当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Piperidine and piperazine inhibitors of fatty acid amide hydrolase targeting excitotoxic pathology.

Piperidine and piperazine inhibitors of fatty acid amide hydrolase targeting excitotoxic pathology.

Abstract：

:FAAH inhibitors offer safety advantages by augmenting the anandamide levels "on demand" to promote neuroprotective mechanisms without the adverse psychotropic effects usually seen with direct and chronic activation of the CB1 receptor. FAAH is an enzyme implicated in the hydrolysis of the endocannabinoid N-arachidonoylethanolamine (AEA), which is a partial agonist of the CB1 receptor. Herein, we report the discovery of a new series of highly potent and selective carbamate FAAH inhibitors and their evaluation for neuroprotection. The new inhibitors showed potent nanomolar inhibitory activity against human recombinant and purified rat FAAH, were selective (>1000-fold) against serine hydrolases MGL and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Evaluation of FAAH inhibitors 9 and 31 using the in vitro competitive activity-based protein profiling (ABPP) assay confirmed that both inhibitors were highly selective for FAAH in the brain, since none of the other FP-reactive serine hydrolases in this tissue were inhibited by these agents. Our design strategy followed a traditional SAR approach and was supported by molecular modeling studies based on known FAAH cocrystal structures. To rationally design new molecules that are irreversibly bound to FAAH, we have constructed "precovalent" FAAH-ligand complexes to identify good binding geometries of the ligands within the binding pocket of FAAH and then calculated covalent docking poses to select compounds for synthesis. FAAH inhibitors 9 and 31 were evaluated for neuroprotection in rat hippocampal slice cultures. In the brain tissue, both inhibitors displayed protection against synaptic deterioration produced by kainic acid-induced excitotoxicity. Thus, the resultant compounds produced through rational design are providing early leads for developing therapeutics against seizure-related damage associated with a variety of disorders.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Lamani M,Malamas MS,Farah SI,Shukla VG,Almeida MF,Weerts CM,Anderson J,Wood JT,Farizatto KLG,Bahr BA,Makriyannis A

doi

10.1016/j.bmc.2019.115096

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

115096

issue

23

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(19)31023-5

journal_volume

27

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • Synthesis and biological evaluation of new flavonoid fatty acid esters with anti-adipogenic and enhancing glucose consumption activities.

    abstract：:Oleoyl Formononetin (OF) has good weight loss activity and hypolipidemic activity, could improve insulin sensitivity and suppress adipogenesis. To acquire better biological activities, three series of flavonoid fatty acid esters were designed and synthesized by optimizing the structure of OF. Their bioactivities were ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.03.063

    authors： Zhao W,Sun J,Xiang H,Zeng YY,Li XB,Xiao H,Chen DY,Ma RL

    更新日期：2011-05-15 00:00:00

  • New acridone-4-carboxylic acid derivatives as potential inhibitors of hepatitis C virus infection.

    abstract：:A new class of compounds--acridone derivatives--was tested using the direct fluorometric helicase activity assay to determine the inhibitory properties of the derivatives towards the NS3 helicase of Hepatitis C virus (HCV). The compounds were also tested as putative transcription inhibitors of in vitro transcription b...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.08.074

    authors： Stankiewicz-Drogon A,Palchykovska LG,Kostina VG,Alexeeva IV,Shved AD,Boguszewska-Chachulska AM

    更新日期：2008-10-01 00:00:00

  • In vitro cytotoxicity of 5-aminosubstituted 20(S)-camptothecins. Part 1.

    abstract：:A number of 5-aminosubstituted 20(S)-camptothecin analogues were prepared via semi-synthesis starting from 20(S)-camptothecin and 9-methoxy 20(S)-camptothecin. In vitro anti-cancer activity of these analogues was determined using 60 human tumor cell line assay. Although water solubility of most of these compounds was ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(99)00130-3

    authors： Subrahmanyam D,Sarma VM,Venkateswarlu A,Sastry TV,Kulakarni AP,Rao DS,Reddy KV

    更新日期：1999-09-01 00:00:00

  • 000Synthesis of new α-aminophosphonates: Evaluation as anti-inflammatory agents and QSAR studies.

