Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors.

Abstract:

:Guided by X-ray crystallography, we have extended the structure-activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor (1) and more potent and equally selective (>20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified. Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells.

journal_name

Bioorg Med Chem Lett

authors

Zhao H,Liu G,Xin Z,Serby MD,Pei Z,Szczepankiewicz BG,Hajduk PJ,Abad-Zapatero C,Hutchins CW,Lubben TH,Ballaron SJ,Haasch DL,Kaszubska W,Rondinone CM,Trevillyan JM,Jirousek MR

doi

10.1016/j.bmcl.2004.08.063

subject

Has Abstract

pub_date

2004-11-15 00:00:00

pages

5543-6

issue

22

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(04)01093-5

journal_volume

14

pub_type

杂志文章
  • Selective alpha1a adrenergic receptor antagonists based on 4-aryl-3,4-dihydropyridine-2-ones.

    abstract::A series of alpha1a receptor antagonists derived from a 4-aryl-3,4-dihydropyridine-2-one heterocycle is disclosed. Potency in the low nanomolar to picomolar range along with high selectivity was obtained. In vivo efficacy in a prostate contraction model in rats was observed with a few derivatives. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(99)00696-4

    authors: Nantermet PG,Barrow JC,Selnick HG,Homnick CF,Freidinger RM,Chang RS,O'Malley SS,Reiss DR,Broten TP,Ransom RW,Pettibone DJ,Olah T,Forray C

    更新日期:2000-08-07 00:00:00

  • Synthesis and the hepatoprotective activity of dibenzocyclooctadiene lignan derivatives.

    abstract::The halogenated and oxidized derivatives (1a-1e, 1a'-1c', 2a-2d, 2a'-2b', 3a-3e, 3' and 3a'-3b') of schizandrin (1), schizandrin B (2) and schisanhenol (3) were synthesized. The hepatoprotective effects of these dibenzocyclooctadiene lignan analogues against CCl4-induced injury were preliminarily evaluated. Most of th...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2014.02.020

    authors: He T,Wang QY,Shi JZ,Fan TY,Yan C,Huang LJ,Liu S,Hao XJ,Mu SZ

    更新日期:2014-04-01 00:00:00

  • Synthesis and evaluation of vancomycin and vancomycin aglycon analogues that bear modifications in the residue 3 asparagine.

    abstract::The synthesis and biological evaluation of a set of residue 3 analogues of vancomycin and its aglycon are described. These investigations follow from the promising biological activity of a protected and synthetically modified vancomycin aglycon analogue in which the asparagine side chain was modified to possess a nitr...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(02)00130-0

    authors: McAtee JJ,Castle SL,Jin Q,Boger DL

    更新日期:2002-05-06 00:00:00

  • Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14.

    abstract::The TAIRE family of kinases are an understudied branch of the CDK kinase family, that have been implicated in a number of cancers. This manuscript describes the design, synthesis and SAR of covalent CDK14 inhibitors, culminating in identification of FMF-04-159-2, a potent, covalent CDK14 inhibitor with a TAIRE kinase ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2019.05.024

    authors: Ferguson FM,Doctor ZM,Ficarro SB,Marto JA,Kim ND,Sim T,Gray NS

    更新日期:2019-08-01 00:00:00

  • 2-Aryl-3-(6-trifluoromethoxy)benzo[d]thiazole-based thiazolidinone hybrids as potential anti-infective agents: Synthesis, biological evaluation and molecular docking studies.

    abstract::The search for new antimicrobial agents is greater than ever due to the perpetual threat of multidrug resistance in known pathogens and the relentless emergence of new infections. In this manuscript, ten thiazole-based thiazolidinone hybrids bearing a 6-trifluoromethoxy substituent on the benzothiazole core were synth...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2020.127718

    authors: Haroun M,Tratrat C,Petrou A,Geronikaki A,Ivanov M,Ciric A,Sokovic M

    更新日期:2021-01-15 00:00:00

  • A simple synthesis of APM ([p-(N-acrylamino)-phenyl]mercuric chloride), a useful tool for the analysis of thiolated biomolecules.

