当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Optimization of halopemide for phospholipase D2 inhibition.

Optimization of halopemide for phospholipase D2 inhibition.

Abstract：

:Halopemide, which was identified by HTS to inhibit phospholipase D2 (PLD2), provided the basis for an exploratory effort to identify potent inhibitors of PLD2 for use as inflammatory mediators. Parallel synthesis and purification were utilized to rapidly identify orally available amide analogs derived from indole 2-carboxylic acids with superior potency versus PLD2.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Monovich L,Mugrage B,Quadros E,Toscano K,Tommasi R,LaVoie S,Liu E,Du Z,LaSala D,Boyar W,Steed P

doi

10.1016/j.bmcl.2007.01.059

subject

Has Abstract

pub_date

2007-04-15 00:00:00

pages

2310-1

issue

8

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(07)00109-6

journal_volume

17

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Synthesis and SAR of 3,5-diamino-piperidine derivatives: novel antibacterial translation inhibitors as aminoglycoside mimetics.

    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

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.12.024

    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

  • Identification of novel inhibitors of BCR-ABL tyrosine kinase via virtual screening.

    abstract：:Inhibition of BCR-ABL tyrosine kinase activity has shown to be essential for the treatment of chronic myelogenous leukemia (CML). However, drug resistance has quickly arisen in recent clinical trials for STI571 (Gleevec), which is the first approved drug of CML by inhibiting ABL tyrosine kinase. It is desirable to dev...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.08.014

    authors： Peng H,Huang N,Qi J,Xie P,Xu C,Wang J,Yang C

    更新日期：2003-11-03 00:00:00

  • Discovery of 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione as a dual inhibitor of the Raf/MEK/ERK and the PI3K/Akt signaling pathways.

    abstract：:A thiazolidine-2,4-dione derivative, 3-(2-aminoethyl)-5-(3-phenyl-propylidene)-thiazolidine-2,4-dione (2), was identified as a dual inhibitor of the Raf/MEK/ extracellular signal-regulated kinase (ERK) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascades. The discovered compound inhibited cell prolifera...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.06.030

    authors： Li Q,Wu J,Zheng H,Liu K,Guo TL,Liu Y,Eblen ST,Grant S,Zhang S

    更新日期：2010-08-01 00:00:00

  • Alpha-keto amides as inhibitors of histone deacetylase.

    abstract：:Alpha-keto ester and amides were found to be potent inhibitors of histone deacetylase. Nanomolar inhibitors against the isolated enzyme and sub-micromolar inhibitors of cellular proliferation were obtained. The alpha-keto amide 30 also exhibited significant anti-tumor effects in an in vivo tumor model. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(03)00685-1

    authors： Wada CK,Frey RR,Ji Z,Curtin ML,Garland RB,Holms JH,Li J,Pease LJ,Guo J,Glaser KB,Marcotte PA,Richardson PL,Murphy SS,Bouska JJ,Tapang P,Magoc TJ,Albert DH,Davidsen SK,Michaelides MR

    更新日期：2003-10-06 00:00:00

  • Design, synthesis and biological evaluation of novel potent MDM2/p53 small-molecule inhibitors.

    abstract：:Regioselective synthesis, biological evaluation and 3D-molecular modeling for a series of novel diastereomeric 2-thioxo-5H-dispiro[imidazolidine-4,3-pyrrolidine-2,3-indole]-2,5(1H)-diones are described. The studied compounds have been tentatively identified as potent small molecule MDM2/p53 PPI inhibitors and can ther...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.09.070

    authors： Ivanenkov YA,Vasilevski SV,Beloglazkina EK,Kukushkin ME,Machulkin AE,Veselov MS,Chufarova NV,Chernyaginab ES,Vanzcool AS,Zyk NV,Skvortsov DA,Khutornenko AA,Rusanov AL,Tonevitsky AG,Dontsova OA,Majouga AG

    更新日期：2015-01-15 00:00:00

  • Synthesis of a Streptococcus pyogenes vaccine candidate based on the M protein PL1 epitope.

    abstract：:Group A streptococcus is a Gram-positive bacteria that causes a range of infectious diseases. Targeting the bacteria, a new self-adjuvanting vaccine candidate, incorporating a carbohydrate carrier and an amino acid-based adjuvant, was synthesised utilising carbohydrate chemistry and solid-phase peptide synthesis proce...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.12.013

    authors： Simerska P,Lu H,Toth I

    更新日期：2009-02-01 00:00:00

  • 3-Hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-2-carboxylates--a new class of HIV-1 integrase inhibitors.

    abstract：:A new class of inhibitors of HIV-1 integrase has been optimized to provide selective and highly efficient strand transfer inhibition. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.02.055

    authors： Donghi M,Kinzel OD,Summa V

    更新日期：2009-04-01 00:00:00

  • Heterocyclic aminopyrrolidine derivatives as melatoninergic agents.

