当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of (2S)-8-[(3R)-3-methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: a novel potent and selective inhibitor of Vps34 for the treatment of solid tumors.

Discovery of (2S)-8-[(3R)-3-methylmorpholin-4-yl]-1-(3-methyl-2-oxobutyl)-2-(trifluoromethyl)-3,4-dihydro-2H-pyrimido[1,2-a]pyrimidin-6-one: a novel potent and selective inhibitor of Vps34 for the treatment of solid tumors.

Abstract：

:Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this lipid kinase in cancer maintenance and progression. Herein, we report the discovery of a series of tetrahydropyrimidopyrimidinone derivatives. Starting with hit compound 1a, medicinal chemistry optimization led to compound 31. This molecule displays potent activity, an exquisite selectivity for Vps34 with excellent properties. The X-ray crystal structure of compound 31 in human Vps34 illustrates how the unique molecular features of the morpholine synthon bestows selectivity against class I PI3Ks. This molecule exhibits suitable in vivo mouse PK parameters and induces a sustained inhibition of Vps34 upon acute administration. Compound 31 constitutes an optimized Vps34 inhibitor that could be used to investigate human cancer biology.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Pasquier B,El-Ahmad Y,Filoche-Rommé B,Dureuil C,Fassy F,Abecassis PY,Mathieu M,Bertrand T,Benard T,Barrière C,El Batti S,Letallec JP,Sonnefraud V,Brollo M,Delbarre L,Loyau V,Pilorge F,Bertin L,Richepin P,Arigon J,

doi

10.1021/jm5013352

subject

Has Abstract

pub_date

2015-01-08 00:00:00

pages

376-400

issue

1

eissn

0022-2623

issn

1520-4804

journal_volume

58

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • 6-Azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX) forms an irreversible bond to the active site of the GluR2 AMPA receptor.

    abstract：:AMPA receptors mediate fast excitatory synaptic transmission and are essential for synaptic plasticity. ANQX, a photoreactive AMPA receptor antagonist, is an important biological probe used to irreversibly inactivate AMPA receptors. Here, using X-ray crystallography and mass spectroscopy, we report that ANQX forms two...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701517b

    authors： Cruz LA,Estébanez-Perpiñá E,Pfaff S,Borngraeber S,Bao N,Blethrow J,Fletterick RJ,England PM

    更新日期：2008-09-25 00:00:00

  • Toward development of targeted nonsteroidal antiandrogen-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-gadolinium complex for prostate cancer diagnostics.

    abstract：:Androgen receptors are present in most advanced prostate cancer specimens, having a critical role in development of this type of cancer. For correct prognosis of patient conditions and treatment monitoring, noninvasive imaging techniques have great advantages over surgical procedures. We developed synthetic methodolog...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100289b

    authors： Marom H,Miller K,Bechor-Bar Y,Tsarfaty G,Satchi-Fainaro R,Gozin M

    更新日期：2010-09-09 00:00:00

  • Synthesis and preliminary biological studies of 4- and 5-[2-hydroxy-3-(isopropylamino)propoxy]benzimidazoles: selective beta2 adrenergic blocking agents.

    abstract：:Benzimidazoles carrying the 2-hydroxy-3-(isopropylamino)propoxy side chain at either the C-4 or C-5 ring positions were synthesized and investigated for beta-adrenergic blocking activity. Both compounds demonstrated beta2 selectivity when evaluated in guinea pig atrial and tracheal preparations. The C-4 isomer was 17 ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00188a019

    authors： Crooks CR,Wright J,Callery PS,Moreton JE

    更新日期：1979-02-01 00:00:00

  • Mapping the Efficiency and Physicochemical Trajectories of Successful Optimizations.

    abstract：:The practices and tactics employed in successful optimizations are examined, judged from the trajectories of ligand efficiency and property evolution. A wide range of targets is analyzed, encompassing a variety of hit finding methods (HTS, fragments, encoded library technology) and types of molecules, including those ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.8b00180

    authors： Young RJ,Leeson PD

    更新日期：2018-08-09 00:00:00

  • Thrombin inhibitors. 2. Amide derivatives of N alpha-substituted L-arginine.

    abstract：:A series of N alpha-(arylsulfonyl)-L-arginine amide derivatives with substituted or unsubstituted naphthalene and heterocyclic compounds as the N alpha-substituent was prepared and tested as inhibitors of the clotting activity of thrombin. N-n-Butyl and N-n-butyl-N-methyl derivatives of N alpha-dansyl-L-arginine amide...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00182a004

    authors： Kikumoto R,Tamao Y,Ohkubo K,Tezuka T,Tonomura S,Okamoto S,Funahara Y,Hijikata A

    更新日期：1980-08-01 00:00:00

  • Regulating the Master Regulator: Controlling Ubiquitination by Thinking Outside the Active Site.

