当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY LETTERS期刊下所有文献 > Identification of pyrazolo[1,5-a]pyrimidine-3-carboxylates as B-Raf kinase inhibitors.

Identification of pyrazolo[1,5-a]pyrimidine-3-carboxylates as B-Raf kinase inhibitors.

Abstract：

:B-Raf kinase plays a critical role in the Raf-MEK-ERK signaling pathway and inhibitors of B-Raf could be used in the treatment of melanomas, colorectal cancer, and other Ras related human cancers. We have identified novel small molecule pyrazolo[1,5-a]pyrimidine derivatives as B-Raf kinase inhibitors. Structure-activity relationship was generated for various regions of the scaffold to improve the biochemical profile.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Gopalsamy A,Ciszewski G,Hu Y,Lee F,Feldberg L,Frommer E,Kim S,Collins K,Wojciechowicz D,Mallon R

doi

10.1016/j.bmcl.2009.03.129

subject

Has Abstract

pub_date

2009-05-15 00:00:00

pages

2735-8

issue

10

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(09)00439-9

journal_volume

19

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS文献大全
  • Radiosynthesis of PET radiotracer as a prodrug for imaging group II metabotropic glutamate receptors in vivo.

    abstract：:Group II metabotropic glutamate receptors (mGluRs) have been implicated in a variety of neurological and psychiatric disorders in recent studies. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers the possibility to visualize and study gro...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.01.039

    authors： Wang JQ,Zhang Z,Kuruppu D,Brownell AL

    更新日期：2012-03-01 00:00:00

  • Sugar Chips immobilized with synthetic sulfated disaccharides of heparin/heparan sulfate partial structure.

    abstract：:Carbohydrate chip technology has a great potential for the high-throughput evaluation of carbohydrate-protein interactions. Herein, we report syntheses of novel sulfated oligosaccharides possessing heparin and heparan sulfate partial disaccharide structures, their immobilization on gold-coated chips to prepare array-t...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.01.069

    authors： Wakao M,Saito A,Ohishi K,Kishimoto Y,Nishimura T,Sobel M,Suda Y

    更新日期：2008-04-01 00:00:00

  • Discovery of anabaenopeptin 679 from freshwater algal bloom material: Insights into the structure-activity relationship of anabaenopeptin protease inhibitors.

    abstract：:Cyanobacteria possess a unique capacity for the production of structurally novel secondary metabolites compared to the biosynthetic abilities of other environmental prokaryotes such as bacteria of the genus Streptomyces. Two different strategies to explore cyanobacteria-derived natural products have been explored prev...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2016.09.008

    authors： Harms H,Kurita KL,Pan L,Wahome PG,He H,Kinghorn AD,Carter GT,Linington RG

    更新日期：2016-10-15 00:00:00

  • The SAR of 4-substituted (6,6-bicyclic) piperidine cathepsin S inhibitors.

    abstract：:A series of competitive, reversible cathepsin S (CatS) inhibitors was investigated. An earlier disclosure detailed the discovery of the 4-(2-keto-1-benzimidazolinyl)-piperidin-1-yl moiety as an effective replacement for the 4-arylpiperazin-1-yl group found in our screening hit. Continued investigation into replacement...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.01.038

    authors： Grice CA,Tays K,Khatuya H,Gustin DJ,Butler CR,Wei J,Sehon CA,Sun S,Gu Y,Jiang W,Thurmond RL,Karlsson L,Edwards JP

    更新日期：2006-04-15 00:00:00

  • Synthesis and biological evaluation of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles as transforming growth factor-β type 1 receptor kinase inhibitors.

    abstract：:A series of 1-substituted-3-(6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)pyrazoles 14a-ae, 16a, 16b, and 21a-c has been prepared and evaluated for their ALK5 inhibitory activity in an enzyme assay and in a cell-based luciferase reporter assay. The 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-N-(4-methoxyphen...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.08.064

    authors： Jin CH,Krishnaiah M,Sreenu D,Subrahmanyam VB,Rao KS,Mohan AV,Park CY,Son JY,Sheen YY,Kim DK