    abstract::This study describes two novel synthetic procedures to prepare APM, a useful tool for the analysis and the purification of thiolated biomolecules. The methods developed are technically simple and robust and allowed the first full characterization of pure APM. Moreover, the efficacy of APM, as a biochemical tool, was d...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.10.051

    authors: Lemau de Talancé V,Bauer F,Hermand D,Vincent SP

    更新日期:2011-12-15 00:00:00

  • On-resin macrocyclization of peptides via intramolecular SnAr reactions.

    abstract::On-resin macrocyclization via an SNAr reaction is employed in the synthesis of tocinoic acid analogs. Specifically, an N-terminal nitrofluorobenzene is attacked by a nucleophilic C-terminal sidechain. The remaining nitro group can be reduced and acylated. NMR is used to compare the conformation of the new macrocyclic ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(99)00356-x

    authors: Fotsch C,Kumaravel G,Sharma SK,Wu AD,Gounarides JS,Nirmala NR,Petter RC

    更新日期:1999-08-02 00:00:00

  • Total synthesis of mololipids: a new series of anti-HIV Moloka'iamine derivatives.

    abstract::A new family of bioactive bromotyrosine derivatives, termed mololipids, was recently isolated from a Hawaiian sponge, but could not be resolved into individual components by chromatography. To complete their structural characterization and better understand structure-activity relationships, the first pure samples of d...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(00)00543-6

    authors: Schoenfeld RC,Lumb JP,Fantini J,Ganem B

    更新日期:2000-12-04 00:00:00

  • Discovery and biological evaluation of adamantyl amide 11beta-HSD1 inhibitors.

    abstract::A series of adamantyl amide 11beta-HSD1 inhibitors has been discovered and chemically modified. Selected compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess excellent cellular potency in human and murine 11beta-HSD1 assays. Good pharmacodynamic characteristics are observed in ex vivo assays. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2007.02.057

    authors: Webster SP,Ward P,Binnie M,Craigie E,McConnell KM,Sooy K,Vinter A,Seckl JR,Walker BR

    更新日期:2007-05-15 00:00:00

  • Comparison of 2-phenylspiroindenes and 2-phenylspiroindenediones as estrogen receptor ligands--modeling and binding data don't agree!

    abstract::A series of 2-phenylspiroindenediones was prepared. The spiroindenediones were found to be less active than the corresponding spiroindenes as estrogen receptor ligands and failed to demonstrate the receptor subtype selectivity that had been anticipated from molecular modeling. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2003.12.058

    authors: Blizzard TA,Mosley RT,Birzin ET,Chan W,Hammond ML

    更新日期:2004-03-08 00:00:00

  • Design, semisynthesis and potent cytotoxic activity of novel 10-fluorocamptothecin derivatives.

    abstract::Fluorination is a well-known strategy for improving the bioavailability of bioactive molecules in the lead optimization phase of drug discovery projects. In an attempt to improve the antitumor activity of camptothecins (CPTs), novel 10-fluoro-CPT derivatives were designed, synthesized and evaluated for cytotoxicity ag...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2017.09.012

    authors: Yang CJ,Song ZL,Goto M,Hsu PL,Zhang XS,Yang QR,Liu YQ,Wang MJ,Morris-Natschke SL,Shang XF,Lee KH

    更新日期:2017-10-15 00:00:00

  • Potent and selective 5-LO inhibitor bearing benzothiophene pharmacophore: discovery of MK-5286.

