当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Synthesis and biological evaluation of 1,2,4-trisubstituted imidazoles and 1,3,5-trisubstituted pyrazoles as inhibitors of transforming growth factor beta type 1 receptor (ALK5).

Synthesis and biological evaluation of 1,2,4-trisubstituted imidazoles and 1,3,5-trisubstituted pyrazoles as inhibitors of transforming growth factor beta type 1 receptor (ALK5).

Abstract：

:Two series of nitrogenous heterocycle compounds--1,2,4-trisubstituted imidazoles and 1,3,5-trisubstituted pyrazoles have been synthesized and evaluated for their ALK5 inhibitory activity and cytotoxicity in TGFbeta-Smad2 assay and MTT assay, respectively. The ALK4/5/7 inhibitory activity of some compound was also evaluated in ALK4/5/7 autophosphorylation assays. Compounds 6c and 14c showed relatively potent ALK5 inhibition while weak cytotoxicity. At the same time, compounds 6c and 14c display relatively better ALK5 selectivity versus ALK4/ALK7 (nearly 10-fold) compared with SB431542, a well known ALK5 inhibitor. Compound 6g2 proved to be a moderately selective ALK4 inhibitor versus ALK5 and ALK7 (>10-fold). The binding mode of 14c generated by flexible docking study shows that 14c fits well into the site cavity of ALK5 by forming several tight interactions.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Li X,Wang L,Long L,Xiao J,Hu Y,Li S

doi

10.1016/j.bmcl.2009.04.066

subject

Has Abstract

pub_date

2009-08-15 00:00:00

pages

4868-72

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)00565-4

journal_volume

19

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • 1-(2-Naphthyl)-1H-pyrazole-5-carboxylamides as potent factor Xa inhibitors. Part 2: A survey of P4 motifs.

    abstract：:A variety of P4 motifs have been examined to increase the binding affinity and in vitro anticoagulant potency of our biphenyl 1-(2-naphthyl)-1H-pyrazole-5-carboxylamide-based fXa inhibitors. Highly potent 2-naphthyl-P1 fXa inhibitors (K(i)< or =2 nM) with improved in vitro anticoagulant activity (2xTG< or =1 microM) a...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.12.053

    authors： Jia ZJ,Wu Y,Huang W,Zhang P,Clizbe LA,Goldman EA,Sinha U,Arfsten AE,Edwards ST,Alphonso M,Hutchaleelaha A,Scarborough RM,Zhu BY

    更新日期：2004-03-08 00:00:00

  • Antiangiogenic properties of substituted (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol/one analogs and their derivatives.

    abstract：:In the past half century research efforts have defined a critical role for angiogenesis in tumor growth and metastasis. We previously reported that inhibition of a novel target, ENOX1, by a (Z)-2-benzylindol-3-ylmethylene) quinuclidin-3-ol, suppressed tumor angiogenesis. The present study was undertaken in order to es...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.10.060

    authors： Venkateswaran A,Reddy YT,Sonar VN,Muthusamy V,Crooks PA,Freeman ML,Sekhar KR

    更新日期：2010-12-15 00:00:00

  • Marine sponge alkaloids as a source of anti-bacterial adjuvants.

    abstract：:Novel approaches that do not rely upon developing microbicidal compounds are sorely needed to combat multidrug resistant (MDR) bacteria. The potential of marine secondary metabolites to serve as a source of non-traditional anti-bacterial agents is demonstrated by showing that pyrrole-imidazole alkaloids inhibit biofil...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.11.018

    authors： Melander RJ,Liu HB,Stephens MD,Bewley CA,Melander C

    更新日期：2016-12-15 00:00:00

  • Discovery of indole-derived pyridopyrazine-1,6-dione γ-secretase modulators that target presenilin.

    abstract：:Herein we describe design strategies that led to the discovery of novel pyridopyrazine-1,6-dione γ-secretase modulators (GSMs) incorporating an indole motif as a heterocyclic replacement for a naphthyl moiety that was present in the original lead 9. Tactics involving parallel medicinal chemistry and in situ monomer sy...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.12.059

    authors： Pettersson M,Johnson DS,Humphrey JM,Am Ende CW,Evrard E,Efremov I,Kauffman GW,Stepan AF,Stiff CM,Xie L,Bales KR,Hajos-Korcsok E,Murrey HE,Pustilnik LR,Steyn SJ,Wood KM,Verhoest PR

