Design, synthesis and biological evaluation of N-phenylthieno[2,3-d]pyrimidin-4-amines as inhibitors of FGFR1.

Abstract:

:Fibroblast grow factor receptor 1 (FGFR1) is an important anti-cancer target that plays crucial role in oncogenesis and oncogenic angiogenesis. The structure-activity relationship (SAR) of N-phenylthieno[2,3-d]pyrimidin-4-amines was investigated. Binding of active compounds with FGFR1 kinase was analyzed by molecular modeling studies. Selected active thieno[2,3-d]pyrimidines were tested for selectivity and antiproliferative activity. The most active compounds, 3-({6-phenylthieno[2,3-d]pyrimidin-4-yl}amino)phenol and 3-({5-phenylthieno[2,3-d]pyrimidin-4-yl}amino)phenol have IC₅₀ 0.16 and 0.18 μM, respectively. The results presented here may help to identify new thienopyrimidines with optimized cell growth inhibitory activity which may be further used as anticancer agents.

journal_name

Bioorg Med Chem

authors

Gryshchenko AA,Bdzhola VG,Balanda AO,Briukhovetska NV,Kotey IM,Golub AG,Ruban TP,Lukash LL,Yarmoluk SM

doi

10.1016/j.bmc.2014.12.044

subject

Has Abstract

pub_date

2015-05-01 00:00:00

pages

2287-93

issue

9

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(14)00892-X

journal_volume

23

pub_type

杂志文章
  • In vitro antitumor activities of 2,6-di-[2-(heteroaryl)vinyl]pyridines and pyridiniums.

    abstract::The in vitro antitumor activities of 2,6-di-[2-(heteroaryl)vinyl]pyridines versus the standard National Cancer Institute 60 cell lines panel and of 2,6-di-[2-(heteroaryl)vinyl] pyridinium cations versus MCF7 (human mammary carcinoma) and LNCap (prostate carcinoma) cell lines are reported. Antiproliferative effects in ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00142-6

    authors: Barresi V,Condorelli DF,Fortuna CG,Musumarra G,Scirè S

    更新日期:2002-09-01 00:00:00

  • Spectroscopic, computational modeling and cytotoxicity of a series of meso-phenyl and meso-thienyl-BODIPYs.

    abstract::A series of twenty-two BODIPY compounds were synthesized, containing various meso-phenyl and meso-thienyl groups, and their spectroscopic and structural properties were investigated using both experimental and computational methods. Further functionalization of the BODIPY framework via iodination at the 2,6-pyrrolic p...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.07.017

    authors: Gibbs JH,Robins LT,Zhou Z,Bobadova-Parvanova P,Cottam M,McCandless GT,Fronczek FR,Vicente MG

    更新日期:2013-09-15 00:00:00

  • Synthesis and properties of triplex-forming oligonucleotides containing 2'-O-(2-methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine.

    abstract::2'-O-(2-Methoxyethyl)-5-(3-aminoprop-1-ynyl)-uridine phosphoramidite (MEPU) has been synthesized from d-ribose and 5-iodouracil and incorporated into triplex-forming oligonucleotides (TFOs) by automated solid-phase oligonucleotide synthesis. The TFOs gave very high triplex stability with their target duplexes as measu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.07.005

    authors: Lou C,Xiao Q,Brennan L,Light ME,Vergara-Irigaray N,Atkinson EM,Holden-Dye LM,Fox KR,Brown T

    更新日期:2010-09-01 00:00:00

  • Chemical synthesis, cytotoxicity, selectivity and bioavailability of 5α-androstane-3α,17β-diol derivatives.

    abstract::Aminosteroid derivatives represent a new family of compounds with promising antiproliferative activity over different cancer cell lines. Among all the aminosteroid derivatives synthesised in our laboratory, we have identified E-37P as one of the more potent when tested in vitro. Unfortunately, the pharmacokinetic prop...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.09.026

    authors: Ayan D,Maltais R,Hospital A,Poirier D

    更新日期:2014-11-01 00:00:00

  • Application of descriptors based on Lipinski's rules in the QSPR study of aqueous solubilities.

    abstract::We complement new physically interpretable descriptors inspired by the Lipinski's rules of drug bioavailability with others obtained from the Dragon 3.0 software, in order to find the best QSPR relationship for aqueous solubilities of 100 structurally heterogeneous organic, drug-like compounds. The simultaneous linear...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.03.044

    authors: Duchowicz PR,Talevi A,Bellera C,Bruno-Blanch LE,Castro EA

    更新日期:2007-06-01 00:00:00

  • Synthesis, biological evaluation, and metabolic stability of acrylamide derivatives as novel CCR3 antagonists.