    abstract：:In this paper, we report the synthesis of a new series of α-aminophosphonates derivatives based in an efficient three-component reaction. All compounds prepared showed significant anti-inflammatory activity, being the compounds 1a, 1c, 1d, 1f, 2b and 2c the most promising ones, in terms of maximal efficacy (over 95%),...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.12.041

    authors： Romero-Estudillo I,Viveros-Ceballos JL,Cazares-Carreño O,González-Morales A,de Jesús BF,López-Castillo M,Razo-Hernández RS,Castañeda-Corral G,Ordóñez M

    更新日期：2019-06-15 00:00:00

  • Synthesis, characterization and biological activity of complexes of lanthanum(III) with 2-(1'-phenyl- 2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline and 2-(1'-p-phenol-2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline.

    abstract：:Two novel ligands 2-(1'-phenyl-2'-carboxyl-3'-aza-n-butyl)-1,10-phenanthroline (L1) and 2-(1'-p-phenol-2'-carboxyl-3'-aza-butyl)-1,10-phenanthroline (L2), and their La(III) complexes of La(III)L1, La(III)(L1)(2), La(III)L2, and La(III)(L2)(2), were synthesized and characterized by (1)H NMR, elemental analysis, IR, the...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.09.032

    authors： Zhao G,Li F,Lin H,Lin H

    更新日期：2007-01-01 00:00:00

  • 'Carba'-carfentanil (trans isomer): a μ opioid receptor (MOR) partial agonist with a distinct binding mode.

    abstract：:There is strong evidence to indicate that a positively charged nitrogen of endogenous and exogenous opioid ligands forms a salt bridge with the Asp residue in the third transmembrane helix of opioid receptors. To further examine the role of this electrostatic interaction in opioid receptor binding and activation, we s...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.07.033

    authors： Weltrowska G,Lemieux C,Chung NN,Guo JJ,Wilkes BC,Schiller PW

    更新日期：2014-09-01 00:00:00

  • Development of a platform for activatable fluorescent substrates of glucose transporters (GLUTs).

    abstract：:We have developed a platform for activatable fluorescent substrates of glucose transporters (GLUTs). We firstly conjugated fluorescein to glucosamine via an amide or methylene linker at the C-2 position of d-glucosamine, but the resulting compounds, FLG1 and FLG2, showed no uptake into MIN6 cells. So, we changed the f...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.02.055

    authors： Takasugi T,Hanaoka K,Sasaki A,Ikeno T,Komatsu T,Ueno T,Yamada K,Urano Y

    更新日期：2019-05-15 00:00:00

  • G-quadruplex DNA cleavage preference and identification of a perylene diimide G-quadruplex photocleavage agent using a rapid fluorescent assay.

    abstract：:A rapid fluorescence assay for G-quadruplex DNA cleavage was used to investigate the preference of TMPyP4 photochemical and Mn·TMPyP4 oxidative cleavage. Both agents most efficiently cleave the c-Myc promoter G-quadruplex. Direct PAGE analysis of selected assay samples showed that for a given cleavage agent, different...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.10.017

    authors： Schoonover M,Kerwin SM

    更新日期：2012-12-15 00:00:00

  • Sulfonamide-1,2,4-triazole derivatives as antifungal and antibacterial agents: synthesis, biological evaluation, lipophilicity, and conformational studies.

    abstract：:A series of 10 new 5-[2-(substituted sulfamoyl)-4,5-dimethoxy-benzyl]-4aryl-s-triazole-3-thiones were synthesized and evaluated for in vitro antifungal and antibacterial activity. All compounds tested showed significant antifungal activity against all the micromycetes, compared to the commercial fungicide bifonazole. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.10.082

    authors： Ezabadi IR,Camoutsis C,Zoumpoulakis P,Geronikaki A,Soković M,Glamocilija J,Cirić A

    更新日期：2008-02-01 00:00:00

  • Synthesis and structure-activity relationship of new 1,5-dialkyl-1,5-benzodiazepines as cholecystokinin-2 receptor antagonists.

    abstract：:This article deals with the synthesis and the activities of some 1,5-dialkyl-3-arylureido-1,5-benzodiazepin-2,4-diones which were prepared as potential CCK2 antagonists, with the intention to find a possible follow up of our lead compound GV150013, showing an improved pharmacokinetic profile. The phenyl ring at N-5 wa...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.05.057

    authors： Roberts K,Ursini A,Barnaby R,Cassarà PG,Corsi M,Curotto G,Donati D,Feriani A,Finizia G,Marchioro C,Niccolai D,Oliosi B,Polinelli S,Ratti E,Reggiani A,Tedesco G,Tranquillini ME,Trist DG,van Amsterdam FT

