Cyclopenta[g]quinazoline-based antifolates: the effect of the chirality at the 6-position on the inhibition of thymidylate synthase (TS).

abstract：:Aminobenzyloxyarylamide derivatives 1a-i and 2a-t were designed and synthesized as novel selective κ opioid receptor (KOR) antagonists. The benzoyl amide moiety of LY2456302 was changed into N-hydroxybenzamide and benzisoxazole-3(2H)-one to investigate whether it could increase the binding affinity or selectivity for ...

journal_title：Bioorganic & medicinal chemistry letters

authors： He G,Song Q,Wang J,Xu A,Peng K,Zhu Q,Xu Y

更新日期：2020-07-01 00:00:00

abstract：:The 1,3-dipolar cycloaddition of azomethine ylides derived from acenaphthenequinone and alpha-amino acids viz. sarcosine, phenylglycine, 1,3-thiazolane-4-carboxylic acid and proline to a series of 2,6-bis[(E)-arylmethylidene]cyclohexanones afforded novel spiro-heterocycles chemo-, regio- and stereoselectively in quant...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ranjith Kumar R,Perumal S,Manju SC,Bhatt P,Yogeeswari P,Sriram D

更新日期：2009-07-01 00:00:00

abstract：:Previously, potent factor Xa inhibitors were described based on a pyrazole core. Modifications of the pyrazole core have provided additional novel, highly potent factor Xa inhibitors. This manuscript will describe the synthesis and biological activity of factor Xa inhibitors containing the 1H-pyrazolo[4,3-d]pyrimidin-...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fevig JM,Cacciola J,Buriak J Jr,Rossi KA,Knabb RM,Luettgen JM,Wong PC,Bai SA,Wexler RR,Lam PY

更新日期：2006-07-15 00:00:00

abstract：:The enantioselective activation of nitroalkanes was attempted on the basis of the complexation between chiral guanidinium and nitronate through two hydrogen bonds. The proposed enantioselective activation was applied to the diastereo- and enantioselective Henry (nitroaldol) reaction of nitroalkanes with aldehydes usin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ube H,Terada M

更新日期：2009-07-15 00:00:00

abstract：:A series of NN703 analogues with lysine mimetics combined with naphthyl- or biphenylalanine in the core has been prepared and tested in vitro in a rat pituitary cell based assay and subsequently in vivo in pigs in a single dose at 50 nmol/kg. Re-introduction of certain pharmacophores in the C-terminal of NN703, which ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hansen TK,Ankersen M,Raun K,Hansen BS

更新日期：2001-07-23 00:00:00

abstract：:Moutan Cortex is a well-known herb in traditional Korean, Chinese, and Japanese anti-diabetic formulae. In the current study, we investigated the metabolic effects of isolated triterpenes (1-7) in HepG2 cells under high glucose conditions. These compounds remakably stimulated AMP-activated protein kinase (AMPK), GSK-3...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ha do T,Tuan DT,Thu NB,Nhiem NX,Ngoc TM,Yim N,Bae K

更新日期：2009-10-01 00:00:00

abstract：:A novel neomycin-methidium conjugate was synthesized. The covalent linkage of the aminoglycoside to an intercalator, a derivative of ethidium bromide, results in a new conjugate capable of selective recognition of the DNA:RNA hybrid duplex. Spectroscopic methods: UV, CD, fluorescence, and calorimetric techniques: DSC ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Shaw NN,Xi H,Arya DP

更新日期：2008-07-15 00:00:00

abstract：:A series of oligo-peptide based catalysts were prepared using Fmoc solid-phase peptide synthesis. It was found that peptides with N-terminal proline residues catalyzed an aldol reaction yielding enantiomeric enriched product. Peptide H-Pro-Glu-Leu-Phe-OH catalyzed the reaction with good activity and moderate enantiose...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kofoed J,Nielsen J,Reymond JL

