Synthesis, biological assays and QSAR studies of N-(9-benzyl-2-phenyl-8-azapurin-6-yl)-amides as ligands for A1 adenosine receptors.

Abstract:

:2-Phenyl-9-benzyl-8-azapurines, bearing at the 6 position an amido group interposed between the 8-azapurine moiety and an alkyl or a substituted phenyl group, have been synthesised and assayed as ligands for adenosine receptors. All the compounds show high affinity for the A(1) adenosine receptor, and many of them also show a good selectivity for A(1) with respect to A(2A) and A(3) adenosine receptors. Based on the quite rich library containing such compounds and relevant biological data, QSAR models, able to rationalise the results and to give a quantitative estimate of the observed trends were also developed. The obtained models can assist in the design of new compounds selectively active on A(1) adenosine receptor.

journal_name

Bioorg Med Chem

authors

Giorgi I,Leonardi M,Pietra D,Biagi G,Borghini A,Massarelli I,Ciampi O,Bianucci AM

doi

10.1016/j.bmc.2009.01.060

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

1817-30

issue

5

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(09)00105-9

journal_volume

17

pub_type

杂志文章
  • 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

  • Synthesis of quinolinomorphinan-4-ol derivatives as δ opioid receptor agonists.

    abstract::The previously reported morphinan derivative SN-28 showed high selectivity and agonist activity for the δ opioid receptor. In the course of examining the structure-activity relationship of SN-28 derivatives, the derivatives with the 4-hydroxy group (SN-24, 26, 27) showed higher selectivities for the δ receptor over th...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.11.047

    authors: Ida Y,Nemoto T,Hirayama S,Fujii H,Osa Y,Imai M,Nakamura T,Kanemasa T,Kato A,Nagase H

    更新日期:2012-01-15 00:00:00

  • Synthesis and elastase-inhibiting activity of 2-pyridinyl-isothiazol-3(2H)-one 1,1-dioxides.

    abstract::The synthesis of a series of new isothiazol-3(2H)-one 1,1-dioxides with halogenated (mostly fluorinated) pyridinyl and pentafluorophenyl substituents at 2-position is reported. These compounds (18-24) became easily accessible from 2-thiocyanato-1-carboxaldehydes and aminopyridines, pentafluoroaniline, respectively, by...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.07.049

    authors: Eilfeld A,González Tanarro CM,Frizler M,Sieler J,Schulze B,Gütschow M

    更新日期:2008-09-01 00:00:00

  • Synthesis of 11C-labelled (R)-OHDMI and CFMME and their evaluation as candidate radioligands for imaging central norepinephrine transporters with PET.

    abstract::(R)-1-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-3-methylamino-propan-2-ol ((R)-OHDMI) and (S,S)-1-cyclopentyl-2-(5-fluoro-2-methoxy-phenyl)-1-morpholin-2-yl-ethanol (CFMME) were synthesized and found to be potent inhibitors of norepinephrine reuptake. Each was labelled efficiently in its methyl group with carbon-11 (t(1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.10.065

    authors: Schou M,Pike VW,Sóvágó J,Gulyás B,Gallagher PT,Dobson DR,Walter MW,Rudyk H,Farde L,Halldin C

    更新日期:2007-01-15 00:00:00

  • Synthesis of heteroaromatic tropeines and heterogeneous binding to glycine receptors.

    abstract::Heteroaromatic carboxylic esters of (nor)tropine were synthesized. Tropine esters displaced [(3)H]strychnine binding to glycine receptors of rat spinal cord with low Hill slopes. Two-site displacement resulted in nanomolar IC(50,1) and micromolar IC(50,2) values, and IC(50,2)/IC(50,1) ratios up to 615 depending on the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.08.029

    authors: Maksay G,Vincze Z,Nemes P

    更新日期:2009-10-01 00:00:00

  • A-ring and E-ring modifications of the cytotoxic alkaloid Luotonin A: Synthesis, computational and biological studies.

    abstract::A series of new Luotonin A derivatives with substituents at rings A and E was synthesized, together with some E-ring-unsubstituted derivatives. Subsequently, the compound library was examined in silico for their binding into a previously proposed site in the DNA/topoisomerase I binary complex. Whereas no convincing co...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115443

    authors: Ibric A,Battisti V,Deckardt S,Haller AV,Lee C,Prötsch C,Langer T,Heffeter P,Schueffl HH,Marian B,Haider N

