Open Medicinal Chemistry Journal最新文献_第6页

Synthesis and Biological Evaluation of Macrocyclized Betulin Derivatives as a Novel Class of Anti-HIV-1 Maturation Inhibitors. 一类新型抗hiv -1成熟抑制剂大环化桦木素衍生物的合成及生物学评价

Open Medicinal Chemistry Journal Pub Date : 2014-09-03 eCollection Date: 2014-01-01 DOI: 10.2174/1874104501408010023

Jun Tang, Stacey A Jones, Jerry L Jeffery, Sonia R Miranda, Cristin M Galardi, David M Irlbeck, Kevin W Brown, Charlene B McDanal, Nianhe Han, Daxin Gao, Yongyong Wu, Bin Shen, Chunyu Liu, Caiming Xi, Heping Yang, Rui Li, Yajun Yu, Yufei Sun, Zhimin Jin, Erjuan Wang, Brian A Johns

引用次数: 20

Basic aspects of the pharmacodynamics of tolperisone, a widely applicable centrally acting muscle relaxant. tolperisone的药效学基本方面，一种广泛应用的中枢作用肌肉松弛剂。

Open Medicinal Chemistry Journal Pub Date : 2014-07-11 eCollection Date: 2014-01-01 DOI: 10.2174/1874104501408010017

Kornelia Tekes

引用次数: 19

Nitropropenyl benzodioxole, an anti-infective agent with action as a protein tyrosine phosphatase inhibitor. 硝基丙烯基苯并二恶茂，一种具有蛋白酪氨酸磷酸酶抑制剂作用的抗感染剂。

Open Medicinal Chemistry Journal Pub Date : 2014-05-30 eCollection Date: 2014-01-01 DOI: 10.2174/1874104501408010001

Kylie S White, Gina Nicoletti, Robert Borland

{"title":"Nitropropenyl benzodioxole, an anti-infective agent with action as a protein tyrosine phosphatase inhibitor.","authors":"Kylie S White, Gina Nicoletti, Robert Borland","doi":"10.2174/1874104501408010001","DOIUrl":"10.2174/1874104501408010001","url":null,"abstract":"We report on the activities of a broad spectrum antimicrobial compound,nitropropenyl benzodioxole (NPBD) which are of relevance to its potential as an anti-infective drug. These investigations support the proposal that a major mechanism of NPBD is action as a tyrosine mimetic, competitively inhibiting bacterial and fungal protein tyrosine phosphatases (PTP). NPBD did not affect major anti-bacterial drug targets, namely, ATP production, cell wall or cell membrane integrity, or transcription and translation of RNA. NPBD inhibited bacterial YopH and human PTP1B and not human CD45 in enzyme assays. NPBD inhibited PTP-associated bacterial virulence factors, namely, endospore formation in Bacillus cereus, prodigiosin secretion in Serratia marcescens , motility in Proteus spp., and adherence and invasion of mammalian cells by Yersinia enterocolitica . NPBD acts intracellularly to inhibit the early development stages of the Chlamydia trachomatis infection cycle in mammalian cells known to involve sequestration of host cell PTPs. NPBD thus both kills pathogens and inhibits virulence factors relevant to early infection, making it a suitable candidate for development as an anti-infective agent, particularly for pathogens that enter through, or cause infections at, mucosal surfaces. Though much is yet to be understood about bacterial PTPs, they are proposed as suitable anti-infective targets and have been linked to agents similar to NPBD. The structural and functional diversity and heterogeneous distribution of PTPs across microbial species make them suitably selective targets for the development of both broadly active and pathogen-specific drugs. ","PeriodicalId":39133,"journal":{"name":"Open Medicinal Chemistry Journal","volume":"8 ","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2014-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/b6/TOMCJ-8-1.PMC4073595.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32466474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis of Some 4,5-Dihydrothieno[3,2-e][1,2,4]Triazolo[4,3-a] Pyrimi-dine-2-Carboxamides as Anti-Inflammatory and Analgesic Agents. 作为抗炎镇痛剂的一些 4,5-二氢噻吩并[3,2-e][1,2,4]三唑并[4,3-a]嘧啶-2-甲酰胺的合成。

