October 2011 – RSC Medicinal Chemistry Blog

Archive for October, 2011

Hot Perspective: Reviewing current knowledge on DNA methylation aspects

31 Oct 2011

In this MedChemComm article*, Nadine Martinet and colleagues at the Universities of Nice-Sophia Antipolis and Poitiers (France) provide a timely overview of the current knowledge concerning DNA methyltransferases (DNMT) biology and the two main classes of DNMT inhibtors, also highlighting epigenetic anti-cancer therapeutic strategies.

Read the article for FREE for the next 4 weeks!

Small molecules DNA methyltransferases inhibitors
Nadine Martinet, Benoît Y. Michel, Philippe Bertrand and Rachid Benhida
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00194A, Review

*This article will be part of MedChemComm’s web theme issue on Epigenetics, coming soon.

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New compound class for treating hepatitis C virus

31 Oct 2011

Researchers from Biotica, UK have discovered a new compound class called sangamides with the potential to treat hepatitis C. Sangamides are amide derivatives of sanglifehrin A – a cyclophilin-binding polyketide natural product. Non-immunosuppressive analogues of sanglifehrin A are currently under development as hepatitis C virus therapies, but suffer from lengthy synthetic processes, and some adverse affects including drug-drug interactions.

The newly developed sangamides display improved potency and good pharmcokinetic properties that make them potentially suitable for once-a-day oral treatment of chronic hepatitis C infection. Download the article for the full details:

Sangamides, a new class of cyclophilin-inhibiting host-targeted antivirals for treatment of HCV infection
Steven J. Moss, Michael Bobardt, Pieter Leyssen, Nigel Coates, Udayan Chatterji, Xie Dejian, Teresa Foster, Jinlun Liu, Mohammad Nur-e-Alam, Dipen Suthar, Chen Yongsheng, Tony Warneck, Ming-Qiang Zhang, Johan Neyts, Philippe Gallay, Barrie Wilkinson and Matthew A. Gregory
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C1MD00227A

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Top ten accessed articles in September

26 Oct 2011

This month sees the following articles in MedChemComm that are in the top ten most accessed:

2-Anilinonicotinyl linked 1,3,4-oxadiazole derivatives: Synthesis, antitumour activity and inhibition of tubulin polymerization
Ahmed Kamal, Y. V. V. Srikanth, Thokhir B. Shaik, M. Naseer A. Khan, Md. Ashraf, M. Kashi Reddy, K. Anil Kumar and Shasi V. Kalivendi
Med. Chem. Commun., 2011, 2, 819-823
DOI: 10.1039/C0MD00177E

Towards biocompatible nanovalves based on mesoporous silica nanoparticles
Ying-Wei Yang
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00158B

Minisci reactions: Versatile CH-functionalizations for medicinal chemists
Matthew A. J. Duncton
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00134E

Molecular obesity, potency and other addictions in drug discovery
Michael M. Hann
Med. Chem. Commun., 2011, 2, 349-355
DOI: 10.1039/C1MD00017A

Intramolecular hydrogen bonding to improve membrane permeability and absorption in beyond rule of five chemical space
Alexander Alex, David S. Millan, Manuel Perez, Florian Wakenhut and Gavin A. Whitlock
Med. Chem. Commun., 2011, 2, 669-674
DOI: 10.1039/C1MD00093D

The development of quinolone esters as novel antimalarial agents targeting the Plasmodium falciparum bc 1 protein complex
Robin Cowley, Suet Leung, Nicholas Fisher, Mohammed Al-Helal, Neil G. Berry, Alexandre S. Lawrenson, Raman Sharma, Alison E. Shone, Stephen A. Ward, Giancarlo A. Biagini and Paul M. O′Neill
Med. Chem. Commun., 2012, Advance Article
DOI: 10.1039/C1MD00183C

