A nonionic inhibitor with high specificity for the UDP-Gal donor binding site of human blood group B galactosyltransferase: design, synthesis, and characterization.

abstract：:Both HIV-EP1 (also called PRDII-BF1 or MBP-1), a zinc finger protein, and NF-kappa B, a Rel family protein, bind to kappa B site present in the enhancer of multiple cellular and viral genes involved in immune function and inflammatory response including HIV-1 LTR and human interferon beta gene. When cells are exposed ...

journal_title：Journal of medicinal chemistry

authors： Otsuka M,Fujita M,Aoki T,Ishii S,Sugiura Y,Yamamoto T,Inoue J

更新日期：1995-08-18 00:00:00

abstract：:Antimicrobial resistance (AMR) represents a hot topic in drug discovery. Besides the identification of new antibiotics, the use of nonantibiotic molecules to block resistance mechanisms is a powerful alternative. Bacterial efflux pumps exert an early step in AMR development by allowing bacteria to grow at subinhibitor...

journal_title：Journal of medicinal chemistry

authors： Felicetti T,Cannalire R,Pietrella D,Latacz G,Lubelska A,Manfroni G,Barreca ML,Massari S,Tabarrini O,Kieć-Kononowicz K,Schindler BD,Kaatz GW,Cecchetti V,Sabatini S

更新日期：2018-09-13 00:00:00

abstract：:Protein disulfide isomerase (PDI) is responsible for nascent protein folding in the endoplasmic reticulum (ER) and is critical for glioblastoma survival. To improve the potency of lead PDI inhibitor BAP2 (( E)-3-(3-(4-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzonitrile), we designed and synthesized 67 analogues. We determ...

journal_title：Journal of medicinal chemistry

authors： Yang S,Shergalis A,Lu D,Kyani A,Liu Z,Ljungman M,Neamati N

更新日期：2019-04-11 00:00:00

abstract：:The therapeutic success of peptidic GLP-1 receptor agonists for treatment of type 2 diabetes mellitus (T2DM) motivated our search for orally bioavailable small molecules that can activate the GLP-1 receptor (GLP-1R) as a well-validated target for T2DM. Here, the discovery and characterization of a potent and selective...

journal_title：Journal of medicinal chemistry

authors： Méndez M,Matter H,Defossa E,Kurz M,Lebreton S,Li Z,Lohmann M,Löhn M,Mors H,Podeschwa M,Rackelmann N,Riedel J,Safar P,Thorpe DS,Schäfer M,Weitz D,Breitschopf K

更新日期：2020-03-12 00:00:00

abstract：:Lysosomotropic detergents, which kill mammalian cells by disrupting lysosomal membranes, have now been found to be antifungals also. All strains in our assay are susceptible. The mode of action is as yet undetermined, but intracellular vacuoles may be the primary targets. ...

journal_title：Journal of medicinal chemistry

authors： Firestone RA,Pisano JM,Garrity GM,Fromtling RA,Zimmerman SB

更新日期：1987-08-01 00:00:00

abstract：:The photolabile (diazomethyl)carbonyl function was introduced into the 8-position of 2-(N,N-di-n-propyl-amino)-1,2,3,4-tetrahydronaphthalene in three ways, resulting in the ether 8-[[(diazomethyl)carbonyl]methoxy]-2-(N,N-di-n-propylamino)-1,2,3,4- tetrahydronaphthalene (2), the ester 8-(diazoacetoxy)-2-(N,N-di-n-propy...

journal_title：Journal of medicinal chemistry

authors： Kline TB,Nelson DL,Namboodiri K

更新日期：1990-03-01 00:00:00

abstract：:Proton magnetic spectra have been recorded for muscarine and two biologically active cyclopentane analogues. In order to observe homonuclear intramolecular nuclear Overhauser effects, the -N+(CH3)3 signal was irradiated and increases in integrated intensities for other key signals in the molecule were observed. The re...

journal_title：Journal of medicinal chemistry

authors： de Fontaine DL,Ternai B,Zupan JA,Givens RS,Wiley RA

更新日期：1978-07-01 00:00:00

abstract：:The endocannabinoid hydrolyzing enzyme FAAH uses a nonclassical catalytic triad (namely, Ser-Ser-Lys instead of Ser-Asp-His) to cleave its endogenous substrates. Because inhibiting FAAH has a clear therapeutic potential, we previously developed β-lactam-type inhibitors of hFAAH. Here, we report the synthesis of five n...

journal_title：Journal of medicinal chemistry

authors： Feledziak M,Muccioli GG,Lambert DM,Marchand-Brynaert J

更新日期：2011-10-13 00:00:00

abstract：:Hydroxyurea, hydroxyguanidine, and some thiosemicarbazones have been shown to have anticancer and antiviral activities. One of their possible sites of action is the enzyme ribonucleotide reductase (RR). Combination of the structural features of these compounds led to the design and synthesis of the Schiff bases of N-h...