    更新日期：2011-10-15 00:00:00

  • Carbonic anhydrase inhibitors: Inhibition of the new membrane-associated isoform XV with phenols.

    abstract：:Inhibition of the newest isoform of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), CA XV, with a series of phenols was investigated. Murine CA XV showed an inhibition profile by phenols distinct of those of the cytosolic human isoforms CA I and II. Phenol and some of its 2-, 3-, and 4-substituted derivatives i...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.04.077

    authors： Innocenti A,Hilvo M,Scozzafava A,Parkkila S,Supuran CT

    更新日期：2008-06-15 00:00:00

  • Synthesis and biological evaluation of 3-phenethylazetidine derivatives as triple reuptake inhibitors.

    abstract：:We report the synthesis of 3-phenethylazetidine derivatives 2 and their biological activities against 5-HT, NE and DA transporters as well as microsomal stability, CYP inhibition, and hERG inhibition profiles. Compound 2at showed most potent triple reuptake inhibitor with good selectivity as a candidate for depression...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2014.06.026

    authors： Yun J,Han M,Song C,Cheon SH,Choi K,Hahn HG

    更新日期：2014-08-01 00:00:00

  • Synthesis, antimycobacterial and cytotoxic activity of α,β-unsaturated amides and 2,4-disubstituted oxazoline derivatives.

    abstract：:The synthesis of six α,β,-unsaturated amides and six 2,4-disubstituted oxazolines derivatives and their evaluation against two Mycobacterium tuberculosis strains (sensitive H37Rv and a resistant clinical isolate) is reported. 2,4-Disubstituted oxazolines (S)-3b,d,e were the most active in the sensitive strain with a M...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2017.01.024

    authors： Avalos-Alanís FG,Hernández-Fernández E,Carranza-Rosales P,López-Cortina S,Hernández-Fernández J,Ordóñez M,Guzmán-Delgado NE,Morales-Vargas A,Velázquez-Moreno VM,Santiago-Mauricio MG

    更新日期：2017-02-15 00:00:00

  • Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents.

    abstract：:Fourty-two thiazolyl-pyrazoline derivatives were synthesized to screen for their EGFR kinase inhibitory activity. Compound 4-(4-chlorophenyl)-2-(3-(3,4-dimethylphenyl)-5-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazole (11) displayed the most potent EGFR TK inhibitory activity with IC(50) of 0.06 μM, which was comparable ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.07.010

    authors： Lv PC,Li DD,Li QS,Lu X,Xiao ZP,Zhu HL

    更新日期：2011-09-15 00:00:00

  • Challenges in the development of mGluR5 positive allosteric modulators: the discovery of CPPHA.

    abstract：:This Letter describes, for the first time, the synthesis and SAR, developed through an iterative analog library approach, that led to the discovery of the positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR5 CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5 PAMs...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.11.081

    authors： Zhao Z,Wisnoski DD,O'Brien JA,Lemaire W,Williams DL Jr,Jacobson MA,Wittman M,Ha SN,Schaffhauser H,Sur C,Pettibone DJ,Duggan ME,Conn PJ,Hartman GD,Lindsley CW

    更新日期：2007-03-01 00:00:00

  • Structural requirements of (E)-6-benzylidene-4a-methyl-4,4a,5,6,7,8-hexahydronaphthalen-2(3H)-one derivatives as novel melanogenesis inhibitors.

    abstract：:Chalcone type compound 1a ((E)-6'-benzylidene-4a'-methyl-4',4a',7',8'-tetrahydro-3'H-spiro[[1,3]dithiolane-2,2'-naphthalen]-5'(6'H)-one) was discovered as an potent inhibitor in melanogenesis. To define its structure-activity relationship, a series of analogs 1b-n, dithiolane truncated 2a-b and ring A removed 3a-e wer...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2011.02.060

    authors： Thanigaimalai P,Lee KC,Sharma VK,Rao EV,Roh E,Kim Y,Jung SH

    更新日期：2011-04-01 00:00:00

  • Structure based design of a series of potent and selective non peptidic PTP-1B inhibitors.