    abstract：:The labeling of proteins with ubiquitin/ubiquitin-like (Ubl) proteins is crucial for several physiological processes and in the onset of various diseases. Recently, targeting ubiquitin protein labeling has shifted toward the use of allosteric mechanisms over classical activity-based approaches. Allosteric enzyme regul...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.6b01346

    authors： Paiva SL,da Silva SR,de Araujo ED,Gunning PT

    更新日期：2018-01-25 00:00:00

  • Benzodiazepine receptor binding and anticonflict activity in a series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines devoid of anticonvulsant properties.

    abstract：:A series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines were synthesized and tested for their ability to inhibit the binding of [3H]diazepam to rat brain receptors in vitro. Compounds bearing a phenyl, 4-methoxyphenyl, or methyl group at position 3 and a dialkylamino group at position 6 showed the highest affinit...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00147a034

    authors： Toja E,Tarzia G,Barone D,Luzzani F,Gallico L

    更新日期：1985-09-01 00:00:00

  • Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit.

    abstract：:We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the alpha(3) receptor subtype with 5-fold selectivity in binding affinity over alpha(1). This paper describes a detailed investigation of the substituents on this core structure at bot...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm040883v

    authors： Russell MG,Carling RW,Atack JR,Bromidge FA,Cook SM,Hunt P,Isted C,Lucas M,McKernan RM,Mitchinson A,Moore KW,Narquizian R,Macaulay AJ,Thomas D,Thompson SA,Wafford KA,Castro JL

    更新日期：2005-03-10 00:00:00

  • Benzothiopyranoindazoles, a new class of chromophore modified anthracenedione anticancer agents. Synthesis and activity against murine leukemias.

    abstract：:The synthesis of the benzothiopyranoindazoles, a new class of chromophore modified anthracenediones related to mitoxantrone, is described. In this structural class the quinone moiety, which is believed to be responsible for the cardiotoxicity of the anthracyclines, has been designed out. The synthesis of the benzothio...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00403a009

    authors： Showalter HD,Angelo MM,Berman EM,Kanter GD,Ortwine DF,Ross-Kesten SG,Sercel AD,Turner WR,Werbel LM,Worth DF

    更新日期：1988-08-01 00:00:00

  • Efficient preparations of the beta-glucuronides of dihydroartemisinin and structural confirmation of the human glucuronide metabolite.

    abstract：:New and greatly improved preparations of the 12alpha,1'beta- (5) and 12beta,1'beta- (6) glucuronides of dihydroartemisinin (DHA, 2) are reported using anomeric hydroxy and imidate glucuronate intermediates. Comparison of the synthetic and natural materials shows that the human metabolite of DHA is the 12alpha-epimer 5...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm001061a

    authors： O'Neill PM,Scheinmann F,Stachulski AV,Maggs JL,Park BK

    更新日期：2001-04-26 00:00:00

  • Quantitative structure-activity relationships of antitumor guanidinothiazolecarboxamides with survival enhancement for therapy in the 3LL Lewis lung carcinoma model.

    abstract：:Guanidinothiazolecarboxamides (GTCs) are a novel class of antitumor agents found to be systemically active against experimental pulmonary metastases of 3LL Lewis lung carcinoma. A series of substituted benzothiazole GTCs were found to produce enhancement of survival in this model by using 8 days of intraperitoneal dos...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00111a009

    authors： Schnur RC,Gallaschun RJ,Singleton DH,Grissom M,Sloan DE,Goodwin P,McNiff PA,Fliri AF,Mangano FM,Olson TH

    更新日期：1991-07-01 00:00:00

  • Discovery of dual leucine zipper kinase (DLK, MAP3K12) inhibitors with activity in neurodegeneration models.

    abstract：:Dual leucine zipper kinase (DLK, MAP3K12) was recently identified as an essential regulator of neuronal degeneration in multiple contexts. Here we describe the generation of potent and selective DLK inhibitors starting from a high-throughput screening hit. Using proposed hinge-binding interactions to infer a binding m...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm5013984

    authors： Patel S,Cohen F,Dean BJ,De La Torre K,Deshmukh G,Estrada AA,Ghosh AS,Gibbons P,Gustafson A,Huestis MP,Le Pichon CE,Lin H,Liu W,Liu X,Liu Y,Ly CQ,Lyssikatos JP,Ma C,Scearce-Levie K,Shin YG,Solanoy H,Stark KL,Wa

    更新日期：2015-01-08 00:00:00

  • Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent.

    abstract：:Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg(-1) dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00134

    authors： Singh P,Kaur S,Kaur J,Singh G,Bhatti R

    更新日期：2016-04-28 00:00:00

  • Resolution, absolute stereochemistry, and pharmacology of the S-(+)- and R-(-)-isomers of the apparent partial AMPA receptor agonist (R,S)-2-amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid [(R,S)-APPA].