    abstract::Our laboratory has identified several acrylamide derivatives with potent CCR3 inhibitory activity. In the present study, we evaluated the in vitro metabolic stability (CL(int); mL/min/kg) of these compounds in human liver microsomes (HLMs), and assessed the relationship between their structures and CL(int) values. Amo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.06.066

    authors: Sato I,Morihira K,Inami H,Kubota H,Morokata T,Suzuki K,Ohno K,Iura Y,Nitta A,Imaoka T,Takahashi T,Takeuchi M,Ohta M,Tsukamoto S

    更新日期:2009-08-15 00:00:00

  • Novel hexadentate and pentadentate chelators for ⁶⁴Cu-based targeted PET imaging.

    abstract::A series of new hexadentate and pentadentate chelators were designed and synthesized as chelators of (64)Cu. The new pentadentate and hexadentate chelators contain different types of donor groups and are expected to form neutral complexes with Cu(II). The new chelators were evaluated for complex kinetics and stability...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.02.041

    authors: Sin I,Kang CS,Bandara N,Sun X,Zhong Y,Rogers BE,Chong HS

    更新日期:2014-04-15 00:00:00

  • Screening helix-threading peptides for RNA binding using a thiazole orange displacement assay.

    abstract::The fluorescent intercalator displacement assay using thiazole orange has been adapted to the study of RNA-binding helix-threading peptides (HTPs). This assay is highly sensitive with HTP-binding RNAs and provides binding affinity data in good agreement with quantitative ribonuclease footprinting without the need for ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.08.066

    authors: Krishnamurthy M,Schirle NT,Beal PA

    更新日期:2008-10-01 00:00:00

  • Vinyldiaminotriazine-acridine conjugate as G-quadruplex alkylating agent.

    abstract::Higher-order structures of nucleic acids have become widely noted for their biological consequences and the discovery of an alkylating small molecule for these structures has been of interest due to its therapeutic potential. We previously developed the vinyldiaminotriazine (VDAT)-acridine conjugate as a T-T mismatch ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.05.030

    authors: Hazemi ME,Onizuka K,Kobayashi T,Usami A,Sato N,Nagatsugi F

    更新日期:2018-07-23 00:00:00

  • On the nature of the irreversible inhibition of histidine ammonia lyase by cysteine and dioxygen.

    abstract::The irreversible inhibition of histidine ammonia lyase by L-cysteine and dioxygen has been reexamined. After denaturation and consecutive digestion of the inhibited enzyme by trypsin and endoproteinase Glu-C, the generated chromophoric system (lambda max = 340 nm) remained intact and was isolated in an octapeptide con...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(96)00091-0

    authors: Weber K,Rétey J

    更新日期:1996-07-01 00:00:00

  • Predicting multiple drugs side effects with a general drug-target interaction thermodynamic Markov model.

    abstract::Most of present molecular descriptors just consider the molecular structure. In the present article we pretend extending the use of Markov chain models to define novel molecular descriptors, which consider in addition to molecular structure other parameters like target site or toxic effect. Specifically, this molecula...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.11.030

    authors: González-Díaz H,Cruz-Monteagudo M,Molina R,Tenorio E,Uriarte E

    更新日期:2005-02-15 00:00:00

  • Alpha-1-C-octyl-1-deoxynojirimycin as a pharmacological chaperone for Gaucher disease.

    abstract::The most common lysosomal storage disorder, Gaucher disease, is caused by inefficient folding and trafficking of certain variants of lysosomal beta-glucosidase (beta-Glu, also known as beta-glucocerebrosidase). Recently, Sawker et al. reported that the addition of subinhibitory concentrations (10 microM) of the pharma...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.08.003

    authors: Yu L,Ikeda K,Kato A,Adachi I,Godin G,Compain P,Martin O,Asano N

    更新日期:2006-12-01 00:00:00

  • 1-Methylpyridinium-4-(4-phenylmethanethiosulfonate) iodide, MTS-MPP+, a novel scanning cysteine accessibility method (SCAM) reagent for monoamine transporter studies.

    abstract::A novel substituted cysteine accessibility method (SCAM) reagent was developed for monoamine uptake transporters. The new reagent, MTS-MPP(+), was a derivative of the neurotoxin and transporter substrate MPP(+). MTS-MPP(+) labeled cysteine residues introduced into the serotonin transporter protein. Although it did not...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.09.058

    authors: Gallardo-Godoy A,Torres-Altoro MI,White KJ,Barker EL,Nichols DE

    更新日期:2007-01-01 00:00:00

  • Sequential and parallel dual labeling of nanoparticles using click chemistry.

