当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Design, chemical synthesis and biological evaluation of 3-spiromorpholinone/3-spirocarbamate androsterone derivatives as inhibitors of 17β-hydroxysteroid dehydrogenase type 3.

Design, chemical synthesis and biological evaluation of 3-spiromorpholinone/3-spirocarbamate androsterone derivatives as inhibitors of 17β-hydroxysteroid dehydrogenase type 3.

Abstract：

:17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a key enzyme involved in the biosynthesis of testosterone and dihydrotestosterone. These hormones are known to stimulate androgen-dependent prostate cancer. In order to generate effective inhibitors of androgen biosynthesis without androgenic effect, we synthesized a new family of 3-spiromorpholinone and 3-spirocarbamate androsterone derivatives bearing diversified hydrophobic groups. We also tested their inhibitory activity in a microsomal fraction of 17β-HSD3-containing rat testes, and their androgenic effect on androgen-sensitive LAPC-4 cells. From our first structure-activity relationship (SAR) study, we noted that compound 7e inhibited 17β-HSD3 (77% at 0.1 μM) compared to our reference compound RM-532-105 (76% at 0.1 μM), but exhibited a residual androgenic effect. A library of 7e analogue compounds was next synthesized in order to generate compounds with reduced androgenic activity. In this new SAR study, the sulfonamide compound 7e21 and the carboxamide compound 7e22 inhibited 17β-HSD3 (IC50 = 28 and 88 nM, respectively). These two compounds were not androgenic and not cytotoxic even at the highest concentration tested, but their inhibitory activity decreased in intact LNCaP cells overexpressing 17β-HSD3 (LNCaP[17β-HSD3]). Structural modifications of these two lead compounds could however be tested to produce a second generation of 17β-HSD3 inhibitors.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Djigoué GB,Kenmogne LC,Roy J,Maltais R,Poirier D

doi

10.1016/j.bmc.2015.07.049

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

5433-51

issue

17

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(15)00633-1

journal_volume

23

pub_type

杂志文章

相关文献

BIOORGANIC & MEDICINAL CHEMISTRY文献大全
  • 18F-Labeled indole-based analogs as highly selective radioligands for imaging sigma-2 receptors in the brain.

    abstract：:We have designed and synthesized a series of indole-based σ2 receptor ligands containing 5,6-dimethoxyisoindoline or 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline as pharmacophore. In vitro competition binding assays showed that all ten ligands possessed low nanomolar affinity (Ki=1.79-5.23nM) for σ2 receptors and high...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.05.019

    authors： Wang L,Ye J,He Y,Deuther-Conrad W,Zhang J,Zhang X,Cui M,Steinbach J,Huang Y,Brust P,Jia H

    更新日期：2017-07-15 00:00:00

  • Synthesis and anti-HIV evaluation of water-soluble calixarene-based bithiazolyl podands.

    abstract：:Nine anionic water-soluble calix[4]arene species, incorporating sulfonate, carboxylate or phosphonate groups, six of them incorporating two 2,2'-bithiazole subunits in alternate position at the lower rim, have been synthesised and evaluated as anti-HIV agents on various HIV strains and cells of the lymphocytic lineage...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.11.016

    authors： Mourer M,Psychogios N,Laumond G,Aubertin AM,Regnouf-de-Vains JB

    更新日期：2010-01-01 00:00:00

  • The design and optimization of a series of 2-(pyridin-2-yl)-1H-benzimidazole compounds as allosteric glucokinase activators.

    abstract：:The optimization of a series of benzimidazole glucokinase activators is described. We identified a novel and potent achiral benzimidazole derivative as an allosteric GK activator. This activator was designed and synthesized via removal of the chiral center of the lead compound, 6-(N-acylpyrrolidin-2-yl)benzimidazole. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2009.05.037

    authors： Takahashi K,Hashimoto N,Nakama C,Kamata K,Sasaki K,Yoshimoto R,Ohyama S,Hosaka H,Maruki H,Nagata Y,Eiki J,Nishimura T

    更新日期：2009-10-01 00:00:00

  • A specific substrate-inhibitor, a 2'-deoxy-2'-fluorouridine-containing oligoribonucleotide, against human RNase L.

    abstract：:We examined the properties of RNA analogues containing 2'-deoxy-2'-alpha-fluorouridine (1) or 2'-O-methyluridine (2) as inhibitors against human RNase L, that cleaves a single-stranded RNA in the presence of 2',5'-linked oligoadenylate (2-5A). The RNA analogue, FF, containing two molecules of 1 in place of uridine eff...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2003.08.025

    authors： Ueno Y,Yamada Y,Nakanishi M,Kitade Y

    更新日期：2003-11-17 00:00:00

  • An azido-oxazolidinone antibiotic for live bacterial cell imaging and generation of antibiotic variants.

