Reverse fosmidomycin derivatives against the antimalarial drug target IspC (Dxr).

abstract：:The five dopamine receptor subtypes (D1-5) are activated by the endogenous catecholamine dopamine. Sustained research has sought to identify selective ligands for receptor subtypes. In particular, activation of the D1 receptor has attracted attention due to its promising role in neurological diseases. Initial attempts...

journal_title：Journal of medicinal chemistry

authors： Hall A,Provins L,Valade A

更新日期：2019-01-10 00:00:00

abstract：:A series of imidazo[1,2-b]thiazole derivatives is shown to activate the NAD(+)-dependent deacetylase SIRT1, a potential new therapeutic target to treat various metabolic disorders. This series of compounds was derived from a high throughput screening hit bearing an oxazolopyridine core. Water-solubilizing groups could...

journal_title：Journal of medicinal chemistry

authors： Vu CB,Bemis JE,Disch JS,Ng PY,Nunes JJ,Milne JC,Carney DP,Lynch AV,Smith JJ,Lavu S,Lambert PD,Gagne DJ,Jirousek MR,Schenk S,Olefsky JM,Perni RB

更新日期：2009-03-12 00:00:00

abstract：:The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biolo...

journal_title：Journal of medicinal chemistry

authors： Kuo EA,Hambleton PT,Kay DP,Evans PL,Matharu SS,Little E,McDowall N,Jones CB,Hedgecock CJ,Yea CM,Chan AW,Hairsine PW,Ager IR,Tully WR,Williamson RA,Westwood R

更新日期：1996-11-08 00:00:00

abstract：:The cyclic somatostatin analogue cyclo[Pro(1)-Phe(2)-D-Trp(3)-Lys(4)-Thr(5)-Phe(6)] (L-363,301) displays high biological activity in inhibiting the release of growth hormone, insulin, and glucagon. According to the sequence of L-363,301, we synthesized a number of cyclic hexa- and pentapeptides containing nonnatural a...

journal_title：Journal of medicinal chemistry

authors： Sukopp M,Schwab R,Marinelli L,Biron E,Heller M,Várkondi E,Pap A,Novellino E,Kéri G,Kessler H

更新日期：2005-04-21 00:00:00

abstract：:Glucagon-like peptide-1 (GLP-1) has the ability to lower the blood glucose level, and its regulatory functions make it an attractive therapeutic agent for the treatment of type 2 diabetes. However, its rapid degradation by enzymes like dipeptidyl peptidase-IV (DPP-IV) and neutral endopeptidase (NEP) 24.11 severely com...

journal_title：Journal of medicinal chemistry

authors： Murage EN,Gao G,Bisello A,Ahn JM

更新日期：2010-09-09 00:00:00

abstract：:Prodrug-mediated utilization of the cytochrome P450 (CYP) 1A1 to obtain the selective release of potent anticancer products within cancer tissues is a promising approach in chemotherapy. We herein report the rationale, preparation, biological evaluation, and mechanism of action of phenyl 4-(2-oxo-3-alkylimidazolidin-1...

journal_title：Journal of medicinal chemistry

authors： Fortin S,Charest-Morin X,Turcotte V,Lauvaux C,Lacroix J,Côté MF,Gobeil S,C-Gaudreault R

更新日期：2017-06-22 00:00:00

abstract：:We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected E. coli strains. One of the most interesting candidates, compound 86, was shown to inhibit specifically bacterial LPS heptosylation on efflux pum...

journal_title：Journal of medicinal chemistry

authors： Desroy N,Denis A,Oliveira C,Atamanyuk D,Briet S,Faivre F,LeFralliec G,Bonvin Y,Oxoby M,Escaich S,Floquet S,Drocourt E,Vongsouthi V,Durant L,Moreau F,Verhey TB,Lee TW,Junop MS,Gerusz V

更新日期：2013-02-28 00:00:00

abstract：:(-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first thymidine kinase-activated nucleoside that is significantly active against all of the clinically significant NRTI-resistant HIV-1 mutants, including AZT (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). To understand the molec...

journal_title：Journal of medicinal chemistry

authors： Chu CK,Yadav V,Chong YH,Schinazi RF

更新日期：2005-06-16 00:00:00

abstract：:Whereas the 2-propyl- and 2-butyl-5,6-(methylenedioxy)indene calcium antagonists reversed the spasmogenic action of several agonists including PGF2alpha and acetylcholine at 5 X 10(-5) to 10(-4) M on the rat ileum, the corresponding 5,6-dimethoxy analogues exhibited spasmogenic activity at higher concentration (10(-4)...

journal_title：Journal of medicinal chemistry

authors： Witiak DT,Kakodkar SV,Brunst GE,Baldwin JR,Rahwan RG

更新日期：1978-12-01 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 F9/Yde/Fml pilus, tipped with the FmlH adhesin, has been shown to provide uropathogenic Escherichia coli (UPEC) a fitness advantage in urinary tract infections (UTIs). Here, we used X-ray structure guided design to optimize our previously described ortho-biphenyl Gal and GalNAc FmlH antagonists such as compound 1 ...

