A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I.

abstract：:Several p-terphenyl compounds have been isolated from the edible Chinese mushroom Thelephora vialis. Vialinin A, a p-terphenyl compound, strongly inhibits tumor necrosis factor-α production and release. Vialinin A inhibits the enzymatic activity of ubiquitin-specific peptidase 5, one of the target molecules in RBL-2H3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yoshioka Y,Namiki D,Makiuchi M,Sugaya K,Onose J,Ashida H,Abe N

更新日期：2016-09-01 00:00:00

abstract：:Novel prostaglandin E2 receptor 4 (EP4) agonists featuring a pyridone core and an allylic alcohol ω-chain were discovered. These agonists were shown to be selective over EP1, EP2 and EP3. Analogs harboring a 4-carboxylic acid phenethyl α-chain displayed improved potency over those containing an n-heptanoic acid chain....

journal_title：Bioorganic & medicinal chemistry letters

authors： Dorich S,Cox JH,Burch JD,Chagnon F,Chen B,Léger S,St-Onge M,Fader LD

更新日期：2020-05-15 00:00:00

abstract：:The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vasudevan A,Conner SE,Gentles RG,Faghih R,Liu H,Dwight W,Ireland L,Kang CH,Esbenshade TA,Bennani YL,Hancock AA

更新日期：2002-11-04 00:00:00

abstract：:Identification of a number of highly potent M2 receptor antagonists with >100-fold selectivity against the M1 and M3 receptor subtypes is described. In the rat microdialysis assay, this series of compounds showed pronounced enhancement of brain acetylcholine release after oral administration. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang Y,Chackalamannil S,Hu Z,Clader JW,Greenlee W,Billard W,Binch H,Crosby G,Ruperto V,Duffy RA,McQuade R,Lachowicz JE

更新日期：2000-10-16 00:00:00

abstract：:Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family bearing a p-alkylphenyl side chain have been synthesised and tested for their antiviral activity against Varicella-Zoster virus (VZV). While the alkyl chain analogues were shown to retain full antiviral activity against VZV, these ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Angell A,McGuigan C,Garcia Sevillano L,Snoeck R,Andrei G,De Clercq E,Balzarini J

更新日期：2004-05-17 00:00:00

abstract：:We herein report a group of allosteric inhibitors of integrin alpha(2)beta(1) based on an arylamide scaffold. Compound 4 showed an IC(50) of 4.80 microM in disrupting integrin I-domain/collagen binding in an ELISA. These arylamide compounds are able to block collagen binding to integrin alpha(2)beta(1) on the platelet...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yin H,Gerlach LO,Miller MW,Moore DT,Liu D,Vilaire G,Bennett JS,DeGrado WF

更新日期：2006-07-01 00:00:00

abstract：:The efflux transporter protein P-glycoprotein (P-gp) is capable of affecting the central distribution of diverse neurotherapeutics, including opioid analgesics, through their active removal from the brain. P-gp located at the blood brain barrier has been implicated in the development of tolerance to opioids and demons...

journal_title：Bioorganic & medicinal chemistry letters

authors： Metcalf MD,Rosicky AD,Hassan HE,Eddington ND,Coop A,Cunningham CW,Mercer SL

更新日期：2014-08-01 00:00:00

abstract：:A series of 10-hydroxy-7,8-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-diones was synthesized and tested for their inhibition of HIV-1 replication in cell culture. Structure-activity studies indicated that high antiviral potency against wild-type virus as well as viruses containing integrase mutation...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wiscount CM,Williams PD,Tran LO,Embrey MW,Fisher TE,Sherman V,Homnick CF,Donnette Staas D,Lyle TA,Wai JS,Vacca JP,Wang Z,Felock PJ,Stillmock KA,Witmer MV,Miller MD,Hazuda DJ,Day AM,Gabryelski LJ,Ecto LT,Schleif WA

更新日期：2008-08-15 00:00:00

abstract：:Introduction of a nitrogen atom into the 6-position of a series of pyrazolo[3,4-b]pyridines led to a dramatic improvement in the potency of GSK-3 inhibition. Rationalisation of the binding mode suggested participation of a putative structural water molecule, which was subsequently confirmed by X-ray crystallography. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Witherington J,Bordas V,Haigh D,Hickey DM,Ife RJ,Rawlings AD,Slingsby BP,Smith DG,Ward RW

更新日期：2003-05-05 00:00:00

abstract：:A novel cys-annexin A5 with a single cysteine-residue at its concave side has been developed by site-directed mutagenesis to allow conjugation through thiol-chemistry without affecting its apoptotic cell binding properties and was derivatized with HYNIC in a 1:1 stoichiometry. Similar to that of the 1st generation 99m...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fonge H,de Saint Hubert M,Vunckx K,Rattat D,Nuyts J,Bormans G,Ni Y,Reutelingsperger C,Verbruggen A

