Identification of a selective inhibitor of murine intestinal alkaline phosphatase (ML260) by concurrent ultra-high throughput screening against human and mouse isozymes.

abstract：:A protein without natural binding functions was engineered to bind HIV-1 integrase. Phage display selections applied a library of variants based on the C-terminal domain of the eye lens protein human γS-crystallin. Multiple loop regions were altered to encode libraries with ≈3.6 × 10(11) different variants. A crystall...

journal_title：Bioorganic & medicinal chemistry letters

authors： Moody IS,Verde SC,Overstreet CM,Edward Robinson W Jr,Weiss GA

更新日期：2012-09-01 00:00:00

abstract：:A series of potent ALK5 inhibitors were designed using a SBDD approach and subsequently optimized to improve drug likeness. Starting with a 4-substituted quinoline screening hit, SAR was conducted using a ALK5 binding model to understand the binding site and optimize activity. The resulting inhibitors displayed excell...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sabat M,Wang H,Scorah N,Lawson JD,Atienza J,Kamran R,Hixon MS,Dougan DR

更新日期：2017-05-01 00:00:00

abstract：:An indole compound with a strong purple-red color was produced by boiling a solution of indican under acidic conditions and purified by chromatographies on DEAE-650S Toyopearl TSK-gel and silica-gel columns. The purple-red compound purified was identified as indoxyl red, on the basis of FAB Mass, (13)C NMR, (1)H NMR, ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Song J,Kitamatsu M,Imamura K,Ohmori H,Watanabe K,Nakanishi K

更新日期：2013-02-01 00:00:00

abstract：:A versatile route for the synthesis of homochiral alpha-ketoamide analogues of amino acids is described. Incorporation of this functionality into peptide sequences using either solution or solid-phase chemistry resulted in potent inhibitors of the Hepatitis C Virus NS3 proteinase. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Beevers R,Carr MG,Jones PS,Jordan S,Kay PB,Lazell RC,Raynham TM

更新日期：2002-02-25 00:00:00

abstract：:Sixteen new and one known unsymmetrical open-chain diacylamines were synthesized by sodium methoxide catalyzed acylation of amides with carboxylic esters and acylamino-carboxylic esters, or acylureas with acylamino-carboxylic esters and alpha-amino acid esters. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Weisz I,Roboz J,Wolf I,Szabo J,Bekesi JG

更新日期：1998-11-17 00:00:00

abstract：:Oligonucleotides consisting of 2'-deoxy-2'(S)-ethinyl-thymidine,-uridine, and -adenosine have been prepared. Whereas the modified pyrimidine oligonucleotides uniformly lead to weaker pairing affinity with DNA and RNA complements, the corresponding adenine oligonucleotides show enhanced thermal stability in duplexes wi...

journal_title：Bioorganic & medicinal chemistry letters

authors： Buff R,Hunziker J

更新日期：1998-03-03 00:00:00

abstract：:As a continuation of our efforts to discover and develop the apoptosis inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the SAR of 4-aryl-4H-chromenes with modifications at the 7- and 5-, 6-, 8-positions. It was found that a small hydrophobic group, such as NMe2, NH2, NHEt, and OMe, is preferred at...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kemnitzer W,Kasibhatla S,Jiang S,Zhang H,Zhao J,Jia S,Xu L,Crogan-Grundy C,Denis R,Barriault N,Vaillancourt L,Charron S,Dodd J,Attardo G,Labrecque D,Lamothe S,Gourdeau H,Tseng B,Drewe J,Cai SX

更新日期：2005-11-01 00:00:00

abstract：:Starting from a weak omeprazole screening hit, replacement of the pyridine with a 1,3-benzodioxole moiety, modification of the thioether linkage, and substitution of the benzimidazole pharmacophore led to the discovery of nanomolar BRS-3 agonists. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Carlton DL,Collin-Smith LJ,Daniels AJ,Deaton DN,Goetz AS,Laudeman CP,Littleton TR,Musso DL,Morgan RJ,Szewczyk JR,Zhang C

更新日期：2008-10-15 00:00:00

abstract：:A modified vancomycin binding pocket (D-O-E ring) incorporating an alpha-hydroxy-beta-amino acid at the AA4 position is designed and synthesized. Some of these compounds display potent bioactivities against both sensitive- and resistant-strains (8 microg/ml against VREF). Both the lipidated aminoglucose and the struct...

journal_title：Bioorganic & medicinal chemistry letters

authors： Jia Y,Gonzalez-Zamora E,Ma N,Liu Z,Bois-Choussy M,Malabarba A,Brunati C,Zhu J

更新日期：2005-10-15 00:00:00

abstract：:Functionalized 1,3-teraryls, synthesized through ring transformation of 6-aryl-3-carbomethoxy-4-methylthio-2H-pyran-2-one from arylketone have been screened for their hepatoprotective activity and of them have demonstrated significant protection in animal model. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Ram VJ,Goel A,Patnaik GK

