当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of novel highly potent hepatitis C virus NS5A inhibitor (AV4025).

Discovery of novel highly potent hepatitis C virus NS5A inhibitor (AV4025).

Abstract：

:A series of next in class small-molecule hepatitis C virus (HCV) NS5A inhibitors with picomolar potency containing 2-pyrrolidin-2-yl-5-{4-[4-(2-pyrrolidin-2-yl-1H-imidazol-5-yl)buta-1,3-diynyl]phenyl}-1H-imidazole cores was designed based on the SAR studies available for the reported NS5A inhibitors. Compound 13a (AV4025), with (S,S,S,S)-stereochemistry (EC50 = 3.4 ± 0.2 pM, HCV replicon genotype 1b), was dramatically more active than were the compounds with two (S)- and two (R)-chiral centers. Human serum did not significantly reduce the antiviral activity (<4-fold). Relatively favorable pharmacokinetic features and good oral bioavailability were observed during animal studies. Compound 13a was well tolerated in rodents (in mice, LD50 = 2326 mg/kg or higher), providing a relatively high therapeutic index. During safety, pharmacology and subchronic toxicity studies in rats and dogs, it was not associated with any significant pathological or clinical findings. This compound is currently being evaluated in phase I/II clinical trials for the treatment of HCV infection.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Ivachtchenko AV,Mitkin OD,Yamanushkin PM,Kuznetsova IV,Bulanova EA,Shevkun NA,Koryakova AG,Karapetian RN,Bichko VV,Trifelenkov AS,Kravchenko DV,Vostokova NV,Veselov MS,Chufarova NV,Ivanenkov YA

doi

10.1021/jm500951r

subject

Has Abstract

pub_date

2014-09-25 00:00:00

pages

7716-30

issue

18

eissn

0022-2623

issn

1520-4804

journal_volume

57

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Synthesis of novel 3,7-substituted-2-(3',4'-dihydroxyphenyl)flavones with improved antioxidant activity.

    abstract：:A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000951n

    authors： van Acker FA,Hageman JA,Haenen GR,van Der Vijgh WJ,Bast A,Menge WM

    更新日期：2000-10-05 00:00:00

  • Synthesis and biological evaluation of new imidazole, pyrimidine, and purine derivatives and analogs as inhibitors of xanthine oxidase.

    abstract：:Several derivatives of 4,5-disubstituted imidazole, 2,4,5-trisubstituted pyrimidine, 2-substituted purine, thiazolo[3,2-alpha]purine, [1,3]thiazino[3,2-alpha]purine, thiazolo[2,3-i]purine, [1,3]thiazino-[2,3-i]purine, and 6-substituted pyrazolo[3,4-d]pyrimidine were synthesized and tested as inhibitors of the xanthine...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm950876u

    authors： Biagi G,Costantini A,Costantino L,Giorgi I,Livi O,Pecorari P,Rinaldi M,Scartoni V

    更新日期：1996-06-21 00:00:00

  • Reversible ketomethylene-based inhibitors of human neutrophil proteinase 3.

    abstract：:Neutrophil serine proteases, proteinase 3 (PR3) and human neutrophil elastase (HNE), are considered as targets for chronic inflammatory diseases. Despite sharing high sequence similarity, the two enzymes have different substrate specificities and functions. While a plethora of HNE inhibitors exist, PR3 specific inhibi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500782s

    authors： Budnjo A,Narawane S,Grauffel C,Schillinger AS,Fossen T,Reuter N,Haug BE

    更新日期：2014-11-26 00:00:00

  • Probing the subpockets of factor Xa reveals two binding modes for inhibitors based on a 2-carboxyindole scaffold: a study combining structure-activity relationship and X-ray crystallography.

    abstract：:Structure-activity relationships within a series of highly potent 2-carboxyindole-based factor Xa inhibitors incorporating a neutral P1 ligand are described with particular emphasis on the structural requirements for addressing subpockets of the factor Xa enzyme. Interactions with the subpockets were probed by systema...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0490540

    authors： Nazaré M,Will DW,Matter H,Schreuder H,Ritter K,Urmann M,Essrich M,Bauer A,Wagner M,Czech J,Lorenz M,Laux V,Wehner V