    abstract：:An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile 'click' chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure-activity relationships or conjugated to fluorophores to gen...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.05.054

    authors： Phetsang W,Blaskovich MA,Butler MS,Huang JX,Zuegg J,Mamidyala SK,Ramu S,Kavanagh AM,Cooper MA

    更新日期：2014-08-15 00:00:00

  • Search for alpha-helical propensity in the receptor-bound conformation of glucagon-like peptide-1.

    abstract：:To elucidate the receptor-bound conformation of glucagon-like peptide-1 (GLP-1), a series of conformationally constrained GLP-1 analogues were synthesized by introducing lactam bridges between Lys(i) and Glu(i)(+4) to form alpha-helices at various positions. The activity and affinity of these analogues to GLP-1 recept...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.10.006

    authors： Murage EN,Schroeder JC,Beinborn M,Ahn JM

    更新日期：2008-12-01 00:00:00

  • Discovery and structure activity relationship of the first potent cryptosporidium FIKK kinase inhibitor.

    abstract：:FIKKs are parasite-specific protein kinases with distinctive sequence motifs and their biological roles have not been completely elucidated. Here, we report the first potent Cryptosporidium FIKK (CpFIKK) inhibitor. We identified 4b as a potent (IC50=0.2nM) inhibitor of CpFIKK catalytic activity. In addition, we identi...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2017.01.036

    authors： Osman KT,Ye J,Shi Z,Toker C,Lovato D,Jumani RS,Zuercher W,Huston CD,Edwards AM,Lautens M,Santhakumar V,Hui R

    更新日期：2017-03-01 00:00:00

  • Characterization, bioinformatic analysis and dithiocarbamate inhibition studies of two new α-carbonic anhydrases, CAH1 and CAH2, from the fruit fly Drosophila melanogaster.

    abstract：:Carbonic anhydrases (CAs) are essential and ubiquitous enzymes. Thus far, there are no articles on characterization of Drosophila melanogaster α-CAs. Data from invertebrate CA studies may provide opportunities for anti-parasitic drug development because α-CAs are found in many parasite or parasite vector invertebrates...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.08.046

    authors： Syrjänen L,Tolvanen ME,Hilvo M,Vullo D,Carta F,Supuran CT,Parkkila S

    更新日期：2013-03-15 00:00:00

  • Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII.

    abstract：:The transmembrane isoforms of carbonic anhydrase (hCA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this paper, we present a new class of C-glycosides incorporating the methoxyaryl moiety, that was designed to selectively target and in...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.07.052

    authors： Riafrecha LE,Rodríguez OM,Vullo D,Supuran CT,Colinas PA

    更新日期：2014-10-01 00:00:00

  • Muscarinic subtypes profile modulation within a series of new antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine.

    abstract：:A set of new muscarinic antagonists, bridged bicyclic derivatives of 2,2-diphenyl-[1,3]-dioxolan-4-ylmethyl-dimethylamine (1), was synthesized and tested to evaluate their affinity and selectivity for M(1), M(2), M(3) and M(4) receptor subtypes. The conformational constraint of 1 in a bicyclic structure, and the varia...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00431-0

    authors： Piergentili A,Gentili F,Ghelfi F,Marucci G,Pigini M,Quaglia W,Giannella M

    更新日期：2003-09-01 00:00:00

  • Allosteric inhibitors of hepatitis C virus NS5B polymerase thumb domain site II: structure-based design and synthesis of new templates.

    abstract：:Chronic hepatitis C virus (HCV) infections are a significant medical problem worldwide. The NS5B Polymerase of HCV plays a central role in virus replication and is a prime target for the discovery of new treatment options. We recently disclosed 1H-benzo[de]isoquinoline-1,3(2H)-diones as allosteric inhibitors of NS5B P...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2010.03.024

    authors： Malancona S,Donghi M,Ferrara M,Martin Hernando JI,Pompei M,Pesci S,Ontoria JM,Koch U,Rowley M,Summa V

    更新日期：2010-04-15 00:00:00

  • Cyclopropane-ring formation in the acyl groups of chlorosome glycolipids is crucial for acid resistance of green bacterial antenna systems.

    abstract：:Green photosynthetic bacteria have unique light-harvesting antenna systems called chlorosomes. Chlorobaculum tepidum, a model organism of the bacteria, biosynthesized monogalactosyl- and rhamnosylgalactosyldiacylglycerides possessing a methylene-bridged palmitoleyl group characterized by a cis-substituted cyclopropane...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2013.04.030

    authors： Mizoguchi T,Tsukatani Y,Harada J,Takasaki S,Yoshitomi T,Tamiaki H

    更新日期：2013-07-01 00:00:00

  • Synthesis of tetravalent LacNAc-glycoclusters as high-affinity cross-linker against Erythrina cristagalli agglutinin.