    abstract::Bioorthogonal 'click' reactions have recently emerged as promising tools for chemistry and biological applications. By using a combination of two different 'click' reactions, 'double-click' strategies have been developed to attach multiple labels onto biomacromolecules. These strategies require multi-step modification...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.07.015

    authors: Zong H,Goonewardena SN,Chang HN,Otis JB,Baker JR Jr

    更新日期:2014-11-01 00:00:00

  • New cannabinoid receptor antagonists as pharmacological tool.

    abstract::Synthesis and pharmacological evaluation of a new series of cannabinoid receptor antagonists of indazole ether derivatives have been performed. Pharmacological evaluation includes radioligand binding assays with [3H]-CP55940 for CB1 and CB2 receptors and functional activity for cannabinoid receptors on isolated tissue...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115672

    authors: González-Naranjo P,Pérez C,Girón R,Sánchez-Robles EM,Martín-Fontelles MI,Carrillo-López N,Martín-Vírgala J,Naves M,Campillo NE,Páez JA

    更新日期:2020-10-01 00:00:00

  • The antioxidant role of bile pigments evaluated by chemical tests.

    abstract::Bilirubin, biliverdin and their serum albumin complexes were tested as oxyradical scavengers (superoxide generated by the xanthine/xanthine oxidase system and peroxyl radical-trapping antioxidant ability). As superoxide scavengers the free bile pigments showed activities near to that of serum albumin, higher than the ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)82013-1

    authors: Farrera JA,Jaumà A,Ribó JM,Peiré MA,Parellada PP,Roques-Choua S,Bienvenue E,Seta P

    更新日期:1994-03-01 00:00:00

  • Structure and biological evaluation of novel cytotoxic sterol glycosides from the marine red alga Peyssonnelia sp.

    abstract::Bioactivity-guided fractionation of the extract from a Fijian red alga Peyssonnelia sp. led to the isolation of two novel sterol glycosides 19-O-β-d-glucopyranosyl-19-hydroxy-cholest-4-en-3-one (1) and 19-O-β-d-N-acetyl-2-aminoglucopyranosyl-19-hydroxy-cholest-4-en-3-one (2), and two known alkaloids indole-3-carboxald...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.10.010

    authors: Lin AS,Engel S,Smith BA,Fairchild CR,Aalbersberg W,Hay ME,Kubanek J

    更新日期:2010-12-01 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

  • Mechanism of the melanogenesis stimulation activity of (-)-cubebin in murine B16 melanoma cells.

    abstract::(-)-Cubebin showed a melanogenesis stimulation activity in a concentration-dependent manner in murine B16 melanoma cells without any significant effects on cell proliferation. Tyrosinase activity was increased at 24-72 h after addition of cubebin to B16 cells, and then intracellular melanin amount was increased at 48-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.04.046

    authors: Hirata N,Naruto S,Ohguchi K,Akao Y,Nozawa Y,Iinuma M,Matsuda H

    更新日期:2007-07-15 00:00:00

  • Synthesis, anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives.

    abstract::The action of the coumarin-type drugs and related compounds is reviewed to their VKOR antagonistic effects. In our study, twenty 3-pyridinyl, pyrimidinyl and pyrazolyl-4-hydroxycoumarin derivatives were synthesized. A comparative in vivo (CT, PT determination) and in vitro (measurement of PIVKA-II levels) anticoagulan...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.04.009

    authors: Abdelhafez OM,Amin KM,Batran RZ,Maher TJ,Nada SA,Sethumadhavan S

    更新日期:2010-05-15 00:00:00

  • Chemical synthesis of tetracyclic terpenes and evaluation of antagonistic activity on endothelin-A receptors and voltage-gated calcium channels.

    abstract::A class of tetracyclic terpenes was synthesized and evaluated for antagonistic activity of endothelin-1 (ET-1) induced vasoconstriction and inhibitory activity of voltage-activated Ca(2+) channels. Three repeated Robinson annulation reactions were utilized to construct the tetracyclic molecules. A stereoselective redu...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.06.055

    authors: Lu J,Aguilar A,Zou B,Bao W,Koldas S,Shi A,Desper J,Wangemann P,Xie XS,Hua DH

    更新日期:2015-09-01 00:00:00

  • Hippuryl-alpha-methylphenylalanine and hippuryl-alpha-methylphenyllactic acid as substrates for carboxypeptidase A. Syntheses, kinetic evaluation and mechanistic implication.

    abstract::(R)- and (S)-Hippuryl-alpha-methylphenylalanine [(R)- and (S)-Hipp-alpha-MePhe] and (S)-hippuryl-alpha-methylphenyllactic acid [(S)-Hipp-alpha-MeOPhe] were synthesized and evaluated as substrates for carboxypeptidase A (CPA) in an effort to shed further light on the catalytic mechanism of the enzyme. The rate of CPA-c...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)00006-7

    authors: Lee M,Kim DH

    更新日期:2000-04-01 00:00:00

  • A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects.