    abstract：:A series of benzotriazole phenyldifluoromethylphosphonic acids were found to be potent PTP-1B inhibitors. Molecular modeling on the X-ray crystal structure of the lead structure led to the design of potent PTP-1B inhibitors that show moderate selectivity against TC-PTP, a very closely related protein tyrosine phosphat...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2003.11.076

    authors： Lau CK,Bayly CI,Gauthier JY,Li CS,Therien M,Asante-Appiah E,Cromlish W,Boie Y,Forghani F,Desmarais S,Wang Q,Skorey K,Waddleton D,Payette P,Ramachandran C,Kennedy BP,Scapin G

    更新日期：2004-02-23 00:00:00

  • Synthesis of the new pseudo-symmetrical tamoxifen derivatives and their anti-tumor activity.

    abstract：:Three new pseudo-symmetrical tamoxifen derivatives, RID-B (15), C (16), and D (17), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of the pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 15 strongly inhibits the viability of HL-6...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2007.02.037

    authors： Shiina I,Sano Y,Nakata K,Kikuchi T,Sasaki A,Ikekita M,Hasome Y

    更新日期：2007-05-01 00:00:00

  • Cyclic imides as potent and selective alpha-1A adrenergic receptor antagonists.

    abstract：:We disclose a new compound class of potent and selective alpha-1A adrenergic receptor antagonists exemplified by the geminally, disubstituted cyclic imide 7. The optimization of lead compounds resulting in the cyclic imide motif is highlighted. The results of in vitro and in vivo studies of selected compounds are pres...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00320-1

    authors： DiPardo RM,Patane MA,Newton RC,Price R,Broten TP,Chang RS,Ransom RW,Di Salvo J,Freidinger RM,Bock MG

    更新日期：2001-07-23 00:00:00

  • Discovery of biaryl inhibitors of H+/K+ ATPase.

    abstract：:We report the identification of a novel biaryl template for H(+)/K(+) ATPase inhibition. Evaluation of critical SAR features within the biaryl imidazole framework and the use of pharmacophore modelling against known imidazopyridine and azaindole templates suggested that the geometry of the molecule is key to achieving...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.12.040

    authors： Garton N,Bailey N,Bamford M,Demont E,Farre-Gutierrez I,Hutley G,Bravi G,Pickering P

    更新日期：2010-02-01 00:00:00

  • Synthesis and antiviral activity of novel D- and L-2'-azido-2',3'-dideoxyribofuranosyl-4'-thiopyrimidines and purines.

    abstract：:Novel D- and L-2'-azido-2',3'-dideoxyribofuranosyl-4'-thiopyrimidines and purines have been synthesized starting from L-xylose and D-xylose, respectively. Among synthesized compounds tested against several viruses such as HIV-1, HSV-1, HSV-2, and HCMV, D-beta-N6-methyladenine (ent-22a) and D-alpha-N6-methyladenine (en...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(01)00006-3

    authors： Kim HO,Kim YH,Suh H,Jeong LS

    更新日期：2001-02-26 00:00:00

  • Polymer-supported catalysts: enantioselective hydrogenation and hydrogen transfer reduction.

    abstract：:Different types of heterogenized catalysts were involved in asymmetric reactions. Hydrogen transfer reduction was performed with amino alcohols derived from poly((S)-(GMA-co-EGDMA or DVB)) and hydrogenation with BINAP grafted onto PEG or copolymerized with isocyanates as ligands. Attempts of catalysts recycling are re...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(02)00258-5

    authors： Saluzzo C,Lamouille T,Hérault D,Lemaire M

    更新日期：2002-07-22 00:00:00

  • Syntheses and biological evaluation of ring-C modified colchicine analogs.