Designing glucokinase activators with reduced hypoglycemia risk: discovery of N,N-dimethyl-5-(2-methyl-6-((5-methylpyrazin-2-yl)-carbamoyl)benzofuran-4-yloxy)pyrimidine-2-carboxamide as a clinical candidate for the treatment of type 2 diabetes
Jeffrey A. Pfefferkorn, Angel Guzman-Perez, Peter J. Oates, John Litchfield, Gary Aspnes, Arindrajit Basak, John Benbow, Martin A. Berliner, Jianwei Bian, Chulho Choi, Kevin Freeman-Cook, Jeffrey W. Corbett, Mary Didiuk, Joshua R. Dunetz, Kevin J. Filipski, William M. Hungerford, Christopher S. Jones, Kapil Karki, Anthony Ling, Jian-Cheng Li, Leena Patel, Christian Perreault, Hud Risley, James Saenz, Wei Song, Meihua Tu, Robert Aiello, Karen Atkinson, Nicole Barucci, David Beebe, Patricia Bourassa, Francis Bourbounais, Anne M. Brodeur, Rena Burbey, Jing Chen, Theresa D’Aquila, David R. Derksen, Nahor Haddish-Berhane, Cong Huang, James Landro, Amanda Lee Lapworth, Margit MacDougall, David Perregaux, John Pettersen, Alan Robertson, Beijing Tan, Judith L. Treadway, Shenping Liu, Xiayang Qiu, John Knafels, Mark Ammirati, Xi Song, Paul DaSilva-Jardine, Spiros Liras, Laurel Sweet and Timothy P. Rolph
Med. Chem. Commun., 2011, 2, 828-839
DOI: 10.1039/c1md00116g

Discovery of CP-866,087, a mu opioid receptor antagonist for the treatment of alcohol abuse and dependence
Stanton F. McHardy, Steven D. Heck, Sara Guediche, Monica Kalman, Martin P. Allen, Meihua Tu, Dianne K. Bryce, Anne W. Schmidt, Michelle Vanase-Frawley, Ernesto Callegari, Shawn Doran, Nicholas J. Grahame, Stafford McLean and Spiros Liras
Med. Chem. Commun., 2011, 2, 1001-1005
DOI: 10.1039/C1MD00164G

Synthesis and evaluation of novel 5-sulfonyl-indolin-2-ones as potent cytotoxic agents
Yu Luo, Feng Xiao, Shijing Qian, Qiaojun He, Wei Lu and Bo Yang
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00105A

Design, synthesis and antiproliferative activity of urocanic-chalcone hybrid derivatives
Alexander Ciupa, Natalie J. Griffiths, Stephanie K. Light, Pauline J. Wood and Lorenzo Caggiano
Med. Chem. Commun., 2011, 2,1011-1015
DOI: 10.1039/C1MD00155H

Why not take a look at the articles today and blog your thoughts and comments below.

Fancy submitting an article to MedChemComm? Then why not submit to us today or alternatively email us your suggestions.

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Current progress in inhibiting Stat5 protein signalling

14 Oct 2011

This mini-review from Patrick Gunning et al. looks at progress made towards inhibiting Stat5, a member of the Stat family of signalling proteins, that is connected to many cancers, including acute myeloid leukemias and prostate cancer.

Areas covered include both direct and indirect inhibition:

Bcr/Abl inhibitors
FLT3 inhibitors
Jak2 inhibitors
truncation inhibitors
Binding to DNA
Disrupting dimerisation

Inhibitors of Stat5 protein signalling
Abbarna A. Cumaraswamy, Aleksandra Todic, Diana Resetca, Mark D. Minden and Patrick T. Gunning
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00175B

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Poster prize winner at the 16th SCI/RSC Medicinal Chemistry Symposium

12 Oct 2011

I am delighted to report that Dr Martine Keenan from Epichem Pty Ltd (Murdoch, Australia) was the winner of the MedChemComm poster prize at the recent 16th SCI/RSC Medicinal Chemistry Symposium that took place at Churchill College in Cambridge, UK, from 11 to 14 September.

The symposium was jointly organised by the Society of Chemical Industry and the Royal Society of Chemistry, and gave a splendid overview of some of the new strategies in Medicinal Chemistry and Pharmaceutical Research.

Martine’s winning poster entitled ‘Collaborative drug discovery for neglected diseases: novel compounds for the treatment of Chagas Disease’ presents the identification and development of two novel compound series active against the intracellular protozoan parasite Trypanosoma cruzi, the causative agent of the Chagas disease. Endemic in 21 countries across Latin America, the Chagas disease is responsible for more deaths in this region than Malaria, or any other parasite-born disease, and is currently spreading to developed countries including Australia, USA, Japan or Spain. This award winning work is the result of a collaborative drug discovery consortium established by not-for-profit, drug research and development organisation Drugs for Neglected Diseases initiative (DNDi).

