2017年1月31日火曜日

2017年1月28日土曜日

Rhodanine Antibacterial Agents 2016

See For Examples;

1.
http://pubs.acs.org/action/doSearch?AllField=Rhodanine+Antibacterial&startPage=&sortBy=Earliest

2.
http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01620

3. As Recent Survey;

http://pubs.acs.org/action/doSearch?AllField=Rhodanine+Reductase+Inhibitor&pageSize=20&startPage=0

http://pubs.acs.org/doi/abs/10.1021/jm8002284

http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01620

2017年1月16日月曜日

2017年1月12日木曜日

2017年1月11日水曜日

2017年1月10日火曜日

Drug Repositioning for Tropical Diseases 2016

Article

Repositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for Neglected Tropical Diseases: Structure–Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis

Andrew M. Thompson^*^†, Patrick D. O’Connor^†, Adrian Blaser^†, Vanessa Yardley^‡, Louis Maes^§, Suman Gupta^∥, Delphine Launay^⊥, Denis Martin^⊥, Scott G. Franzblau^#, Baojie Wan^#, Yuehong Wang^#, Zhenkun Ma^¶, and William A. Denny^†

^† Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand

^‡ Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom

^§ Laboratory for Microbiology, Parasitology and Hygiene, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium

^∥ Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow 226031, India

^⊥ Drugs for Neglected Diseases Initiative, 15 Chemin Louis Dunant, 1202 Geneva, Switzerland

^# Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, United States

^¶ Global Alliance for TB Drug Development, 40 Wall Street, New York 10005, United States

J. Med. Chem., 2016, 59 (6), pp 2530–2550

DOI: 10.1021/acs.jmedchem.5b01699

Publication Date (Web): February 22, 2016

*Phone: (+649) 923-6145. Fax: (+649) 373-7502. E-mail: am.thompson@auckland.ac.nz.

Abstract

6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole derivatives

were initially studied for tuberculosis within a backup program for the clinical trial agent pretomanid (PA-824). Phenotypic screening of representative examples against kinetoplastid diseases unexpectedly led to the identification of DNDI-VL-2098 as a potential first-in-class drug candidate for visceral leishmaniasis (VL). Additional work was then conducted to delineate its essential structural features, aiming to improve solubility and safety without compromising activity against VL. While the 4-nitroimidazole portion was specifically required, several modifications to the aryloxy side chain were well-tolerated e.g., exchange of the linking oxygen for nitrogen (or piperazine), biaryl extension, and replacement of phenyl rings by pyridine. Several less lipophilic analogues displayed improved aqueous solubility, particularly at low pH, although stability toward liver microsomes was highly variable. Upon evaluation in a mouse model of acute Leishmania donovani infection, one phenylpyridine derivative (37) stood out, providing efficacy surpassing that of the original preclinical lead.

Supporting Information

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jmedchem.5b01699.

Additional biological assay data, graphs of pharmacokinetic data, experimental procedures and characterizations for compounds, combustion analytical data, representative NMR spectra, and discussion of 2D NMR results (PDF)
Molecular formula strings spreadsheet (CSV)

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Citation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.

Development of a Scalable Process for the Synthesis of DNDI-VL-2098: A Potential Preclinical Drug Candidate for the Treatment of Visceral Leishmaniasis

Vijay S. Satam, Srinivasa Rao Pedada, Pasumpon Kamaraj, Nakita Antao, Apoorva Singh, Rama Mohan Hindupur, and Hari N. Pati , Andrew M. Thompson , Delphine Launay and Denis Martin

Organic Process Research & Development 2016 Article ASAP

Abstract | Full Text HTML | PDF | PDF w/ Links
Antimicrobial Resistance: Is the World UNprepared?

PLOS Medicine 2016, e1002130
Synthesis of optically active trifluoromethyl-substituted 2,3-dihydroimidazo[2,1-b]oxazoles

Grzegorz Mlostoń, Aneta Wróblewska, Heinz Heimgartner

Journal of Fluorine Chemistry 2016 189, 1-6
The anti-tubercular drug delamanid as a potential oral treatment for visceral leishmaniasis

Stephen Patterson, Susan Wyllie, Suzanne Norval, Laste Stojanovski, Frederick RC Simeons, Jennifer L Auer, Maria Osuna-Cabello, Kevin D Read, Alan H Fairlamb

eLife 2016 5,

AntiMicrobial Rhodanines As Enoyl Reductase InhA 2017

ER InhA

Article

In Silico Driven Design and Synthesis of Rhodanine Derivatives as Novel Antibacterials Targeting the Enoyl Reductase InhA

Liudas Slepikas^†^‡○, Gianpaolo Chiriano^†○, Remo Perozzo^†, Sébastien Tardy^†, Agata Kranjc^†, Ophélie Patthey-Vuadens^†, Hajer Ouertatani-Sakouhi^§, Sébastien Kicka^∥, Christopher F. Harrison^⊥, Tiziana Scrignari^#, Karl Perron^#, Hubert Hilbi^⊥^∇, Thierry Soldati^∥, Pierre Cosson^§, Eduardas Tarasevicius^‡, and Leonardo Scapozza^*^†

^† School of Pharmaceutical Sciences, Department of Pharmaceutical Biochemistry, University of Geneva and University of Lausanne, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland

^‡ Faculty of Pharmacy, Lithuanian University of Health Sciences, LT 44307 Kaunas, Lithuania