    更新日期:2020-05-01 00:00:00

  • Synthesis and biological evaluation of new flavonoid fatty acid esters with anti-adipogenic and enhancing glucose consumption activities.

    abstract::Oleoyl Formononetin (OF) has good weight loss activity and hypolipidemic activity, could improve insulin sensitivity and suppress adipogenesis. To acquire better biological activities, three series of flavonoid fatty acid esters were designed and synthesized by optimizing the structure of OF. Their bioactivities were ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.03.063

    authors: Zhao W,Sun J,Xiang H,Zeng YY,Li XB,Xiao H,Chen DY,Ma RL

    更新日期:2011-05-15 00:00:00

  • Design and synthesis of novel pyrimido[4,5-b]azepine derivatives as HER2/EGFR dual inhibitors.

    abstract::A novel 7,6 fused bicyclic scaffold, pyrimido[4,5-b]azepine was designed to fit into the ATP binding site of the HER2/EGFR proteins. The synthesis of this scaffold was accomplished by an intramolecular Claisen-type condensation. As the results of optimization lead us to 4-anilino and 6-functional groups, we discovered...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.02.014

    authors: Kawakita Y,Seto M,Ohashi T,Tamura T,Yusa T,Miki H,Iwata H,Kamiguchi H,Tanaka T,Sogabe S,Ohta Y,Ishikawa T

    更新日期:2013-04-15 00:00:00

  • Model studies for isolation of G-quadruplex-forming DNA sequences through a pull-down strategy with macrocyclic polyoxazole.

    abstract::G-quadruplexes (G4s) are non-B DNA structures present in guanine-rich regions of gene regulatory areas, promoters and CpG islands, but their occurrence and functions remain incompletely understood. Thus, methodology to identify G4 sequences is needed. Here, we describe the synthesis of a novel cyclic hepta-oxazole com...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.02.056

    authors: Iida K,Tsushima Y,Ma Y,Sedghi Masoud S,Sakuma M,Yokoyama T,Yoshida W,Ikebukuro K,Nagasawa K

    更新日期:2019-04-15 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

  • Chemical synthesis and biochemical characterization of cyclic oligonucleotides containing acyl groups at both 5'- and 3'-terminal positions.

    abstract::Modified oligonucleotides, whose ON-OFF switch of hybridization can be controlled by an external stimulus, are important to understanding life phenomena and efficient treatment of diseases. The ON-OFF switch can be completely controlled by chemical modification of the oligonucleotide such as cyclization. However, thei...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115799

    authors: Nishizawa S,Ohkubo A

    更新日期:2020-12-01 00:00:00

  • 3,5-Diaryl-1H-pyrazole as a molecular scaffold for the synthesis of apoptosis-inducing agents.

    abstract::The scaffold of 3,5-diaryl-1H-pyrazole was selected as a molecular template to synthesize novel growth-inhibitory agents in the present study. Our findings suggested that analogs bearing electron-withdrawing groups on one ring while electron-donating groups on another reveal significant activities. In particular, 26 b...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.03.016

    authors: Shaw AY,Liau HH,Lu PJ,Yang CN,Lee CH,Chen JY,Xu Z,Flynn G

    更新日期:2010-05-01 00:00:00

  • X-ray crystallographic structure of ABT-378 (lopinavir) bound to HIV-1 protease.

    abstract::The crystal structure of ABT-378 (lopinavir), bound to the active site of HIV-1 protease is described. A comparison with crystal structures of ritonavir, A-78791, and BILA-2450 shows some analogous features with previous reported compounds. A cyclic urea unit in the P(2) position of ABT-378 is novel and makes two bide...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00051-2

    authors: Stoll V,Qin W,Stewart KD,Jakob C,Park C,Walter K,Simmer RL,Helfrich R,Bussiere D,Kao J,Kempf D,Sham HL,Norbeck DW

    更新日期:2002-08-01 00:00:00

  • Biased and unbiased strategies to identify biologically active small molecules.

    abstract::Small molecules are central players in chemical biology studies. They promote the perturbation of cellular processes underlying diseases and enable the identification of biological targets that can be validated for therapeutic intervention. Small molecules have been shown to accurately tune a single function of plurip...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.bmc.2014.04.019

    authors: Abet V,Mariani A,Truscott FR,Britton S,Rodriguez R

    更新日期:2014-08-15 00:00:00

  • 4-Aminophenyl acetamides and propanamides as potent transient receptor potential vanilloid 1 (TRPV1) ligands.

