Open Medicinal Chemistry Journal最新文献_第9页

Glycine transport inhibitors for the treatment of schizophrenia. 甘氨酸转运抑制剂治疗精神分裂症。

Open Medicinal Chemistry Journal Pub Date : 2010-05-27 DOI: 10.2174/1874104501004010010

Kenji Hashimoto

{"title":"Glycine transport inhibitors for the treatment of schizophrenia.","authors":"Kenji Hashimoto","doi":"10.2174/1874104501004010010","DOIUrl":"https://doi.org/10.2174/1874104501004010010","url":null,"abstract":"Multiple lines of evidence indicate that hypofunction of glutamatergic neurotransmission via N-methyl-D-aspartate (NMDA) receptors might be implicated in the pathophysiology of schizophrenia, suggesting that increasing NMDA receptor function via pharmacological manipulation could provide a new strategy for the management of schizophrenia. Currently, the glycine modulatory sites on NMDA receptors present the most attractive therapeutic targets for the treatment of schizophrenia. One means of enhancing NMDA receptor neurotransmission is to increase the availability of the obligatory co-agonist glycine at modulatory sites on the NMDA receptors through the inhibition of glycine transporter-1 (GlyT-1) on glial cells. Clinical studies have demonstrated that the GlyT-1 inhibitor sarcosine (N-methyl glycine) shows antipsychotic activity in patients with schizophrenia. Accordingly, a number of pharmaceutical companies have developed novel and selective GlyT-1 inhibitors for the treatment of schizophrenia. This paper provides an overview of the various GlyT-1 inhibitors and their therapeutic potential.","PeriodicalId":39133,"journal":{"name":"Open Medicinal Chemistry Journal","volume":"4 ","pages":"10-9"},"PeriodicalIF":0.0,"publicationDate":"2010-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5e/40/TOMCJ-4-10.PMC3023951.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29614728","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: 91

Design and Synthesis of Imidazopyrimidine Derivatives as Potent iNOS Dimerization Inhibitors. 作为强效 iNOS 二聚化抑制剂的咪唑嘧啶衍生物的设计与合成。

Open Medicinal Chemistry Journal Pub Date : 2009-11-18 DOI: 10.2174/1874104500903010008

Guo-Hua Chu, Bertrand Le Bourdonnec, Minghua Gu, Christopher W Ajello, Lara K Leister, Ian Sellitto, Joel A Cassel, Paul A Tuthill, Heather O' Hare, Robert N Dehaven, Roland E Dolle

引用次数: 0

Monitoring by HPLC of chamomile flavonoids exposed to rat liver microsomal metabolism. 大鼠肝微粒体代谢暴露洋甘菊黄酮的HPLC监测。

Open Medicinal Chemistry Journal Pub Date : 2009-07-29 DOI: 10.2174/1874104500903010001

Georg Petroianu, Eva Szoke, Huba Kalász, Péter Szegi, Rudolf Laufer, Bernadett Benko, Ferenc Darvas, Kornélia Tekes

{"title":"Monitoring by HPLC of chamomile flavonoids exposed to rat liver microsomal metabolism.","authors":"Georg Petroianu, Eva Szoke, Huba Kalász, Péter Szegi, Rudolf Laufer, Bernadett Benko, Ferenc Darvas, Kornélia Tekes","doi":"10.2174/1874104500903010001","DOIUrl":"https://doi.org/10.2174/1874104500903010001","url":null,"abstract":"Three major flavonoid chamomile components (quercetin, apigenin-7-O-glucoside and rutin) were subjected to oxidative metabolism by cytochrome P-450 of rat liver microsomal preparations. Changes over time in their respective concentrations were followed using reversed-phase HPLC with UV detection. No clean-up had to be applied as only the specific flavonoid had to be separated from the background components originating from the rat liver microsome.Neither the concentration of apigenin-7-O-glucoside nor that of the diglycoside rutin decreased during one hour of exposure to rat microsomal treatment. In contrast, the concentration of quercetin, a lipophilic aglycon, decreased.Our analytical HPLC results complement the in silico calculated lipophilicity (logP) of these compounds; the relatively high lipophilicity of quercetin appears to predispose it to oxidative metabolism in order to decrease its fat solubility. In contrast the much less lipophilic compounds apigenin-7-O-glucoside and rutin were resistant in vitro to microsomal treatment.","PeriodicalId":39133,"journal":{"name":"Open Medicinal Chemistry Journal","volume":"3 ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2009-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b0/ec/TOMCJ-3-1.PMC2729991.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28362210","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: 6

Synthesis and Bronchodilator Studies of Some Novel 6-Alkyl/Aryl-1,2,4-Triazino[4,3-c]Quinazolines. 新型6-烷基/芳基1,2,4-三嗪基[4,3-c]喹唑啉的合成及支气管扩张剂研究。

Open Medicinal Chemistry Journal Pub Date : 2008-12-17 DOI: 10.2174/1874104500802010101

Rajan Subramanian Kombu, Raghu Prasad Mailavaram, Harikrishna Devalapally, Prabhakar Marsanapalli Chinnappa, Rama Krishna Devarakonda, Raghu Ram Rao Akkinepally

引用次数: 5

The utility of oligopeptidase in brain-targeting delivery of an enkephalin analogue by prodrug design. 寡肽酶在前药设计脑啡肽类似物脑靶向递送中的应用。

Open Medicinal Chemistry Journal Pub Date : 2008-10-20 DOI: 10.2174/1874104500802010097