    abstract::The strategy and SAR studies that led to the discovery of a novel potent and orally available 5-lipoxygenase (5-LO) inhibitor 3-(4-fluorophenyl)-6-({4-[(1S)-1-hydroxy-1-(trifluoromethyl)propyl]-1H-1,2,3-triazol-1-yl}methyl)-1-benzothiophene-2-carboxamide ((S)-2l or MK-5286) were described. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.10.024

    authors: Li L,Berthelette C,Chateauneuf A,Ouellet M,Sturino CF,Wang Z

    更新日期:2010-12-15 00:00:00

  • Diastereoselective synthesis of fused cyclopropyl-3-amino-2,4-oxazine β-amyloid cleaving enzyme (BACE) inhibitors and their biological evaluation.

    abstract::The diastereoselective synthesis and structure activity relationship (SAR) of a series of fused cyclopropyl-3-amino-2,4-oxazine (2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-amine)-containing BACE inhibitors is described. Through these efforts compound 2 was identified as a potent (cell IC50 = 15 nM) BACE inhibitor with accep...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2018.01.056

    authors: Low JD,Bartberger MD,Cheng Y,Whittington D,Xue Q,Wood S,Allen JR,Minatti AE

    更新日期:2018-04-01 00:00:00

  • (2S,2'R)-analogue of LG190178 is a major active isomer.

    abstract::Vitamin D receptor (VDR) ligands are therapeutic agents for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism. VDR ligands also show immense potential as therapeutic agents for autoimmune diseases and cancers of the skin, prostate, colon, and breast as well as leukemia. LG190178 is a novel no...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2007.11.007

    authors: Hakamata W,Sato Y,Okuda H,Honzawa S,Saito N,Kishimoto S,Yamashita A,Sugiura T,Kittaka A,Kurihara M

    更新日期:2008-01-01 00:00:00

  • Synthesis and SAR study of pyrrolo[3,4-b]pyridin-7(6H)-one derivatives as melanin concentrating hormone receptor 1 (MCH-R1) antagonists.

    abstract::The discovery and optimization of novel pyrrolo[3,4-b]pyridin-7(6H)-one MCH-R1 antagonists are described. A systematic SAR study probing the effects of aryl-, benzyl- and arylthio-substituents at the 2-position of the pyrrolo[3,4-b]pyridin-7(6H)-ones led to identification of the 2-[(4-fluorophenyl)thio] derivative 7b ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.01.053

    authors: Lim CJ,Kim JY,Lee BH,Oh KS,Yi KY

    更新日期:2013-03-15 00:00:00

  • Synthesis and protective effects of coumarin derivatives against oxidative stress induced by doxorubicin.

    abstract::The use of doxorubicin (DOX) in the treatment of solid tumors is limited by cardiotoxicity essentially due to oxidative stress generation. The aim of this study was to identify coumarin derivatives displaying a protective antioxidant activity without affecting DOX antitumoral efficiency. A set of eighteen coumarinic d...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2007.12.004

    authors: Beillerot A,Domínguez JC,Kirsch G,Bagrel D

    更新日期:2008-02-01 00:00:00

  • Synthesis and protonation behavior of a water-soluble N-fused porphyrin: conjugation with an oligoarginine by click chemistry.

    abstract::A water-soluble derivative of N-fused porphyrin (NFP) possessing a nona-arginine (R9) peptide tail was synthesized for the first time by a Cu(I)-catalyzed azide-alkyne 'click' reaction. In aqueous solution, at pH 8, the conjugated molecule (NFP-R9) exists as free base and protonated below pH<6.5 to form monoprotonated...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.03.066

    authors: Ikawa Y,Harada H,Toganoh M,Furuta H

    更新日期:2009-05-01 00:00:00

  • Pyrimido-oxazepine as a versatile template for the development of inhibitors of specific kinases.

    abstract::Pyrimido-oxazepine based sub-micromolar inhibitors (2-4) for Aurora and FLT-3 were designed and synthesized. These preliminary results supported the potential use of pyrimido-oxazepines as a versatile template for developing specific kinase inhibitors. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2005.08.098

    authors: Pan W,Liu H,Xu YJ,Chen X,Kim KH,Milligan DL,Columbus J,Hadari YR,Kussie P,Wong WC,Labelle M