    更新日期：2015-02-15 00:00:00

  • An analysis of the 'legal high' mephedrone.

    abstract：:'Legal highs' are compounds, plant or fungal material which can be readily bought from the internet without legal restriction and the single chemicals may be structurally related to illegal drugs of abuse such as the amphetamines. Several recent deaths in the UK have been attributed to these legal highs and unfortunat...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.05.065

    authors： Gibbons S,Zloh M

    更新日期：2010-07-15 00:00:00

  • N-heterocyclic dicarboxylic acids: broad-spectrum inhibitors of metallo-β-lactamases with co-antibacterial effect against antibiotic-resistant bacteria.

    abstract：:In an effort to identify novel, broad-spectrum inhibitors against the metallo-β-lactamases (MβLs), several N-heterocyclic derivatives were tested as inhibitors of MβLs CcrA, ImiS, and L1, which are representative enzymes from the distinct MβL subclasses. Three N-heterocyclic dicarboxylic acid derivatives were competit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.06.074

    authors： Feng L,Yang KW,Zhou LS,Xiao JM,Yang X,Zhai L,Zhang YL,Crowder MW

    更新日期：2012-08-15 00:00:00

  • Porphyrins containing nitric oxide donors: Synthesis and cancer cell-oriented NO release.

    abstract：:Four novel porphyrins containing nitric oxide (NO) donors were synthesized, and the structures of all the products were characterized by IR, UV-vis, (1)H NMR, and elementary analysis. Interestingly, these new compounds not only were able to release NO, but also showed cancer cell-oriented accumulation. Higher accumula...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.02.005

    authors： Liu W,Liu C,Gong C,Lin W,Guo C

    更新日期：2009-03-15 00:00:00

  • pH-Dependant fluorescence switching of an i-motif structure incorporating an isomeric azobenzene/pyrene fluorophore.

    abstract：:In this study, we synthesized an Azo-py phosphoramidite, featuring azobenzene and pyrene units, as a novel fluorescent and isomeric (trans- and cis-azobenzene units) material, which we incorporated in an i-motif DNA sequence. We then monitored the structural dynamics and changes in fluorescence as the modified DNA seq...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.04.015

    authors： Joo HN,Van Thi Nguyen T,Chae HK,Seo YJ

    更新日期：2017-06-01 00:00:00

  • High affinity sialoside ligands of myelin associated glycoprotein.

    abstract：:Myelin associated glycoprotein (Siglec-4) is a myelin adhesion receptor, that is, well established for its role as an inhibitor of axonal outgrowth in nerve injury, mediated by binding to sialic acid containing ligands on the axonal membrane. Because disruption of myelin-ligand interactions promotes axon outgrowth, we...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.04.068

    authors： Zeng Y,Rademacher C,Nycholat CM,Futakawa S,Lemme K,Ernst B,Paulson JC

    更新日期：2011-09-01 00:00:00

  • Montmorillonite K-10 catalyzed cyclization of N-ethoxycarbonyl-N'-arylguanidines: access to pyrimido[4,5-c]carbazole and pyrimido[5,4-b]indole derivatives.

    abstract：:Two new heterocycles, pyrimido[4,5-c]carbazole and pyrimido[5,4-b]indole, were prepared in three steps from 3-aminocarbazole and 3-aminoindole, respectively. The key Friedel-Crafts intramolecular cyclization was realized under microwave irradiation using montmorillonite K-10 clay as a catalyst. The pyrimido[4,5-c]carb...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.05.028

    authors： Debray J,Zeghida W,Baldeyrou B,Mahieu C,Lansiaux A,Demeunynck M

    更新日期：2010-07-15 00:00:00

  • Inhibitory potential of flavonoids on PtdIns(3,4,5)P3 binding with the phosphoinositide-dependent kinase 1 pleckstrin homology domain.