K Prokai-Tatrai, H-S Kim, L Prokai

引用次数: 8

Two- and three-dimensional quantitative structure-activity relationships studies on a series of liver x receptor ligands. 一系列肝脏x受体配体的二维和三维定量构效关系研究。

Open Medicinal Chemistry Journal Pub Date : 2008-10-07 DOI: 10.2174/1874104500802010087

Káthia M Honório, Lívia B Salum, Richard C Garratt, Igor Polikarpov, Adriano D Andricopulo

引用次数: 8

Design of anticancer agents utilizing streptozocin for in silico optimization of properties and pattern recognition identification of group features. 利用链脲佐菌素设计抗癌药物的性能优化和模式识别识别的群体特征。

Open Medicinal Chemistry Journal Pub Date : 2008-09-02 DOI: 10.2174/1874104500802010081

Ronald Bartzatt

{"title":"Design of anticancer agents utilizing streptozocin for in silico optimization of properties and pattern recognition identification of group features.","authors":"Ronald Bartzatt","doi":"10.2174/1874104500802010081","DOIUrl":"https://doi.org/10.2174/1874104500802010081","url":null,"abstract":"Streptozocin has been shown to be useful in the clinical treatment of malignant neuroendocrine tumors of the pancreas. The poor prognosis for patients having malignant tumors of pancreas suggests the investigation and development of new therapeutics. Nine analogs to streptozocin are determined by in silico physicochemical analysis and generation of structures by modeling from functional group isosteres. In these analogs is preserved the alkylating nitrosourea moiety, however, the covalently bonded substituent has significant hydrogen bonding sites and may include a ring structure. Analogs retain a broad range in lipophilicity, having a range of Log P from -2.798 (hydrophilic) to 3.001 (lipophilic). Standard deviation of molecular masses is only 12.6% of the group mean, so a small alteration in size occurs which is also reflected by only a 15.5% deviation in molecular volumes. Streptozocin and seven analogs show zero violations of the Rule of 5 which suggests favorable bioavailability. All compounds showed at least seven hydrogen bond acceptors with a strong positive correlation between hydrophilicity to the total number of hydrogen bond acceptors and donors. Analysis of similarity (ANOSIM) and discriminant analysis determined that streptozocin is highly similar to all nine analogs. However hierarchical cluster analysis and K-means cluster analysis were able to elucidate patterns of associations and differentiation among the ten compounds. This study demonstrates the efficacy of utilizing in silico optimization and pattern recognition to elucidate potential anticancer drugs.","PeriodicalId":39133,"journal":{"name":"Open Medicinal Chemistry Journal","volume":" ","pages":"81-6"},"PeriodicalIF":0.0,"publicationDate":"2008-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/7f/TOMCJ-2-81.PMC2709472.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40019611","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

The investigation of structure-activity relationships of tacrine analogues: electronic-topological method. 塔克林类似物构效关系的研究:电子拓扑方法。

Open Medicinal Chemistry Journal Pub Date : 2008-08-06 DOI: 10.2174/1874104500802010075

Murat Saracoglu, Fatma Kandemirli

引用次数: 9

A New Method for Radiosynthesis of C-Labeled Carbamate Groups and its Application for a Highly Efficient Synthesis of the Kappa-Opioid Receptor Tracer [C]GR103545. C标记氨基甲酸酯基的放射性合成及其在kappa -阿片受体示踪剂合成中的应用[j]。

Open Medicinal Chemistry Journal Pub Date : 2008-07-16 DOI: 10.2174/1874104500802010072

B W Schoultz, E Arstad, J Marton, F Willoch, A Drzezga, H-J Wester, G Henriksen

引用次数: 14

Transcorneal permeation in a corneal device of non-steroidal anti-inflammatory drugs in drug delivery systems. 药物输送系统中的非类固醇消炎药在角膜装置中的经角膜渗透。

Open Medicinal Chemistry Journal Pub Date : 2008-05-22 DOI: 10.2174/1874104500802010066

R Valls, E Vega, M L Garcia, M A Egea, J O Valls

{"title":"Transcorneal permeation in a corneal device of non-steroidal anti-inflammatory drugs in drug delivery systems.","authors":"R Valls, E Vega, M L Garcia, M A Egea, J O Valls","doi":"10.2174/1874104500802010066","DOIUrl":"10.2174/1874104500802010066","url":null,"abstract":"This work is focused on the ex vivo study of corneal permeation of two anti-inflammatory drugs: diclofenac, and flurbiprofen (as a model of hydrophilic and lipophilic drug, respectively) loaded to cyclodextrins or polymeric nanoparticles in order to determine differences in their corneal permeation against free drug or commercial eye drops. These studies were carried out in a corneal device designed and developed in our laboratory. In this work the habitual conditions for the permeation studies were modified to reproduce the behaviour when eye drops were administered. For this reason a new tetracompartmental pharmacokinetic model was developed. The complex formation of diclofenac with cyclodextrins and the flurbiprofen loaded to polymeric nanoparticles has been shown as effective procedures to remarkably increase the bioavailability of the anti-inflammatory drugs. The efficiency of polymeric nanoparticles of Poly (D-L lactic-coglycolyc) acid and poly-epsilon-caprolacton as intraocular targeting of NSAIDs has also been proved, being the latter polymer more effective to increase the flurbiprofen corneal permeation. The apparent corneal permeability coefficient of samples has been calculated getting a low permeation values for free drugs.","PeriodicalId":39133,"journal":{"name":"Open Medicinal Chemistry Journal","volume":" ","pages":"66-71"},"PeriodicalIF":0.0,"publicationDate":"2008-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40019608","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