    abstract::A series of 2-(3,5-substituted 4-aminophenyl)acetamide and propanamide derivatives were investigated as human TRPV1 antagonists. The analysis of the structure-activity relationship indicated that 2-(3,5-dihalo 4-aminophenyl)acetamide analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.07.040

    authors: Kim C,Ann J,Lee S,Kim E,Choi S,Blumberg PM,Frank-Foltyn R,Bahrenberg G,Stockhausen H,Christoph T,Lee J

    更新日期:2018-08-15 00:00:00

  • A quencher-free molecular beacon design based on pyrene excimer fluorescence using pyrene-labeled UNA (unlocked nucleic acid).

    abstract::A quencher-free molecular beacon capable of generating pyrene excimer fluorescence has been constructed using strategically positioned pyrene-UNA monomers. Hybridization of a fully complementary RNA target was accompanied by a pyrene excimer emission increase of more than 900%, and detection of RNA in living cells was...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.04.062

    authors: Karlsen KK,Okholm A,Kjems J,Wengel J

    更新日期:2013-10-15 00:00:00

  • Homology modelling and active-site-mutagenesis study of the catalytic domain of the pneumococcal phosphorylcholine esterase.

    abstract::Streptococcus pneumoniae is among the major human pathogens. Several interactions of this bacterium with its host appear to have been mediated by bacterial cell wall components. Specifically, phosphorylcholine residues covalently attached to teichoic and lipoteichoic acids serve as anchors for many surface-located pro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.06.060

    authors: Campillo NE,Páez JA,Lagartera L,Gonzalez A

    更新日期:2005-12-01 00:00:00

  • Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3 or 2-CH3.

    abstract::A series of twenty two (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3 or 2-CH3 was designed, synthesized and evaluated for anticonvulsant activity in rodent models of seizures: maximal electroshock (MES) test, subcutaneous pentylenetetrazole (scPTZ) test, and 6-Hz test. There...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.11.014

    authors: Gunia-Krzyżak A,Żelaszczyk D,Rapacz A,Żesławska E,Waszkielewicz AM,Pańczyk K,Słoczyńska K,Pękala E,Nitek W,Filipek B,Marona H

    更新日期:2017-01-15 00:00:00

  • Design, synthesis and biological evaluation of novel 4-phenoxy-6,7-disubstituted quinolines possessing (thio)semicarbazones as c-Met kinase inhibitors.

    abstract::In continuing our efforts to identify small molecules able to inhibit c-Met kinase, three series of novel 6,7-disubstituted-4-phenoxyquinoline derivatives (23a-w, 26a-d and 30a-d) bearing (thio)semicarbazone scaffold were designed, synthesized and evaluated for their cytotoxicity. The biological data revealed that mos...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.02.003

    authors: Zhai X,Bao G,Wang L,Cheng M,Zhao M,Zhao S,Zhou H,Gong P

    更新日期:2016-03-15 00:00:00

  • Synthesis of new chemical entities from paracetamol and NSAIDs with improved pharmacodynamic profile.

    abstract::It was envisaged to combine high antipyretic activity of paracetamol into commonly used NSAIDs. To achieve this goal new chemical entities were synthesized by chemically combining paracetamol and NSAIDs, and biologically evaluated for their antipyretic, analgesic, anti-inflammatory and ulcerogenic potential. The acid ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.08.017

    authors: Yadav MR,Nimekar DM,Ananthakrishnan A,Brahmkshatriya PS,Shirude ST,Giridhar R,Parmar A,Balaraman R

    更新日期:2006-12-15 00:00:00

  • Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors.

    abstract::A new series of flavonoid derivatives have been designed, synthesized and evaluated as potent AChE inhibitors. Most of them showed more potent inhibitory activities to AChE than rivastigmine. The most potent inhibitor isoflavone derivative 10d inhibit AChE with a IC(50) of 4 nM and showed high BChE/AChE inhibition rat...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.07.072

    authors: Sheng R,Lin X,Zhang J,Chol KS,Huang W,Yang B,He Q,Hu Y

    更新日期:2009-09-15 00:00:00

  • Synthesis and insecticidal activity of chromanone and chromone analogues of diacylhydrazines.