    abstract：:Many membrane-associated proteins are involved in various signaling pathways, including the phosphoinositide 3-kinase (PI3K) pathway, which has key roles in diverse cellular processes. Disruption of the activities of these proteins is involved in the development of disease in humans, making these proteins promising ta...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.12.051

    authors： Kang Y,Kim BG,Kim S,Lee Y,Yoon Y

    更新日期：2017-02-01 00:00:00

  • Evaluation of HIV-1 inhibition by stereoisomers and analogues of the sesquiterpenoid hydroquinone peyssonol A.

    abstract：:Peyssonol A, a brominated natural product with documented anti-HIV-1 activity, was synthesized racemically along with 6 isomers and 15 truncated analogues and synthetic precursors. These compounds were screened in a cell-based assay against a recombinant HIV-1 strain to investigate structure-activity relationships. Th...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.01.098

    authors： Treitler DS,Li Z,Krystal M,Meanwell NA,Snyder SA

    更新日期：2013-04-01 00:00:00

  • SAR of a series of inhaled A(2A) agonists and comparison of inhaled pharmacokinetics in a preclinical model with clinical pharmacokinetic data.

    abstract：:COPD is a major cause of mortality in the western world. A(2A) agonists are postulated to reduce the lung inflammation that causes COPD. The cardiovascular effects of A(2A) agonists dictate that a compound needs to be delivered by inhalation to be therapeutically useful. The pharmacological and pharmacokinetic SAR of ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.05.027

    authors： Mantell SJ,Stephenson PT,Monaghan SM,Maw GN,Trevethick MA,Yeadon M,Walker DK,Selby MD,Batchelor DV,Rozze S,Chavaroche H,Lemaitre A,Wright KN,Whitlock L,Stuart EF,Wright PA,Macintyre F

    更新日期：2009-08-01 00:00:00

  • Polyether ionophores-promising bioactive molecules for cancer therapy.

    abstract：:The natural polyether ionophore antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the polyether ionophores undergoing pre-clinical evaluation are reviewed. Most of polyether ionophores have shown potent activity against the ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章,评审

    doi：10.1016/j.bmcl.2012.09.046

    authors： Huczyński A

    更新日期：2012-12-01 00:00:00

  • Interpreting the effect of methyl group at the three carbon bridge of (-)-huperzine A on its anticholinesterase activity by molecular dynamics method.

    abstract：:Based on the recently resolved crystal structure of complex (-)-huperzine A-AChE, we simulated the interaction between (-)-huperzine A analogues and AChE using molecular dynamics method. It was revealed that the methyl group at the three carbon bridge of (-)-huperzine A can form a weak hydrogen bond with the phenol hy...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00042-0

    authors： Liu DX,Jiang H,Wang QM,Chen KX,Ji RY

    更新日期：1998-03-03 00:00:00

  • Activation of mitogen activated protein kinase (MAPK) during D-galactosamine intoxication in the rat liver.

    abstract：:A significant increase in plasma glutamate-oxaloacetate transaminase and glutamate-pyruvate transaminase was observed 6 h after intraperitoneal administration of D-galactosamine (D-Galn). Three hours after administration of D-Galn, the vitamin C concentration in the liver decreased significantly compared to that in a ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.02.057

    authors： Nishioka H,Kishioka T,Iida C,Fujii K,Ichi I,Kojo S

    更新日期：2006-06-01 00:00:00

  • Chemical space screening around Phe3 in opioid peptides: Modulating µ versus δ agonism by Suzuki-Miyaura cross-couplings.

    abstract：:In this study, affinities and activities of derivatized analogues of Dmt-dermorphin[1-4] (i.e. Dmt-d-Ala-Phe-GlyNH2, Dmt = 2',6'-dimethyl-(S)-tyrosine) for the µ opioid receptor (MOP) and δ opioid receptor (DOP) were evaluated using radioligand binding studies, functional cell-based assays and isolated organ bath expe...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.05.015

    authors： Willemse T,Eiselt E,Hollanders K,Schepens W,van Vlijmen HWT,Chung NN,Blais V,Holleran B,Longpré JM,Schiller PW,Maes BUW,Sarret P,Gendron L,Ballet S

    更新日期：2018-07-15 00:00:00

  • Synthesis of thiophene-2-carboxamidines containing 2-aminothiazoles and their biological evaluation as urokinase inhibitors.