    abstract：:Four kinds of tetravalent double-headed glycoclusters [(LacNAc)4-DHGs] were designed with linkers of varying lengths consisting of alkanedioic carboxyamido groups (C6, C12, C18 and C24) between two bi-antennary LacNAc-glycosides. These glycoclusters served as high-affinity cross-linking ligands for the LacNAc-binding ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.11.026

    authors： Ogata M,Chuma Y,Yasumoto Y,Onoda T,Umemura M,Usui T,Park EY

    更新日期：2016-01-01 00:00:00

  • Oligonucleotide-templated reactions based on Peptide Nucleic Acid (PNA) probes: concept and biomedical applications.

    abstract：:Sensing technologies based on Peptide Nucleic Acids (PNAs) and oligonucleotide-templated chemistry are perfectly suited for biomedical applications (e.g., diagnosis, prognosis and stratification of diseases) and could compete well with more traditional amplification technologies using expensive dual-labelled oligonucl...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2014.05.071

    authors： Choi Y,Metcalf G,Sleiman MH,Vair-Turnbull D,Ladame S

    更新日期：2014-08-15 00:00:00

  • Selective carriers of norepinephrine and ammonium ions: ionophoric properties and molecular modelling studies of diester crown compounds containing a 1,3-bis(1H-pyrazol-1-yl)propane unit.

    abstract：:Ionophoric properties of dipyrazolic crowns and podands containing a 1,3-bis(1H-pyrazol-1-yl)propane unit in their structure are described. They show selectivity of ammonium vs alkali cations and interesting norepinephrine transport rates. A molecular modelling study has been used to elucidate the superstructures of t...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(96)00250-7

    authors： Rodríguez-Franco MI,Fierros M,Martínez A,Navarro P,Conde S

    更新日期：1997-02-01 00:00:00

  • Synthesis and study of the cancer cell growth inhibitory properties of alpha-, gamma-tocopheryl and gamma-tocotrienyl 2-phenylselenyl succinates.

    abstract：:Vitamin E succinate selenium-conjugated molecules were synthesized and their apoptogenic properties were evaluated. 4-Methyl-2-phenylselenyl succinate (4) was prepared by the reaction of sodium benzeneselenolate with 2-bromosuccinic anhydrite in methanol solution. The methyl ester was converted to the acid (5) by hydr...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2005.11.045

    authors： Vraka PS,Drouza C,Rikkou MP,Odysseos AD,Keramidas AD

    更新日期：2006-04-15 00:00:00

  • The role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D.

    abstract：:Extensive molecular modeling based on crystallographic data was used to aid the design of synthetic analogues of the fungicidal naturally occurring respiration inhibitors crocacins A and D, and an inhibitor binding model to the mammalian cytochrome bc(1) complex was constructed. Simplified analogues were made which sh...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.10.030

    authors： Crowley PJ,Berry EA,Cromartie T,Daldal F,Godfrey CR,Lee DW,Phillips JE,Taylor A,Viner R

    更新日期：2008-12-15 00:00:00

  • Isolation, structure, and antibacterial activity of thiazomycin A, a potent thiazolyl peptide antibiotic from Amycolatopsis fastidiosa.

    abstract：:Thiazolyl peptides are a class of thiazole-rich macrocyclic potent antibacterial agents. Recently, we described thiazomycin, a new member of thiazolyl peptides, discovered by a thiazolyl peptide specific chemical screening. This method also allowed for the discovery of a new thiazolyl peptide, thiazomycin A, which car...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.08.079

    authors： Zhang C,Zink DL,Ushio M,Burgess B,Onishi R,Masurekar P,Barrett JF,Singh SB

    更新日期：2008-10-01 00:00:00

  • Preparation, antimicrobial evaluation, and mutagenicity of [2-hydroxyaryl]-[1-methyl-5-nitro-1H-2-imidazolyl]methanols , [5-tert-butyl-2-methylaminophenyl]-[1-methyl-5-nitro-1H-2-imidazo lyl]me thanol, and [2-hydroxyaryl]-[1-methyl-5-nitro-1H-2-imidazolyl

    abstract：:Efficient preparations of the titled compounds are described, their antimicrobial activity and mutagenic properties being evaluated. Some of the studied compounds are nonmutagenic and present a MIC as low as some of the usual standards in the field. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(97)00138-7

    authors： Arredondo Y,Moreno-Mañas M,Pleixats R,Palacín C,Raga MM,Castelló JM,Ortiz JA

    更新日期：1997-10-01 00:00:00

  • Binding of 2,4-disubstituted morpholines at human D4 dopamine receptors.