    abstract::Diacylhydrazine derivatives have been identified as one of the most important insect growth regulators. A variety of diacylhydrazine derivatives were designed and synthesized in recent years due to their unique action mechanism, simple structure, and environmental benign character. This paper describes the molecular d...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.01.008

    authors: Zhao PL,Li J,Yang GF

    更新日期:2007-03-01 00:00:00

  • The influence of halogen substituents on the biological properties of sulfur-containing flavonoids.

    abstract::A series of halogen-substituted tricyclic flavonoids containing a 1,3-dithiol-2-ylium moiety has been synthesized from the corresponding 3-dithiocarbamic flavanones. The influence of halogen substituents on the antibacterial properties of the tricyclic flavonoids has been investigated against Staphylococcus aureus and...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.05.044

    authors: Bahrin LG,Sarbu LG,Hopf H,Jones PG,Babii C,Stefan M,Birsa ML

    更新日期:2016-07-15 00:00:00

  • Development of a purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells and induce the degradation of Her2 tyrosine kinase.

    abstract::The first published synthesis and characterization of a purine-scaffold library of hsp90 inhibitors is presented. The purine-scaffold represents a platform for the creation of easily synthesizable and derivatizable soluble molecules that are amenable for oral administration. The most active compound of the series (71)...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00253-5

    authors: Chiosis G,Lucas B,Shtil A,Huezo H,Rosen N

    更新日期:2002-11-01 00:00:00

  • 2D QSAR and similarity studies on cruzain inhibitors aimed at improving selectivity over cathepsin L.

    abstract::Hologram quantitative structure-activity relationships (HQSAR) were applied to a data set of 41 cruzain inhibitors. The best HQSAR model (Q(2)=0.77; R(2)=0.90) employing Surflex-Sim, as training and test sets generator, was obtained using atoms, bonds, and connections as fragment distinctions and 4-7 as fragment size....

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.10.048

    authors: Freitas RF,Oprea TI,Montanari CA

    更新日期:2008-01-15 00:00:00

  • Synthesis and biological evaluation of pyrimidine derivatives as novel human Pin1 inhibitors.

    abstract::Pin1 (Protein interacting with NIMA1) is a cis-trans isomerase and promotes the amide bond rotation of phosphoSer/Thr-Pro motifs in its substrates. Inhibition of Pin1 might be a novel strategy for developing anticancer agents. Herein, a series of pyrimidine derivatives were synthesized and their Pin1 inhibitory activi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2018.03.024

    authors: Cui G,Jin J,Chen H,Cao R,Chen X,Xu B

    更新日期:2018-05-01 00:00:00

  • A para-nitrophenol phosphonate probe labels distinct serine hydrolases of Arabidopsis.

    abstract::Activity-based protein profiling represents a powerful methodology to probe the activity state of enzymes under various physiological conditions. Here we present the development of a para-nitrophenol phosphonate activity-based probe with structural similarities to the potent agrochemical paraoxon. We demonstrate that ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.06.041

    authors: Nickel S,Kaschani F,Colby T,van der Hoorn RA,Kaiser M

    更新日期:2012-01-15 00:00:00

  • Adenosine receptors: new opportunities for future drugs.

    abstract::This review summarises current knowledge on adenosine receptors, an important G protein-coupled receptor. The four known adenosine receptor subtypes A1, A2A, A2B, and A3 are discussed with special reference to the opportunities for drug development. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/s0968-0896(98)00038-8

    authors: Poulsen SA,Quinn RJ

    更新日期:1998-06-01 00:00:00

  • Novel inhibitors targeting PPM1D phosphatase potently suppress cancer cell proliferation.

    abstract::Protein phosphatase magnesium-dependent 1δ (PPM1D, Wip1) is a p53 inducible serine/threonine phosphatase. PPM1D is a promising target protein in cancer therapy since overexpression, missense mutations, truncating mutations, and gene amplification of PPM1D are reported in many tumors, including breast cancer and neurob...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.08.042

    authors: Ogasawara S,Kiyota Y,Chuman Y,Kowata A,Yoshimura F,Tanino K,Kamada R,Sakaguchi K

    更新日期:2015-10-01 00:00:00

  • The conformation and activity relationship of fused analogs of DuP753.

    abstract::We have prepared three conformationally restricted analogs of DuP753 in which one of the phenyl rings in the biphenyl moiety is fused to the imidazole ring, and have investigated the conformation-biological activity relationship of these compounds. Conformational analysis on DuP753 and these compounds confirms that a ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(95)00002-x

    authors: Yoo SE,Shin YA,Lee SH,Kim NJ

    更新日期:1995-03-01 00:00:00