更新日期：1998-03-03 00:00:00

abstract：:Bisubstrate analog inhibitors in which a nicotinamide mimic is attached to a series of structurally diversified guanidines (arginine mimics) were synthesized and evaluated for inhibition of cholera toxin. The mechanism-based bisubstrate inhibitors were up to 1400-fold more potent than the natural substrate NAD+ and 40...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhang G

更新日期：2008-07-01 00:00:00

abstract：:A class of small molecules displaying comparable activities with peptide ligands BAM22 and corticostatin-14 at both the human and rhesus monkey MrgX1 and MrgX2 receptors, respectively, was discovered. A comparative study to compare solid-phase and solution-phase chemistries for the efficient synthesis of the active cl...

journal_title：Bioorganic & medicinal chemistry letters

authors： Malik L,Kelly NM,Ma JN,Currier EA,Burstein ES,Olsson R

更新日期：2009-03-15 00:00:00

abstract：:A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hattori K,Kohchi Y,Oikawa N,Suda H,Ura M,Ishikawa T,Miwa M,Endoh M,Eda H,Tanimura H,Kawashima A,Horii I,Ishitsuka H,Shimma N

更新日期：2003-03-10 00:00:00

abstract：:The first silanediol inhibitor of thermolysin is reported, prepared by analogy with the Grobelny/Bartlett phosphinate inhibitor. A Cbz group on nitrogen proved to be unstable to the triflic acid mediated silanediol deprotection and was replaced with a dihydrocinnamoyl group. The silanediol was prepared in high purity ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Kim J,Glekas A,McN Sieburth S

更新日期：2002-12-16 00:00:00

abstract：:Benzothiazole benzimidazole (S)-isothiazolidinone ((S)-IZD) derivatives 5 were discovered through a peptidomimetic modification of the tripeptide (S)-IZD protein tyrosine phosphatase 1B (PTP1B) inhibitor 1. These derivatives are potent, competitive, and reversible inhibitors of PTP1B with improved caco-2 permeability....

journal_title：Bioorganic & medicinal chemistry letters

authors： Sparks RB,Polam P,Zhu W,Crawley ML,Takvorian A,McLaughlin E,Wei M,Ala PJ,Gonneville L,Taylor N,Li Y,Wynn R,Burn TC,Liu PC,Combs AP

更新日期：2007-02-01 00:00:00

abstract：:Amyloid-beta peptide (Aβ) has been recognized to interact with numerous proteins, which may lead to pathological changes in cell metabolism of Alzheimer's disease (AD) patients. One such known metabolic enzyme is mitochondrial amyloid-binding alcohol dehydrogenase (ABAD), also known as 17β-hydroxysteroid dehydrogenase...

journal_title：Bioorganic & medicinal chemistry letters

authors： Hroch L,Benek O,Guest P,Aitken L,Soukup O,Janockova J,Musil K,Dohnal V,Dolezal R,Kuca K,Smith TK,Gunn-Moore F,Musilek K

更新日期：2016-08-01 00:00:00

abstract：:New analogues of the previously described 3-aryl pyridone KOR agonists have been synthesised by parallel synthetic methods, both in solution- and with solid-phase chemistry, making use of the well known and versatile Mitsunobu, Suzuki and Buchwald reactions. Opioid receptor binding data for the compounds produced is r...

journal_title：Bioorganic & medicinal chemistry letters

authors： Semple G,Andersson BM,Chhajlani V,Georgsson J,Johansson MJ,Rosenquist A,Swanson L

更新日期：2003-03-24 00:00:00

abstract：:Incorporation of 5-propynylamino and 5-propynyl alpha-2'-deoxyuridine into alpha-oligonucleotides (alpha-ON) allows high-affinity targeting of complementary DNA for alpha-ON with anionic and neutral backbone but not for cationic alpha-ON, revealing clues on the role of the amino group of the propynylamino on the forma...

journal_title：Bioorganic & medicinal chemistry letters

authors： Deglane G,Morvan F,Debart F,Vasseur JJ

更新日期：2007-02-15 00:00:00

abstract：:A series of 1-benzoyl isoquinolines, based on compound 1, was synthesized and evaluated for their ability to displace IGF-I from its complex with IGF-binding protein-3. Successful modifications of 1 included the replacement of the 3,4-dihydroxybenzoyl group with a substituted benzyl group. These alternations culminate...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zhu YF,Wilcoxen K,Gross T,Connors P,Strack N,Gross R,Huang CQ,McCarthy JR,Xie Q,Ling N,Chen C

更新日期：2003-06-02 00:00:00

abstract：:Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel IT...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lo HY,Bentzien J,Fleck RW,Pullen SS,Khine HH,Woska JR Jr,Kugler SZ,Kashem MA,Takahashi H

更新日期：2008-12-01 00:00:00

abstract：:N-substituted chitosan and quaternized chitosan were synthesized and their antioxidant activity against hydroxyl radicals was assessed, respectively. Compared with the antioxidant activity of chitosan, the results indicated that the two kinds of chitosan derivatives had different scavenging ability on hydroxyl radical...

