当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Preparation and optimization of new 4-(2-(indolin-1-yl)-2-oxoethyl)-2-morpholinothiazole-5-carboxylic acid and amide derivatives as potent and selective PI3Kβ inhibitors.

Preparation and optimization of new 4-(2-(indolin-1-yl)-2-oxoethyl)-2-morpholinothiazole-5-carboxylic acid and amide derivatives as potent and selective PI3Kβ inhibitors.

Abstract：

:In our continuous efforts to identify and develop novel targeted cancer treatments, a new morpholino-thiazole scaffold active against PI3Kβ has been identified. This Letter reports the optimization of this compound class to develop PI3Kβ isoform-selective inhibitors with suitable pharmacological properties.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Certal V,Halley F,Virone-Oddos A,Filoche-Rommé B,Carry JC,Gruss-Leleu F,Bertin L,Guizani H,Pilorge F,Richepin P,Karlsson A,Charrier V,Abecassis PY,Vincent L,Nicolas JP,Lengauer C,Garcia-Echeverria C,Schio L

doi

10.1016/j.bmcl.2014.02.004

subject

Has Abstract

pub_date

2014-03-15 00:00:00

pages

1506-10

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(14)00125-5

journal_volume

24

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Prenylated xanthones as potential P-glycoprotein modulators.

    abstract：:Dimethylallyl (DMA) derivatives of a naturally occurring xanthone (decussatin 1) were prepared. Their activity as potential P-glycoprotein inhibitors was monitored by affinity of direct binding and compared to that of corresponding DMA-flavones. Both classes of compounds exhibited the same structure-activity relations...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00234-1

    authors： Tchamo DN,Dijoux-Franca MG,Mariotte AM,Tsamo E,Daskiewicz JB,Bayet C,Barron D,Conseil G,Di Pietro A

    更新日期：2000-06-19 00:00:00

  • Structure-based design of flavone-based inhibitors of wild-type and T315I mutant of ABL.

    abstract：:The existence of drug resistance caused by mutations in the break-point cluster region-Abelson (BCR-ABL) tyrosine kinase domain remains a clinical challenge due to limited treatment options for effective CML therapies. Here, we report a series of flavone-based common inhibitors equipotent for the wild type and the mos...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.05.095

    authors： Choe H,Kim J,Hong S

    更新日期：2013-08-01 00:00:00

  • An amide-based sulfenamide prodrug of gamma secretase inhibitor BMS-708163 delivers parent drug from an oral conventional solid dosage form in male beagle dog.

    abstract：:The objective of this Letter is to report the first (to our knowledge) in vivo proof of concept for a sulfenamide prodrug to orally deliver a poorly soluble drug containing a weakly-acidic NH-acid from a conventional solid dosage formulation. This proof of concept was established using BMS-708163 (1), a gamma secretas...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2019.126856

    authors： Guarino VR,Olson RE,Everlof JG,Wang N,McDonald I,Haskell R,Clarke W,Lentz KA

    更新日期：2020-02-01 00:00:00

  • Synthesis and evaluation of novel phosphoramidate prodrugs of 2'-methyl cytidine as inhibitors of hepatitis C virus NS5B polymerase.

    abstract：:A variety of new prodrugs of 2'-methyl cytidine based on acyloxy ethylamino phosphoramidates have been synthesized and tested in vitro and in vivo for their biological activity. Compared with the parent drug a 10- to 20-fold increase in formation of nucleotide triphosphate in rat and human hepatocytes could be achieve...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.01.035

    authors： Donghi M,Attenni B,Gardelli C,Marco AD,Fiore F,Giuliano C,Laufer R,Leone JF,Pucci V,Rowley M,Narjes F

    更新日期：2009-03-01 00:00:00

  • DNA-templated click chemistry for creation of novel DNA binding molecules.

    abstract：:We have developed a new methodology for producing new molecules that bind to dsDNA using DNA-templated click chemistry. The click reactions between the minor groove binding peptide and acridine intercalators were accelerated by the addition of dsDNA. Furthermore, the resulting peptide-acridine conjugate showed a sligh...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.074

    authors： Imoto S,Hirohama T,Nagatsugi F

    更新日期：2008-10-15 00:00:00

  • Synthesis and evaluation of novel 8-oxo-8H-cyclopenta[a]acenaphthylene-7-carbonitriles as long-wavelength fluorescent markers for hypoxic cells in solid tumor.

    abstract：:Novel bioreductive and long-wavelength fluorescent markers for hypoxic cells in solid tumor, 9-isocyano-8H-acenaphtho[l,2-b]pyrrol-8-one with the side chain of 2-nitroimidazole, were designed, synthesized, and evaluated in V79 379A Chinese hamster cells in vitro. Compounds A(2) and A(4) showed good hypoxic-oxic fluore...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.12.031

    authors： Liu Y,Xu Y,Qian X,Xiao Y,Liu J,Shen L,Li J,Zhang Y

    更新日期：2006-03-15 00:00:00

  • Trace amine-associated receptor 1 (TAAR1) is activated by amiodarone metabolites.