    abstract：:The synthesis of a series of 2,4-disubstituted morpholines is described and their affinities at human dopamine receptors reported. The orally bioavailable 7-azaindole compound 11 has nanomolar affinity at the hD4 receptor with > 1000-fold selectivity over the hD2 receptor. ...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(97)00176-4

    authors： Showell GA,Emms F,Marwood R,O'Connor D,Patel S,Leeson PD

    更新日期：1998-01-01 00:00:00

  • Synthesis of biotinylated xestoquinone that retains inhibitory activity against Ca2+ ATPase of skeletal muscle myosin.

    abstract：:Xestoquinone isolated from a marine sponge binds to skeletal muscle myosin and inhibits its Ca(2+) ATPase activity. In this study, we first examined xestoquinone and its analogues to assess the relationships between structure and myosin Ca(2+) ATPase inhibitory activity. On the basis of the resultant data, we then des...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00276-1

    authors： Nakamura M,Kakuda T,Oba Y,Ojika M,Nakamura H

    更新日期：2003-07-17 00:00:00

  • Novel inhibitors of RANKL-induced osteoclastogenesis: Design, synthesis, and biological evaluation of 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-diones.

    abstract：:A series of novel 6-(2,4-difluorophenyl)-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione derivatives were synthesized and evaluated for their inhibitory effects on osteoclast activities by using TRAP-staining assay. Among the tested compounds, 3d and 3h exhibited more potent osteoclast-inhibitory activities than the le...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2015.06.007

    authors： Lee CC,Liu FL,Chen CL,Chen TC,Liu FC,Ahmed Ali AA,Chang DM,Huang HS

    更新日期：2015-08-01 00:00:00

  • A novel sesquiterpene lactone from Centaurea pullata: structure elucidation, antimicrobial activity, and prediction of pharmacokinetic properties.

    abstract：:A novel elemanolide with an alpha-methyl-gamma-lactone moiety, 8alpha-O-(4-hydroxy-2-methylenebutanoyloxy)melitensine, in addition to four known sesquiterpene lactones also bearing the same lactone ring, melitensin, 11beta,13 dihydrosalonitenolide, 8alpha-hydroxy-11beta,13-dihydro-4-epi-sonchucarpolide, and 8alpha-hyd...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2008.01.056

    authors： Djeddi S,Karioti A,Sokovic M,Koukoulitsa C,Skaltsa H

    更新日期：2008-04-01 00:00:00

  • Synthesis of 1-D- and 1-L-myo-inosityl 2-N-acetamido-2-deoxy-alpha-D-glucopyranoside establishes substrate specificity of the Mycobacterium tuberculosis enzyme AcGI deacetylase.

    abstract：:Mycothiol (MSH, 1-D-myo-inosityl 2-(N-acetyl-L-cysteinyl)amido-2-deoxy-alpha-D-glucopyranoside) is the principal low molecular weight thiol in actinomycetes. The enzyme 1-D-myo-inosityl 2-N-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase (AcGI deacetylase) is involved in the biosynthesis of MSH and forms the fre...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00154-8

    authors： Nicholas GM,Eckman LL,Kovác P,Otero-Quintero S,Bewley CA

    更新日期：2003-06-12 00:00:00

  • Directed evolution of N-acetylneuraminic acid aldolase to catalyze enantiomeric aldol reactions.

    abstract：:Expanding the scope of substrate specificity and stereoselectivity is of current interest in enzyme catalysis. Using error-prone PCR for in vitro directed evolution, the Neu5Ac aldolase from Escherichia coli has been altered to improve its catalytic activity toward enantiomeric substrates including N-acetyl-L-mannosam...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(03)00052-x

    authors： Wada M,Hsu CC,Franke D,Mitchell M,Heine A,Wilson I,Wong CH

    更新日期：2003-05-01 00:00:00

  • Synthesis and biological evaluation of pyridazine derivatives as novel HIV-1 NNRTIs.

    abstract：:In continuation of our efforts toward identification and optimization of novel non-nucleoside reverse transcriptase inhibitors (NNRTIs), we have employed a structure-based bioisosterism strategy, with which a new series of diarylpyridazine (DAPD) derivatives were synthesized and evaluated for their anti-HIV-1 (human i...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/j.bmc.2012.12.049

    authors： Li D,Zhan P,Liu H,Pannecouque C,Balzarini J,De Clercq E,Liu X

    更新日期：2013-04-01 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

  • Synthesis and structure-activity data of some new epibatidine analogues.

    abstract：:The high-pressure Diels-Alder reaction of N-carbomethyoxypyrroles and phenyl vinyl sulfone affords versatile intermediates for the palladium-catalyzed preparation of new epibatidine analogues. Structure-activity relationships of new epibatidine analogues are presented. High affinities of Ki = 0.81 and 2.6 nM for the [...

    journal_title：Bioorganic & medicinal chemistry

    pub_type： 杂志文章

    doi：10.1016/s0968-0896(98)00163-1

    authors： Seerden JP,Tulp MT,Scheeren HW,Kruse CG

    更新日期：1998-11-01 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

  • 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