    abstract：:The serine protease urokinase (uPa) has been implicated in the progression of both breast and prostate cancer. Utilizing structure based design, the synthesis of a series of substituted 4-[2-amino-1,3-thiazolyl]-thiophene-2-carboxamidines is described. Further optimization of this series by substitution of the termina...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00102-0

    authors： Wilson KJ,Illig CR,Subasinghe N,Hoffman JB,Rudolph MJ,Soll R,Molloy CJ,Bone R,Green D,Randall T,Zhang M,Lewandowski FA,Zhou Z,Sharp C,Maguire D,Grasberger B,DesJarlais RL,Spurlino J

    更新日期：2001-04-09 00:00:00

  • Pyrido pyrimidinones as selective agonists of the high affinity niacin receptor GPR109A: optimization of in vitro activity.

    abstract：:Pyrido pyrimidinones are selective agonists of the human high affinity niacin receptor GPR109A (HM74A). They show no activity on the highly homologous low affinity receptor GPR109B (HM74). Starting from a high throughput screening hit the in vitro activity of the pyrido pyrimidinones was significantly improved providi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.07.108

    authors： Peters JU,Kühne H,Dehmlow H,Grether U,Conte A,Hainzl D,Hertel C,Kratochwil NA,Otteneder M,Narquizian R,Panousis CG,Ricklin F,Röver S

    更新日期：2010-09-15 00:00:00

  • Design and synthesis of potent, isoxazole-containing renin inhibitors.

    abstract：:The design and optimization of a novel isoxazole S(1) linker for renin inhibitor is described herein. This effort culminated in the identification of compound 18, an orally bioavailable, sub-nanomolar renin inhibitor even in the presence of human plasma. When compound 18 was found to inhibit CYP3A4 in a time dependent...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.03.014

    authors： Fournier PA,Arbour M,Cauchon E,Chen A,Chefson A,Ducharme Y,Falgueyret JP,Gagné S,Grimm E,Han Y,Houle R,Lacombe P,Lévesque JF,MacDonald D,Mackay B,McKay D,Percival MD,Ramtohul Y,St-Jacques R,Toulmond S

    更新日期：2012-04-15 00:00:00

  • Further studies on anti-invasive chemotypes: An excursion from chalcones to curcuminoids.

    abstract：:In our ongoing search for new anti-invasive chemotypes, we have made an excursion from previously reported potent 1,3-diarylpropenones (chalcones) to congeners bearing longer linkers between the aromatic moieties. Nine 1,ω-diarylalkenones, including curcumin and bisdemethoxycurcumin, were evaluated in the chick heart ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2015.01.027

    authors： Roman BI,De Ryck T,Verhasselt S,Bracke ME,Stevens CV

    更新日期：2015-03-01 00:00:00

  • In vitro biotransformations of the prostaglandin D2 (DP) antagonist MK-0524 and synthesis of metabolites.

    abstract：:Metabolites of the potent DP antagonist, MK-0524, were generated using in vitro systems including hepatic microsomes and hepatocytes. Four metabolites (two hydroxylated diastereomers, a ketone and an acyl glucuronide) were characterized by LC-MS/MS and 1H NMR. Larger quantities of these metabolites were prepared by ei...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.10.055

    authors： Nicoll-Griffith DA,Seto C,Aubin Y,Lévesque JF,Chauret N,Day S,Silva JM,Trimble LA,Truchon JF,Berthelette C,Lachance N,Wang Z,Sturino C,Braun M,Zamboni R,Young RN

    更新日期：2007-01-15 00:00:00

  • Design, synthesis and evaluation of novel N-phenylbutanamide derivatives as KCNQ openers for the treatment of epilepsy.

    abstract：:KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novel N-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activity in vitro...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2018.05.019

    authors： Yang S,Lu D,Ouyang P

    更新日期：2018-09-15 00:00:00

  • Structure-based design and synthesis of potent benzothiazole inhibitors of interleukin-2 inducible T cell kinase (ITK).

    abstract：:Inhibition of the non-receptor tyrosine kinase ITK, a component of the T-cell receptor signalling cascade, may represent a novel treatment for allergic asthma. Here we report the structure-based optimization of a series of benzothiazole amides that demonstrate sub-nanomolar inhibitory potency against ITK with good cel...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.09.069

    authors： MacKinnon CH,Lau K,Burch JD,Chen Y,Dines J,Ding X,Eigenbrot C,Heifetz A,Jaochico A,Johnson A,Kraemer J,Kruger S,Krülle TM,Liimatta M,Ly J,Maghames R,Montalbetti CA,Ortwine DF,Pérez-Fuertes Y,Shia S,Stein DB,Tran

