当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Synthesis and SAR of indazole-pyridine based protein kinase B/Akt inhibitors.

Synthesis and SAR of indazole-pyridine based protein kinase B/Akt inhibitors.

Abstract：

:A series of heteroaryl-pyridine containing inhibitors of Akt are reported. The synthesis and structure-activity relationships are discussed, leading to the discovery of a indazole-pyridine analogue (K(i)=0.16 nM). These compounds bind in the ATP binding site, are potent, ATP competitive, and reversible inhibitors of Akt activity. No selectivity amongst the Akt isoforms is observed for this analogue, but there is good selectivity against an panel of other kinases. It is least selective for other members of the AGC family of kinases but is nonetheless 40-fold selective for Akt over PKA. The compound shows cellular activity and significantly slows tumor growth in vivo.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Woods KW,Fischer JP,Claiborne A,Li T,Thomas SA,Zhu GD,Diebold RB,Liu X,Shi Y,Klinghofer V,Han EK,Guan R,Magnone SR,Johnson EF,Bouska JJ,Olson AM,de Jong R,Oltersdorf T,Luo Y,Rosenberg SH,Giranda VL,Li Q

doi

10.1016/j.bmc.2006.06.047

subject

Has Abstract

pub_date

2006-10-15 00:00:00

pages

6832-46

issue

20

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(06)00511-6

journal_volume

14

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • Halogenated derivatives QSAR model using spectral moments to predict haloacetic acids (HAA) mutagenicity.

    abstract：:The risk of the presence of haloacetic acids in drinking water as chlorination by-products and the shortage of experimental mutagenicity data for most of them requires a research work. This paper describes a QSAR model to predict direct mutagenicity for these chemicals. The model, able to describe more than 90% of the...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.03.070

    authors： Pérez-Garrido A,González MP,Escudero AG

    更新日期：2008-05-15 00:00:00

  • Further optimization of sulfonamide analogs as EP1 receptor antagonists: synthesis and evaluation of bioisosteres for the carboxylic acid group.

    abstract：:4-{[2-[(2-Furylsulfonyl)(isobutyl)amino]-5-(trifluoromethyl)phenoxy]methyl}benzoic acid analogs 2a and b and a series of the acid analogs, in which the carboxylic acid residue of 2b was replaced with various kinds of carboxylic acid bioisosteres, were synthesized and evaluated as EP1 receptor antagonists. Compound 2b ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.06.067

    authors： Naganawa A,Matsui T,Ima M,Saito T,Murota M,Aratani Y,Kijima H,Yamamoto H,Maruyama T,Ohuchida S,Nakai H,Toda M

    更新日期：2006-11-01 00:00:00

  • The tetrahydroxanthone-dimer phomoxanthone A is a strong inducer of apoptosis in cisplatin-resistant solid cancer cells.

    abstract：:Platinum compounds are the first-line therapy for many types of cancer. However, drug resistance has frequently been reported for and is a major limitation of platinum-based chemotherapy in the clinic. In the current study, we examined the anti-tumor activity of phomoxanthone A (PXA), a tetrahydroxanthone dimer isolat...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.115044

    authors： Wang C,Engelke L,Bickel D,Hamacher A,Frank M,Proksch P,Gohlke H,Kassack MU

    更新日期：2019-10-01 00:00:00

  • A study on the conversion of indanones into carbostyrils.

    abstract：:We have surveyed the utility of Beckmann rearrangement for the conversion of indanones into carbostyrils. Initial attempts at the conversion of 6-methoxy indanone oxime under classical conditions resulted in the formation of the two unusual products: 2-sulfonyloxyindanone and the dimeric product. This unusual rearrang...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00116-0

    authors： Torisawa Y,Nishi T,Minamikawa Ji

    更新日期：2003-05-15 00:00:00

  • Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2-aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors.

    abstract：:A series of 31 N,N-disubstituted 2-amino-5-halomethyl-2-thiazolines was designed, synthesized, and evaluated for inhibitory potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE). The compounds did not inhibit AChE; the most active compounds inhibited BChE and CaE with I...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.01.031

    authors： Makhaeva GF,Boltneva NP,Lushchekina SV,Serebryakova OG,Stupina TS,Terentiev AA,Serkov IV,Proshin AN,Bachurin SO,Richardson RJ

    更新日期：2016-03-01 00:00:00

  • Total syntheses of three copper (II) tetracarboranylphenylporphyrins containing 40 or 80 boron atoms and their biological properties in EMT-6 tumor-bearing mice.