更新日期：2003-08-04 00:00:00

abstract：:The novel analysis method consisting of size-exclusion chromatography (SEC) and HRMS analysis was firstly applied in the discovery of potential inhibitors towards cancer drug targets. With vascular endothelial growth factor receptor (VEGFR-2) as a target, dynamic combinatorial libraries (DCLs) were prepared by reactin...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang Z,Fang Z,He W,Wang Z,Gan H,Tian Q,Guo K

更新日期：2016-04-01 00:00:00

abstract：:Detailed structure-activity relationships of the C3-phenyl moiety that allow for the optimization of antiviral potency of a series of 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione inhibitors of HIV capsid (CA) assembly are described. Combination of favorable substitutions gave additive SAR and allowed for the identifica...

journal_title：Bioorganic & medicinal chemistry letters

authors： Fader LD,Landry S,Goulet S,Morin S,Kawai SH,Bousquet Y,Dion I,Hucke O,Goudreau N,Lemke CT,Rancourt J,Bonneau P,Titolo S,Amad M,Garneau M,Duan J,Mason S,Simoneau B

更新日期：2013-06-01 00:00:00

abstract：:An HTS screening campaign identified a series of low molecular weight phenols that showed excellent selectivity (>100-fold) for HDAC1/HDAC2 over other Class I and Class II HDACs. Evolution and optimization of this HTS hit series provided HDAC1-selective (SHI-1) compounds with excellent anti-proliferative activity and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wilson KJ,Witter DJ,Grimm JB,Siliphaivanh P,Otte KM,Kral AM,Fleming JC,Harsch A,Hamill JE,Cruz JC,Chenard M,Szewczak AA,Middleton RE,Hughes BL,Dahlberg WK,Secrist JP,Miller TA

更新日期：2008-03-15 00:00:00

abstract：:We have developed a novel series of pyrrolidine derived BACE-1 inhibitors. The potency of the weak initial lead structure was enhanced using library-based SAR methods. The series was then further advanced by rational design while maintaining a minimal ligand binding efficiency threshold. Ultimately, the co-crystal str...

journal_title：Bioorganic & medicinal chemistry letters

authors： Stachel SJ,Steele TG,Petrocchi A,Haugabook SJ,McGaughey G,Katharine Holloway M,Allison T,Munshi S,Zuck P,Colussi D,Tugasheva K,Wolfe A,Graham SL,Vacca JP

更新日期：2012-01-01 00:00:00

abstract：:Several unnatural derivatives of narciclasine were prepared in which the C-7 carbon was replaced with nitrogen. The 7-aza derivative and its N-oxide were prepared by the coupling of iodopicolinic acid with a conduramine unit derived chemoenzymatically from bromobenzene. Intramolecular Heck reaction was used to constru...

journal_title：Bioorganic & medicinal chemistry letters

authors： Vshyvenko S,Reisenauer MR,Rogelj S,Hudlicky T

更新日期：2014-09-01 00:00:00

abstract：:We recently described a new family of bioactive molecules with interesting anti-cancer activities: the N-(4-(3-aminophenyl)thiazol-2-yl)acetamides. The lead compound of the series (1) displays significant anti-proliferative and cytotoxic activities against a panel of cancer cell lines, either sensitive or resistant to...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ronco C,Millet A,Plaisant M,Abbe P,Hamouda-Tekaya N,Rocchi S,Benhida R

更新日期：2017-05-15 00:00:00

abstract：:To investigate the stability of 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentafuranosylcytosine 3'-phosphoric acid, its thymidine ester was prepared via the phosphoramidite method using allyl protection for the phosphate function. This ester is stable under acidic conditions but extremely labile under basic conditions, de...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hayakawa Y,Kawai R,Otsuki K,Kataoka M,Matsuda A

更新日期：1998-09-22 00:00:00

abstract：:Aminoglycoside antibiotics target an internal RNA loop within the bacterial ribosomal decoding site. Here, we describe the synthesis and SAR of novel 3,5-diamino-piperidine derivatives as aminoglycoside mimetics, and show they act as inhibitors of bacterial translation and growth. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhou Y,Gregor VE,Ayida BK,Winters GC,Sun Z,Murphy D,Haley G,Bailey D,Froelich JM,Fish S,Webber SE,Hermann T,Wall D

