Novel peptidomimetics containing a vinyl ester moiety as highly potent and selective falcipain-2 inhibitors.

abstract：:The antibacterial 4H-4-oxoquinolizines were introduced recently to overcome bacterial resistance to fluoroquinolones. They exhibit potent antibacterial activity against Gram-positive, Gram-negative, and anaerobic organisms and are highly active against some quinolone-resistant bacteria including quinolone-resistant MR...

journal_title：Journal of medicinal chemistry

authors： Ma Z,Chu DT,Cooper CS,Li Q,Fung AK,Wang S,Shen LL,Flamm RK,Nilius AM,Alder JD,Meulbroek JA,Or YS

更新日期：1999-10-07 00:00:00

abstract：:A facile route to perillyl alcohol (POH) differential glycosylation and the corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in vitro studies revealed a sugar dependent antiproliferative activity and the inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of represen...

journal_title：Journal of medicinal chemistry

authors： Nandurkar NS,Zhang J,Ye Q,Ponomareva LV,She QB,Thorson JS

更新日期：2014-09-11 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：:Libraries of novel trisubstituted benzimidazoles were created through rational drug design. A good number of these benzimidazoles exhibited promising MIC values in the range of 0.5-6 μg/mL (2-15 μM) for their antibacterial activity against Mtb H37Rv strain. Moreover, five of the lead compounds also exhibited excellent...

journal_title：Journal of medicinal chemistry

authors： Kumar K,Awasthi D,Lee SY,Zanardi I,Ruzsicska B,Knudson S,Tonge PJ,Slayden RA,Ojima I

更新日期：2011-01-13 00:00:00

abstract：:Sulfur mustard (SM) is a highly toxic chemical warfare agent. A satisfactory treatment regimen is not yet available for this toxicant. In a search for an effective antidote against SM, a series of novel S-2(omega-aminoalkylamino)ethyl alkyl/aryl thioethers [H(2)N(CH(2))(n)()NHCH(2)CH(2)SR], where R = alky, alicyclic, ...

journal_title：Journal of medicinal chemistry

authors： Pathak U,Raza SK,Kulkarni AS,Vijayaraghvan R,Kumar P,Jaiswal DK

更新日期：2004-07-15 00:00:00

abstract：:A series of substituted phenyl analogues of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles has been synthesized and evaluated in vitro against several human rhinovirus (HRV) serotypes. Substituents in the 2-position greatly enhanced activity when compared to the unsubstituted compound. Many of these ...

journal_title：Journal of medicinal chemistry

authors： Diana GD,Oglesby RC,Akullian V,Carabateas PM,Cutcliffe D,Mallamo JP,Otto MJ,McKinlay MA,Maliski EG,Michalec SJ

更新日期：1987-02-01 00:00:00

abstract：:Tipifarnib (R115777), an inhibitor of human protein farnesyltransferase (PFT), is shown to be a highly potent inhibitor of Trypanosoma cruzi growth (ED(50) = 4 nM). Surprisingly, this is due to the inhibition of cytochrome P450 sterol 14-demethylase (CYP51, EC 1.14.13.70). Homology models of the T. cruzi CYP51 were us...

journal_title：Journal of medicinal chemistry

authors： Hucke O,Gelb MH,Verlinde CL,Buckner FS

更新日期：2005-08-25 00:00:00

abstract：:(+)-12-Fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2a) and (+)-15-epi-12-fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2b) were prepared from the readily available (-)-7-fluorospiro[bicyclo[2.2.1]hept-5-ene-2,2'-[1,3]dioxolane]-7-methanol (3). Fluoroprostaglandins 2a and 2b possess truly signific...

journal_title：Journal of medicinal chemistry

authors： Grieco PA,Takigawa T

更新日期：1981-07-01 00:00:00

abstract：:Autophagy is a lysosome-dependent mechanism of intracellular degradation for maintaining cellular homeostasis. Dysregulation of autophagy has been verified to be closely linked to a number of human diseases. Consequently, targeting autophagy has been highlighted as a novel therapeutic strategy for clinical utility. Mo...