    abstract：:Three carboranyltetraphenylporphyrins containing 40 or 80 boron atoms were synthesized and evaluated for their biodistribution and toxicity in EMT-6 tumor-bearing mice. Copper (II) meso-5,10,15,20-tetrakis[3-methoxy-4-(o-carboranylmethoxy)phenyl]porphyrin, 6, and copper (II) meso-5,10,15,20-tetrakis[3-hydroxy-4-(o-car...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.04.010

    authors： Wu H,Micca PL,Makar MS,Miura M

    更新日期：2006-08-01 00:00:00

  • QSAR for non-nucleoside inhibitors of HIV-1 reverse transcriptase.

    abstract：:By means of QSAR algorithms we model the potency pIC(90) [mM] of 154 non-nucleoside reverse transcriptase inhibitors (NNRTI) of the wild-type HIV-1 virus, considered as the second generation analogues of Efavirenz. In addition, 56 inhibitors of the K-103N viral mutant form are also investigated. A pool of 1494 theoret...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.05.027

    authors： Duchowicz PR,Fernández M,Caballero J,Castro EA,Fernández FM

    更新日期：2006-09-01 00:00:00

  • New substrates and inhibitors of gamma-aminobutyric acid aminotransferase containing bioisosteres of the carboxylic acid group: design, synthesis, and biological activity.

    abstract：:A series of potential substrates of gamma-aminobutyric acid aminotransferase (GABA-AT) with lipophilic bioisosteres of the carboxylic acid group (2-7) were synthesized and tested. Most of the synthesized compounds showed substrate activities with GABA-AT; 1H-tetrazole-5-propanamine (6) was the best of those tested. Th...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.09.067

    authors： Yuan H,Silverman RB

    更新日期：2006-03-01 00:00:00

  • Isoform-specific phosphoinositide 3-kinase inhibitors from an arylmorpholine scaffold.

    abstract：:Phosphoinositide 3-kinases (PI3-Ks) are an ubiquitous class of signaling enzymes that regulate diverse cellular processes including growth, differentiation, and motility. Physiological roles of PI3-Ks have traditionally been assigned using two pharmacological inhibitors, LY294002 and wortmannin. Although these compoun...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.06.022

    authors： Knight ZA,Chiang GG,Alaimo PJ,Kenski DM,Ho CB,Coan K,Abraham RT,Shokat KM

    更新日期：2004-09-01 00:00:00

  • Antibacterial activity of indolyl-quinolinium derivatives and study their mode of action.

    abstract：:Filamenting temperature-sensitive mutant Z (FtsZ) is recognized as a promising target for new antibiotics development because of its high conservatism and pivotal role in the bacteria cell division. The aromatic heterocyclic scaffold of indole is known showing merit medical functions in antiviral and antimicrobial. In...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.02.024

    authors： Cai S,Yuan W,Li Y,Huang X,Guo Q,Tang Z,Fang Z,Lin H,Wong WL,Wong KY,Lu YJ,Sun N

    更新日期：2019-04-01 00:00:00

  • pH-dependent production of himeic acid A and its non-enzymatic conversions to himeic acids B and C.

    abstract：:The fungus Aspergillus japonicus MF275 produces himeic acid A (1), containing a 4-pyrone ring, along with its congeners, himeic acids B (2) and C (3). During culture, 1 was gradually converted to 3, the corresponding 4-pyridone derivative. A study of the relationship between the culture pH and the fungal metabolites s...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2018.02.034

    authors： Katsuki A,Kato H,Tahara Y,Hashimoto M,Fujii I,Tsukamoto S

    更新日期：2018-05-01 00:00:00

  • Synthesis and biological evaluation of 4,5-dihydro-1H-pyrazole derivatives as potential nNOS/iNOS selective inhibitors. Part 2: Influence of diverse substituents in both the phenyl moiety and the acyl group.

    abstract：:In a preliminary article, we reported a series of 4,5-dihydro-1H-pyrazole derivatives as neuronal nitric oxide synthase (nNOS) inhibitors. Here we present the data about the inhibition of inducible nitric oxide synthase (iNOS) of these compounds. In general, we can confirm that these pyrazoles are nNOS selective inhib...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.05.016

    authors： Carrión MD,Chayah M,Entrena A,López A,Gallo MA,Acuña-Castroviejo D,Camacho ME

    更新日期：2013-07-15 00:00:00

  • New analogs of SYA013 as sigma-2 ligands with anticancer activity.

    abstract：:Our previous study has revealed 4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl)butan-1-one·2HCl (SYA013) 1 as a sigma ligand with moderate selectivity for the sigma-2 receptor. Given the overexpression of sigma receptors in solid tumors and reports of sigma ligands with anticancer activities, we selected 1...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.04.012

    authors： Asong G,Zhu XY,Bricker B,Andey T,Amissah F,Lamango N,Ablordeppey SY

    更新日期：2019-06-15 00:00:00

  • Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: New design with improved properties.