journal_title：Journal of medicinal chemistry

authors： T'ang A,Lien EJ,Lai MM

更新日期：1985-08-01 00:00:00

abstract：:Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these di...

journal_title：Journal of medicinal chemistry

authors： Ng HP,May K,Bauman JG,Ghannam A,Islam I,Liang M,Horuk R,Hesselgesser J,Snider RM,Perez HD,Morrissey MM

更新日期：1999-11-04 00:00:00

abstract：:C-terminal fragment analogues of the leech anticoagulant peptide hirudin represent a unique class of thrombin inhibitors that blocks thrombin's cleavage of fibrinogen but does not block the catalytic site of thrombin. In this paper, a series of synthetic peptides were prepared by solid-phase methodology to determine t...

journal_title：Journal of medicinal chemistry

authors： Owen TJ,Krstenansky JL,Yates MT,Mao SJ

更新日期：1988-05-01 00:00:00

abstract：:Various D- and L-thietanose nucleosides were synthesized from D- and L-xylose. The four-membered thietane ring was efficiently synthesized by the cyclization of 1-thioacetyl-3-mesylate (4/38) under basic conditions. Condensation with various heterocyclic bases was conducted via Pummerer-type rearrangement to afford va...

journal_title：Journal of medicinal chemistry

authors： Choo H,Chen X,Yadav V,Wang J,Schinazi RF,Chu CK

更新日期：2006-03-09 00:00:00

abstract：:In this study, we describe novel inhibitors against Francisella tularensis SchuS4 FabI identified from structure-based in silico screening with integrated molecular dynamics simulations to account for induced fit of a flexible loop crucial for inhibitor binding. Two 3-substituted indoles, 54 and 57, preferentially bou...

journal_title：Journal of medicinal chemistry

authors： Hu X,Compton JR,Abdulhameed MD,Marchand CL,Robertson KL,Leary DH,Jadhav A,Hershfield JR,Wallqvist A,Friedlander AM,Legler PM

更新日期：2013-07-11 00:00:00

abstract：:Two molecules with known growth hormone secretagogue (GHS) agonist activity were used as templates to computationally screen approximately 80000 compounds. A total of 108 candidate compounds were selected, and five of them were found to be active in the low-micromolar range in both cell-based and direct binding assays...

journal_title：Journal of medicinal chemistry

authors： Shoda M,Harada T,Kogami Y,Tsujita R,Akashi H,Kouji H,Stahura FL,Xue L,Bajorath J

更新日期：2004-08-12 00:00:00

abstract：:A fragment-based docking procedure followed by substructure search were used to identify active-site beta-secretase inhibitors from a composite set of about 300 000 and a library of nearly 180 000 small molecules, respectively. EC(50) values less than 10 microM were measured in at least one of two different mammalian ...

journal_title：Journal of medicinal chemistry

authors： Huang D,Lüthi U,Kolb P,Edler K,Cecchini M,Audetat S,Barberis A,Caflisch A

更新日期：2005-08-11 00:00:00

abstract：:The tremendous therapeutic potential of voltage-gated sodium channels (Na(v)s) has been the subject of many studies in the past and is of intense interest today. Na(v)1.7 channels in particular have received much attention recently because of strong genetic validation of their involvement in nociception. Here we summa...

journal_title：Journal of medicinal chemistry

authors： de Lera Ruiz M,Kraus RL

更新日期：2015-09-24 00:00:00

abstract：:The 3,4-dichloro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for 18F-positron emission tomography (18F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacolog...

journal_title：Journal of medicinal chemistry

authors： Ott J,Spilhaug MM,Maschauer S,Rafique W,Jakobsson JE,Hartvig K,Hübner H,Gmeiner P,Prante O,Riss PJ

更新日期：2020-09-10 00:00:00

abstract：:Cathepsin K is a major drug target for osteoporosis and related-bone disorders. Using a combination of virtual combinatorial chemistry, QSAR modeling, and molecular docking studies, a series of cathepsin K inhibitors based on N-(functionalized benzoyl)-homocycloleucyl-glycinonitrile scaffold was developed. In order to...

journal_title：Journal of medicinal chemistry

authors： Borišek J,Vizovišek M,Sosnowski P,Turk B,Turk D,Mohar B,Novič M

更新日期：2015-09-10 00:00:00

abstract：:Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme involved in intracellular cholesterol esterification. Arterial wall infiltration by macrophages and subsequent uncontrolled esterification of cholesterol leading to foam cell formation is believed to be an important process which leads to the developmen...

journal_title：Journal of medicinal chemistry

authors： Maduskuie TP Jr,Wilde RG,Billheimer JT,Cromley DA,Germain S,Gillies PJ,Higley CA,Johnson AL,Pennev P,Shimshick EJ