    更新日期：2005-07-14 00:00:00

  • Synthesis and evaluation of oxodioxolenylmethyl carbamate prodrugs of pseudomycins.

    abstract：:With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C' 3. It is rather encouraging to note that several members of the newly synthesi...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm000425w

    authors： Sun X,Rodriguez M,Zeckner D,Sachs B,Current W,Boyer R,Paschal J,McMillian C,Chen SH

    更新日期：2001-08-02 00:00:00

  • Novel vanilloid receptor-1 antagonists: 2. Structure-activity relationships of 4-oxopyrimidines leading to the selection of a clinical candidate.

    abstract：:A series of novel 4-oxopyrimidine TRPV1 antagonists was evaluated in assays measuring the blockade of capsaicin or acid-induced influx of calcium into CHO cells expressing TRPV1. The investigation of the structure-activity relationships in the heterocyclic A-region revealed the optimum pharmacophoric elements required...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm070190p

    authors： Doherty EM,Fotsch C,Bannon AW,Bo Y,Chen N,Dominguez C,Falsey J,Gavva NR,Katon J,Nixey T,Ognyanov VI,Pettus L,Rzasa RM,Stec M,Surapaneni S,Tamir R,Zhu J,Treanor JJ,Norman MH

    更新日期：2007-07-26 00:00:00

  • Discovery of Potent Myeloid Cell Leukemia-1 (Mcl-1) Inhibitors That Demonstrate in Vivo Activity in Mouse Xenograft Models of Human Cancer.

    abstract：:Overexpression of myeloid cell leukemia-1 (Mcl-1) in cancers correlates with high tumor grade and poor survival. Additionally, Mcl-1 drives intrinsic and acquired resistance to many cancer therapeutics, including B cell lymphoma 2 family inhibitors, proteasome inhibitors, and antitubulins. Therefore, Mcl-1 inhibition ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.8b01991

    authors： Lee T,Christov PP,Shaw S,Tarr JC,Zhao B,Veerasamy N,Jeon KO,Mills JJ,Bian Z,Sensintaffar JL,Arnold AL,Fogarty SA,Perry E,Ramsey HE,Cook RS,Hollingshead M,Davis Millin M,Lee KM,Koss B,Budhraja A,Opferman JT,Kim K

    更新日期：2019-04-25 00:00:00

  • Synthesis, SAR, and series evolution of novel oxadiazole-containing 5-lipoxygenase activating protein inhibitors: discovery of 2-[4-(3-{(r)-1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetam

    abstract：:The synthesis, structure-activity relationship (SAR), and evolution of a novel series of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent FLAP binding potency (IC50 < 10 nM) and pot...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm501185j

    authors： Takahashi H,Riether D,Bartolozzi A,Bosanac T,Berger V,Binetti R,Broadwater J,Chen Z,Crux R,De Lombaert S,Dave R,Dines JA,Fadra-Khan T,Flegg A,Garrigou M,Hao MH,Huber J,Hutzler JM,Kerr S,Kotey A,Liu W,Lo HY,Lok

    更新日期：2015-02-26 00:00:00

  • Discovery of potent, nonsystemic apical sodium-codependent bile acid transporter inhibitors (Part 1).

    abstract：:Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codepe...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm040215+

    authors： Tremont SJ,Lee LF,Huang HC,Keller BT,Banerjee SC,Both SR,Carpenter AJ,Wang CC,Garland DJ,Huang W,Jones C,Koeller KJ,Kolodziej SA,Li J,Manning RE,Mahoney MW,Miller RE,Mischke DA,Rath NP,Fletcher T,Reinhard EJ,Tol

    更新日期：2005-09-08 00:00:00

  • Human somatostatin receptor specificity of backbone-cyclic analogues containing novel sulfur building units.

    abstract：:Somatostatin-14 (somatostatin) and its clinically available analogues octreotide, lanreotide, and vapreotide are potent inhibitors of growth hormone, insulin, and glucagon release. Recently, a novel backbone cyclic somatostatin analogue c(GABA-Phe-Trp-(D)Trp-Lys-Thr-Phe-GlyC3-NH(2)) (analogue 1, PTR 3173) that possess...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0100281

    authors： Gazal S,Gelerman G,Ziv O,Karpov O,Litman P,Bracha M,Afargan M,Gilon C

    更新日期：2002-04-11 00:00:00

  • Synthesis and biological studies of 3-(beta-D-ribofuranosyl)-2,3,-dihydro-6H-1,3-oxazine-2,6-dione, a new pyrimidine nucleoside analog related to uridine.