    更新日期:2005-12-15 00:00:00

  • Synthesis and evaluation of 1-(4-[¹⁸F]fluoroethyl)-7-(4'-methyl)curcumin with improved brain permeability for β-amyloid plaque imaging.

    abstract::Alzheimer's disease is characterized by the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. We previously developed [(18)F]fluoropropylcurcumin ([(18)F]FP-curcumin), which demonstrated excellent binding affinity (K(i)=0.07 nM) for Aβ(1-40) aggregates and good pharmacokinetics in...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2011.08.003

    authors: Lee I,Yang J,Lee JH,Choe YS

    更新日期:2011-10-01 00:00:00

  • Identification and SAR of novel diaminopyrimidines. Part 1: The discovery of RO-4, a dual P2X(3)/P2X(2/3) antagonist for the treatment of pain.

    abstract::P2X purinoceptors are ligand-gated ion channels whose endogenous ligand is ATP. Both the P2X(3) and P2X(2/3) receptor subtypes have been shown to play an important role in the regulation of sensory function and dual P2X(3)/P2X(2/3) antagonists offer significant potential for the treatment of pain. A high-throughput sc...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.02.003

    authors: Carter DS,Alam M,Cai H,Dillon MP,Ford AP,Gever JR,Jahangir A,Lin C,Moore AG,Wagner PJ,Zhai Y

    更新日期:2009-03-15 00:00:00

  • Theoretical elucidation on structure-antioxidant activity relationships for indolinonic hydroxylamines.

    abstract::Indolinonic hydroxylamines (IH), representing a new type of antioxidants, are comparative to alpha-tocopherol to protect lipids from oxidation. To elucidate the structure-activity relationship for IH, B3LYP/6-31G(d, p) method was employed to calculate the O-H bond dissociation enthalpy (BDE), a theoretical parameter t...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(01)00724-7

    authors: Zhang HY,Wang LF

    更新日期:2002-01-21 00:00:00

  • Inhibition of human neuraminidase 3 (NEU3) by C9-triazole derivatives of 2,3-didehydro-N-acetyl-neuraminic acid.

    abstract::We report the synthesis of a series of C9 and N5Ac modified analogs of 2,3-didehydro-N-acetyl-neuraminic acid (DANA) and their inhibitory potency for the human neuraminidase 3 (NEU3) enzyme. We were able to generate a small library of compounds through the synthesis of azide derivatives of DANA, followed by Cu-catalyz...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.09.111

    authors: Zou Y,Albohy A,Sandbhor M,Cairo CW

    更新日期:2010-12-15 00:00:00

  • Synthesis and evaluation of phenylequine for antimalarial activity in vitro and in vivo.

    abstract::Synthesis of the potent antiplasmodial 4-aminoquinoline, phenylequine (PQ), is reported for the first time. PQ and the two analogues show increased efficacy in moving from the chloroquine sensitive D10 to the chloroquine resistant K1 strain in vitro. The in vivo efficacy of PQ, and salts thereof, have been determined ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2009.12.030

    authors: Blackie MA,Yardley V,Chibale K

    更新日期:2010-02-01 00:00:00

  • Synthesis and biological evaluations of novel bendazac lysine analogues as potent anticataract agents.

    abstract::Novel bendazac analogues and their salts have been designed and prepared. The resulting compounds (13c-d, 15c, 17c) showed very good aqueous solubility (>100 mg/mL). An in vitro assay showed that most of the resulting compounds had potent protective activity against the oxidative damage. Particularly, compound 13d was...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2010.02.061

    authors: Shen H,Gou S,Shen J,Zhu Y,Zhang Y,Chen X

    更新日期:2010-04-01 00:00:00

  • 2-Amino-[1,2,4]triazolo[1,5-a]pyridines as JAK2 inhibitors.