    abstract：:Amiodarone (Cordarone, Wyeth-Ayerst Pharmaceuticals) is a clinically available drug used to treat a wide variety of cardiac arrhythmias. We report here the synthesis and characterization of a panel of potential amiodarone metabolites that have significant structural similarity to thyroid hormone and its metabolites th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.013

    authors： Snead AN,Miyakawa M,Tan ES,Scanlan TS

    更新日期：2008-11-15 00:00:00

  • Insights into the substrate specificity of the MutT pyrophosphohydrolase using structural analogues of 8-oxo-2'-deoxyguanosine nucleotide.

    abstract：:The bacterial repair enzyme MutT hydrolyzes the damaged nucleotide OdGTP (the 5'-triphosphate derivative of 8-oxo-2'-deoxyguanosine; OdG), which is a known mutagen and has been linked to antibacterial action. Previous work has indicated important roles for the C8-oxygen, N7-hydrogen, and C2-exocyclic amine during OdGT...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.02.083

    authors： Hamm ML,McFadden EJ,Ghio M,Lindell MA,Gerien KS,O'Handley SF

    更新日期：2016-04-15 00:00:00

  • Substituted sulfonamide bioisosteres of 8-hydroxyquinoline as zinc-dependent antibacterial compounds.

    abstract：:A series of substituted sulfonamide bioisosteres of 8-hydroxyquinoline were evaluated for their antibacterial activity against the common mastitis causative pathogens Streptococcus uberis, Staphylococcus aureus and Escherichia coli, both in the presence and absence of supplementary zinc. Compounds 9a-e, 10a-c, 11a-e, ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127110

    authors： McGowan JE,Harper AD,Davison EK,Jeong JY,Mros S,Harbison-Price N,Van Zuylen EM,Knottenbelt MK,Heikal A,Ferguson SA,McConnell MA,Cook GM,Krittaphol W,Walker GF,Brimble MA,Rennison D

    更新日期：2020-06-01 00:00:00

  • Molecular modeling aided design of nicotinic acid receptor GPR109A agonists.

    abstract：:A homology model of the nicotinic acid receptor GPR109A was constructed based on the X-ray crystal structure of bovine rhodopsin. An HTS hit was docked into the homology model. Characterization of the binding pocket by a grid-based surface calculation of the docking model suggested that a larger hydrophobic body plus ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.030

    authors： Deng Q,Frie JL,Marley DM,Beresis RT,Ren N,Cai TQ,Taggart AK,Cheng K,Carballo-Jane E,Wang J,Tong X,Waters MG,Tata JR,Colletti SL

    更新日期：2008-09-15 00:00:00

  • Discovery of novel bacterial elongation condensing enzyme inhibitors by virtual screening.

    abstract：:The elongation condensing enzymes in the bacterial fatty acid biosynthesis pathway represent desirable targets for the design of novel, broad-spectrum antimicrobial agents. A series of substituted benzoxazolinones was identified in this study as a novel class of elongation condensing enzyme (FabB and FabF) inhibitors ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.03.033

    authors： Zheng Z,Parsons JB,Tangallapally R,Zhang W,Rock CO,Lee RE

    更新日期：2014-06-01 00:00:00

  • Structure activity relationship of substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-4).

    abstract：:Bacterial resistance is rapidly growing, necessitating the need to discover new agents. Novel bacterial topoisomerase inhibitors (NBTIs) are new class of broad-spectrum antibacterial agents targeting bacterial DNA gyrase and topoisomerase IV. This class of inhibitors binds to an alternative binding site relative to fl...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.04.002

    authors： Singh SB,Kaelin DE,Wu J,Miesel L,Tan CM,Meinke PT,Olsen DB,Lagrutta A,Wei C,Peng X,Wang X,Fukuda H,Kishii R,Takei M,Shibata T,Ohata K,Takano H,Kurasaki H,Takeuchi T,Nishimura A,Fukuda Y

    更新日期：2015-06-01 00:00:00

  • Discovery of ML326: The first sub-micromolar, selective M5 PAM.

    abstract：:This Letter describes the further chemical optimization of the M5 PAM MLPCN probes ML129 and ML172. A multi-dimensional iterative parallel synthesis effort quickly explored isatin replacements and a number of southern heterobiaryl variations with no improvement over ML129 and ML172. An HTS campaign identified several ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.03.032

    authors： Gentry PR,Bridges TM,Lamsal A,Vinson PN,Smith E,Chase P,Hodder PS,Engers JL,Niswender CM,Daniels JS,Conn PJ,Wood MR,Lindsley CW