^§ Department of Cell Physiology and Metabolism, CMU, Rue Michel-Servet 1 CH-1211 Geneva, Switzerland

^∥ Department of Biochemistry, University of Geneva, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland

^⊥ Max von Pettenkofer Institute, Department of Medicine, Ludwig-Maximilians University Munich, 80336 Munich, Germany

^# Microbiology Unit, Department of Botany and Plant Biology, University of Geneva, CH-1211 Geneva, Switzerland

^∇ Institute of Medical Microbiology, Department of Medicine, University of Zürich, Gloriastrasse 30/32, CH-8006 Zürich, Switzerland

J. Med. Chem., 2016, 59 (24), pp 10917–10928

DOI: 10.1021/acs.jmedchem.5b01620

Publication Date (Web): January 5, 2016

*Phone: +41223793363. Fax: +41223793360. E-mail: leonardo.scapozza@unige.ch.

Abstract

Here, we report on the design, synthesis, and biological evaluation of 4-thiazolidinone (rhodanine) derivatives targeting Mycobacterial tuberculosis (Mtb) trans-2-enoyl-acyl carrier protein reductase (InhA). Compounds having bulky aromatic substituents at position 5 and a tryptophan residue at position N-3 of the rhodanine ring were the most active against InhA, with IC₅₀ values ranging from 2.7 to 30 μM. The experimental data showed consistent correlations with computational studies. Their antimicrobial activity was assessed against Mycobacterium marinum (Mm) (a model for Mtb), Pseudomonas aeruginosa (Pa), Legionella pneumophila (Lp), and Enterococcus faecalis (Ef) by using anti-infective, antivirulence, and antibiotic assays. Nineteen out of 34 compounds reduced Mm virulence at 10 μM. 33 exhibited promising antibiotic activity against Mm with a MIC of 0.21 μM and showed up to 89% reduction of Lp growth in an anti-infective assay at 30 μM. 32 showed high antibiotic activity against Ef, with a MIC of 0.57 μM.

Supporting Information

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jmedchem.5b01620.

Experimental details are reported including: IC₅₀ curve of triclosan toward Mtb InhA, the inhibitory activity and IC₅₀ values of derivatives 1–34 toward Mtb InhA, in vitro antibacterial activity values of compounds 1–34, HPLC analyses of the newly synthesized compounds described here (PDF)
Molecular formula strings (CSV)

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Discovery of Mycobacterium tuberculosis InhA Inhibitors by Binding Sites Comparison and Ligands Prediction

Tanja Štular, Samo Lešnik, Kaja Rožman, Julia Schink, Mitja Zdouc, An Ghysels, Feng Liu, Courtney C. Aldrich, V. Joachim Haupt, Sebastian Salentin, Simone Daminelli, Michael Schroeder, Thierry Langer, Stanislav Gobec, Dušanka Janežič, and Janez Konc

Journal of Medicinal Chemistry 2016 59 (24), 11069-11078

Abstract | Full Text HTML | PDF | PDF w/ Links
Quinolidene-rhodanine conjugates: Facile synthesis and biological evaluation

Dnyaneshwar D. Subhedar, Mubarak H. Shaikh, Bapurao B. Shingate, Laxman Nawale, Dhiman Sarkar, Vijay M. Khedkar, Firoz A. Kalam Khan, Jaiprakash N. Sangshetti

European Journal of Medicinal Chemistry 2017 125, 385-399
Target-based approaches for the discovery of new antimycobacterial drugs

Chiara Borsari, Stefania Ferrari, Alberto Venturelli, Maria Paola Costi

Drug Discovery Today 2016 ,

2017年1月31日火曜日

遺伝子の本体が 核酸：

即ち ＤＮＡ＋ＲＮＡであるという

セントラルドグマが 確立されてはや

半世紀が過ぎた。

今の問題はさらに微細にかつ正確に

そのセントラルドグマを 駆動するトリガーは何かを

突きとめることであるが いとも簡単な答えの

選択肢は 日常にある。

エピゲネチック・インヂューサーの候補；

１．光

２．温度＝圧力

３．時間

４．反応場（容積）。。。

つまりは

地球という反応場における

太陽と時間が

生命を支配 しているのである。。。

2017年1月28日土曜日

Wikipedia:

2017年1月16日月曜日

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2017年1月12日木曜日

Please Visit These Sites；

And More For Further Directions:

TOCHIGI=SUI

１． http://www.pharmacrea.com/topics/

２． http://www.pharmacrea.com/product/

３． http://www.pharmacrea.com/

Please See For Basic Information;

KEGG DRUGS：

2017年1月11日水曜日

See For Example;

2017年1月10日火曜日

Article

Repositioning Antitubercular 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazoles for Neglected Tropical Diseases: Structure–Activity Studies on a Preclinical Candidate for Visceral Leishmaniasis

Abstract

6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole derivatives

PDF

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ER InhA

Article

In Silico Driven Design and Synthesis of Rhodanine Derivatives as Novel Antibacterials Targeting the Enoyl Reductase InhA

Abstract

PDF

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遺伝子の本体が　核酸：

即ち　ＤＮＡ＋ＲＮＡであるという

セントラルドグマが　確立されてはや　

そのセントラルドグマを　駆動するトリガーは何かを

突きとめることであるが　いとも簡単な答えの

選択肢は　日常にある。

生命を支配　しているのである。。。

Please　Visit　These　Sites；

１．　http://www.pharmacrea.com/topics/

Please See　For　Basic　Information;

KEGG　DRUGS：