journal_title：Journal of medicinal chemistry

authors： He S,Li Q,Jiang X,Lu X,Feng F,Qu W,Chen Y,Sun H

更新日期：2018-06-14 00:00:00

abstract：:Focal adhesion kinase (FAK) is a nonreceptor intracellular tyrosine kinase that plays an essential role in cancer cell adhesion, survival, proliferation, and migration through both its enzymatic activities and scaffolding functions. Overexpression of FAK has been found in many human cancer cells from different origins...

journal_title：Journal of medicinal chemistry

authors： Lu Y,Sun H

更新日期：2020-12-10 00:00:00

abstract：:A series of analogues of the (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptor agonist BnTetAMPA (5b) were synthesized and characterized pharmacologically in radioligand binding assays at native and cloned AMPA receptors and functionally by two-electrode voltage clamp electrophysiology at ...

journal_title：Journal of medicinal chemistry

authors： Wang SY,Larsen Y,Navarrete CV,Jensen AA,Nielsen B,Al-Musaed A,Frydenvang K,Kastrup JS,Pickering DS,Clausen RP

更新日期：2016-03-10 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：:Forty-three pyrimidine derivatives, mainly containing the 4-aminopyrimidine system, have been prepared and evaluated as inhibitors of deoxycytidine kinase. The most effective inhibitors were 2-alkylthio-4-aminopyrimidines and 1-alky-1-cytosines. The best inhibitors in both groups were those with large alkyl substituen...

journal_title：Journal of medicinal chemistry

authors： Ward AD,Baker BR

更新日期：1977-01-01 00:00:00

abstract：:Privileged structures are ligand substructures that are widely used to generate high-affinity ligands for more than one type of receptor. To explain this, we surmised that there must be some common feature in the target proteins. For a set of class A GPCRs, we found a good correlation between conservation patterns of ...

journal_title：Journal of medicinal chemistry

authors： Bondensgaard K,Ankersen M,Thøgersen H,Hansen BS,Wulff BS,Bywater RP

更新日期：2004-02-12 00:00:00

abstract：:Human melanocortin receptors (hMCRs) have been challenging targets to develop ligands that are explicitly selective for each of their subtypes. To modulate the conformational preferences of the melanocortin ligands and improve the biofunctional agonist/antagonist activities and selectivities, we have applied a backbon...

journal_title：Journal of medicinal chemistry

authors： Cai M,Marelli UK,Bao J,Beck JG,Opperer F,Rechenmacher F,McLeod KR,Zingsheim MR,Doedens L,Kessler H,Hruby VJ

更新日期：2015-08-27 00:00:00

abstract：:To provide practical means for rapidly scanning the extensive experimental combinatorial chemistry libraries now available for high-throughput screening (HTS), it is essential to establish computational virtual ligand screening (VLS) techniques to rapidly identify out of a large library all active compounds against a ...

journal_title：Journal of medicinal chemistry

authors： Floriano WB,Vaidehi N,Zamanakos G,Goddard WA 3rd

更新日期：2004-01-01 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：:HCV infection is considered a silent epidemic because most people infected do not develop acute symptoms. Instead, the disease progresses to a chronic state leading to cirrhosis and hepatocarcinoma. Novel therapies are needed to combat this major health threat. The HCV NS3 serine protease has been the target of contin...

journal_title：Journal of medicinal chemistry

authors： Velázquez F,Venkatraman S,Blackman M,Pinto P,Bogen S,Sannigrahi M,Chen K,Pichardo J,Hart A,Tong X,Girijavallabhan V,Njoroge FG

更新日期：2009-02-12 00:00:00

abstract：:A systematic exploration of bioisosteric replacements for furan and thiophene cores in a series of potent A2BAR antagonists has been carried out using the nitrogen-walk approach. A collection of 42 novel alkyl 4-substituted-2-methyl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates, which contain 18 differe...