    abstract：:6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), a key enzyme in the folate biosynthetic pathway, catalyzes the pyrophosphoryl transfer from ATP to 6-hydroxymethyl-7,8-dihydropterin. The enzyme is essential for microorganisms, is absent from humans, and is not the target for any existing antibiotics. Theref...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2011.11.032

    authors： Shi G,Shaw G,Liang YH,Subburaman P,Li Y,Wu Y,Yan H,Ji X

    更新日期：2012-01-01 00:00:00

  • Inhibitors of the glycine transporter type-2 (GlyT-2): synthesis and biological activity of benzoylpiperidine derivatives.

    abstract：:A series of benzoylpiperidine analogs related to 4a was prepared, and their ability to inhibit the uptake of [(14)C]-glycine in COS7 cells transfected with human glycine transporter type-2 (GlyT-2) was evaluated. Small structural changes to the benzoylpiperidine region of the molecule led to a significant decrease in ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2004.05.044

    authors： Wolin RL,Santillán A Jr,Tang L,Huang C,Jiang X,Lovenberg TW

    更新日期：2004-08-15 00:00:00

  • An increase in side-group hydrophobicity largely improves the potency of ritonavir-like inhibitors of CYP3A4.

    abstract：:Identification of structural determinants required for potent inhibition of drug-metabolizing cytochrome P450 3A4 (CYP3A4) could help develop safer drugs and more effective pharmacoenhancers. We utilize a rational inhibitor design to decipher structure-activity relationships in analogues of ritonavir, a highly potent ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115349

    authors： Samuels ER,Sevrioukova IF

    更新日期：2020-03-15 00:00:00

  • Discovery of novel phenoxazinone derivatives as DKK1/LRP6 interaction inhibitors: Synthesis, biological evaluation and structure-activity relationships.

    abstract：:Amino derivatives of NCI8642 were synthesized and evaluated as inhibitors of DKK1/LRP6 interactions. The new inhibitors were able to activate the Wnt signaling pathway as indicated by the increased levels of β-catenin, and decrease the DKK1-induced Tau phosphorylation at serine 396. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2016.01.025

    authors： Thysiadis S,Mpousis S,Avramidis N,Katsamakas S,Balomenos A,Remelli R,Efthimiopoulos S,Sarli V

    更新日期：2016-03-01 00:00:00

  • Design, synthesis, in vitro, and in silico studies of novel diarylimidazole-1,2,3-triazole hybrids as potent α-glucosidase inhibitors.

    abstract：:In this work, new derivatives of diarylimidazole-1,2,3-triazole 7a-p were designed, synthesized, and evaluated for their in vitro α-glucosidase inhibitory activity. All compounds showed potent inhibitory activity in the range of IC50 = 90.4-246.7 µM comparing with acarbose as the standard drug (IC50 = 750.0 µM). Among...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2019.115148

    authors： Saeedi M,Mohammadi-Khanaposhtani M,Asgari MS,Eghbalnejad N,Imanparast S,Faramarzi MA,Larijani B,Mahdavi M,Akbarzadeh T

    更新日期：2019-12-01 00:00:00

  • RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: synthesis and biological evaluation.

    abstract：:(+/-)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR. This agent has an excellent pharmacokinetic profile and is highly efficacious in ro...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.05.012

    authors： McDermott LA,Simcox M,Higgins B,Nevins T,Kolinsky K,Smith M,Yang H,Li JK,Chen Y,Ke J,Mallalieu N,Egan T,Kolis S,Railkar A,Gerber L,Luk KC

    更新日期：2005-08-15 00:00:00

  • QSAR by LFER model of HIV protease inhibitor mannitol derivatives using FA-MLR, PCRA, and PLS techniques.

    abstract：:The present quantitative structure-activity relationship (QSAR) study attempts to explore the structural and physicochemical requirements of mannitol derivatives for HIV protease inhibitory activity using linear free energy related model of Hansch. QSAR models have been developed using electronic (Hammett sigma), hydr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.09.022

    authors： Leonard JT,Roy K

    更新日期：2006-02-15 00:00:00

  • Lipophilic derivatives of leu-enkephalinamide: in vitro permeability, stability and in vivo nasal delivery.

