Synthesis of a novel, recyclable, solid-phase acylating reagent.

abstract：:Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to both the P2' and P3' side chains. Enzyme inhibition and antibacterial activity data revealed that a variety of substituents are tolerated at the P2' and ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Davies SJ,Ayscough AP,Beckett RP,Clements JM,Doel S,Pratt LM,Spavold ZM,Thomas SW,Whittaker M

更新日期：2003-08-18 00:00:00

abstract：:A library of 26 novel carboxamides deriving from natural fislatifolic acid has been prepared. The synthetic strategy involved a bio-inspired Diels-Alder cycloaddition, followed by functionalisations of the carbonyl moiety. All the compounds were evaluated on Bcl-xL, Mcl-1 and Bcl-2 proteins. In this series of cyclohex...

journal_title：Bioorganic & medicinal chemistry letters

authors： Gapil Tiamas S,Daressy F,Abou Samra A,Bignon J,Steinmetz V,Litaudon M,Fourneau C,Hoong Leong K,Ariffin A,Awang K,Desrat S,Roussi F

更新日期：2020-04-01 00:00:00

abstract：:Based on the molecular modelling studies, a rational modification of the lead molecule was made to develop highly potent compounds showing anti-cancer activity against human breast cancer cell lines MCF 7, MDA-MB-468 and T-47D. The most potent compounds have Log P and total polar surface area 4.4-5.4 and 59.8 Å, respe...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kaur M,Singh P

更新日期：2019-01-01 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：:Myelin is a lipid multilayer involved in the rate of nerve transmission, and its loss is a pathological feature of multiple sclerosis in brains. Since in vivo imaging of myelin may be useful for drug development, early diagnosis, and monitoring the disease stage, we designed, synthesized, and evaluated eight novel rad...

journal_title：Bioorganic & medicinal chemistry letters

authors： Watanabe H,Sakai S,Iikuni S,Shimizu Y,Shirakawa H,Kaneko S,Ono M

更新日期：2020-12-15 00:00:00

abstract：:A graftable LDV (Leu-Asp-Val) peptidomimetic molecule (B-c) has been prepared from 3-(5-amino-2-hydroxy)phenyl-propionic acid, as alpha(4)beta(1) (VLA-4) integrin ligand. For that purpose, the mechanism of 3-(4-azidophenyl)propionic acid rearrangement has been revisited. Activation of Durapore DVPP-hydrophilic membran...

journal_title：Bioorganic & medicinal chemistry letters

authors： Momtaz M,Rerat V,Gharbi S,Gérard E,Pourcelle V,Marchand-Brynaert J

更新日期：2008-02-01 00:00:00

abstract：:A series of novel methyl 5-substituted 1H-benzo[d]imidazol-2-ylcarbamates were designed, synthesized, and their acrosin inhibitory activities evaluated in vitro. The results of acrosin inhibitory activity showed that all title compounds were more potent than the control TLCK. Compound 4w displayed the most potent acro...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu X,Chen Q,Zhu J,Fan Y,Ding L,Zhao J,Han G,Tian W,Qi J,Zhou Y,Lv J

更新日期：2012-05-15 00:00:00

abstract：:Coibamide A is a highly potent antiproliferative cyclic depsipeptide, which was originally isolated from a Panamanian marine cyanobacterium. In this study, the synthesis of coibamide A has been investigated using Fmoc-based solid-phase peptide synthesis followed by the cleavage of the resulting linear peptide from the...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nabika R,Suyama TL,Hau AM,Misu R,Ohno H,Ishmael JE,McPhail KL,Oishi S,Fujii N

更新日期：2015-01-15 00:00:00

abstract：:Monocyclic beta-lactams have been identified as potent and selective inhibitors of the human cytomegalovirus protease (HCMV) N(o). Two series of these inhibitors are described, a peptidyl series of compounds and non-peptidic molecules featuring lower molecular weights. The SAR work that lead to the discovery of these ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Déziel R,Malenfant E

更新日期：1998-06-02 00:00:00

abstract：:This study investigated the molecular mechanism of saponarin, a flavone glucoside, in the regulation of insulin sensitivity. Saponarin suppressed the rate of gluconeogenesis and increased cellular glucose uptake in HepG2 and TE671 cells by regulating AMPK. Using an in vitro kinase assay, we showed that saponarin did n...

journal_title：Bioorganic & medicinal chemistry letters

authors： Seo WD,Lee JH,Jia Y,Wu C,Lee SJ

更新日期：2015-11-15 00:00:00

abstract：:The stereoselective synthesis and biological activity of NPS 1407 (4a), (S)-(-)-3-amino-1,1-bis(3-fluorophenyl)butane, a potent, stereoselective antagonist of the NMDA receptor, are described. The racemate (4) was found to be active at the NMDA receptor in an in vitro assay, prompting the synthesis of the individual s...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moe ST,Smith DL,DelMar EG,Shimizu SM,Van Wagenen BC,Balandrin MF,Chien YE,Raszkiewicz JL,Artman LD,White HS,Mueller AL