journal_title：Journal of medicinal chemistry

authors： Maddirala AR,Klein R,Pinkner JS,Kalas V,Hultgren SJ,Janetka JW

更新日期：2019-01-24 00:00:00

abstract：:In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (MMP-2 IC(50) = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structu...

journal_title：Journal of medicinal chemistry

authors： Cherney RJ,Mo R,Meyer DT,Hardman KD,Liu RQ,Covington MB,Qian M,Wasserman ZR,Christ DD,Trzaskos JM,Newton RC,Decicco CP

更新日期：2004-06-03 00:00:00

abstract：:The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a c...

journal_title：Journal of medicinal chemistry

authors： Drew MG,Metcalfe J,Dascombe MJ,Ismail FM

更新日期：2006-10-05 00:00:00

abstract：:Inhibition of histone deacetylases (HDACs) leads to growth arrest, differentiation, or apoptosis of tumor cell lines, suggesting HDACs as promising targets for cancer therapy. At present, only one HDAC inhibitor (HDACi) is used in therapy: suberoylanilide hydroxamic acid (SAHA). Here, we describe the synthesis and bio...

journal_title：Journal of medicinal chemistry

authors： Oger F,Lecorgne A,Sala E,Nardese V,Demay F,Chevance S,Desravines DC,Aleksandrova N,Le Guével R,Lorenzi S,Beccari AR,Barath P,Hart DJ,Bondon A,Carettoni D,Simonneaux G,Salbert G

更新日期：2010-03-11 00:00:00

abstract：:2,6-Dipeptidyl-anthraquinones are a promising class of nucleic acid-binding compounds that act as NC inhibitors in vitro. We designed, synthesized, and tested new series of 2,6-disubstituted-anthraquinones, which are able to bind viral nucleic acid substrates of NC. We demonstrate here that these novel derivatives int...

journal_title：Journal of medicinal chemistry

authors： Frecentese F,Sosic A,Saccone I,Gamba E,Link K,Miola A,Cappellini M,Cattelan MG,Severino B,Fiorino F,Magli E,Corvino A,Perissutti E,Fabris D,Gatto B,Caliendo G,Santagada V

更新日期：2016-03-10 00:00:00

abstract：:Quadruplex-forming sequences are widely prevalent in human and other genomes, including bacterial ones. These sequences are over-represented in eukaryotic telomeres, promoters, and 5' untranslated regions. They can form quadruplex structures, which may be transient in many situations in normal cells since they can be ...

journal_title：Journal of medicinal chemistry

authors： Neidle S

更新日期：2016-07-14 00:00:00

abstract：:This report describes the syntheses and structure-activity relationships of 8-(4-methoxyphenyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF(1)) receptor antagonists. CRF(1) receptor antagonists may be potential anxiolytic or antidepressant drugs. This research culminated in the discove...

journal_title：Journal of medicinal chemistry

authors： Gilligan PJ,He L,Clarke T,Tivitmahaisoon P,Lelas S,Li YW,Heman K,Fitzgerald L,Miller K,Zhang G,Marshall A,Krause C,McElroy J,Ward K,Shen H,Wong H,Grossman S,Nemeth G,Zaczek R,Arneric SP,Hartig P,Robertson DW,T

更新日期：2009-05-14 00:00:00

abstract：:The synthesis of a series of substituted heterocyclic alkoxypropionic acids is described. They were evaluated for antiinflammatory effects in two animal models of chronic inflammation; adjuvant arthritis and type II collagen arthritis in the rat. The desired profile of biological activity was characterized by the redu...

journal_title：Journal of medicinal chemistry

authors： Self CR,Barber WE,Machin PJ,Osbond JM,Smithen CE,Tong BP,Wickens JC,Bloxham DP,Bradshaw D,Cashin CH

更新日期：1991-02-01 00:00:00

abstract：:Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex...

journal_title：Journal of medicinal chemistry

authors： Lemaire S,Yamashiro D,Li CH

更新日期：1976-03-01 00:00:00

abstract：:The effect of substitution in the acyclic structure of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds. Preparation of 1-[(2-alkyloxyethoxy)methyl]-6- (phenylthio)thymine (2-4) derivatives was carried out ...

journal_title：Journal of medicinal chemistry

authors： Tanaka H,Takashima H,Ubasawa M,Sekiya K,Nitta I,Baba M,Shigeta S,Walker RT,De Clercq E,Miyasaka T

更新日期：1992-12-11 00:00:00

abstract：:The synthesis and biological evaluation of novel prodrugs for use in the antibody directed enzyme prodrug therapy (ADEPT) of cancer based on the cytotoxic antibiotic duocarmycin SA (1) are described. In this approach, we investigated the influence of the sugar moiety of the glycosidic prodrug on the QIC(50) values as ...

