Design and synthesis of 4-[3,5-dioxo-11-oxa-4,9-diazatricyclo[5.3.1.0(2,6)]undec-4-yl]-2-trifluoromethyl-benzonitriles as androgen receptor antagonists.

abstract：:Damage to DNA is caused by ionizing radiation, genotoxic chemicals or collapsed replication forks. When DNA is damaged or cells fail to respond, a mutation that is associated with breast or ovarian cancer may occur. Mammalian cells control and stabilize the genome using a cell cycle checkpoint to prevent damage to DNA...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang YL,Lin CY,Shih KC,Huang JW,Tang CY

更新日期：2013-12-01 00:00:00

abstract：:Five-coordinated oxovanadium(IV) complexes with ciprofloxacin and various uninegative bidentate amino acids have been prepared. The structure of complexes has been investigated using spectral, physicochemical, mass spectroscopy, and elemental analyses. The antimicrobial activities (MIC) of the complexes, ligands, meta...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patel MN,Patel SH,Chhasatia MR,Parmar PA

更新日期：2008-12-15 00:00:00

abstract：:A series of 1-(quinoliloxypropyl)-4-aryl-piperazines has been synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypic behaviour in mice. The 8-hydroxyquinoline ether derivative 14 has emerged as an important lead compound showing a potenti...

journal_title：Bioorganic & medicinal chemistry letters

authors： Bali A,Malhotra S,Dhir H,Kumar A,Sharma A

更新日期：2009-06-01 00:00:00

abstract：:We report here the synthesis and biological evaluation of a series of 37 compounds as precursors of potent antimalarial bis-thiazolium salts (T3 and T4). These prodrugs were either thioester, thiocarbonate or thiocarbamate type and were synthesized in one step by reaction of an alkaline solution of the parent drug wit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Caldarelli SA,Boisbrun M,Alarcon K,Hamzé A,Ouattara M,Salom-Roig X,Maynadier M,Wein S,Peyrottes S,Pellet A,Calas M,Vial H

更新日期：2010-07-01 00:00:00

abstract：:We report, for the first time, that certain N-acetylthiourea derivatives serve as highly potent and isozyme selective activators for the recombinant form of human histone deacetylase-8 in the assay system containing Fluor-de-Lys as a fluorescent substrate. The experimental data reveals that such activating feature is ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Singh RK,Mandal T,Balsubramanian N,Viaene T,Leedahl T,Sule N,Cook G,Srivastava DK

更新日期：2011-10-01 00:00:00

abstract：:Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipide...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yu P,Liu W,Ren J,Wang Y,Ning Y,Huang M,Hu X,Wei L,Ji M,Cai J

更新日期：2019-08-15 00:00:00

abstract：:A new hepatitis C virus (HCV) protease inhibitor designated as Sch 351633 (1) was isolated from the fungus, Penicillium griseofulvum. Structure elucidation of 1 was accomplished by analysis of spectroscopic data, which determined compound 1 to be a bicyclic hemiketal lactone. Compound 1 exhibited inhibitory activity i...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu M,Mierzwa R,He L,King A,Patel M,Pichardo J,Hart A,Butkiewicz N,Puar MS

更新日期：1999-07-19 00:00:00

abstract：:The vertebrate Cys-loop family of ligand-gated ion channels (LGICs) are comprised of nicotinic acetylcholine (nAChR), serotonin type 3 (5-HT3R), γ-aminobutyric acid (GABAAR), and glycine (GlyR) receptors. Here, we review efforts to discover selective small molecules targeting one or more Cys-loop receptors, with a foc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sparling BA,DiMauro EF

更新日期：2017-08-01 00:00:00

abstract：:2-Octyl gamma-bromoacetoacetate (O gamma Br), an endogenous compound originally isolated from human cerebrospinal fluid (CSF), has previously been demonstrated to increase REM sleep duration in cats. Based on the chemical structure of O gamma Br and its reported sleep-inducing effects, we synthesized O gamma Br along ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Patricelli MP,Patterson JE,Boger DL,Cravatt BF

更新日期：1998-03-17 00:00:00

abstract：:Five new p-terphenyls named prenylterphenyllin D (1), prenylterphenyllin E (2), 2'-O-methylprenylterphenyllin (3), 4-O-methylprenylterphenyllin (4) and 3'-O-methylterphenyllin (5) together with seven known compounds (6-12), were isolated from cultures of Aspergillus sp. YXf3. The structures of the new compounds were e...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yan W,Wuringege,Li SJ,Guo ZK,Zhang WJ,Wei W,Tan RX,Jiao RH