    更新日期：2013-05-15 00:00:00

  • ⁹⁹mTc-(Me)FGCDEVD, a potential tracer for apoptosis detection.

    abstract：:(Me)FGC(Bz)DEVD was radiolabeled with technetium-99m in high yield. This tracer was preferentially accumulated in apoptotic cells in the in vitro studies. Tumor uptake occurred in vivo after cisplatin injection due to the apoptosis induction, which not observed in the untreated tumors. Therefore, (99m)Tc-(Me)FGCDEVD i...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.12.088

    authors： Bohn P,Mouchard F,Rouvet J,de Boisgrollier AC,Vera P

    更新日期：2013-03-01 00:00:00

  • Use of gamma-aminopropyl-coated glass surface for the patterning of oligonucleotides through oxime bond formation.

    abstract：:The present work reports on the preparation of glass surfaces coated with NPPOC-protected aminooxy groups and their use for the patterning of oligonucleotides on glass slides and in capillary tubes. The method involves the use of surfaces coated with amino groups using (gamma-aminopropyl)triethoxy silane and subsequen...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.03.054

    authors： Dendane N,Hoang A,Defrancq E,Vinet F,Dumy P

    更新日期：2008-04-15 00:00:00

  • Structure activity relationships of benzylproline-derived inhibitors of the glutamine transporter ASCT2.

    abstract：:The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.12.063

    authors： Singh K,Tanui R,Gameiro A,Eisenberg G,Colas C,Schlessinger A,Grewer C

    更新日期：2017-02-01 00:00:00

  • Synthesis and biological evaluation of a series of novel pyridinecarboxamides as potential multi-receptor antipsychotic drugs.

    abstract：:In previous study, a series of benzamides was identified as potent antipsychotic agents. As a continuation of the program to discover novel antipsychotics, herein we reported the evaluation of a series of pyridinecarboxamide derivatives. The most promising compound 7h not only held good activities on dopamine D2, sero...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.01.038

    authors： Xu M,Wang Y,Yang F,Wu C,Wang Z,Ye B,Jiang X,Zhao Q,Li J,Liu Y,Zhang J,Tian G,He Y,Shen J,Jiang H

    更新日期：2018-02-15 00:00:00

  • A regiospecific synthesis of a series of 1-sulfonyl azepinoindoles as potent 5-HT6 ligands.

    abstract：:A regiospecific synthesis of a series of 1-sulfonyl azepinoindoles as potent 5-HT6 ligands is reported. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.06.030

    authors： Liu KG,Lo JR,Comery TA,Zhang GM,Zhang JY,Kowal DM,Smith DL,Di L,Kerns EH,Schechter LE,Robichaud AJ

    更新日期：2008-07-15 00:00:00

  • Design, synthesis, and biological evaluation of novel aminopyrimidinylisoindolines as AXL kinase inhibitors.

    abstract：:A novel series of aminopyrimidinylisoindoline derivatives 1a-w having an aminopyrimidine scaffold as a hinge region binding motif were designed and synthesized. Among them, six compounds showed potent inhibitory activities against AXL kinase with IC50 values of submicromolar range. Especially, compound 1u possessing (...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.10.013

    authors： Choi MJ,Roh EJ,Hur W,Lee SH,Sim T,Oh CH,Lee SH,Kim JS,Yoo KH

    更新日期：2018-12-15 00:00:00

  • Second generation N-(1,2-diphenylethyl)piperazines as dual serotonin and noradrenaline reuptake inhibitors: improving metabolic stability and reducing ion channel activity.

    abstract：:New N-(1,2-diphenylethyl)piperazines 6 are disclosed as dual serotonin and noradrenaline reuptake inhibitors (SNRI) which may have potential in treating stress urinary incontinence (SUI). In this Letter, we present new data for SNRI PF-526014 (4) including performance in a canine in vivo model of SUI, cardiovascular a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.04.052

    authors： Fray MJ,Fish PV,Allan GA,Bish G,Clarke N,Eccles R,Harrison AC,Le Net JL,Phillips SC,Regan N,Sobry C,Stobie A,Wakenhut F,Westbrook D,Westbrook SL,Whitlock GA

    更新日期：2010-06-15 00:00:00

  • Tags for labeling protein N-termini with subtiligase for proteomics.

    abstract：:The peptide ligase subtiligase, derived from subtilisin, has been employed in the identification of protein N-termini in complex mixtures. Here, the peptide ester substrates for the ligation reaction were optimized with respect to solubility, resulting in greater incorporation of the N-terminal tags. Additionally, the...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.08.044

    authors： Yoshihara HA,Mahrus S,Wells JA

    更新日期：2008-11-15 00:00:00

  • Synthesis and anti-HIV activities of urea-PETT analogs belonging to a new class of potent non-nucleoside HIV-1 reverse transcriptase inhibitors.