    更新日期：2011-07-15 00:00:00

  • Synthesis, structural elucidation and in vitro antiparasitic activity against Trypanosoma cruzi and Leishmania chagasi parasites of novel tetrahydro-1-benzazepine derivatives.

    abstract：:Forty six new 1,4-epoxy-2-exo-aryl- and cis-2-aryl-4-hydroxytetrahydro-1-benzazepine derivatives were synthesized and fully characterized. All compounds were tested in vitro against both Trypanosoma cruzi and Leishmania chagasi parasites and also for cytotoxicity using Vero and THP-1 mammalian cell lines. Many of the ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.05.018

    authors： Gómez-Ayala S,Castrillón JA,Palma A,Leal SM,Escobar P,Bahsas A

    更新日期：2010-07-01 00:00:00

  • Reaction of 2'-deoxycytidine with peroxynitrite in the presence of ammonium bromide.

    abstract：:Peroxynitrite, a reactive nitrogen species generated from nitric oxide and superoxide anion radical, is an endogenous potential risk factor for human cancer. When 2'-deoxycytidine was incubated with peroxynitrite at neutral pH and 37 degrees C, the reaction was greatly enhanced by the addition of ammonium bromide. Bot...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.03.007

    authors： Suzuki T,Ida K,Uchibe S,Inukai M

    更新日期：2008-05-01 00:00:00

  • Hantzsch 1,4-dihydropyridines containing a diazen-1-ium-1,2-diolate nitric oxide donor moiety to study calcium channel antagonist structure-activity relationships and nitric oxide release.

    abstract：:A group of racemic 3-isopropyl 5-[(2-piperazin-1-yl)ethyl] 1,4-dihydro-2,6-dimethyl-4-(pyridyl)-3,5-pyridinedicarboxylates (12a-c), 3-isopropyl 5-{2-[4-nitrosopiperazinyl]ethyl} 1,4-dihydro-2,6-dimethyl-4-(pyridyl)-3,5-pyridinedicarboxylates (14a-c) and 3-isopropyl 5-{2-[(O(2)-acetoxymethyldiazen-1-ium-1,2-diolate)(N,...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.12.002

    authors： Nguyen JT,Velázquez CA,Knaus EE

    更新日期：2005-03-01 00:00:00

  • Amphipathic benzoic acid derivatives: synthesis and binding in the hydrophobic tunnel of the zinc deacetylase LpxC.

    abstract：:The first committed step in lipid A biosynthesis is catalyzed by uridine diphosphate-(3-O-(R-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase (LpxC), a zinc-dependent deacetylase, and inhibitors of LpxC may be useful in the development of antibacterial agents targeting a broad spectrum of Gram-negative bacteria. H...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.01.044

    authors： Shin H,Gennadios HA,Whittington DA,Christianson DW

    更新日期：2007-04-01 00:00:00

  • Synthesis and antimalarial evaluation of a screening library based on a tetrahydroanthraquinone natural product scaffold.

    abstract：:As part of a research program aimed at discovering new antimalarial leads from Australian macrofungi a unique fungi-derived prefractionated library was screened against a chloroquine-sensitive Plasmodium falciparum line (3D7) using a radiometric growth inhibition assay. A library fraction derived from a Cortinarius sp...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.09.052

    authors： Choomuenwai V,Andrews KT,Davis RA

    更新日期：2012-12-15 00:00:00

  • The phytoalexins brassilexin and camalexin inhibit cyclobrassinin hydrolase, a unique enzyme from the fungal pathogen Alternaria brassicicola.

    abstract：:Alternaria brassicicola is a fungal pathogen of many agriculturally important cruciferous crops. Cyclobrassinin hydrolase (CH) is an enzyme produced by A. brassicicola that catalyzes the transformation of the cruciferous phytoalexin cyclobrassinin into S-methyl[(2-sulfanyl-1H-indolyl-3)methyl]carbamothioate. The purif...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.11.005

    authors： Pedras MS,Minic Z

    更新日期：2014-01-01 00:00:00

  • Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53-MDM2 interaction. Part 2.