    abstract：:Leu-enkephalin is an endogenous pain modulating opioid pentapeptide. Its development as a potential pharmaceutic has been hampered by poor membrane permeability and susceptibility to enzymatic degradation. The addition of an unnatural amino acid containing a lipidic side chain at the N-terminus and the modification of...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.12.042

    authors： Cros CD,Toth I,Blanchfield JT

    更新日期：2011-02-15 00:00:00

  • Electronic effects of para-substitution on acetophenones in the reaction of rat liver 3alpha-hydroxysteroid dehydrogenase.

    abstract：:Stereoselective reductive metabolism of various p-substituted acetophenone derivatives was studied using isolated rat liver 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD). Kinetic experiments were performed and analyzed by measuring the products by HPLC using a chiral column. The results demonstrated that the presen...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2007.10.096

    authors： Uwai K,Konno N,Yasuta Y,Takeshita M

    更新日期：2008-02-01 00:00:00

  • Design, synthesis and anticonvulsant properties of new N-Mannich bases derived from 3-phenylpyrrolidine-2,5-diones.

    abstract：:The synthesis and anticonvulsant properties of new N-Mannich bases of 3-phenyl- (9a-d), 3-(2-chlorophenyl)- (10a-d), 3-(3-chlorophenyl)- (11a-d) and 3-(4-chlorophenyl)-pyrrolidine-2,5-diones (12a-d) were described. The key synthetic strategies involve the formation of 3-substituted pyrrolidine-2,5-diones (5-8), and th...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.07.029

    authors： Kamiński K,Obniska J,Chlebek I,Wiklik B,Rzepka S

    更新日期：2013-11-01 00:00:00

  • HSP90-like artificial chaperone activity based on indole beta-cyclodextrin.

    abstract：:Indole beta-cyclodextrin (beta-1) was found to be able to prevent aggregation of citrate synthase (CS) on heating condition. As a result, beta-1 showed anti-CS aggregation in this system by regulating in early stage. The depression mechanism of beta-1 for aggregation of CS is as follows: the beta-1 formed a complex wi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2006.12.040

    authors： Toda M,Itoh H,Kondo Y,Hamada F

    更新日期：2007-03-01 00:00:00

  • New carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; synthesis, X-ray crystallography and anticancer activity.

    abstract：:An amine group was synthesized starting from an optically active bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of a key 6-chloropurine intermediate. This was then reacted with ammonia and selected amines obtaining new adenine- and 6-substituted adenine conformationally constrained carbo...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.10.056

    authors： Tănase CI,Drăghici C,Căproiu MT,Shova S,Mathe C,Cocu FG,Enache C,Maganu M

    更新日期：2014-01-01 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

  • 1,2,3-Selenadiazole thioacetanilides: synthesis and anti-HIV activity evaluation.

    abstract：:The development of new HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) offers the possibility of generating novel structures of increased potency. Based on the bioisosteric principle, novel series of 1,2,3-selenadiazole thioacetanilide derivatives were designed, and synthesized using an original synthet...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.07.027

    authors： Zhan P,Liu X,Fang Z,Pannecouque C,De Clercq E

    更新日期：2009-09-01 00:00:00

  • Synthesis and evaluation of 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine mono- and diesters as potential prodrugs of penciclovir.

    abstract：:2-Amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (7), and its mono- and diesters 8-15 were prepared and evaluated for their potential as prodrugs of penciclovir. Treatment of 2-amino-6-chloro-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (5) with trimethylamine in THF followed by a reaction of the resulting ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(98)00263-6

    authors： Kim DK,Lee N,Kim HT,Im GJ,Kim KH

    更新日期：1999-03-01 00:00:00

  • Synthesis and antiviral/antitumor evaluation of 2-amino- and 2-carboxamido-3-arylsulfonylthiophenes and related compounds as a new class of diarylsulfones.

    abstract：:Based on general SARs previously described for anti-HIV-1 diarylsulfone derivatives, a series of 2-amino- and 2-carboxamido-3-arylsulfonylthiophenes has been prepared and evaluated as potential antiviral and antitumor agents. In cell culture, some of the 2-aminothiophenes exhibited moderate and selective activity agai...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(00)00333-3

    authors： Stephens CE,Felder TM,Sowell JW Sr,Andrei G,Balzarini J,Snoeck R,De Clercq E

    更新日期：2001-05-01 00:00:00

  • Design, synthesis of novel 4,5-dihydroisoxazole-containing benzamide derivatives as highly potent FtsZ inhibitors capable of killing a variety of MDR Staphylococcus aureus.

    abstract：:Antibiotic resistance among clinically significant bacterial pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. As a pa...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2020.115729

    authors： Song D,Bi F,Zhang N,Qin Y,Liu X,Teng Y,Ma S

    更新日期：2020-11-01 00:00:00