    abstract：:A series of chiral heterocyclic aminopyrrolidine derivatives was synthesized as novel melatoninergic ligands. Binding affinity assays were performed on cloned human MT(1) and MT(2) receptors, stably expressed in NIH3T3 cells. Compound 16 was identified as an orally bioavailable agonist at MT(1) and MT(2) melatonin rec...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.09.030

    authors： Sun LQ,Chen J,Mattson RJ,Epperson JR,Deskus JA,Li WS,Takaki K,Hodges DB,Iben L,Mahle CD,Ortiz A,Molstad D,Ryan E,Yeleswaram K,Xu C,Luo G

    更新日期：2003-12-15 00:00:00

  • Improved performance by replacing iminodiacetic residues with glyceryl residues in symmetrically branched oligoglycerols.

    abstract：:Synthesis of a symmetrically branched diglycerol (BGL002, involving one iminodiacetic residue) as a G2 dendron, and the tetradecaglycerol (BGL014, involving one iminodiacetic residue) as a G4 dendron, is described. Several members of the BGL family of G2-G4 dendrons were assembled, with G2 bearing four hydroxyl groups...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.06.064

    authors： Nemoto H,Ishihara A,Araki T,Katagiri A,Kamiya M,Matsushita T,Hattori H,Mimura Y,Tomoda Y,Yamasaki M

    更新日期：2011-08-15 00:00:00

  • Discovery of novel nonsteroidal glucocorticoid receptor modulators.

    abstract：:A new class of selective nonsteroidal glucocorticoid receptor modulators typified by N-[3-[benzyl-(4-chloro-2-fluoro-benzyl)-amino]-2-methyl-phenyl]-methanesulfonamide 19 has been discovered. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.02.013

    authors： Link JT,Sorensen BK,Patel J,Emery M,Grynfarb M,Goos-Nilsson A

    更新日期：2004-05-03 00:00:00

  • Structure-activity relationships of 2-aryl-1H-indole inhibitors of the NorA efflux pump in Staphylococcus aureus.

    abstract：:The synthesis of 22 2-aryl-1H-indoles, including 12 new compounds, has been achieved via Pd- or Rh-mediated methodologies, or selective electrophilic substitution. All three methods were based on elaborations from simple indole precursors. SAR studies on these indoles and 2-phenyl-1H-indole in Staphylococcus aureus as...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.06.093

    authors： Ambrus JI,Kelso MJ,Bremner JB,Ball AR,Casadei G,Lewis K

    更新日期：2008-08-01 00:00:00

  • Optimization of benzimidazole series as opioid receptor-like 1 (ORL1) antagonists: SAR study directed toward improvement of selectivity over hERG activity.

    abstract：:A structure-activity relationship (SAR) study on the benzimidazole series of opioid receptor-like 1 (ORL1) antagonists related to 1 is described. Optimization of 1 by introduction of a hydrophilic substituent into the thioether part resulted in identification of potent ORL1 antagonists with high selectivity over bindi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.04.022

    authors： Kobayashi K,Kato T,Yamamoto I,Shimizu A,Mizutani S,Asai M,Kawamoto H,Ito S,Yoshizumi T,Hirayama M,Ozaki S,Ohta H,Okamoto O

    更新日期：2009-06-01 00:00:00

  • Fluorescent metal ion indicators based on benzoannelated crown systems: a green fluorescent indicator for intracellular sodium ions.

    abstract：:The synthesis and metal binding properties of cation-sensitive fluorescent indicators intended for biological applications are described. The increase of the crown ether ring size enhances the affinity for larger cations, but weakens the fluorescent response and selectivity. A compound having a 15-crown-5 chelator dir...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.02.017

    authors： Martin VV,Rothe A,Gee KR

    更新日期：2005-04-01 00:00:00

  • 1,5-Biaryl pyrrole derivatives as EP1 receptor antagonists. Structure-activity relationships of 6-substituted and 5,6-disubstituted benzoic acid derivatives.

    abstract：:Herein we describe the SAR of 1,5-biaryl pyrrole derivatives, with substituents in the 6-position of the benzoic acid moiety, as EP(1) receptor antagonists. Substitution at this position was well tolerated and led to the identification of several analogues with high affinity for the EP(1) receptor that displayed good ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.11.059

    authors： Hall A,Brown SH,Chessell IP,Chowdhury A,Clayton NM,Coleman T,Giblin GM,Hammond B,Healy MP,Johnson MR,Metcalf A,Michel AD,Naylor A,Novelli R,Spalding DJ,Sweeting J,Winyard L

    更新日期：2007-02-15 00:00:00

  • The discovery of an orally efficacious positive allosteric modulator of the calcium sensing receptor containing a dibenzylamine core.