    abstract：:Five series of novel 3,4,5-trisubstituted aminothiophene derivatives and analogs were designed and synthesized based on our previous studies. All target compounds were evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferation activities against A549 and PC3 tumor cell lines. Twelve compounds di...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.03.070

    authors： Wang W,Lv D,Qiu N,Zhang L,Hu C,Hu Y

    更新日期：2013-06-01 00:00:00

  • The effect of the length and flexibility of the side chain of basic amino acids on the binding of antimicrobial peptides to zwitterionic and anionic membrane model systems.

    abstract：:The intent of this investigation was to determine the effect of varying the side chain length of the basic amino acids residues on the binding of a series of antimicrobial peptides (AMPs) to zwitterionic and anionic LUVs, SUVs and micelles. These AMPs are based on the incorporation of three dipeptide units consisting ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.01.015

    authors： Russell AL,Williams BC,Spuches A,Klapper D,Srouji AH,Hicks RP

    更新日期：2012-03-01 00:00:00

  • Novel sulfonamide bearing coumarin scaffolds as selective inhibitors of tumor associated carbonic anhydrase isoforms IX and XII.

    abstract：:Four novel scaffolds consisting of total 24 compounds (1a-1o, 2a-2c, 3a-3c and 4a-4c) bearing aromatic sulfonamide and coumarin moieties connected through various linkers were synthesized in order to synergize the inhibition potential of both the moieties against four selected human carbonic anhydrase isoforms (hCA I,...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.04.052

    authors： Chandak N,Ceruso M,Supuran CT,Sharma PK

    更新日期：2016-07-01 00:00:00

  • Synthesis and cytotoxicity of methyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione derivatives.

    abstract：:2- and 3-Methyl-4,8-dihydrobenzo[1,2-b:5,4-b']dithiophene-4,8-dione and related derivatives were synthesized and evaluated in vitro by NCI against eight cancer types. Compounds 12-15 showed significant activity against melanoma, NCI-H23 non-small cell lung cancer, and MDA-MB-435 and MDA-N breast cancer cell lines; 2-h...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(98)00241-7

    authors： Chao YH,Kuo SC,Ku K,Chiu IP,Wu CH,Mauger A,Wang HK,Lee KH

    更新日期：1999-06-01 00:00:00

  • Synthesis and biological relationships of 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives as antimitotic agents.

    abstract：:As part of a continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives and their salts were synthesized and evaluated. Preliminary screening showed that carboxylic acid analogs containing a m-fluoro substituted 2-p...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.09.041

    authors： Lai YY,Huang LJ,Lee KH,Xiao Z,Bastow KF,Yamori T,Kuo SC

    更新日期：2005-01-03 00:00:00

  • Palladium(II) saccharinate complexes with bis(2-pyridylmethyl)amine induce cell death by apoptosis in human breast cancer cells in vitro.

    abstract：:The outcomes of breast cancer patients are still poor although new compounds have recently been introduced into the clinic. Therefore, novel chemical approaches are required. In the present study, palladium(II) and corresponding platinum(II) complexes containing bis(2-pyridylmethyl)amine (bpma) and saccharine were syn...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.03.073

    authors： Ari F,Ulukaya E,Sarimahmut M,Yilmaz VT

    更新日期：2013-06-01 00:00:00

  • Characterization, bioinformatic analysis and dithiocarbamate inhibition studies of two new α-carbonic anhydrases, CAH1 and CAH2, from the fruit fly Drosophila melanogaster.

    abstract：:Carbonic anhydrases (CAs) are essential and ubiquitous enzymes. Thus far, there are no articles on characterization of Drosophila melanogaster α-CAs. Data from invertebrate CA studies may provide opportunities for anti-parasitic drug development because α-CAs are found in many parasite or parasite vector invertebrates...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.08.046

    authors： Syrjänen L,Tolvanen ME,Hilvo M,Vullo D,Carta F,Supuran CT,Parkkila S

    更新日期：2013-03-15 00:00:00

  • Synthesis and antiproliferative activity of derivatives of the phyllanthusmin class of arylnaphthalene lignan lactones.