Open Medicinal Chemistry Journal Pub Date : 2013-11-29 eCollection Date: 2013-01-01 DOI: 10.2174/1874104501307010039

Omaima G Shaaban, Ola H Rizk, Aida E Bayad, Ibrahim M El-Ashmawy

引用次数: 0

Docking Studies of Methylthiomorpholin Phenols (LQM300 Series) with Angiotensin-Converting Enzyme (ACE). 甲基噻吩啉酚类化合物(LQM300系列)与血管紧张素转换酶(ACE)对接研究。

Open Medicinal Chemistry Journal Pub Date : 2013-11-23 eCollection Date: 2013-01-01 DOI: 10.2174/1874104501307010030

Víctor H Vázquez-Valadez, V H Abrego, Pablo A Martínez, Gabriela Torres, Oscar Zúñiga, Daniel Escutia, Rebeca Vilchis, Ana Ma Velázquez, Luisa Martínez, Mónica Ruiz, Brígida Camacho, Rafael López-Castañares, Enrique Angeles

引用次数: 7

Development of a Peptide-derived orally-active kappa-opioid receptor agonist targeting peripheral pain. 针对外周性疼痛的肽衍生口服活性kappa-阿片受体激动剂的开发。

Open Medicinal Chemistry Journal Pub Date : 2013-11-04 eCollection Date: 2013-01-01 DOI: 10.2174/1874104501307010016

Francis M Hughes, Brooke E Shaner, Justin O Brower, R Jeremy Woods, Thomas A Dix

{"title":"Development of a Peptide-derived orally-active kappa-opioid receptor agonist targeting peripheral pain.","authors":"Francis M Hughes, Brooke E Shaner, Justin O Brower, R Jeremy Woods, Thomas A Dix","doi":"10.2174/1874104501307010016","DOIUrl":"https://doi.org/10.2174/1874104501307010016","url":null,"abstract":"Kappa-opioid agonists are particularly efficacious in the treatment of peripheral pain but suffer from central nervous system (CNS)-mediated effects that limit their development. One promising kappa-agonist is the peptidic compound CR665. Although not orally available, CR665 given i.v. exhibits high peripheral to CNS selectivity and benefits patients with visceral and neuropathic pain. In this study we have generated a series of derivatives of CR665 and screened them for oral activity in the acetic acid-induced rat writhing assay for peripheral pain. Five compounds were further screened for specificity of activation of kappa receptors as well as agonism and antagonism at mu and delta receptors, which can lead to off-target effects. All active derivatives engaged the kappa receptor with EC50s in the low nM range while agonist selectivity for kappa over mu or delta was >11,000-200,000-fold. No antagonist activity was detected. One compound was chosen for further analysis (Compound 9). An oral dose response of 9 in rats yielded an EC50 of 4.7 mg/kg, approaching a druggable level for an oral analgesic. To assess the peripheral selectivity of this compound an i.v. dose response in rats was assessed in the writhing assay and hotplate assay (an assay of CNS-mediated pain). The EC50 in the writhing assay was 0.032 mg/kg while no activity was detectable in the hotplate assay at doses as high as 30 mg/kg, indicating a peripheral selectivity of >900-fold. We propose that compound 9 is a candidate for development as an orally-available peripherally-restricted kappa agonist. ","PeriodicalId":39133,"journal":{"name":"Open Medicinal Chemistry Journal","volume":"7 ","pages":"16-22"},"PeriodicalIF":0.0,"publicationDate":"2013-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/e0/TOMCJ-7-16.PMC3821081.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31857463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 25

Roles of PI3K/AKT/PTEN Pathway as a Target for Pharmaceutical Therapy. PI3K/AKT/PTEN通路作为药物治疗靶点的作用

Open Medicinal Chemistry Journal Pub Date : 2013-10-31 eCollection Date: 2013-01-01 DOI: 10.2174/1874104501307010023