journal_title：Journal of medicinal chemistry

authors： Mallo-Abreu A,Prieto-Díaz R,Jespers W,Azuaje J,Majellaro M,Velando C,García-Mera X,Caamaño O,Brea J,Loza MI,Gutiérrez-de-Terán H,Sotelo E

更新日期：2020-07-23 00:00:00

abstract：:A three-dimensional model of the AT1 receptor was constructed by means of a homology modeling procedure, using the X-ray structure of bovine rhodopsin as the initial template and taking into account the available site-directed mutagenesis data. The docking of losartan and its active metabolite EXP3174, followed by 1 n...

journal_title：Journal of medicinal chemistry

authors： Tuccinardi T,Calderone V,Rapposelli S,Martinelli A

更新日期：2006-07-13 00:00:00

abstract：:N-(5,5-Diacetoxypent-1-yl)doxorubicin (DAPDOX) (3), a new, water-soluble analogue of doxorubicin, has been synthesized by coupling doxorubicin with 5-oxopentane-1,1-diacetate in the presence of NaBH3CN. This analogue was designed to be converted to the corresponding aldehyde, N-(5-oxopent-1-yl)doxorubicin, in the pres...

journal_title：Journal of medicinal chemistry

authors： Cherif A,Farquhar D

更新日期：1992-08-21 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 polyhalogenated benzimidazole nucleosides 2,5, 6-trichloro-1-(beta-D-ribofuranosyl)benzimidazole (TCRB) and the 2-bromo analogue (BDCRB) were synthesized in our laboratory and established as potent and selective inhibitors of human cytomegalovirus (HCMV) with a novel mode of action. In an effort to study the behav...

journal_title：Journal of medicinal chemistry

authors： Zhu Z,Lippa B,Drach JC,Townsend LB

更新日期：2000-06-15 00:00:00

abstract：:The discovery of a new zinc binding chemotype from screening a nonbiased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted 2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the...

journal_title：Journal of medicinal chemistry

authors： Chrysanthopoulos PK,Mujumdar P,Woods LA,Dolezal O,Ren B,Peat TS,Poulsen SA

更新日期：2017-09-14 00:00:00

abstract：:Some 2-aryloxymethyl-2,3,5,6-tetrahydro-1,4-oxazines have been shown to possess marked antidepressant activity. The 1,4-oxazines were synthesized by lithium aluminum hydride reduction of the readily available 6-aryloxymethyl-2,3,5,6-tetrahydro-1,4-oxazin-3-ones. High antidepressant activity was associated with ortho s...

journal_title：Journal of medicinal chemistry

authors： Greenwood DT,Mallion KB,Todd AH,Turner RW

更新日期：1975-06-01 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：:2-Alkylchromen-4-one 6-O-sulfamates, a new class of potent steroid sulfatase (STS) inhibitors, were evaluated for their estrogenic potential. Structure-activity relationships for estrogenic activity were identified; however, no correlation with STS inhibition was found. Estrogenicity is favored by bulky side chains an...

journal_title：Journal of medicinal chemistry

authors： Nussbaumer P,Winiski AP,Billich A

更新日期：2003-11-06 00:00:00

abstract：:An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to unders...

journal_title：Journal of medicinal chemistry

authors： Snow RJ,Cardozo MG,Morwick TM,Busacca CA,Dong Y,Eckner RJ,Jacober S,Jakes S,Kapadia S,Lukas S,Panzenbeck M,Peet GW,Peterson JD,Prokopowicz AS 3rd,Sellati R,Tolbert RM,Tschantz MA,Moss N

更新日期：2002-08-01 00:00:00

abstract：:An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to ...

journal_title：Journal of medicinal chemistry

authors： Cushman M,Nagarathnam D,Gopal D,Chakraborti AK,Lin CM,Hamel E

更新日期：1991-08-01 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