更新日期：2000-11-06 00:00:00

abstract：:A focused set of heterocyclic quinones based on the benzothiazole, benzoxazole, benzimidazole, indazole and isoindole was prepared and screened with respect to the inhibition of the phosphatase activity of CDC25C. Benzoxazole- and benzothiazole-diones were at least 50 times more potent in inhibiting CDC25C than their ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lavergne O,Fernandes AC,Bréhu L,Sidhu A,Brézak MC,Prévost G,Ducommun B,Contour-Galcera MO

更新日期：2006-01-01 00:00:00

abstract：:A series of 1-isoquinolinylguanidines are shown to be potent inhibitors of uPA with selectivity over tPA and plasmin. Potency is enhanced by the presence of a 4-halo and a 7-aryl substituent, particularly when substituted by a 3-carboxylic acid group. Compound 13j (UK-356,202) combines excellent potency and selectivit...

journal_title：Bioorganic & medicinal chemistry letters

authors： Barber CG,Dickinson RP,Fish PV

更新日期：2004-06-21 00:00:00

abstract：:The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a 'one pot' procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochon...

journal_title：Bioorganic & medicinal chemistry letters

authors： Andreu I,Cabedo N,Tormo JR,Bermejo A,Mello R,Cortes D

更新日期：2000-07-03 00:00:00

abstract：:This SAR study has shown that the salicylanilide is the pharmacophore for inhibition of the bacterial two-component system. Hydrophobic substituents improve the potency of inhibitors in this series; however, hydrophobicity is not the sole determinant for inhibition; structural and electronic requirements also exist. C...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hlasta DJ,Demers JP,Foleno BD,Fraga-Spano SA,Guan J,Hilliard JJ,Macielag MJ,Ohemeng KA,Sheppard CM,Sui Z,Webb GC,Weidner-Wells MA,Werblood H,Barrett JF

更新日期：1998-07-21 00:00:00

abstract：:The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK(1) antagonists in vitro and efficacious in vivo with minimal interactions with P(450) liver enzymes. Oxadiazole analog 22 was determined to have exc...

journal_title：Bioorganic & medicinal chemistry letters

authors： Young JR,Eid R,Turner C,DeVita RJ,Kurtz MM,Tsao KL,Chicchi GG,Wheeldon A,Carlson E,Mills SG

更新日期：2007-10-01 00:00:00

abstract：:The shift in apparent IC(50) that attends addition of serum proteins to in vitro cellular, enzymatic, and receptor binding assays can be used to determine the dissociation constant for compound-serum protein complexes. We show here that a simple linear relationship exists between the apparent IC(50) in the presence of...

journal_title：Bioorganic & medicinal chemistry letters

authors： Rusnak DW,Lai Z,Lansing TJ,Rhodes N,Gilmer TM,Copeland RA

更新日期：2004-05-03 00:00:00

abstract：:Several newer isosteric analogues of glycosyl phosphates, namely of glycosyl phosphoramidates, were synthesized in good yields using Staudinger reaction of their corresponding azides with trimethyl phosphite followed by de-O-acetylation. The structure and conformation of the fully protected analogue synthesized, namel...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kannan T,Vinodhkumar S,Varghese B,Loganathan D

更新日期：2001-09-17 00:00:00

abstract：:The enzyme ATP citrate lyase (ACL) catalyzes the formation of cytosolic acetyl CoA, the starting material for de novo lipid and cholesterol biosynthesis. The dysfunction and upregulation of ACL in numerous cancers makes it an attractive target for developing anticancer therapies. ACL inhibition by shRNA knockdown limi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jernigan FE,Hanai JI,Sukhatme VP,Sun L

更新日期：2017-02-15 00:00:00

abstract：:The effect of 2'-O-(N-methylcarbamoyl)ethyl (MCE) modification on splice-switching oligonucleotides (SSO) was systematically evaluated. The incorporation of five MCE nucleotides at the 5'-termini of SSOs effectively improved the splice switching effect. In addition, the incorporation of 2'-O-(N-methylcarbamoylethyl)-5...

journal_title：Bioorganic & medicinal chemistry letters

authors： Masaki Y,Yamamoto K,Inde T,Yoshida K,Maruyama A,Nagata T,Tanihata J,Takeda S,Sekine M,Seio K

更新日期：2019-01-15 00:00:00

abstract：:Radioligands are powerful tools for examining the pharmacological profiles of chemical leads and thus facilitate drug discovery. In this study, we identified and characterized 3-([1,1,1-(3)H]methyl)-2-(4-{[3-(1-pyrrolidinyl)propyl]oxy} phenyl)-4(3H)-quinazolinone ([(3)H]1) as a potent and selective radioligand for his...