    abstract：:(R,S)-2-Amino-3-(3-hydroxy-5-phenylisoxazol-4-yl)propionic acid ((R,S)-APPA) is the only partial agonist at the (R,S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) subtype of excitatory amino acid receptors so far described. In light of the pharmacological interest in partial agonists, we have now a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00033a003

    authors： Ebert B,Lenz S,Brehm L,Bregnedal P,Hansen JJ,Frederiksen K,Bøgesø KP,Krogsgaard-Larsen P

    更新日期：1994-04-01 00:00:00

  • Studies of pyrrolo[1,2-alpha]benzimidazolequinone DT-diaphorase substrate activity, topoisomerase II inhibition activity, and DNA reductive alkylation.

    abstract：:The influence of structure on DT-diaphorase substrate activity, topoisomerase II inhibition activity, and DNA reductive alkylation was studied for the 6-aziridinylpyrrolo[1,2-alpha]benzimidazolequinones (PBIs) and the 6-acetamidopyrrolo[1,2-alpha]benzimidazolequinones (APBIs). The PBIs are reductively activated by DT-...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm960546p

    authors： Skibo EB,Gordon S,Bess L,Boruah R,Heileman MJ

    更新日期：1997-04-25 00:00:00

  • Synthesis and antimalarial activity of cyclic peroxides, 1,2,4,5, 7-pentoxocanes and 1,2,4,5-tetroxanes.

    abstract：:A variety of 1,2,4,5,7-pentoxocane and 1,2,4,5-tetroxane derivatives were prepared as potential peroxide antimalarial agents. In both series of cyclic peroxides, the steric and electronic effects of the substituents attached to the peroxide ring exert a remarkable influence on the antimalarial activity. For some cycli...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm990014j

    authors： Kim HS,Shibata Y,Wataya Y,Tsuchiya K,Masuyama A,Nojima M

    更新日期：1999-07-15 00:00:00

  • The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate.

    abstract：:A series of different synthetic approaches to novel GABA uptake inhibitors are described, leading to examples which are derivatives of nipecotic acid and guvacine, substituted at nitrogen by 4,4-diaryl-3-butenyl or 2-(diphenylmethoxy)ethyl moieties. The in vitro value for inhibition of [3H]-GABA uptake in rat synaptos...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00064a005

    authors： Andersen KE,Braestrup C,Grønwald FC,Jørgensen AS,Nielsen EB,Sonnewald U,Sørensen PO,Suzdak PD,Knutsen LJ

    更新日期：1993-06-11 00:00:00

  • Effect of structural change on acute toxicity and antiinflammatory activity in a series of imidazothiazoles and thiazolobenzimidazoles.

    abstract：:The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes,...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00137a022

    authors： Powers LJ,Fogt SW,Ariyan ZS,Rippin DJ,Heilman RD,Matthews RJ

    更新日期：1981-05-01 00:00:00

  • Selectivity determinants of inhibitor binding to human 20alpha-hydroxysteroid dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme and the potent inhibitor 3,5-dichlorosalicylic acid.

    abstract：:The crystal structure of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in ternary complex with the coenzyme NADP (+) and the potent inhibitor 3,5-dichlorosalicylic acid was determined at a resolution of 1.8 A. The inhibitor is held in place by a network of hydrogen bonding interactions with the active site resid...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm8003575

    authors： Dhagat U,Endo S,Sumii R,Hara A,El-Kabbani O

    更新日期：2008-08-14 00:00:00

  • Synthesis and antiviral activity of deoxy analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents.

    abstract：:The effect of substitution in the acyclic structure of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine (HEPT) on anti-HIV-1 activity was investigated by synthesizing a series of deoxy analogs and related compounds. Preparation of 1-[(2-alkyloxyethoxy)methyl]-6- (phenylthio)thymine (2-4) derivatives was carried out ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00103a009

    authors： Tanaka H,Takashima H,Ubasawa M,Sekiya K,Nitta I,Baba M,Shigeta S,Walker RT,De Clercq E,Miyasaka T

    更新日期：1992-12-11 00:00:00

  • Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity.

    abstract：:CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b01300

    authors： Li B,Ni S,Mao F,Chen F,Liu Y,Wei H,Chen W,Zhu J,Lan L,Li J

    更新日期：2018-01-11 00:00:00

  • How Frequently Are Pan-Assay Interference Compounds Active? Large-Scale Analysis of Screening Data Reveals Diverse Activity Profiles, Low Global Hit Frequency, and Many Consistently Inactive Compounds.