更新日期：2008-07-01 00:00:00

abstract：:The first example of dual inhibitors for matrix metalloproteinase (MMP) and cathepsin is described. An appropriate alignment of peptide-parts and two different specific functional groups in one molecule led to the discovery of a potent dual inhibitor (3a). ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamamoto M,Ikeda S,Kondo H,Inoue S

更新日期：2002-02-11 00:00:00

abstract：:The synthesis and anti-angiogenic activities of linomide and its analogues are reported. Three of the analogues are 3.3-69 times more potent than linomide at inhibiting blood vessel formation in the CAM angiogenesis assay. These compounds possessed considerable anti-proliferative activity against isolated HUVEC cells ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shi J,Xiao Z,Ihnat MA,Kamat C,Pandit B,Hu Z,Li PK

更新日期：2003-03-24 00:00:00

abstract：:In the course of ongoing research on protein tyrosine phosphatase 1B (PTP1B) inhibitory compounds from Antarctic lichens, four new diterpene furanoids, hueafuranoids A-D (1-4) have been isolated from the MeOH extract of Antarctic lichen Huea sp. by various chromatographic methods. The structures of these compounds wer...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cui Y,Yim JH,Lee DS,Kim YC,Oh H

更新日期：2012-12-15 00:00:00

abstract：:We report the design, synthesis, and structure-activity relationship (SAR) of a series of novel pyrido[2,3-d]pyrimidin-7-one compounds as potent Abl kinase inhibitors. We evaluate their specificity profile against a panel of human recombinant kinases, as well as their biological profile toward a panel of well-characte...

journal_title：Bioorganic & medicinal chemistry letters

authors： Antczak C,Veach DR,Ramirez CN,Minchenko MA,Shum D,Calder PA,Frattini MG,Clarkson B,Djaballah H

更新日期：2009-12-15 00:00:00

abstract：:A series of genistein derivatives, prepared by alkylation and difluoromethylation, were tested for their inhibitory effects on the hydrogen peroxide induced impairment in human umbilical vein endothelial (HUVE-12) cells in vitro. The HUVE-12 cells were pretreated with either the vehicle solvent (DMSO), genistein, or d...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fu XH,Wang L,Zhao H,Xiang HL,Cao JG

更新日期：2008-01-15 00:00:00

abstract：:The multiple-step, one-pot procedure for a series of 2-substituted-3-phosphono-1-thia-4-aza-2-cyclohexene-5-carboxylates, analogues of the natural, sulfur amino acid metabolite lanthionine ketimine (LK), its 5-ethyl ester (LKE) and 2-substituted LKEs is described. Initiating the synthesis with the Michaelis-Arbuzov pr...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shen D,Hensley K,Denton TT

更新日期：2018-02-15 00:00:00

abstract：:The 2',6'-dimethyl-l-tyrosine (Dmt) enhances receptor affinity, functional bioactivity and in vivo analgesia of opioid peptides. To further investigate its direct influence on these opioid parameters, we developed a series of compounds (H-Dmt-NH-X). Among them, H-Dmt-NH-CH(3) showed the highest affinity (K(i)mu=7.45 n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fujita Y,Tsuda Y,Motoyama T,Li T,Miyazaki A,Yokoi T,Sasaki Y,Ambo A,Niizuma H,Jinsmaa Y,Bryant SD,Lazarus LH,Okada Y

更新日期：2005-02-01 00:00:00

abstract：:A novel class of 1-[4-(1H-benzoimidazol-2-yl)-phenyl]-3-[4-(1H-benzoimidazol-2-yl)-phenyl]-ureas are described as potent inhibitors of heparanase. Among them are 1,3-bis-[4-(1H-benzoimidazol-2-yl)-phenyl]-urea (7a) and 1,3-bis-[4-(5,6-dimethyl-1H-benzoimidazol-2-yl)-phenyl]-urea (7d), which displayed good heparanase i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pan W,Miao HQ,Xu YJ,Navarro EC,Tonra JR,Corcoran E,Lahiji A,Kussie P,Kiselyov AS,Wong WC,Liu H

更新日期：2006-01-15 00:00:00

abstract：:The structure-activity relationship of various N-acyl-Gly-, N-acyl-Sar-, and N-blocked-boroPro derivatives against three prolyl peptidases was explored. Several N-acyl-Gly- and N-blocked-boroPro compounds showed low nanomolar inhibitory activity against fibroblast activation protein (FAP) and prolyl oligopeptidase (PO...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tran T,Quan C,Edosada CY,Mayeda M,Wiesmann C,Sutherlin D,Wolf BB

更新日期：2007-03-01 00:00:00

abstract：:Prodrug esters of the indolocarbazole CEP-751 (KT-6587) were prepared with the goal of identifying water soluble, stable but cleavable forms for intravenous dosing. A dipeptide proform Lys-beta-Ala (16, CEP-2563/KT-8391) was identified for advancement to clinical trials. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hudkins RL,Iqbal M,Park CH,Goldstein J,Herman JL,Shek E,Murakata C,Mallamo JP