    更新日期：2013-12-01 00:00:00

  • Substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles as Src kinase inhibitors.

    abstract：:A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitor...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00577-2

    authors： Berger D,Dutia M,Powell D,Wissner A,DeMorin F,Raifeld Y,Weber J,Boschelli F

    更新日期：2002-10-21 00:00:00

  • Pyrazole-based factor Xa inhibitors containing N-arylpiperidinyl P4 residues.

    abstract：:The synthesis, SAR, pharmacokinetic profile, and modeling studies of both monocyclic and fused pyrazoles containing substituted N-arylpiperidinyl P4 moieties that are potent and selective factor Xa inhibitors will be discussed. Fused pyrazole analog 16a, with a 2'-methylsulfonylphenyl piperidine P4 group, was shown to...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.11.071

    authors： Qiao JX,Cheng X,Smallheer JM,Galemmo RA,Drummond S,Pinto DJ,Cheney DL,He K,Wong PC,Luettgen JM,Knabb RM,Wexler RR,Lam PY

    更新日期：2007-03-01 00:00:00

  • Discovery and characterization of potent and selective 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acids as S1P₁ agonists.

    abstract：:S1P(1) receptor driven lymphopenia has proven utility in the treatment of an array of autoimmune disease states. As a part of our efforts to develop potent and selective S1P(1) receptor agonists, we have identified a novel chemical series of 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acid S1P(1) r...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.05.110

    authors： Buzard D,Han S,Thoresen L,Moody J,Lopez L,Kawasaki A,Schrader T,Sage C,Gao Y,Edwards J,Barden J,Thatte J,Fu L,Solomon M,Liu L,Al-Shamma H,Gatlin J,Le M,Xing C,Espinola S,Jones RM

    更新日期：2011-10-01 00:00:00

  • Polar substitutions in the benzenesulfonamide ring of celecoxib afford a potent 1,5-diarylpyrazole class of COX-2 inhibitors.

    abstract：:Several chemical modifications in the N(1)-benzenesulfonamide ring of celecoxib are presented. The series with a hydroxymethyl group adjacent to the sulfonamide was found to be the most potent modification that yielded many compounds selectively active against COX-2 enzyme in vitro. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.10.027

    authors： Singh SK,Reddy PG,Rao KS,Lohray BB,Misra P,Rajjak SA,Rao YK,Venkateswarlu A

    更新日期：2004-01-19 00:00:00

  • Novel and potent transforming growth factor beta type I receptor kinase domain inhibitor: 7-amino 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-quinolines.

    abstract：:A novel series of 7-amino 4-(2-pyridin-2-yl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)-quinolines was synthesized and their TbetaR-1 inhibitory, p38 MAPK inhibitory, and TbetaR-1-dependent cellular activity were evaluated. Compound 5a was found to be a highly potent in the enzyme assay and TbetaR-1-dependent cellular ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.04.065

    authors： Li HY,Wang Y,Yan L,Campbell RM,Anderson BD,Wagner JR,Yingling JM

    更新日期：2004-07-05 00:00:00

  • Design and synthesis of the tumor-activated prodrug of dihydropyrimidine dehydrogenase (DPD) inhibitor, RO0094889 for combination therapy with capecitabine.

    abstract：:A series of tumor-activated prodrugs of the inhibitors of dihydropyrimidine dehydrogenase (DPD), an enzyme catabolizing 5-fluorouracil (5-FU: 4g), has been designed and synthesized. RO0094889 (11c) is a prodrug of 5-vinyluracil (4c), a known DPD inhibitor, and was designed to generate 4c selectively in tumor tissues b...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)01082-x

    authors： Hattori K,Kohchi Y,Oikawa N,Suda H,Ura M,Ishikawa T,Miwa M,Endoh M,Eda H,Tanimura H,Kawashima A,Horii I,Ishitsuka H,Shimma N

    更新日期：2003-03-10 00:00:00