更新日期：2007-03-01 00:00:00

abstract：:Inhibition of the aspartyl protease renin is considered as an efficient approach for treating hypertension. Lately, we described the discovery of a novel class of direct renin inhibitors which comprised a pyrrolidine scaffold (e.g., 2). Based on the X-ray structure of the lead compound 2 bound to renin we predicted th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sellner H,Cottens S,Cumin F,Ehrhardt C,Kosaka T,Lorthiois E,Ostermann N,Webb RL,Rigel DF,Wagner T,Maibaum J

更新日期：2015-04-15 00:00:00

abstract：:A series of didzein derivatives were synthesized and assessed for stimulation of osteoblast differentiation using primary cultures of rat calvarial osteoblasts. Data suggested that three synthetic analogs, 1c, 3a and 3c were several folds more potent than daidzein in stimulating differentiation and mineralization of o...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yadav DK,Gautam AK,Kureel J,Srivastava K,Sahai M,Singh D,Chattopadhyay N,Maurya R

更新日期：2011-01-15 00:00:00

abstract：:Our first generation of hydroxyethylamine BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improv...

journal_title：Bioorganic & medicinal chemistry letters

authors： Charrier N,Clarke B,Cutler L,Demont E,Dingwall C,Dunsdon R,Hawkins J,Howes C,Hubbard J,Hussain I,Maile G,Matico R,Mosley J,Naylor A,O'Brien A,Redshaw S,Rowland P,Soleil V,Smith KJ,Sweitzer S,Theobald P,Vesey D,

更新日期：2009-07-01 00:00:00

abstract：:Two new trichothecene sesquiterpenes, trichobreols D (1) and E (2), were isolated from the culture broth of marine-derived Trichoderma cf. brevicompactum together with trichobreol A (3). The structures of 1 and 2 were assigned on the basis of their spectroscopic data. Compound 1 inhibited the growth of two yeast-like ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yamazaki H,Yagi A,Takahashi O,Yamaguchi Y,Saito A,Namikoshi M,Uchida R

更新日期：2020-09-01 00:00:00

abstract：:Cyclin-dependent kinase 5 (CDK5) is a serine-threonine protein kinase that plays a significant role in neuronal development. In association with p25, CDK5 abnormally phosphorylates a number of cellular targets involved in neurodegenerative disorders. Using active site homology and previous structure-activity relations...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaller MR,Zhong W,Henley C,Magal E,Nguyen T,Powers D,Rzasa RM,Wang W,Xiong X,Norman MH

更新日期：2009-12-01 00:00:00

abstract：:Early studies led to the identification of 11β-aryl-4',5'-dihydrospiro[estra-4,9-diene-17β,4'-oxazole] analogs with potent and more selective antiprogestational activity compared to antiglucocorticoid activity than mifepristone. In the present study, we replaced the 4'-dimethylaminophenyl group of mifepristone with th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jin C,Fix SE,Kepler JA,Cook CE

更新日期：2012-02-15 00:00:00

abstract：:The synthesis of nine bivalent lactosides (based on ditriazoles, diamides, a glycocyclophane and an acyclic analogue of the glycocyclophane) and one monovalent lactosyl triazole facilitated the assessment of the sensitivity of plant/animal lectins to this type of ligand display. The inhibitory potency of the compounds...

journal_title：Bioorganic & medicinal chemistry letters

authors： André S,Jarikote DV,Yan D,Vincenz L,Wang GN,Kaltner H,Murphy PV,Gabius HJ

更新日期：2012-01-01 00:00:00

abstract：:The CXCR2 SAR of a series of bicyclic antagonists such as the 2-aminothiazolo[4,5-d]pyrimidine 3b was investigated by systematic variation of the fused pyrimidine-based heterocyclic cores. Replacement of the aminothiazole ring with a 2-thiazolone alternative led to a series of thiazolo[4,5-d]pyrimidine-2(3H)-one antag...