    abstract::The advancement of a series of ligand efficient 2-amino-[1,2,4]triazolo[1,5-a]pyridines, initially identified from high-throughput screening, to a JAK2 inhibitor with pharmacodynamic activity in a mouse xenograft model is disclosed. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.06.008

    authors: Siu M,Pastor R,Liu W,Barrett K,Berry M,Blair WS,Chang C,Chen JZ,Eigenbrot C,Ghilardi N,Gibbons P,He H,Hurley CA,Kenny JR,Cyrus Khojasteh S,Le H,Lee L,Lyssikatos JP,Magnuson S,Pulk R,Tsui V,Ultsch M,Xiao Y,Zh

    更新日期:2013-09-01 00:00:00

  • In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting.

    abstract::The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this gener...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2015.09.004

    authors: Sun W,Chu T

    更新日期:2015-10-15 00:00:00

  • Design and synthesis of functionalized piperazin-1yl-(E)-stilbenes as inhibitors of 17α-hydroxylase-C17,20-lyase (Cyp17).

    abstract::The synthesis of steroid hormones is critical to human physiology and improper regulation of either the synthesis of these key molecules or activation of the associated receptors can lead to disease states. This has led to intense interest in developing compounds capable of modulating the synthesis of steroid hormones...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2018.05.040

    authors: Blass BE,Iyer P,Abou-Gharbia M,Childers WE,Gordon JC,Ramanjulu M,Morton G,Arumugam P,Boruwa J,Ellingboe J,Mitra S,Reddy Nimmareddy R,Paliwal S,Rajasekhar J,Shivakumar S,Srivastava P,Tangirala RS,Venkataramanaiah K,Bob

    更新日期:2018-07-15 00:00:00

  • Investigation of an F-18 oxytocin receptor selective ligand via PET imaging.

    abstract::The compound 1-(1-(2-(2-(2-fluoroethoxy)-4-(piperidin-4-yloxy)phenyl)acetyl)piperidin-4-yl)-3,4-dihydroquinolin-2(1H)-one (1) was synthesized and positively evaluated in vitro for high potency and selectivity with human oxytocin receptors. The positron emitting analogue, [F-18]1, was synthesized and investigated in vi...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.07.045

    authors: Smith AL,Freeman SM,Voll RJ,Young LJ,Goodman MM

    更新日期:2013-10-01 00:00:00

  • Interaction of binuclear xylylthiolato(2,2',2"-terpyridine)platinum(II) complexes with DNA.

    abstract::The new binuclear platinum(II) complexes, (1,3-benzenedimethanethiolate-S)di(2,2',2"-terpyridine)diplatinum(II) chloride tetrahydrate, 5, and (1,4-benzenedimethanethiolate-S)di(2,2',2"-terpyridine)diplatinum(II) chloride tetrahydrate, 6, were synthesized in order to investigate the binding of platinum(II) complex with...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/s0960-894x(03)00012-x

    authors: Kurosaki H,Yamakawa N,Sumimoto M,Kimura K,Goto M

    更新日期:2003-03-10 00:00:00

  • Benzimidazole-carboxamides as potent and bioavailable stearoyl-CoA desaturase (SCD1) inhibitors from ligand-based virtual screening and chemical optimization.

    abstract::The discovery of potent benzimidazole stearoyl-CoA desaturase (SCD1) inhibitors by ligand-based virtual screening is described. ROCS 3D-searching gave a favorable chemical motif that was subsequently optimized to arrive at a chemical series of potent and promising SCD1 inhibitors. In particular, compound SAR224 was se...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章

    doi:10.1016/j.bmcl.2013.01.030

    authors: Matter H,Zoller G,Herling AW,Sanchez-Arias JA,Philippo C,Namane C,Kohlmann M,Pfenninger A,Voss MD

    更新日期:2013-03-15 00:00:00