更新日期：2017-01-01 00:00:00

abstract：:Prostate cancer is the most frequently diagnosed cancer and is one of the leading causes of male cancer death in the world. Recently, in the course of our screening for a novel anticancer compound, we synthesized carbocyclic analogs of pyrrolo[2,3-d]pyrimidine nucleoside; compounds 5, and 6. In the current study, we r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Suh H,Choi KW,Lee J,Ryou C,Rhee H,Lee CH

更新日期：2016-02-15 00:00:00

abstract：:Phosphopeptide prodrugs bearing two S-acyl-2-thioethyl (SATE) biolabile phosphate protections were developed. They are capable to inhibit the Shc/Grb2 interaction and MAP kinases (ERK1 and ERK2) phosphorylation in cellular assay. The S-acetyl-2-thioethyl (MeSATE) analogue showed an IC50 of 1 microM in the inhibition o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu WQ,Vidal M,Mathé C,Périgaud C,Garbay C

更新日期：2000-04-03 00:00:00

abstract：:The inhibitive activities of the human immunodeficiency virus protease inhibitors ritonavir (RTV) boosted indinavir (IDV) and RTV boosted lopinavir (LPV) for erythrocytic stage malaria were evaluated in rhesus macaques. The IDV/RTV regimen effectively inhibits the replication of Plasmodium knowlesi with clinically rel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Qin L,Qin L,Xu W,Zhao S,Chen X

更新日期：2015-04-01 00:00:00

abstract：:Enedione derivatives of thieno[2,3-d]oxazinones are nanomolar inhibitors of CMV protease which act through a novel dual acylation of the catalytic serine and alkylation of the protease cysteine 161 via a Michael addition to the enedione moiety of the inhibitor. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pinto IL,Jarvest RL,Clarke B,Dabrowski CE,Fenwick A,Gorczyca MM,Jennings LJ,Lavery P,Sternberg EJ,Tew DG,West A

更新日期：1999-02-08 00:00:00

abstract：:A novel class of benzocinnolinones analogs of irdabisant were designed and synthesized as histamine H3R antagonists/inverse agonists. Modifications to the pyridazinone portion of the core and linker led to the identification of molecules with excellent target potency and selectivity with improved rat pharmacokinetic p...

journal_title：Bioorganic & medicinal chemistry letters

authors： Josef KA,Aimone LD,Lyons J,Raddatz R,Hudkins RL

更新日期：2012-06-15 00:00:00

abstract：:2,3-Dihydro-3,8-diphenylbenzo[1,4]oxazines were identified as a new class of potent cholesteryl ester transfer protein inhibitors. The most potent compound 6a (IC50=26 nM) possessed a favorable pharmacokinetic profile with good oral bioavailability in rat (F=53%) and long human liver microsome stability (t(1/2)=62 min...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang A,Prouty CP,Pelton PD,Yong M,Demarest KT,Murray WV,Kuo GH

更新日期：2010-02-15 00:00:00

abstract：:Paclitaxel (PTX) was complexed with beta-cyclodextrin (1), 2,6-dimethyl-beta-cyclodextrin (2) and 2,3,6-trimethyl-beta-cyclodextrin (3). PTX-CYD complexes were characterized both at the solid and liquid states. Experimental findings are in agreement with molecular modeling analysis, which showed different PTX-CYD inte...

journal_title：Bioorganic & medicinal chemistry letters

authors： Alcaro S,Ventura CA,Paolino D,Battaglia D,Ortuso F,Cattel L,Puglisi G,Fresta M

更新日期：2002-06-17 00:00:00

abstract：:N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-[18F]fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, a new potential positron emission tomography tracer for imaging cancer tyrosine kinase, has been prepared by the nucleophilic substitution of the nitro-precursor N-[2-(diethylamino)ethyl]...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang JQ,Miller KD,Sledge GW,Zheng QH

更新日期：2005-10-01 00:00:00

abstract：:A series of alpha-alkyl-alpha-amino-beta-sulphone hydroxamates was prepared and evaluated for potency versus MMP-2 and MMP-13, and for selectivity versus MMP-1. Low nanomolar potency was obtained with selectivity versus MMP-1 ranging from >10 to >1000. Selected compounds were orally bioavailable. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Becker DP,DeCrescenzo G,Freskos J,Getman DP,Hockerman SL,Li M,Mehta P,Munie GE,Swearingen C