    abstract：:Reaction of the trimethylsilyl derivative of 2,3-dihydro-6H-1,3-oxazine-2,6-dione (2, "uracil anhydride") with protected 1-O-acetylribofuranoses in the presence of stannic chloride gave the corresponding block nucleosides. 3-(2,3-5-Tri-O-2',2',2'-trichloroethoxycarbonyl-beta-d-ribofuranosyl)-2,3-dihydro-6H-1,3-oxazine...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00227a013

    authors： Chwang TL,Wood WF,Parkhurst JR,Nesnow S,Danenberg PV,Heidelberger C

    更新日期：1976-05-01 00:00:00

  • Discovery of (2E)-3-{2-butyl-1-[2-(diethylamino)ethyl]-1H-benzimidazol-5-yl}-N-hydroxyacrylamide (SB939), an orally active histone deacetylase inhibitor with a superior preclinical profile.

    abstract：:A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC1 enzyme and COLO 205 cellular IC(50)), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC(50)), and clog...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm2003552

    authors： Wang H,Yu N,Chen D,Lee KC,Lye PL,Chang JW,Deng W,Ng MC,Lu T,Khoo ML,Poulsen A,Sangthongpitag K,Wu X,Hu C,Goh KC,Wang X,Fang L,Goh KL,Khng HH,Goh SK,Yeo P,Liu X,Bonday Z,Wood JM,Dymock BW,Kantharaj E,Su

    更新日期：2011-07-14 00:00:00

  • Fragment Molecular Orbital Method Applied to Lead Optimization of Novel Interleukin-2 Inducible T-Cell Kinase (ITK) Inhibitors.

    abstract：:Inhibition of inducible T-cell kinase (ITK), a nonreceptor tyrosine kinase, may represent a novel treatment for allergic asthma. In our previous reports, we described the discovery of sulfonylpyridine (SAP), benzothiazole (BZT), indazole (IND), and tetrahydroindazole (THI) series as novel ITK inhibitors and how comput...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b00045

    authors： Heifetz A,Trani G,Aldeghi M,MacKinnon CH,McEwan PA,Brookfield FA,Chudyk EI,Bodkin M,Pei Z,Burch JD,Ortwine DF

    更新日期：2016-05-12 00:00:00

  • Ocular Hypotensive Response in Nonhuman Primates of (8R)-1-[(2S)-2-Aminopropyl]-8,9-dihydro-7H-pyrano[2,3-g]indazol-8-ol a Selective 5-HT2 Receptor Agonist.

    abstract：:Recently, it has been reported that 5-HT2 receptor agonists effectively reduce intraocular pressure (IOP) in a nonhuman primate model of glaucoma. Although 1-[(2S)-2-aminopropyl]indazol-6-ol (AL-34662) was shown to have good efficacy in this nonhuman primate model of ocular hypertension as well as a desirable physicoc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00857

    authors： May JA,Sharif NA,McLaughlin MA,Chen HH,Severns BS,Kelly CR,Holt WF,Young R,Glennon RA,Hellberg MR,Dean TR

    更新日期：2015-11-25 00:00:00

  • 2-Fluoroformycin and 2-aminoformycin. Synthesis and biological activity.

    abstract：:Syntheses of 2-fluoroformycin [7-amino-5-fluoro-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2b) and 2-aminoformycin [5,7-diamino-3-(beta-D-ribofuranosyl)pyrazolo[4,3-d]pyrimidine] (2c) are described. Cytotoxicity data are given for 2b and 2c alone as well as with added pentostatin. Kinetic parameters for adeno...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00149a033

    authors： Secrist JA 3rd,Shortnacy AT,Montgomery JA

    更新日期：1985-11-01 00:00:00

  • Structure-Based Scaffold Repurposing for G Protein-Coupled Receptors: Transformation of Adenosine Derivatives into 5HT2B/5HT2C Serotonin Receptor Antagonists.