更新日期：1995-03-31 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：:A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives...

journal_title：Journal of medicinal chemistry

authors： Manoury PM,Binet JL,Dumas AP,Lefèvre-Borg F,Cavero I

更新日期：1986-01-01 00:00:00

abstract：:The phenolic "A-ring" of natural and synthetic estrogen receptor (ER) ligands was effectively replaced by a planar six-member ring formed through an intramolecular hydrogen bond within a salicylaldoxime. Thus, oxime 1, a structural analogue of a triarylethylene estrogen, showed a significant binding affinity for the E...

journal_title：Journal of medicinal chemistry

authors： Minutolo F,Bertini S,Papi C,Carlson KE,Katzenellenbogen JA,Macchia M

更新日期：2001-11-22 00:00:00

abstract：:Insulin secretion by pancreatic β-cells in response to glucose or other secretagogues is tightly coupled to membrane potential. Various studies have highlighted the prospect of enhancing insulin secretion in a glucose-dependent manner by blocking voltage-gated potassium channels (K(v)) and calcium-activated potassium ...

journal_title：Journal of medicinal chemistry

authors： Nguyen TT,Folch B,Létourneau M,Truong NH,Doucet N,Fournier A,Chatenet D

更新日期：2014-03-27 00:00:00

abstract：:We recently designed a group of novel exosite-2-directed sulfated, small, allosteric inhibitors of thrombin. To develop more potent inhibitors, monosulfated benzofuran tri- and tetrameric homologues of the parent designed dimers were synthesized in seven to eight steps and found to exhibit a wide range of potencies. A...

journal_title：Journal of medicinal chemistry

authors： Sidhu PS,Abdel Aziz MH,Sarkar A,Mehta AY,Zhou Q,Desai UR

更新日期：2013-06-27 00:00:00

abstract：:CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the h...

journal_title：Journal of medicinal chemistry

authors： Ortiz Zacarías NV,van Veldhoven JPD,den Hollander LS,Dogan B,Openy J,Hsiao YY,Lenselink EB,Heitman LH,IJzerman AP

更新日期：2019-12-26 00:00:00

abstract：:BRAF is a serine/threonine kinase that is mutated in a range of cancers, including 50-70% of melanomas, and has been validated as a therapeutic target. We have designed and synthesized mutant BRAF inhibitors containing pyridoimidazolone as a new hinge-binding scaffold. Compounds have been obtained which have low nanom...

journal_title：Journal of medicinal chemistry

authors： Niculescu-Duvaz D,Gaulon C,Dijkstra HP,Niculescu-Duvaz I,Zambon A,Ménard D,Suijkerbuijk BM,Nourry A,Davies L,Manne H,Friedlos F,Ogilvie L,Hedley D,Whittaker S,Kirk R,Gill A,Taylor RD,Raynaud FI,Moreno-Farre J,Marais

更新日期：2009-04-23 00:00:00

abstract：:A series of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-ones were synthesized and evaluated for anticonvulsant activity in DBA/2 mice against sound-induced seizures and in rats against maximal electroshock-induced seizures. Most of the derivatives showed an anticonvulsant effect better than that of valproate, ...

journal_title：Journal of medicinal chemistry

authors： Chimirri A,De Sarro A,De Sarro G,Grasso S,Trimarchi GR,Zappalà M

更新日期：1989-01-01 00:00:00

abstract：:Janus kinases (JAK1, JAK2, JAK3, and TYK2) are involved in the signaling of multiple cytokines important in cellular function. Blockade of the JAK-STAT pathway with a small molecule has been shown to provide therapeutic immunomodulation. Having identified JAK1 as a possible new target for arthritis at Galapagos, the c...

journal_title：Journal of medicinal chemistry

authors： Menet CJ,Fletcher SR,Van Lommen G,Geney R,Blanc J,Smits K,Jouannigot N,Deprez P,van der Aar EM,Clement-Lacroix P,Lepescheux L,Galien R,Vayssiere B,Nelles L,Christophe T,Brys R,Uhring M,Ciesielski F,Van Rompaey L

更新日期：2014-11-26 00:00:00

abstract：:Nonpeptidic chiral macrocycles were designed on the basis of an analogue of suberoylanilide hydroxamic acid (2) (SAHA, vorinostat) and evaluated against 11 histone deacetylase (HDAC) isoforms. The identification of critical amino acid residues highly conserved in the cap region of HDACs guided the design of the subero...

journal_title：Journal of medicinal chemistry

authors： Auzzas L,Larsson A,Matera R,Baraldi A,Deschênes-Simard B,Giannini G,Cabri W,Battistuzzi G,Gallo G,Ciacci A,Vesci L,Pisano C,Hanessian S

更新日期：2010-12-09 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