    abstract：:Ring-C modified alkaloids were synthesized from colchicine using iminonitroso Diels-Alder reactions in a highly regio- and stereoselective fashion. Several analogs exhibited cytotoxic activity similar to that of colchicine itself against PC-3 and MCF-7 cancer cell lines, by serving as prodrugs of colchicine through re...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.03.056

    authors： Yang B,Zhu ZC,Goodson HV,Miller MJ

    更新日期：2010-06-15 00:00:00

  • Trifluoromethylation of flavonoids and anti-tumor activity of the trifluoromethylated flavonoid derivatives.

    abstract：:3-Trifluoromethylflavonoid derivatives were prepared for the first time by trifluoromethylation of 3-iodoflavonoid derivatives. Other C ring and B ring trifluoromethylated flavonoid derivatives were also prepared. All the compounds were tested for their effect on the U2OS cell cycle in vitro. Bistrifluoromethylated ap...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.07.047

    authors： Wang CL,Li HQ,Meng WD,Qing FL

    更新日期：2005-10-15 00:00:00

  • Synthesis and anti-breast cancer activities of substituted quinolines.

    abstract：:Promising anti-breast cancer agents derived from substituted quinolines were discovered. The quinolines were readily synthesized in a large scale from a sequence of reactions starting from 4-acetamidoanisole. The Michael addition product was isolated as the reaction intermediate in the ring closing reaction of 4-amino...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.04.024

    authors： Shi A,Nguyen TA,Battina SK,Rana S,Takemoto DJ,Chiang PK,Hua DH

    更新日期：2008-06-01 00:00:00

  • Discovery of new diphenyloxazole derivatives containing a pyrrolidine ring: orally active prostacyclin mimetics. Part 2.

    abstract：:Synthetic and biological evaluation of novel diphenyloxazole derivatives containing a pyrrolidine ring, as a prostacyclin mimetic without the PG skeleton, are described. Asymmetric reduction of a ketone using a chiral Ru complex and reductive amination by NaBH(4) produces four isomers of the tetrahydronaphthalene ring...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.04.042

    authors： Hattori K,Okitsu O,Tabuchi S,Taniguchi K,Nishio M,Koyama S,Seki J,Sakane K

    更新日期：2005-07-01 00:00:00

  • Structural modifications of (1S,3S)-3-amino-4-difluoromethylenecyclopentanecarboxylic acid, a potent irreversible inhibitor of GABA aminotransferase.

    abstract：:Low brain levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) lead to convulsions. Inhibition of GABA aminotransferase increases the concentration of GABA and can terminate the convulsions. Earlier we reported the synthesis of (1S,3S)-3-amino-4-difluoromethylenecyclopentanecarboxylic acid (2), whi...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2006.12.119

    authors： Yuan H,Silverman RB

    更新日期：2007-03-15 00:00:00

  • Inhibitory effect on NO production of triterpenes from the fruiting bodies of Ganoderma lucidum.

    abstract：:Four new lanostane triterpenes, butyl lucidenate P (1), butyl lucidenate D(2) (2), butyl lucidenate E(2) (3) and butyl lucidenate Q (4) along with 11 known compounds (5-15) were isolated from the fruiting bodies of Ganoderma lucidum. Their chemical structures were established mainly by 1D and 2D NMR techniques and mas...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2012.12.066

    authors： Tung NT,Cuong TD,Hung TM,Lee JH,Woo MH,Choi JS,Kim J,Ryu SH,Min BS

    更新日期：2013-03-01 00:00:00

  • A divergent chemoenzymatic route to an intermediate for nucleoside analogues.

    abstract：:Two regioisomeric isoxazoline monoacetates 1 and 2 were synthesized from the corresponding diacetate 3 via PPL or PLE catalyzed hydrolysis. With both the enzymes, the initial regioselectivity (approximately 3-4:1) was offset by an intramolecular acyl transfer. In addition to a non-enzymatic catalysis for the acyl tran...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2005.03.033

    authors： Basak A,Bisai S

    更新日期：2005-05-16 00:00:00

  • Carbon analogs of antifungal dioxane-triazole derivatives: synthesis and in vitro activities.

    abstract：:A new series of triazole compounds possessing a carbon atom in place of a sulfur atom were efficiently synthesized and their in vitro antifungal activities were investigated. The carbon analogs showed excellent in vitro activity against Candida, Cryptococcus, and Aspergillus species. The MICs of compound 1c against C....