Satoru Matsuda, Atsuko Nakanishi, Yoko Wada, Yasuko Kitagishi

引用次数: 45

Design and Synthesis of Hydroxyethylene-Based BACE-1 Inhibitors Incorporating Extended P1 Substituents. 含扩展P1取代基的羟乙基BACE-1抑制剂的设计与合成

Open Medicinal Chemistry Journal Pub Date : 2013-03-08 Print Date: 2013-01-01 DOI: 10.2174/1874104501307010001

Veronica Sandgren, Marcus Bäck, Ingemar Kvarnström, Anders Dahlgren

引用次数: 28

Tricyclic Pyrazoles. Part 5. Novel 1,4-Dihydroindeno[1,2-c]pyrazole CB2 Ligands Using Molecular Hybridization Based on Scaffold Hopping. 三环摘要。第5部分。新型1,4-二氢茚[1,2-c]吡唑CB2配体的分子杂交研究。

Open Medicinal Chemistry Journal Pub Date : 2012-01-01 Epub Date: 2012-05-17 DOI: 10.2174/1874104501206010001

Gabriele Murineddu, Battistina Asproni, Stefania Ruiu, Francesco Deligia, Matteo Falzoi, Amedeo Pau, Brian F Thomas, Yanan Zhang, Gérard A Pinna, Luca Pani, Paolo Lazzari

引用次数: 12

Identification of G-Quadruplex Inducers Usinga Simple, Inexpensiveand Rapid High Throughput Assay, and TheirInhibition of Human Telomerase. 用一种简单、廉价、快速、高通量的方法鉴定g -四重诱导剂及其对人类端粒酶的抑制作用

Open Medicinal Chemistry Journal Pub Date : 2012-01-01 Epub Date: 2012-10-19 DOI: 10.2174/1874104501206010020

Maria Florencia Sassano, Alexander P Schlesinger, Michael B Jarstfer

{"title":"Identification of G-Quadruplex Inducers Usinga Simple, Inexpensiveand Rapid High Throughput Assay, and TheirInhibition of Human Telomerase.","authors":"Maria Florencia Sassano, Alexander P Schlesinger, Michael B Jarstfer","doi":"10.2174/1874104501206010020","DOIUrl":"https://doi.org/10.2174/1874104501206010020","url":null,"abstract":"Telomeres are protein and DNA complexes located atchromosome ends. Telomeric DNA is composed of a double stranded region of repetitive DNA followed by single-stranded 3' extension of aG-rich sequence. Single-stranded G-rich sequencescan fold into G-quadruplex structures,and molecules that stabilize G-quadruplexes are known to inhibit the enzyme telomerase and disrupt telomere maintenance. Because telomere maintenance is required for proliferation of cancer cells, G-quadruplex stabilizers have become attractive prospects for anticancer drug discovery.However, telomere-targeting G-quadruplex ligands have yet to enter the clinic owing in part to poor pharmacokinetics and target selectivity. Increasing the pharmacophore diversity of G-quadruplex and specifically telomeric-DNA targeting agents should assist in overcoming these shortcomings. In this work, we report the identification and validation ofligands that bind telomeric DNA and induce G-quadruplex formationusing the NCI Diversity Set I, providing validation of anextremely simple, rapid and high-throughput screen using FRET technology. Hits from the screen were validated by examining telomerase inhibition and G-quadruplex inductionusing CD spectroscopy and DNA polymerase stop assays. We show that two known DNA binding molecules, ellipticine derivativeNSC 176327 (apyridocarbazole) and NSC 305831 (an antiparasitic hetero-cyclediamidine referred to as furamidine and DB75),are selective induceG-quadruplex formation in the human telomeric sequence and bind telomeric DNA quadruplexes in the absence of stabilizing monovalent cations with molar ratios(molecule: DNA)of 4:1and 1.5:1, respectively.","PeriodicalId":39133,"journal":{"name":"Open Medicinal Chemistry Journal","volume":"6 ","pages":"20-8"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/dd/TOMCJ-6-20.PMC3502892.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31066460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9