    abstract：:Adenosine derivatives developed to activate adenosine receptors (ARs) revealed micromolar activity at serotonin 5HT2B and 5HT2C receptors (5HTRs). We explored the structure-activity relationship at 5HT2Rs and modeled receptor interactions in order to optimize affinity and simultaneously reduce AR affinity. Depending o...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.6b01183

    authors： Tosh DK,Ciancetta A,Warnick E,Crane S,Gao ZG,Jacobson KA

    更新日期：2016-12-22 00:00:00

  • Synthesis and benzodiazepine binding activity of a series of novel [1,2,4]triazolo[1,5-c]quinazolin-5(6H)-ones.

    abstract：:Investigation of tricyclic heterocycles related to the 2-arylpyrazolo[4,3-c]quinolin-3(5H)-ones, structures with high affinity for the benzodiazepine (BZ) receptor, led to the synthesis of 2-phenyl-[1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one, a compound with 4 nM binding affinity to the BZ receptor. Analogues were prep...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00105a044

    authors： Francis JE,Cash WD,Barbaz BS,Bernard PS,Lovell RA,Mazzenga GC,Friedmann RC,Hyun JL,Braunwalder AF,Loo PS

    更新日期：1991-01-01 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

  • Discovery of dual target inhibitors against cyclooxygenases and leukotriene A4 hydrolyase.

    abstract：:Dual target inhibitors against COX-2 and LTA(4)H were designed by adding functional groups from a marketed COX-2 inhibitor, Nimesulide, to an existing LTA(4)H inhibitor 1-(2-(4-phenoxyphenoxy) ethyl) pyrrolidine. A series of phenoxyphenyl pyrrolidine compounds were synthesized and tested for their inhibition activitie...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm200063s

    authors： Chen Z,Wu Y,Liu Y,Yang S,Chen Y,Lai L

    更新日期：2011-05-26 00:00:00

  • Generation of ligand-based pharmacophore model and virtual screening for identification of novel tubulin inhibitors with potent anticancer activity.

    abstract：:A pharmacophore model, Hypo1, was built on the basis of 21 training-set indole compounds with varying levels of antiproliferative activity. Hypo1 possessed important chemical features required for the inhibitors and demonstrated good predictive ability for biological activity, with high correlation coefficients of 0.9...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm801649y

    authors： Chiang YK,Kuo CC,Wu YS,Chen CT,Coumar MS,Wu JS,Hsieh HP,Chang CY,Jseng HY,Wu MH,Leou JS,Song JS,Chang JY,Lyu PC,Chao YS,Wu SY

    更新日期：2009-07-23 00:00:00

  • Dipeptidyl peptidase IV dependent water-soluble prodrugs of highly lipophilic bicyclic nucleoside analogues.

    abstract：:We present the first report of the application of the dipeptidyl peptidase IV (DPPIV/CD26) based prodrug approach to hydroxy-containing drug derivatives. In particular, we applied this strategy to the highly lipophilic antiviral drug family of bicyclic furanopyrimidine nucleoside analogues (BCNA) in order to improve t...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm101624e

    authors： Diez-Torrubia A,Balzarini J,Andrei G,Snoeck R,De Meester I,Camarasa MJ,Velázquez S

    更新日期：2011-03-24 00:00:00

  • A novel series of 2,5-substituted tryptamine derivatives as vascular 5HT1B/1D receptor antagonists.

    abstract：:The design, synthesis, and activity of a novel series of 2,5-substituted tryptamine derivatives at vascular 5HT1B-like receptors is described. Several important auxiliary binding sites of the 5HT1B-like receptor have been proposed following various modifications to the 2-substituent and especially to the methylene- or...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm9605849

    authors： Moloney GP,Robertson AD,Martin GR,MacLennan S,Mathews N,Dodsworth S,Sang PY,Knight C,Glen R

    更新日期：1997-07-18 00:00:00

  • Antimitotic agents: structure-activity studies with some pyridine derivatives.

    abstract：:Antitumor activity in mice was observed for the oxime of the previously reported ethyl [6-amino-4-[(1-methyl-2-phenyl-2-oxoethyl)amino]-5-nitropyridin -2-yl] carbamate (8) and several related compounds. These compounds are precursors of the active ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 4), which are potent a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00098a014

    authors： Temple C Jr,Rener GA,Waud WR,Noker PE

    更新日期：1992-10-02 00:00:00

  • Novel DNA groove binding alkylators: design, synthesis, and biological evaluation.