journal_title：Bioorganic & medicinal chemistry letters

authors： Guo Z,Liu H,Chen X,Ji X,Li P

更新日期：2006-12-15 00:00:00

abstract：:A series of benzylidene-1H-indol-2-one (oxindole) derivatives was synthesized and evaluated as cRaf-1 kinase inhibitors. The key features of the molecules were the donor/acceptor motif common to kinase inhibitors and a critical acidic phenol flanked by two substitutions. Diverse 5-position substitutions provided compo...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lackey K,Cory M,Davis R,Frye SV,Harris PA,Hunter RN,Jung DK,McDonald OB,McNutt RW,Peel MR,Rutkowske RD,Veal JM,Wood ER

更新日期：2000-02-07 00:00:00

abstract：:Sulfonyl amidines (1) and phosphoryl amidines (2), which were efficiently synthesized via a Cu-catalyzed one pot reaction, showed potent anti-bone resorptive activity in vitro. Structure activity relationship studies led to the identification of numerous osteoclast differentiation inhibitors. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Lee MY,Kim MH,Kim J,Kim SH,Kim BT,Jeong IH,Chang S,Kim SH,Chang SY

更新日期：2010-01-15 00:00:00

abstract：:Current therapy for blood vessel thrombosis has the risk of leading to gastrointestinal bleeding and thrombocytopenia. We previously reported that a new derivative of diosgenin, compound 5, had significant anti-inflammatory activity superior to that of aspirin, prolonged bleeding time, and inhibited platelet aggregati...

journal_title：Bioorganic & medicinal chemistry letters

authors： Zheng H,Wei Z,Xin G,Ji C,Wen L,Xia Q,Niu H,Huang W

更新日期：2016-07-15 00:00:00

abstract：:An Mg2+ and ATP dependent beta-lactam synthetase (BLS) catalyses formation of a beta-lactam ring during the biosynthesis of clavulanic acid, an important beta-lactamase inhibitor. An epimeric mixture of a 2-methylated derivative of the natural BLS substrate N2-(2-carboxyethyl)-L-arginine was synthesised and found to b...

journal_title：Bioorganic & medicinal chemistry letters

authors： Sleeman MC,MacKinnon CH,Hewitson KS,Schofield CJ

更新日期：2002-02-25 00:00:00

abstract：:An HTS campaign of our corporate compound library resulted in thieno[2,3-b]pyridines derivative hits with mGluR5 negative allosteric modulator effects. During the hit-to-lead development our objective was to improve affinity, and to keep the ligand efficiency values at an acceptable level. After different modification...

journal_title：Bioorganic & medicinal chemistry letters

authors： Nógrádi K,Wágner G,Domány G,Bobok A,Magdó I,Kiss B,Kolok S,Fónagy K,Gyertyán I,Háda V,Kóti J,Gál K,Farkas S,Keserű GM,Greiner I,Szombathelyi Z

更新日期：2014-08-15 00:00:00

abstract：:The discovery of the potency-enhancing effect of 5-substitutions on the novel 2-arylindoles as nonpeptidyl GnRH receptor antagonists led to the identification of several analogues with high affinities on the GnRH receptor. The syntheses and SARs of these 5-substituted-2-arylindole analogues are reported. ...

journal_title：Bioorganic & medicinal chemistry letters

authors： Chu L,Lo JL,Yang YT,Cheng K,Smith RG,Fisher MH,Wyvratt MJ,Goulet MT

更新日期：2001-02-26 00:00:00

abstract：:A series of MT-II related cyclic peptides, based on potent but non-selective hMC4R agonist (Penta-c[Asp-His(6)-DPhe(7)-Arg(8)-Trp(9)-Lys]-NH(2)) was prepared in which His(6) residue was systematically substituted. Two of the most interesting peptides identified in this study are Penta-c[Asp-5-ClAtc-DPhe-Arg-Trp-Lys]-N...

journal_title：Bioorganic & medicinal chemistry letters

authors： Cheung AW,Danho W,Swistok J,Qi L,Kurylko G,Rowan K,Yeon M,Franco L,Chu XJ,Chen L,Yagaloff K

更新日期：2003-04-07 00:00:00

abstract：:A series of novel 2,4,5-trisubstituted 1,3-thiazole derivatives containing hydrazide-hydrazine, and carboxamide moiety including 46 compounds T were synthesized, and evaluated for their antitumor activity in vitro against a panel of five human cancer cell lines. Eighteen title compounds T displayed higher inhibitory a...

journal_title：Bioorganic & medicinal chemistry letters

authors： He H,Wang X,Shi L,Yin W,Yang Z,He H,Liang Y

更新日期：2016-07-15 00:00:00

abstract：:SB-216763 is a novel, potent and selective glycogen synthase kinase-3 (GSK-3) inhibitor with an IC(50) value of 34 nM. [(11)C]SB-216763 (3-(2,4-dichlorophenyl)-4-(1-[(11)C]methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of GSK-3, was first designed and synthesized in 20-30% decay cor...

journal_title：Bioorganic & medicinal chemistry letters

authors： Wang M,Gao M,Miller KD,Sledge GW,Hutchins GD,Zheng QH

更新日期：2011-01-01 00:00:00