更新日期：1998-07-21 00:00:00

abstract：:A series of novel arylsulfonylpropargylglycinamide derivatives was investigated as thrombin inhibitors in which the SAR was focused on substituents at the acetylenic terminus. Several compounds in this series were identified as potent thrombin inhibitors (Ki up to 5 nM) that are highly selective over trypsin and other...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee K,Hwang SY,Park CW

更新日期：1999-04-05 00:00:00

abstract：:Herein, we reported the synthesis of 16 novel steroidal thiosemicarbazone derivatives via the condensation of steroidal ketones and substituted thiosemicarbazides under solvent-free conditions using microwave irradiation. The yields obtained are in the range of 84-96% using microwave method and 46-62% using convention...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhao Z,Shi Z,Liu M,Liu X

更新日期：2012-12-15 00:00:00

abstract：:Nineteen new 2-pyrazoline bearing benzenesulfonamide derivatives were synthesized by condensing chalcones with 4-hydrazinonbenzenesulfonamide hydrochloride. Their chemical structures were proved by means of IR, (1)H NMR, (13)C NMR, mass spectroscopic and elemental analyses data. These compounds were tested at dose of ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rathish IG,Javed K,Ahmad S,Bano S,Alam MS,Pillai KK,Singh S,Bagchi V

更新日期：2009-01-01 00:00:00

abstract：:We have synthesized 3 analogs of the dopamine D2 receptor (D2 DR) antagonist spiperone that can be conjugated to streptavidin-coated quantum dots via a pegylated biotin derivative. Using fluorescent imaging we demonstrate that substitution on the spiro position is tolerated, whilst the length and rigidity of a spacer ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tomlinson ID,Kovtun O,Crescentini TM,Rosenthal SJ

更新日期：2019-04-15 00:00:00

abstract：:Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator in insulin- and leptin-signaling cascades as well as a positive regulator in tumorigenesis, and much attention has been paid to PTP1B inhibitors as potential therapies for diabetes, obesity, and cancer. In the present study, the screening of a compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Li W,Li S,Higai K,Sasaki T,Asada Y,Ohshima S,Koike K

更新日期：2013-11-01 00:00:00

abstract：:Successful efforts to make farnesyl transferase (FT) inhibitors with appropriately tethered ligands designed to interact with a catalytic zinc that exist in the enzyme have been realized. Thus, by introducing either a pyridylmethylamino or propylaminolimidazole amide moieties off the 2-position of the piperidine ring,...

journal_title：Bioorganic & medicinal chemistry letters

authors： Njoroge FG,Vibulbhan B,Pinto P,Strickland C,Kirschmeier P,Bishop WR,Girijavallabhan V

更新日期：2004-12-06 00:00:00

abstract：:A series of N-(piperidin-3-yl)-N-(pyridin-2-yl)piperidine/piperazine-1-carboxamides were identified as small molecule PCSK9 mRNA translation inhibitors. Analogues from this new chemical series, such as 4d and 4g, exhibited improved PCSK9 potency, ADME properties, and in vitro safety profiles when compared to earlier l...

journal_title：Bioorganic & medicinal chemistry letters

authors： Londregan AT,Aspnes G,Limberakis C,Loria PM,McClure KF,Petersen DN,Raymer B,Ruggeri RB,Wei L,Xiao J,Piotrowski DW

更新日期：2018-12-15 00:00:00

abstract：:Tripeptide-derived molecules incorporating C-terminal ketone electrophiles were evaluated as reversible inhibitors of the cysteine-containing human rhinovirus 3C protease (3CP). An optimized example of such compounds displayed potent 3CP inhibition activity (K = 0.0045 microM) and in vitro antiviral properties (EC50=0...

journal_title：Bioorganic & medicinal chemistry letters

authors： Dragovich PS,Zhou R,Webber SE,Prins TJ,Kwok AK,Okano K,Fuhrman SA,Zalman LS,Maldonado FC,Brown EL,Meador JW 3rd,Patick AK,Ford CE,Brothers MA,Binford SL,Matthews DA,Ferre RA,Worland ST

更新日期：2000-01-03 00:00:00

abstract：:In a lead optimization effort towards NS5B NNI inhibitors, two multi-step parallel libraries were designed and successfully synthesized. Through this effort we discovered compound 9B, which achieved rigorous and delicate balance of inhibition across the common genotypes and mutants with <10 nM potency. In addition, th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Xiao D,Dai X,Liu H,He S,Shi ZC,Ludmerer SW,Li F,Nargund R,Palani A

更新日期：2020-04-01 00:00:00

abstract：:Low brain levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) lead to convulsions. Inhibition of GABA aminotransferase increases the concentration of GABA and can terminate the convulsions. Earlier we reported the synthesis of (1S,3S)-3-amino-4-difluoromethylenecyclopentanecarboxylic acid (2), whi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yuan H,Silverman RB

更新日期：2007-03-15 00:00:00