    abstract：:The discovery of a series of novel and orally efficacious type II calcimimetics, developed from the lead compound 1, is described herein. Compound 22 suppressed plasma PTH levels relative to vehicle when dosed orally in a rat pharmacodynamic model. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.07.060

    authors： Harrington PE,St Jean DJ Jr,Clarine J,Coulter TS,Croghan M,Davenport A,Davis J,Ghiron C,Hutchinson J,Kelly MG,Lott F,Lu JY,Martin D,Morony S,Poon SF,Portero-Larragueta E,Reagan JD,Regal KA,Tasker A,Wang M,Yang Y,

    更新日期：2010-09-15 00:00:00

  • Synthesis and SAR of 1,4,5,6-tetrahydropyridazines as potent cannabinoid CB1 receptor antagonists.

    abstract：:The synthesis and structure-activity relationship studies of 1,4,5,6-tetrahydropyridazines are described. The target compounds 3-5 represent a novel class of potent and selective CB1 receptor antagonists. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.08.007

    authors： Lange JH,den Hartog AP,van der Neut MA,van Vliet BJ,Kruse CG

    更新日期：2009-10-01 00:00:00

  • Novel C-seco-taxoids possessing high potency against paclitaxel-resistant cancer cell lines overexpressing class III beta-tubulin.

    abstract：:Novel C-seco-taxoids were synthesized from 10-deacetylbaccatin III and their potencies evaluated against drug-sensitive and drug-resistant cancer cell lines. The drug-resistant cell lines include ovarian cancer cell lines resistant to cisplatin, topotecan, adriamycin and paclitaxel overexpressing class III beta-tubuli...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.04.070

    authors： Pepe A,Sun L,Zanardi I,Wu X,Ferlini C,Fontana G,Bombardelli E,Ojima I

    更新日期：2009-06-15 00:00:00

  • From benzimidazole to indole-5-carboxamide Thumb Pocket I inhibitors of HCV NS5B polymerase. Part 1: indole C-2 SAR and discovery of diamide derivatives with nanomolar potency in cell-based subgenomic replicons.

    abstract：:Replacement of the benzimidazole core of allosteric Thumb Pocket 1 HCV NS5B finger loop inhibitors by more lipophilic indole derivatives provided up to 30-fold potency improvements in cell-based subgenomic replicon assays. Optimization of C-2 substitution on the indole core led to the identification of analogs with EC...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.04.059

    authors： Beaulieu PL,Gillard J,Jolicoeur E,Duan J,Garneau M,Kukolj G,Poupart MA

    更新日期：2011-06-15 00:00:00

  • Advances in Lead Generation.

    abstract：:Lead Generation represents a critical drug discovery phase where chemical starting points and their respective mechanism of action, quality, and potential liabilities are largely predefined. Recent advances such as DNA-encoded libraries or fragment-, chemical biology-, and virtual screening-based approaches are today ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2018.12.001

    authors： Holenz J,Stoy P

    更新日期：2019-02-15 00:00:00

  • Design and synthesis of 2-substituted benzoxazoles as novel PTP1B inhibitors.

    abstract：:A series of benzoxazole compounds containing oxamic acid were synthesized and screened for the PTP1B inhibition. Compound 31d showed best biochemical potency (Ki) of 6.7 μM. Structure-activity relationship were explained with the help of molecular modeling approach. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.02.109

    authors： Chandrasekharappa AP,Badiger SE,Dubey PK,Panigrahi SK,Manukonda SR

    更新日期：2013-05-01 00:00:00

  • Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators.

    abstract：:Results from a 2012 high-throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) against the human muscarinic receptor subtype 1 (M1) for positive allosteric modulators is reported. A content-rich screen utilizing an intracellular calcium mobilization triple-addition protocol allowed for ass...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.11.011

    authors： Han C,Chatterjee A,Noetzel MJ,Panarese JD,Smith E,Chase P,Hodder P,Niswender C,Conn PJ,Lindsley CW,Stauffer SR

    更新日期：2015-01-15 00:00:00

  • Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics.

    abstract：:The present study describes the optimization of a series of novel benzoxazole-piperidine (piperazine) derivatives combining high dopamine D2 and serotonin 5-HT1A, 5-HT2A receptor affinities. Of these derivatives, the pharmacological features of compound 29 exhibited high affinities for the DA D2, 5-HT1A and 5-HT2A rec...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.09.045

    authors： Huang L,Zhang W,Zhang X,Yin L,Chen B,Song J

    更新日期：2015-11-15 00:00:00

  • Quinazolin-4-piperidin-4-methyl sulfamide PC-1 inhibitors: alleviating hERG interactions through structure based design.