更新日期：2001-10-22 00:00:00

abstract：:d-Labeled N-alkylmaleimides have been prepared for specific modification of the terminal SH groups of cysteine residues in proteins or peptides. These reagents are useful tools for quantitative analysis of peptides by stable isotope differential mass spectrometry. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Niwayama S,Kurono S,Matsumoto H

更新日期：2001-09-03 00:00:00

abstract：:Homology modeling of candida lanosterol C-14 demethylase, synthesis and in vitro antifungal activities of cyclohexyl analogs of restricticin are described. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tsukuda T,Shiratori Y,Watanabe M,Ontsuka H,Hattori K,Shirai M,Shimma N

更新日期：1998-07-21 00:00:00

abstract：:A series of novel 5-trans-hydroxyadamantan-2-yl-5,6,7,8-tetrahydropyrazolo[4,3-c]azepin-4(1H)-ones that inhibit 11beta-hydroxysteroid dehydrogenase type 1 are described. We discovered these 7-membered cyclic amide derivatives by introducing a distinctive linker through pharmacophore analysis of known ligands included ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Udagawa S,Sakami S,Takemura T,Sato M,Arai T,Nitta A,Aoki T,Kawai K,Iwamura T,Okazaki S,Takahashi T,Kaino M

更新日期：2013-03-15 00:00:00

abstract：:A unique chromism-based assay technique (CHROBA) using photochromic spiropyran-containing peptides has been firstly established for detection of protein kinase A-catalyzed phosphorylation. The alternative method has advantages that avoid isolation and/or immobilization of kinase substrates to remove excess reagents in...

journal_title：Bioorganic & medicinal chemistry letters

authors： Tomizaki KY,Jie X,Mihara H

更新日期：2005-03-15 00:00:00

abstract：:Syntheses and structure-antiproliferative relationship for oxyphenisatin analogues are described. The cell proliferation data showed that the presence of substituents (especially F, Cl, Me, CF(3), and OMe) in the 6- and 7-position of oxyphenisatin markedly enhanced the potency in the MDA-468 cell line without affectin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Uddin MK,Reignier SG,Coulter T,Montalbetti C,Grånäs C,Butcher S,Krog-Jensen C,Felding J

更新日期：2007-05-15 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：:Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, whic...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ohgane K,Karaki F,Noguchi-Yachide T,Dodo K,Hashimoto Y

更新日期：2014-08-01 00:00:00

abstract：:We have developed a novel series of heteroaromatic BACE-1 inhibitors. These inhibitors interact with the enzyme in a unique fashion that allows for potent binding in a non-traditional paradigm. In addition to the elucidation of their binding profile, we have discovered a pH dependent effect on the binding affinity as ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stachel SJ,Coburn CA,Rush D,Jones KL,Zhu H,Rajapakse H,Graham SL,Simon A,Katharine Holloway M,Allison TJ,Munshi SK,Espeseth AS,Zuck P,Colussi D,Wolfe A,Pietrak BL,Lai MT,Vacca JP

更新日期：2009-06-01 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：:Identification of an HIV integrase inhibitor with micromolar affinity for the CGRP receptor led to the discovery of a series of structurally novel CGRP receptor antagonists. Optimization of this series produced compound 16, a low-molecular weight CGRP receptor antagonist with good pharmacokinetic properties in both ra...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zartman CB,Bell IM,Gallicchio SN,Graham SL,Kane SA,Mallee JJ,Rutledge RZ,Salvatore CA,Vacca JP,Williams TM

更新日期：2011-11-15 00:00:00

abstract：:The proprotein convertases PCSK8 and PCSK4 are, respectively, the 8th and 4th members of Ca(+2)-dependent serine endoprotease of Proprotein Convertase Subtilisin Kexin (PCSK) super family structurally related to the bacterial subtilisin and yeast kexin. The membrane bound PCSK8 (also called SKI-1 or S1P) is implicated...

journal_title：Bioorganic & medicinal chemistry letters

authors： Basak A,Goswami M,Rajkumar A,Mitra T,Majumdar S,O'Reilly P,Bdour HM,Trudeau VL,Basak A

更新日期：2015-01-01 00:00:00