journal_title：Bioorganic & medicinal chemistry letters

authors： Walters I,Austin C,Austin R,Bonnert R,Cage P,Christie M,Ebden M,Gardiner S,Grahames C,Hill S,Hunt F,Jewell R,Lewis S,Martin I,David Nicholls,David Robinson

更新日期：2008-01-15 00:00:00

abstract：:Based upon a previously reported lead compound 1, a series of 1,2-diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines were synthesized and evaluated for improved physiochemical and pharmacokinetic properties while maintaining TRPV1 antagonist activity. Structure-activity relationship studies direc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lebsack AD,Rech JC,Branstetter BJ,Hawryluk NA,Merit JE,Allison B,Rynberg R,Buma J,Rizzolio M,Swanson N,Ao H,Maher MP,Herrmann M,Freedman J,Scott BP,Luo L,Bhattacharya A,Wang Q,Chaplan SR,Wickenden AD,Breitenbucher

更新日期：2010-12-01 00:00:00

abstract：:Two novel constrained l-AP4 analogues, (2S,1'R,2'S)- and (2S,1'S,2'R)-2-(2'-phosphonocyclopropyl)glycines (7) and (8), were synthesized and evaluated as mGluR ligands. Compound 7 showed to be a group III mGluRs agonist with micromolar activity. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Amori L,Serpi M,Marinozzi M,Costantino G,Diaz MG,Hermit MB,Thomsen C,Pellicciari R

更新日期：2006-01-01 00:00:00

abstract：:A series of fluconazole analogues 5-20 incorporating azaindole and indole moieties were prepared using oxirane intermediates synthesized under microwave irradiation. All of the compounds were evaluated in vitro against two clinically important fungi, Candida albicans and Aspergillus fumigatus. Four derivatives 6, 13, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lebouvier N,Pagniez F,Duflos M,Le Pape P,Na YM,Le Baut G,Le Borgne M

更新日期：2007-07-01 00:00:00

abstract：:We describe here a novel 4-amino-2-cyanopyrimidine scaffold for nonpeptidomimetic cathepsin S selective inhibitors. Some of the synthesized compounds have sub-nanomolar potency and high selectivity toward cathepsin S along with promising pharmacokinetic and physicochemical properties. The key structural features of th...

journal_title：Bioorganic & medicinal chemistry letters

authors： Irie O,Yokokawa F,Ehara T,Iwasaki A,Iwaki Y,Hitomi Y,Konishi K,Kishida M,Toyao A,Masuya K,Gunji H,Sakaki J,Iwasaki G,Hirao H,Kanazawa T,Tanabe K,Kosaka T,Hart TW,Hallett A

更新日期：2008-08-15 00:00:00

abstract：:Three novel metabolites of the angiotensin-II (A-II) receptor antagonist tasosartan have been identified in humans, and the syntheses and pharmacologic profiling of these metabolites are reported. Each metabolite bound the human A-II receptor with IC(50)s between 20 and 45nM. The in vivo effects of these compounds in ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Elokdah HM,Friedrichs GS,Chai SY,Harrison BL,Primeau J,Chlenov M,Crandall DL

更新日期：2002-08-05 00:00:00

abstract：:A number of novel 1-(3-arylprop-2-ynyl) substituted 1,2-dihydroquinoline derivatives related to nimesulide and their 2-oxo analogues have been designed as potential inhibitors of PDE4. All these compounds were synthesized by using Sonogashira coupling as a key step. In vitro PDE4B inhibitory properties and molecular m...

journal_title：Bioorganic & medicinal chemistry letters

authors： Pal S,Durgadas S,Nallapati SB,Mukkanti K,Kapavarapu R,Meda CL,Parsa KV,Pal M

更新日期：2011-11-01 00:00:00