Congratulations again to Martine on her award-winning work and to the collaborative drug delivery consortium for their active research on neglected diseases.

Keep up to date with the latest news and research in medicinal chemistry: sign up to the MedChemComm e-alert, check out our blog, and follow us on Twitter.

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Highly selective agonist for the metabotropic glutamate receptor mGluR2

05 Oct 2011

Work from this international collaboration spanning Denmark, Italy, Sweden and the USA brings insights into the synthesis and characterization of a selective agonist for the metabotropic glutamate receptor mGluR2, a potential therapeutic target for neurologic and psychiatric diseases.

The team’s approach to the agonist design was to induce selectivity for mGluR2 over other family members via imposing conformational rigidity into the carbon skeleton of the Glu analogues. This resulted in an increase of selectivity of at least two orders of magnitude compared to homologous mGluR3 as well as mGluR1, 4, 5, 7.

A highly selective agonist for the metabotropic glutamate receptor mGluR2
Simon D. Nielsen, Marica Fulco, Michaela Serpi, Birgitte Nielsen, Maria B. Hansen, Kasper L. Hansen, Christian Thomsen, Robb Brodbeck, Hans Bräuner-Osborne, Roberto Pellicciari, Per-Ola Norrby, Jeremy R. Greenwood and Rasmus P. Clausen

Interested? Why not read this MedChemComm article now! All our content is currently FREE to access .

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Pyridazine-containing drugs and single-step labelling of a matrix metalloprotease inhibitor on the cover of MedChemComm Issue 10

05 Oct 2011

Two hot articles feature on the cover of MedChemComm this month:

The outside front cover features the review from Camille Wermuth, Prestwick Chemical Inc., France, on the applications of pyridazine scaffolds for medicinal chemistry. This article has featured in our Top 10 lists for the last 3 months, so why not take a look at what everyone else has been reading?

Are pyridazines privileged structures?
Camille G. Wermuth
Med. Chem. Commun., 2011, 2, 935-941

The inside front cover is from Chris Overall and David Perrin, demonstrating a technique for easy production of ¹⁸F labelled marimastat, a clinically trialled breast cancer drug, with general applications for PET imaging.

Towards kit-like 18F-labeling of marimastat, a noncovalent inhibitor drug for in vivo PET imaging cancer associated matrix metalloproteases
Ying Li, Richard Ting, Curtis W. Harwig, Ulrich auf dem Keller, Caroline L. Bellac, Philipp F. Lange, James A. H. Inkster, Paul Schaffer, Michael J. Adam, Thomas J. Ruth, Christopher M. Overall and David M. Perrin
Med. Chem. Commun., 2011, 2, 942-949

Read the rest of the issue here

Towards kit-like ¹⁸F-labeling of marimastat, a noncovalent inhibitor drug for in vivo PET imaging cancer associated matrix metalloproteases

Ying Li, Richard Ting, Curtis W. Harwig, Ulrich auf dem Keller, Caroline L. Bellac, Philipp F. Lange, James A. H. Inkster, Paul Schaffer, Michael J. Adam, Thomas J. Ruth, Christopher M. Overall and David M. Perrin

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MedChemComm in the news

05 Oct 2011

Matthew Piggott’s MedChemComm article on modifying MDMA to treat cancer cells has been picked up by an American news website, First Coast News. The article also appeared in our August Top 10 list, so congratulations to the authors!

Read the news story here or go straight to the original research article, Redesigning the designer drug ecstasy: non-psychoactive MDMA analogues exhibiting Burkitt’s lymphoma cytotoxicity

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RSC Medicinal Chemistry Blog

Archive for October, 2011

Hot Perspective: Reviewing current knowledge on DNA methylation aspects

New compound class for treating hepatitis C virus

Top ten accessed articles in September

Current progress in inhibiting Stat5 protein signalling

Poster prize winner at the 16th SCI/RSC Medicinal Chemistry Symposium

Highly selective agonist for the metabotropic glutamate receptor mGluR2

Pyridazine-containing drugs and single-step labelling of a matrix metalloprotease inhibitor on the cover of MedChemComm Issue 10

MedChemComm in the news

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