    abstract::A series of benzene sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.02.027

    authors: Carta F,Di Cesare Mannelli L,Pinard M,Ghelardini C,Scozzafava A,McKenna R,Supuran CT

    更新日期:2015-04-15 00:00:00

  • Novel FXR (farnesoid X receptor) modulators: Potential therapies for cholesterol gallstone disease.

    abstract::Metabolic disorders such as diabetes are known risk factors for developing cholesterol gallstone disease (CGD). Cholesterol gallstone disease is one of the most prevalent digestive diseases, leading to considerable financial and social burden worldwide. Ursodeoxycholic acid (UDCA) is the only bile acid drug approved b...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.06.039

    authors: Yu DD,Andrali SS,Li H,Lin M,Huang W,Forman BM

    更新日期:2016-09-15 00:00:00

  • Tessaric acid derivatives induce G2/M cell cycle arrest in human solid tumor cell lines.

    abstract::A series of analogs were synthesized in a straightforward manner from naturally available sesquiterpenes ilicic acid and tessaric acid. The in vitro antiproliferative activities were examined in the human solid tumor cell lines A2780, HBL-100, HeLa, SW1573, T-47D and WiDr. The most potent analog induced considerably g...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.07.053

    authors: León LG,Donadel OJ,Tonn CE,Padrón JM

    更新日期:2009-09-01 00:00:00

  • Evaluation of novel aryloxyalkyl derivatives of imidazole and 1,2,4-triazole as heme oxygenase-1 (HO-1) inhibitors and their antitumor properties.

    abstract::A novel series of aryloxyalkyl derivatives of imidazole and 1,2,4-triazole, 17-31, was designed and synthesized as inhibitors of heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). Some of these compounds were found to be good inhibitors of HO-1, in particular those carrying an imidazole moiety as azolyl group and a ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.06.040

    authors: Salerno L,Pittalà V,Romeo G,Modica MN,Siracusa MA,Di Giacomo C,Acquaviva R,Barbagallo I,Tibullo D,Sorrenti V

    更新日期:2013-09-01 00:00:00

  • Design and synthesis of novel HDAC8 inhibitory 2,5-disubstituted-1,3,4-oxadiazoles containing glycine and alanine hybrids with anti cancer activity.

    abstract::Oxadiazole is a heterocyclic compound containing an oxygen atom and two nitrogen atoms in a five-membered ring. Of the four oxadiazoles known, 1,3,4-oxadiazole has become an important structural motif for the development of new drugs and the compounds containing 1,3,4-oxadiazole cores have a broad spectrum of biologic...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.09.022

    authors: Pidugu VR,Yarla NS,Pedada SR,Kalle AM,Satya AK

    更新日期:2016-11-01 00:00:00

  • Studies on anti-HIV quinolones: new insights on the C-6 position.

    abstract::The 6-desfluoroquinolones which have been developed by our group represent a promising class of compounds for the treatment of HIV infection since they act on transcriptional regulation, a crucial step in the replication cycle that has not been clinically exploited, yet. Focussing attention on the N-1 and C-6 position...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.11.056

    authors: Massari S,Daelemans D,Manfroni G,Sabatini S,Tabarrini O,Pannecouque C,Cecchetti V

    更新日期:2009-01-15 00:00:00

  • Design and synthesis of thiazolylhydrazone derivatives as inhibitors of chitinolytic N-acetyl-β-d-hexosaminidase.

    abstract::N-acetyl-β-d-hexosaminidase (Hex) is potential target for pesticide design. Here, a series of thiazolylhydrazone derivatives were designed, synthesized and evaluated as competitive inhibitors of OfHex1, a Hex from the agricultural pest Ostrinia furnacalis. The derivative 3k, with a (benzyloxy)methyl group at the N3 at...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.09.014

    authors: Yang H,Liu T,Qi H,Huang Z,Hao Z,Ying J,Yang Q,Qian X

    更新日期:2018-11-01 00:00:00

  • 1,2,4-Thiadiazole acyclic nucleoside phosphonates as inhibitors of cysteine dependent enzymes cathepsin K and GSK-3β.

    abstract::In analogy to antiviral acyclic nucleoside phosphonates, a series of 5-amino-3-oxo-1,2,4-thiadiazol-3(2H)-ones bearing a 2-phosphonomethoxyethyl (PME) or 3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) group at the position 2 of the heterocyclic moiety has been synthesized. Diisopropyl esters of PME- and HPMP-amines have ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2021.115998

    authors: Pomeislová A,Otmar M,Rubešová P,Benýšek J,Matoušová M,Mertlíková-Kaiserová H,Pohl R,Poštová Slavětínská L,Pomeisl K,Krečmerová M

    更新日期:2021-01-06 00:00:00