    abstract：:A group of oligopeptides has been synthesized that are structurally related to the natural antiviral antitumor agents netropsin and distamycin but which bear alkylating functions. Cytostatic activity against both human and murine tumor cell lines as well as their in vitro activity against a range of viruses is reporte...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00397a012

    authors： Krowicki K,Balzarini J,De Clercq E,Newman RA,Lown JW

    更新日期：1988-02-01 00:00:00

  • Structure-activity relationships for the antileishmanial and antitrypanosomal activities of 1'-substituted 9-anilinoacridines.

    abstract：:Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated agai...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm970232h

    authors： Gamage SA,Figgitt DP,Wojcik SJ,Ralph RK,Ransijn A,Mauel J,Yardley V,Snowdon D,Croft SL,Denny WA

    更新日期：1997-08-01 00:00:00

  • Development of 1,4-benzodiazepine cholecystokinin type B antagonists.

    abstract：:A series of 3-(arylureido)-5-phenyl-1,4-benzodiazepines, nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK), are described. Derived by reasoned modification of the CCK-A selective 3-carboxamido-1,4-benzodiazepine, MK-329, this paper chronicles the development of potent, orally effective compounds in ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00078a018

    authors： Bock MG,DiPardo RM,Evans BE,Rittle KE,Whitter WL,Garsky VM,Gilbert KF,Leighton JL,Carson KL,Mellin EC

    更新日期：1993-12-24 00:00:00

  • Synthesis of 1-(3,4-dihydroxy-5-nitrophenyl)-2-phenyl-ethanone and derivatives as potent and long-acting peripheral inhibitors of catechol-O-methyltransferase.

    abstract：:A homologous series of novel nitro-catechol structures (7a-7e) were synthesized and tested as inhibitors of the enzyme catechol-O-methyltransferase (COMT). Increasing chain length was found to have significant impact on both brain penetration and duration of COMT inhibition in the rat. Of this series, compound 7b (1-(...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0109964

    authors： Learmonth DA,Vieira-Coelho MA,Benes J,Alves PC,Borges N,Freitas AP,da-Silva PS

    更新日期：2002-01-31 00:00:00

  • Nonsymmetrical bipiperidyls as inhibitors of vesicular acetylcholine storage.

    abstract：:Introduction of a nitrogen atom into the cyclohexane ring of 2-(4-phenylpiperidinyl)cyclohexanol (vesamicol, AH5183) yielded two positional isomers, 5-azavesamicol (5, prezamicol) and 4-azavesamicol (6, trozamicol). As inhibitors of vesicular acetylcholine transport, 5 and 6 were found to be 147 and 85 times less pote...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00060a005

    authors： Efange SM,Khare A,Parsons SM,Bau R,Metzenthin T

    更新日期：1993-04-16 00:00:00

  • Drug Induced Liver Injury (DILI). Mechanisms and Medicinal Chemistry Avoidance/Mitigation Strategies.

    abstract：:Adverse drug reactions (ADRs) are a common cause of attrition in drug discovery and development and drug-induced liver injury (DILI) is a leading cause of preclinical and clinical drug terminations. This perspective outlines many of the known DILI mechanisms and assessment methods used to evaluate and mitigate DILI ri...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/acs.jmedchem.0c00524

    authors： Norman BH

    更新日期：2020-10-22 00:00:00

  • Property- and structure-guided discovery of a tetrahydroindazole series of interleukin-2 inducible T-cell kinase inhibitors.

    abstract：:Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays a major role in T-cell signaling downstream of the T-cell receptor (TCR), and considerable efforts have been directed toward discovery of ITK-selective inhibitors as potential treatments of inflammatory disorders such as...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm500550e

    authors： Burch JD,Lau K,Barker JJ,Brookfield F,Chen Y,Chen Y,Eigenbrot C,Ellebrandt C,Ismaili MH,Johnson A,Kordt D,MacKinnon CH,McEwan PA,Ortwine DF,Stein DB,Wang X,Winkler D,Yuen PW,Zhang Y,Zarrin AA,Pei Z

    更新日期：2014-07-10 00:00:00