journal_title：Bioorganic & medicinal chemistry letters

authors： Mitobe Y,Ito S,Mizutani T,Nagase T,Sato N,Tokita S

更新日期：2009-08-01 00:00:00

abstract：:Recent studies have found that phthalonitrile derivatives are remarkably potent inhibitors of human monoamine oxidase (MAO) A and B. In an attempt to further determine the structure-activity relationships (SARs) for MAO inhibition by this class of compounds and to discover novel potent MAO inhibitors, the present stud...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chirkova ZV,Kabanova MV,Filimonov SI,Abramov IG,Petzer A,Petzer JP,Firgang SI,Suponitsky KY

更新日期：2015-03-15 00:00:00

abstract：:Based on the recently resolved crystal structure of complex (-)-huperzine A-AChE, we simulated the interaction between (-)-huperzine A analogues and AChE using molecular dynamics method. It was revealed that the methyl group at the three carbon bridge of (-)-huperzine A can form a weak hydrogen bond with the phenol hy...

journal_title：Bioorganic & medicinal chemistry letters

authors： Liu DX,Jiang H,Wang QM,Chen KX,Ji RY

更新日期：1998-03-03 00:00:00

abstract：:Vismodegib is the first FDA approved cancer therapy based on inhibition of aberrant hedgehog signaling. Like most cancer therapies, vismodegib suffered from resistance, even during clinical development. Numerous reports demonstrated that simultaneous blockage of hedgehog and PI3K/AKT/mTOR pathways resulted in signific...

journal_title：Bioorganic & medicinal chemistry letters

authors： Yang Z,Ma H,Sun Z,Luo L,Tian S,Zheng J,Zhang X

更新日期：2015-09-01 00:00:00

abstract：:We have designed and synthesized econazole-derived nitroimidazoles to investigate the antitubercular activity of the nitroimidazole compounds. The introduction of a nitro group at the 4-position of the imidazole on econazole abolished the antitubercular activity. However, alcoholic nitroimidazoles 4 and 6 compounds we...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee SH,Kim S,Yun MH,Lee YS,Cho SN,Oh T,Kim P

更新日期：2011-03-01 00:00:00

abstract：:Nrf2 is the major transcription factor that regulates many of the cytoprotective enzymes involved in the adaptive stress response. Modulation of Nrf2 could be therapeutically useful in a number of disease states. Activation can occur through either an electrophilic or non-electrophilic mechanism. To date, most of the ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Richardson BG,Jain AD,Speltz TE,Moore TW

更新日期：2015-06-01 00:00:00

abstract：:We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which...

journal_title：Bioorganic & medicinal chemistry letters

authors： Harada K,Mizukami J,Watanabe T,Mori G,Ubukata M,Suwa K,Fukuda S,Negoro T,Sato M,Inaba T

更新日期：2019-02-01 00:00:00

abstract：:We disclose a new compound class of potent and selective alpha-1A adrenergic receptor antagonists exemplified by the geminally, disubstituted cyclic imide 7. The optimization of lead compounds resulting in the cyclic imide motif is highlighted. The results of in vitro and in vivo studies of selected compounds are pres...

journal_title：Bioorganic & medicinal chemistry letters

authors： DiPardo RM,Patane MA,Newton RC,Price R,Broten TP,Chang RS,Ransom RW,Di Salvo J,Freidinger RM,Bock MG

更新日期：2001-07-23 00:00:00

abstract：:Screening of the Maybridge compound collection identified 4-arylphthalazinones as micromolar inhibitors of PARP-1 catalytic activity. Subsequent optimisation of both inhibitory activity and metabolic stability led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-ones with low nanomolar, cellular activity...

journal_title：Bioorganic & medicinal chemistry letters

authors： Loh VM Jr,Cockcroft XL,Dillon KJ,Dixon L,Drzewiecki J,Eversley PJ,Gomez S,Hoare J,Kerrigan F,Matthews IT,Menear KA,Martin NM,Newton RF,Paul J,Smith GC,Vile J,Whittle AJ

更新日期：2005-05-02 00:00:00

abstract：:Structure-activity relationships (SAR) of fused 1,2,4-triazolo[1,5-c ]pyrimidine were performed. Various substituents were introduced into the heterocyclic ring to improve the potency of adenosine A(3) receptor binding affinity and A(3)-selectivity against other subtypes. Potent and selective A(3) receptor antagonists...

journal_title：Bioorganic & medicinal chemistry letters

authors： Okamura T,Kurogi Y,Hashimoto K,Sato S,Nishikawa H,Kiryu K,Nagao Y

更新日期：2004-07-16 00:00:00