    abstract：:Undetected pan-assay interference compounds (PAINS) with false-positive activities in assays often propagate through medicinal chemistry programs and compromise their outcomes. Although a large number of PAINS have been classified, often on the basis of individual studies or chemical experience, little has been done s...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.7b00154

    authors： Jasial S,Hu Y,Bajorath J

    更新日期：2017-05-11 00:00:00

  • Discovery of 2-phenylamino-imidazo[4,5-h]isoquinolin-9-ones: a new class of inhibitors of lck kinase.

    abstract：:An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to unders...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020113o

    authors： Snow RJ,Cardozo MG,Morwick TM,Busacca CA,Dong Y,Eckner RJ,Jacober S,Jakes S,Kapadia S,Lukas S,Panzenbeck M,Peet GW,Peterson JD,Prokopowicz AS 3rd,Sellati R,Tolbert RM,Tschantz MA,Moss N

    更新日期：2002-08-01 00:00:00

  • Cholecystokinin antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors.

    abstract：:The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a no...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00116a002

    authors： Kerwin JF Jr,Wagenaar F,Kopecka H,Lin CW,Miller T,Witte D,Stashko M,Nadzan AM

    更新日期：1991-12-01 00:00:00

  • Design and studies of novel 5-substituted alkynylpyrimidine nucleosides as potent inhibitors of mycobacteria.

    abstract：:We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitr...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm058167w

    authors： Rai D,Johar M,Manning T,Agrawal B,Kunimoto DY,Kumar R

    更新日期：2005-11-03 00:00:00

  • Potent, orally active GPIIb/IIIa antagonists containing a nipecotic acid subunit. Structure-activity studies leading to the discovery of RWJ-53308.

    abstract：:Although intravenously administered antiplatelet fibrinogen receptor (GPIIb/IIIa) antagonists have become established in the acute-care clinical setting for the prevention of thrombosis, orally administered drugs for chronic use are still under development. Herein, we present details from our exploration of structure-...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm990418b

    authors： Hoekstra WJ,Maryanoff BE,Damiano BP,Andrade-Gordon P,Cohen JH,Costanzo MJ,Haertlein BJ,Hecker LR,Hulshizer BL,Kauffman JA,Keane P,McComsey DF,Mitchell JA,Scott L,Shah RD,Yabut SC

    更新日期：1999-12-16 00:00:00

  • 2 beta-substituted analogues of cocaine. Synthesis and inhibition of binding to the cocaine receptor.

    abstract：:The potencies of a series of 2 beta-substituted cocaine analogues to displace [3H]-3 beta-(p-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester binding in rat striatal membranes demonstrate the requirement for a 2 beta-substituent with two hydrogen-bond acceptors. The insensitivity of the ester moiety to steric ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00079a017

    authors： Lewin AH,Gao YG,Abraham P,Boja JW,Kuhar MJ,Carroll FI

    更新日期：1992-01-01 00:00:00

  • Discovery of imidazo[1,2-b]thiazole derivatives as novel SIRT1 activators.

    abstract：:A series of imidazo[1,2-b]thiazole derivatives is shown to activate the NAD(+)-dependent deacetylase SIRT1, a potential new therapeutic target to treat various metabolic disorders. This series of compounds was derived from a high throughput screening hit bearing an oxazolopyridine core. Water-solubilizing groups could...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm8012954

    authors： Vu CB,Bemis JE,Disch JS,Ng PY,Nunes JJ,Milne JC,Carney DP,Lynch AV,Smith JJ,Lavu S,Lambert PD,Gagne DJ,Jirousek MR,Schenk S,Olefsky JM,Perni RB

    更新日期：2009-03-12 00:00:00

  • Flavones. 2. Synthesis and structure-activity relationship of flavodilol and its analogues, a novel class of antihypertensive agents with catecholamine depleting properties.

    abstract：:(3-Phenyl-7-flavonoxy)propanolamines have been shown to exhibit antihypertensive activity in spontaneously hypertensive rats. Although they are structurally similar to classical beta-adrenergic blocking compounds, their activity is not due to inhibition of beta-adrenoceptors. In the present study, a series of simple f...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00121a034

    authors： Wu ES,Cole TE,Davidson TA,Dailey MA,Doring KG,Fedorchuk M,Loch JT 3rd,Thomas TL,Blosser JC,Borrelli AR

    更新日期：1989-01-01 00:00:00

  • Characterization of the drug binding specificity of rat liver fatty acid binding protein.

    abstract：:Liver-fatty acid binding protein (L-FABP) is found in high levels in enterocytes and is involved in the cytosolic solubilization of fatty acids during fat absorption. In the current studies, the interaction of L-FABP with a range of lipophilic drugs has been evaluated to explore the potential for L-FABP to provide an ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm701192w

    authors： Chuang S,Velkov T,Horne J,Porter CJ,Scanlon MJ

    更新日期：2008-07-10 00:00:00