13 00:00:00

abstract：:(E)-5-(2-Bromovinyl)isodideoxyuridine (BVisoDDU), synthesized on the basis of molecular modeling, is selectively active against HSV-1 (three different strains) but inactive against HSV-2. Unlike BVDU, BVisoDDU is completely resistant to cleavage by thymidine phosphorylase. BVisoDDU is also the first nucleoside analogu...

journal_title：Journal of medicinal chemistry

authors： Guenther S,Balzarini J,De Clercq E,Nair V

更新日期：2002-12-05 00:00:00

abstract：:Although the majority of proteins used for biomedical research are produced using living systems such as bacteria, biological means for producing proteins can be advantageously complemented by protein semisynthesis or total chemical synthesis. The latter approach is particularly useful when the proteins to be produced...

journal_title：Journal of medicinal chemistry

authors： Agouridas V,El Mahdi O,Melnyk O

更新日期：2020-12-24 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：:Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...

journal_title：Journal of medicinal chemistry

authors： Saitoh M,Kunitomo J,Kimura E,Iwashita H,Uno Y,Onishi T,Uchiyama N,Kawamoto T,Tanaka T,Mol CD,Dougan DR,Textor GP,Snell GP,Takizawa M,Itoh F,Kori M

更新日期：2009-10-22 00:00:00

abstract：:The C-terminal "address" sequences of prodynorphin-derived opioid peptides contain an unusually high proportion of basic residues, which are known to be crucial for conferring high activity and selectivity for kappa-opioid receptors. In an effort to investigate the possibility that the polycationic "tails" may be invo...

journal_title：Journal of medicinal chemistry

authors： Jacobson AR,Tam SW,Sayre LM

更新日期：1991-09-01 00:00:00

abstract：:The important enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is known to regulate intracellular levels of biologically active steroids, namely, androgens and estrogens. In an effort to develop potent inhibitors of 17 beta-HSD for reducing the levels of active steroids, we found that steroidal spiro-gamma-la...

journal_title：Journal of medicinal chemistry

authors： Sam KM,Auger S,Luu-The V,Poirier D

更新日期：1995-10-27 00:00:00

abstract：:The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin as...

journal_title：Journal of medicinal chemistry

authors： Andreani A,Granaiola M,Locatelli A,Morigi R,Rambaldi M,Varoli L,Calonghi N,Cappadone C,Farruggia G,Stefanelli C,Masotti L,Nguyen TL,Hamel E,Shoemaker RH

更新日期：2012-03-08 00:00:00

abstract：:A series of branched-chain sugar isonucleosides was synthesized and evaluated for antiviral activity against herpesviruses. The preparation of homochiral [3S-(3 alpha, 4 beta, 5 alpha)]-2-amino-1, 9-dihydro-9-[tetrahydro-4,5-bis(hydroxymethyl)-3-furanyl]-6H-purin-6-one (7, BMS-181,164) and related compounds was stereo...

journal_title：Journal of medicinal chemistry

authors： Tino JA,Clark JM,Field AK,Jacobs GA,Lis KA,Michalik TL,McGeever-Rubin B,Slusarchyk WA,Spergel SH,Sundeen JE

更新日期：1993-04-30 00:00:00

abstract：:We previously reported that [[N-[3beta-hydroxyllup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two retroviruses are different. In this study, a series of new betul...

journal_title：Journal of medicinal chemistry

authors： Dang Z,Lai W,Qian K,Ho P,Lee KH,Chen CH,Huang L

更新日期：2009-12-10 00:00:00

abstract：:Inhibition of embryonic ectoderm development (EED) is a new cancer therapeutic strategy. Herein, we report our discovery of EEDi-5285 as an exceptionally potent, efficacious, and orally active EED inhibitor. EEDi-5285 binds to the EED protein with an IC50 value of 0.2 nM and inhibits cell growth with IC50 values of 20...

journal_title：Journal of medicinal chemistry

authors： Rej RK,Wang C,Lu J,Wang M,Petrunak E,Zawacki KP,McEachern D,Fernandez-Salas E,Yang CY,Wang L,Li R,Chinnaswamy K,Wen B,Sun D,Stuckey J,Zhou Y,Chen J,Tang G,Wang S

更新日期：2020-07-09 00:00:00

abstract：:This paper describes an extended structure-activity relationships study of aminotetralin-piperazine-based hybrid molecules developed earlier for dopamine D2/D3 receptors. Various analogues as positional isomers have been developed where location of the phenolic hydroxyl group has been varied on the aromatic ring. Betw...

journal_title：Journal of medicinal chemistry

authors： Biswas S,Zhang S,Fernandez F,Ghosh B,Zhen J,Kuzhikandathil E,Reith ME,Dutta AK

更新日期：2008-01-10 00:00:00

abstract：:The understanding of the physiological role of the G-protein coupled serotonin 5-HT(7) receptor is largely rudimentary. Therefore, selective and potent pharmacological tools will add to the understanding of serotonergic effects mediated through this receptor. In this report, we describe two compound classes, chromans ...