    abstract：:A series of arylnaphthalene lignan lactones based on the structure of the phyllanthusmins, a class of potent natural products possessing diphyllin as the aglycone, has been synthesized and screened for activity against multiple cancer cell lines. SAR exploration was performed on both the carbohydrate and lactone moiet...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.03.033

    authors： Woodard JL,Huntsman AC,Patel PA,Chai HB,Kanagasabai R,Karmahapatra S,Young AN,Ren Y,Cole MS,Herrera D,Yalowich JC,Kinghorn AD,Burdette JE,Fuchs JR

    更新日期：2018-05-15 00:00:00

  • Synthesis of new chemical entities from paracetamol and NSAIDs with improved pharmacodynamic profile.

    abstract：:It was envisaged to combine high antipyretic activity of paracetamol into commonly used NSAIDs. To achieve this goal new chemical entities were synthesized by chemically combining paracetamol and NSAIDs, and biologically evaluated for their antipyretic, analgesic, anti-inflammatory and ulcerogenic potential. The acid ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.08.017

    authors： Yadav MR,Nimekar DM,Ananthakrishnan A,Brahmkshatriya PS,Shirude ST,Giridhar R,Parmar A,Balaraman R

    更新日期：2006-12-15 00:00:00

  • Synthesis and biological evaluation of 8-aryl-2-morpholino-7-O-substituted benzo[e][1,3]oxazin-4-ones against DNA-PK, PI3K, PDE3A enzymes and platelet aggregation.

    abstract：:A series of 40 7-(O-substituted)-2-morpholino-8-aryl-4H-benzo[e][1,3]oxazin-4-one derivatives was synthesized. They were prepared via synthesis of a key precursor, 8-bromo-7-hydroxy-2-morpholino-4H-benzo[e][1,3]oxazin-4-one 13 which was amenable to ether synthesis at the 7-position and Suzuki coupling at the 8-positio...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.08.022

    authors： Saifuzzaman M,Morrison R,Zheng Z,Orive S,Hamilton J,Thompson PE,Al-Rawi JMA

    更新日期：2017-10-15 00:00:00

  • Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors: Molecular docking simulation and structure-activity relationship analysis.

    abstract：:A series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC50 value of 0.5 μM and presented a satisfact...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.01.047

    authors： Zhong Y,Xue M,Zhao X,Yuan J,Liu X,Huang J,Zhao Z,Li H,Xu Y

    更新日期：2013-04-01 00:00:00

  • Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase.

    abstract：:A series of 2-phenyl quinoline-4-carboxylic acid derivatives related to brequinar, an inhibitor of human dihydroorotate dehydrogenase (DHODH), has been prepared and evaluated as inhibitors of DHODH from the malaria parasite Plasmodium falciparum. Brequinar was essentially inactive against PfDHODH (IC(50) 880 microM) w...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.01.017

    authors： Boa AN,Canavan SP,Hirst PR,Ramsey C,Stead AM,McConkey GA

    更新日期：2005-03-15 00:00:00

  • 5-(3-Bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine: structure-activity relationships of 7-substituted heteroaryl analogs as non-nucleoside adenosine kinase inhibitors.

    abstract：:4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors of adenosine kinase (AK). We recently identified a potent, orally efficacious analog, 4 containing a 7-pyridylmorpholine substituted ring system as the key structural element of this template. In this report, we disclose the pharmacologi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.03.023

    authors： Matulenko MA,Lee CH,Jiang M,Frey RR,Cowart MD,Bayburt EK,Didomenico S,Gfesser GA,Gomtsyan A,Zheng GZ,McKie JA,Stewart AO,Yu H,Kohlhaas KL,Alexander KM,McGaraughty S,Wismer CT,Mikusa J,Marsh KC,Snyder RD,Diehl MS,

    更新日期：2005-06-01 00:00:00

  • Design, synthesis, and biological evaluation of amide imidazole derivatives as novel metabolic enzyme CYP26A1 inhibitors.

    abstract：:All-trans-retinoic acid (ATRA) as a physiological metabolite of vitamin A is widely applied in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. CYP26A1 enzyme, induced by ATRA in liver and target tissues, metabolizes ATRA into 4-hydroxyl-RA. Inhibition of CYP26A1 metabolic enzyme represents a ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.08.019

    authors： Sun B,Liu K,Han J,Zhao LY,Su X,Lin B,Zhao DM,Cheng MS

    更新日期：2015-10-15 00:00:00