    abstract：:A series of potent specific HIV-1 RT inhibitory compounds is described. The compounds are urea analogs of PETT (PhenylEthylThiazoleThiourea) derivatives and the series includes derivatives with an ethyl linker (1-6) and conformationally restricted analogs (7-13). The antiviral activity is determined both at the RT lev...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00249-2

    authors： Sahlberg C,Noréen R,Engelhardt P,Högberg M,Kangasmetsä J,Vrang L,Zhang H

    更新日期：1998-06-16 00:00:00

  • Quinazoline Based HSP90 Inhibitors: Synthesis, Modeling Study and ADME Calculations Towards Breast Cancer Targeting.

    abstract：:A new 2-thioquinazolinones series was designed and synthesized as HSP90 inhibitors based on the structure of hit compound VII obtained by virtual screening approach. Their in vitro anti-proliferative activity was evaluated against three human cancer cell lines rich in HSP90 namely; colorectal carcinoma (HCT-116), and ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2020.127281

    authors： El-Shafey HW,Gomaa RM,El-Messery SM,Goda FE

    更新日期：2020-08-01 00:00:00

  • Discovery and characterization of the potent, selective and orally bioavailable MMP inhibitor ABT-770.

    abstract：:Modification of the biphenyl portion of MMP inhibitor 2a gave analogue 2i which is greater than 1000-fold selective against MMP-2 versus MMP-1. The stereospecific synthesis of both enantiomers of 2i was achieved beginning with (S)- or (R)-benzyl glycidyl ether. The (S)-enantiomer, 11 (ABT-770), is orally bioavailable ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00032-4

    authors： Curtin ML,Florjancic AS,Heyman HR,Michaelides MR,Garland RB,Holms JH,Steinman DH,Dellaria JF,Gong J,Wada CK,Guo Y,Elmore IB,Tapang P,Albert DH,Magoc TJ,Marcotte PA,Bouska JJ,Goodfellow CL,Bauch JL,Marsh KC,Morgan

    更新日期：2001-06-18 00:00:00

  • Discovery of biaryl inhibitors of H+/K+ ATPase.

    abstract：:We report the identification of a novel biaryl template for H(+)/K(+) ATPase inhibition. Evaluation of critical SAR features within the biaryl imidazole framework and the use of pharmacophore modelling against known imidazopyridine and azaindole templates suggested that the geometry of the molecule is key to achieving...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.12.040

    authors： Garton N,Bailey N,Bamford M,Demont E,Farre-Gutierrez I,Hutley G,Bravi G,Pickering P

    更新日期：2010-02-01 00:00:00

  • Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and 'click' strategy.

    abstract：:To develop more effective antitumor steroidal drugs, we synthesized a library including twenty-two novel cytotoxic 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones and corresponding 1,2,3-triazoles through an abnormal monoepoxide ring-opening/elimination and 'click' reactions. After the cytotoxic evaluation...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.06.028

    authors： Lu XF,Yang Z,Huang NY,He HB,Deng WQ,Zou K

    更新日期：2015-09-01 00:00:00

  • Synthesis of a high-mannose-type glycopeptide analog containing a glucose-asparagine linkage.

    abstract：:The title compound was prepared by enzymatic transfer of oligosaccharide to a synthetic pentapeptide containing the Glc-Asn linkage. The compound was not hydrolyzed by glycoamidases from plant and bacterial sources, but it inhibited both enzymes in the micromolar range. Its activity is compared to other potential inhi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00306-0

    authors： Deras IL,Takegawa K,Kondo A,Kato I,Lee YC

    更新日期：1998-07-07 00:00:00

  • Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression.

    abstract：:A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited po...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.05.034

    authors： Nazreen S,Alam MS,Hamid H,Yar MS,Dhulap A,Alam P,Pasha MA,Bano S,Alam MM,Haider S,Kharbanda C,Ali Y,Pillai KK

    更新日期：2014-07-15 00:00:00

  • An expeditious regioselective synthesis of novel bioactive indole-substituted chromene derivatives via one-pot three-component reaction.

    abstract：:Novel fused 1H-benzo[f]chromen-indole derivatives were synthesized regioselectivly in good to high yields by triethyl amine catalyzed condensation of 3-cyanoacetylindoles, β-naphthol and aryl aldehydes in methanol under ultrasounic irradiations and conventional conditions. The easy work-up of the products, rapidity, a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.07.059

    authors： Hossein nia R,Mamaghani M,Tabatabaeian K,Shirini F,Rassa M

    更新日期：2012-09-15 00:00:00

  • alpha-Alkyl-alpha-amino-beta-sulphone hydroxamates as potent MMP inhibitors that spare MMP-1.

    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

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00557-1

    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