journal_title：Journal of medicinal chemistry

authors： Holmberg P,Sohn D,Leideborg R,Caldirola P,Zlatoidsky P,Hanson S,Mohell N,Rosqvist S,Nordvall G,Johansson AM,Johansson R

更新日期：2004-07-29 00:00:00

abstract：:A molecular model of the alpha(IIb)beta(3) integrin has been developed utilizing (i). the crystal structure of alpha(v)beta(3), (ii). homology model of the alpha(IIb) subdomain, and (iii). the docking of alpha(IIb)beta(3)/alpha(v)beta(3) dual and selective inhibitors into the putative binding sites of alpha(IIb)beta(3...

journal_title：Journal of medicinal chemistry

authors： Feuston BP,Culberson JC,Hartman GD

更新日期：2003-12-04 00:00:00

abstract：:In this study we describe an extension of our previous studies on cis-benzylidenemalononitrile tyrphostins. We have introduced S-aryl substituents in the 5 position (meta vis-a-vis the malononitrile moiety). We find that these compounds are potent blockers of EGFR kinase and its homolog HER-2 kinase. Interestingly, we...

journal_title：Journal of medicinal chemistry

authors： Gazit A,Osherov N,Posner I,Bar-Sinai A,Gilon C,Levitzki A

更新日期：1993-11-12 00:00:00

abstract：:A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys...

journal_title：Journal of medicinal chemistry

authors： Rivier JE,Hoeger C,Erchegyi J,Gulyas J,DeBoard R,Craig AG,Koerber SC,Wenger S,Waser B,Schaer JC,Reubi JC

更新日期：2001-06-21 00:00:00

abstract：:The G protein-coupled chemokine receptors CXCR1 and CXCR2 play key roles in inflammatory diseases and carcinogenesis. In inflammation, they activate and recruit polymorphonuclear cells (PMNs) through binding of the chemokines CXCL1 (CXCR1) and CXCL8 (CXCR1 and CXCR2). Structure-activity studies that examined the effec...

journal_title：Journal of medicinal chemistry

authors： Maeda DY,Peck AM,Schuler AD,Quinn MT,Kirpotina LN,Wicomb WN,Fan GH,Zebala JA

更新日期：2014-10-23 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：:A series of substituted 4-anilinoquinazolines and related compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptor (Flt and KDR) tyrosine kinase activity. Enzyme screening indicated that a narrow structure-activity relationship (SAR) existed for the bicyclic ring system,...

journal_title：Journal of medicinal chemistry

authors： Hennequin LF,Thomas AP,Johnstone C,Stokes ES,Plé PA,Lohmann JJ,Ogilvie DJ,Dukes M,Wedge SR,Curwen JO,Kendrew J,Lambert-van der Brempt C

更新日期：1999-12-30 00:00:00

abstract：:Adverse drug reactions (ADRs) are a common cause of attrition in drug discovery and development and drug-induced liver injury (DILI) is a leading cause of preclinical and clinical drug terminations. This perspective outlines many of the known DILI mechanisms and assessment methods used to evaluate and mitigate DILI ri...

journal_title：Journal of medicinal chemistry

authors： Norman BH

更新日期：2020-10-22 00:00:00

abstract：:A series of 4-methyl-3-(arylthio)furoxans were synthesized by oxidation of 1-(arylthio)-2-methylglyoxymes with dinitrogen tetroxide. Reduction with trimethyl phosphite of the furoxan derivatives afforded the corresponding furazans, while oxidation with an equimolar amount of 30% hydrogen peroxide in acetic acid or wit...

journal_title：Journal of medicinal chemistry

authors： Calvino R,Fruttero R,Ghigo D,Bosia A,Pescarmona GP,Gasco A

更新日期：1992-08-21 00:00:00

abstract：:Influenza virus (IFV) causes periodic global influenza pandemics, resulting in substantial socioeconomic loss and burden on medical facilities. Yearly variation in the effectiveness of vaccines, slow responsiveness to vaccination in cases of pandemic IFV, and emerging resistance to available drugs highlight the need t...

journal_title：Journal of medicinal chemistry

authors： Ju H,Zhang J,Huang B,Kang D,Huang B,Liu X,Zhan P

更新日期：2017-05-11 00:00:00

abstract：:A series of pyridines and other six-membered ring heterocycles connected to a biphenyltetrazole with a -CH2-NR'-link (1) were discovered to be potent angiotensin II antagonists. In the pyrimidine carboxylic acid series (W = CR, X = N, Y = CH, Z = COOH), compounds with an alkyl group (R') on the exocyclic nitrogen were...

journal_title：Journal of medicinal chemistry

authors： Winn M,De B,Zydowsky TM,Altenbach RJ,Basha FZ,Boyd SA,Brune ME,Buckner SA,Crowell D,Drizin I

更新日期：1993-09-03 00:00:00