    abstract：:PC-1 (NPP-1) inhibitors may be useful as therapeutics for the treatment of CDDP (calcium pyrophosphate dehydrate) deposition disease and osteoarthritis. We have identified a series of potent quinazolin-4-piperidin-4-ethyl sulfamide PC-1 inhibitors. The series, however, suffers from high affinity binding to hERG potass...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.04.006

    authors： Patel SD,Habeski WM,Cheng AC,de la Cruz E,Loh C,Kablaoui NM

    更新日期：2009-06-15 00:00:00

  • Eta4-pyrone iron(0)carbonyl complexes as effective CO-releasing molecules (CO-RMs).

    abstract：:The CO-releasing properties of iron(0)tricarbonyl complexes bearing a 2-pyrone ligand have been evaluated. In this report, we demonstrate that the intrinsic stability of the (eta4-2-pyrone)Fe(CO)3 complex influences the extent and rate of CO release, which is affected by the presence of a halogen substituent on the 2-...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.10.085

    authors： Fairlamb IJ,Duhme-Klair AK,Lynam JM,Moulton BE,O'Brien CT,Sawle P,Hammad J,Motterlini R

    更新日期：2006-02-15 00:00:00

  • Achieving structural diversity using the perpendicular conformation of alpha-substituted phenylcyclopropanes to mimic the bioactive conformation of ortho-substituted biphenyl P4 moieties: discovery of novel, highly potent inhibitors of Factor Xa.

    abstract：:Ortho-substituted biphenyl moieties are widely used in drug design. We herein report a successful use of the perpendicular conformation of the alpha-substituted phenylcyclopropyl groups to mimic the aplanar, biologically active conformation of the ortho-substituted biphenyl moieties to achieve structural diversity. Th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.05.095

    authors： Qiao JX,Cheney DL,Alexander RS,Smallwood AM,King SR,He K,Rendina AR,Luettgen JM,Knabb RM,Wexler RR,Lam PY

    更新日期：2008-07-15 00:00:00

  • Synthesis and anti-HSV-1 activity of quinolonic acyclovir analogues.

    abstract：:Several 1-[(2-hydroxy-ethoxy)methyl]-3-carbethoxy-4(1H)quinolones (2a-l) and l-[(2-hydroxy-ethoxy)methyl]-4(1H)quinolone-3-carboxylic acids (3a-j and 3l) were synthesized and 2a-j, 2l and 3a-j, 3l were evaluated against herpes simplex virus type 1 (HSV-1), employing a one-pot reaction: silylation of the desired quinol...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.10.111

    authors： Lucero Bd,Gomes CR,Frugulhetti IC,Faro LV,Alvarenga L,de Souza MC,de Souza TM,Ferreira VF

    更新日期：2006-02-15 00:00:00

  • Lobelane analogues containing 4-hydroxy and 4-(2-fluoroethoxy) aromatic substituents: Potent and selective inhibitors of [(3)H]dopamine uptake at the vesicular monoamine transporter-2.

    abstract：:A series of lobelane and GZ-793A analogues that incorporate aromatic 4-hydroxy and 4-(2-fluoroethoxy) substituents were synthesized and evaluated for inhibition of [(3)H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and the dopamine transporter (DAT), and [(3)H]serotonin uptake at the serotonin...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.03.119

    authors： Joolakanti SR,Nickell JR,Janganati V,Zheng G,Dwoskin LP,Crooks PA

    更新日期：2016-05-15 00:00:00

  • Solid-phase synthesis of 2,3-disubstituted indoles: discovery of a novel, high-affinity, selective h5-HT2A antagonist.

    abstract：:The application of a novel solid-phase synthesis of 2,3-disubstituted indoles utilizing a carbamate indole linker is described resulting in the identification of the novel, high-affinity, selective h5-HT2A antagonist 19. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(00)00558-8

    authors： Smith AL,Stevenson GI,Lewis S,Patel S,Castro JL

    更新日期：2000-12-18 00:00:00

  • Bis-azaaromatic quaternary ammonium salts as antagonists at nicotinic receptors mediating nicotine-evoked dopamine release: An investigation of binding conformation.

    abstract：:A series of conformationally restricted bis-azaaromatic quaternary ammonium salts (3 and 4) have been designed and synthesized in order to investigate the possible binding conformations of N,N'-dodecane-1,12-diyl-bis-3-picolinium dibromide (bPiDDB; 2), a compound which potently inhibits neuronal nicotinic acetylcholin...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.10.052

    authors： Zheng G,Zhang Z,Pivavarchyk M,Deaciuc AG,Dwoskin LP,Crooks PA

    更新日期：2007-12-15 00:00:00

  • Preventive effect of a novel diosgenin derivative on arterial and venous thrombosis in vivo.

    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

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.05.032

    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