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2008.10.055

    authors： Uchida T,Somada A,Kagoshima Y,Konosu T,Oida S

    更新日期：2008-12-15 00:00:00

  • Discovery of 'molecular switches' within a GIRK activator scaffold that afford selective GIRK inhibitors.

    abstract：:This letter describes a multi-dimensional SAR campaign based on a potent, efficacious and selective GIRK1/2 activator (~10-fold versus GIRK1/4 and inactive on nonGIRK 1-containing GIRKs, GIRK 2 or GIRK2/3). Further chemical optimization through an iterative parallel synthesis effort identified multiple 'molecular swit...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2013.06.023

    authors： Wen W,Wu W,Romaine IM,Kaufmann K,Du Y,Sulikowski GA,Weaver CD,Lindsley CW

    更新日期：2013-08-15 00:00:00

  • Synthesis of diacylamines and the preparation of alpha-amino-acylureas, a new type of alpha-amino acid derivatives.

    abstract：:Sixteen new and one known unsymmetrical open-chain diacylamines were synthesized by sodium methoxide catalyzed acylation of amides with carboxylic esters and acylamino-carboxylic esters, or acylureas with acylamino-carboxylic esters and alpha-amino acid esters. ...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/s0960-894x(98)00593-9

    authors： Weisz I,Roboz J,Wolf I,Szabo J,Bekesi JG

    更新日期：1998-11-17 00:00:00

  • A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 to identify new inhibitors of gp120-CD4 protein-protein interactions.

    abstract：:A dynamic target-based pharmacophoric model mapping the CD4 binding site on HIV-1 gp120 was built and used to identify new hits able to inhibit gp120-CD4 protein-protein interactions. Two compounds showed micromolar inhibition of HIV-1 replication in cells attributable to an interference with the entry step of infecti...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2009.09.029

    authors： Caporuscio F,Tafi A,González E,Manetti F,Esté JA,Botta M

    更新日期：2009-11-01 00:00:00

  • Discovery of an exceptionally potent and selective class of fatty acid amide hydrolase inhibitors enlisting proteome-wide selectivity screening: concurrent optimization of enzyme inhibitor potency and selectivity.

    abstract：:The concurrent implementation of a proteome-wide serine hydrolase selectivity screen with traditional efforts to optimize fatty acid amide hydrolase (FAAH) inhibition potency led to the expedited discovery of a new class of exceptionally potent (Ki < 300 pM) and unusually selective (> 100-fold selective) inhibitors. T...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2004.12.085

    authors： Leung D,Du W,Hardouin C,Cheng H,Hwang I,Cravatt BF,Boger DL

    更新日期：2005-03-01 00:00:00

  • Selectivity profiling of novel indene H(1)-antihistamines for the treatment of insomnia.

    abstract：:A series of indene analogs of the H(1)-antihistamine (-)-R-dimethindene was evaluated for selectivity in the search for potentially improved sedative-hypnotics. Variation of the 6-substitutent in the indene core in combination with a pendant electron rich heterocycle led to the identification of several potent H(1)-an...

    journal_title：Bioorganic & medicinal chemistry letters

    pub_type： 杂志文章

    doi：10.1016/j.bmcl.2010.02.055

    authors： Li BF,Moree WJ,Yu J,Coon T,Zamani-Kord S,Malany S,Jalali K,Wen J,Wang H,Yang C,Hoare SR,Petroski RE,Madan A,Crowe PD,Beaton G

    更新日期：2010-04-15 00:00:00