journal_title：Journal of medicinal chemistry

authors： Tietze LF,Schuster HJ,Krewer B,Schuberth I

更新日期：2009-01-22 00:00:00

abstract：:We disclose the design of a novel series of cyanoguanidines that are potent (IC(50) approximately 10-100 nM) and selective (> or = 100-fold) P2X(7) receptor antagonists against the other P2 receptor subtypes such as the P2Y(2), P2X(4), and P2X(3). We also found that these P2X(7) antagonists effectively reduced nocicep...

journal_title：Journal of medicinal chemistry

authors： Perez-Medrano A,Donnelly-Roberts DL,Honore P,Hsieh GC,Namovic MT,Peddi S,Shuai Q,Wang Y,Faltynek CR,Jarvis MF,Carroll WA

更新日期：2009-05-28 00:00:00

abstract：:The effect of aromatic nitro compounds on the oxidative metabolism of representative type I (hexobarbital and aminopyrene) and type II (aniline and zoxazolamine) substrates by cytochrome P-450 dependent liver enzymes was studied. Nitro compounds (nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene) ...

journal_title：Journal of medicinal chemistry

authors： Sternson LA,Gammans RE

更新日期：1976-01-01 00:00:00

abstract：:Detailed molecular models of the free C1B domain of protein kinase C-gamma (PKC-gamma) and the C1B domain with its activator phorbol-12-myristate-13-acetate (PMA) in water solution and in the presence of dipalmitoylphosphatidylcholine (DPPC) bilayer are presented. Molecular dynamics of the free C1B domain reveals hydr...

journal_title：Journal of medicinal chemistry

authors： Hritz J,Ulicny J,Laaksonen A,Jancura D,Miskovsky P

更新日期：2004-12-16 00:00:00

abstract：:Pironetin, the only crystallographically confirmed natural product to target α-tubulin, displays potent cytotoxic activity against sensitive and resistant A2780 ovarian cancer cell lines but is only marginally active in vivo. We now report that pironetin has a short half-life (<7 min) in human liver microsomes, sugges...

journal_title：Journal of medicinal chemistry

authors： Coulup SK,Huang DS,Wong HL,Georg GI

更新日期：2019-02-14 00:00:00

abstract：:Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme that is involved in the de novo synthesis of purine nucleotides. Novel 2-aminooxazoles were synthesized and tested for inhibition of IMPDH catalytic activity. Multiple analogues based on this chemotype were found to inhibit IMPDH with low nanomolar potency. O...

journal_title：Journal of medicinal chemistry

authors： Dhar TG,Shen Z,Guo J,Liu C,Watterson SH,Gu HH,Pitts WJ,Fleener CA,Rouleau KA,Sherbina NZ,McIntyre KW,Shuster DJ,Witmer MR,Tredup JA,Chen BC,Zhao R,Bednarz MS,Cheney DL,MacMaster JF,Miller LM,Berry KK,Harper TW,

更新日期：2002-05-23 00:00:00

abstract：:Aberrant activation of S6 kinase 1 (S6K1) is found in many diseases, including diabetes, aging, and cancer. We developed ATP competitive organometallic kinase inhibitors, EM5 and FL772, which are inspired by the structure of the pan-kinase inhibitor staurosporine, to specifically inhibit S6K1 using a strategy previous...

journal_title：Journal of medicinal chemistry

authors： Qin J,Rajaratnam R,Feng L,Salami J,Barber-Rotenberg JS,Domsic J,Reyes-Uribe P,Liu H,Dang W,Berger SL,Villanueva J,Meggers E,Marmorstein R

更新日期：2015-01-08 00:00:00

abstract：:Peptide modification with fatty acids is an effective method to improve peptide performance. We previously investigated the fatty acid modification of R-lycosin-I, a cytotoxic peptide derived from lycosin-I from the venom of the spider Lycosa singoriensis. In this study, we further investigated the position effects of...

journal_title：Journal of medicinal chemistry

authors： Zhang P,Jian C,Jian S,Zhang Q,Sun X,Nie L,Liu B,Li F,Li J,Liu M,Liang S,Zeng Y,Liu Z

更新日期：2019-12-26 00:00:00

abstract：:A series of (E)-phenoxyacrylic amide derivatives were synthesized and evaluated as hypoxia inducible factor (HIF) 1α inhibitors. The present structure-activity relationship study on this series identified the morpholinoethyl containing ester 4p as a potent inhibitor of HIF-1α under hypoxic conditions (IC50=0.12 μM in ...

journal_title：Journal of medicinal chemistry

authors： Naik R,Won M,Kim BK,Xia Y,Choi HK,Jin G,Jung Y,Kim HM,Lee K

更新日期：2012-12-13 00:00:00

abstract：:New tuftsin/retro-tuftsin conjugates were designed and synthesized using a classical fluorenylmethoxycarbonyl (Fmoc) solid phase procedure. All the peptide conjugates were divided into three series: 1,4-dihydroxyanthraquinone (type A), 1-nitroacridine (type B), and 4-carboxyacridone (type C) derivatives. In type A con...

journal_title：Journal of medicinal chemistry

authors： Kukowska-Kaszuba M,Dzierzbicka K,Serocki M,Skladanowski A

更新日期：2011-04-14 00:00:00