RSC Medicinal Chemistry Blog

Top ten most accessed articles in July

31 Aug 2011

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

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

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

Chemical space as a source for new drugs
Jean-Louis Reymond, Ruud van Deursen, Lorenz C. Blum and Lars Ruddigkeit
Med. Chem. Commun., 2010, 1, 30-38
DOI: 10.1039/c0md00020e

Are pyridazines privileged structures?
Camille G. Wermuth
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00074H

Identification of target family directed bioisosteric replacements
Anne Mai Wassermann and Jürgen Bajorath
Med. Chem. Commun., 2011, 2, 601-606
DOI: 10.1039/C1MD00066G

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, Advance Article
DOI: 10.1039/c1md00116g

Aromatic chloride to nitrile transformation: medicinal and synthetic chemistry
Lyn H. Jones, Nicholas W. Summerhill, Nigel A. Swain and James E. Mills
Med. Chem. Commun., 2010, 1, 309-318
DOI: 10.1039/C0MD00135J

Carbazole‒pyrrolo[2,1-c][1,4]benzodiazepine conjugates: design, synthesis, and biological evaluation
Ahmed Kamal, Rajesh V. C. R. N. C. Shetti, M. Janaki Ramaiah, P. Swapna, K. Srinivasa Reddy, A. Mallareddy, M. P. Narasimha Rao, Mukesh Chourasia, G. Narahari Sastry, Aarti Juvekar, Surekha Zingde, Pranjal Sarma, S. N. C. V. L. Pushpavalli and Manika Pal-Bhadra
Med. Chem. Commun., 2011, 2, 780-788
DOI: 10.1039/c1md00072a

Optimized glucuronidation of dual pharmacology β-2 agonists/M3 antagonists for the treatment of COPD
Laura Hilton, Rachel Osborne, Amy S. Kenyon, Helen Baldock, Mark E. Bunnage, Jane Burrows, Nick Clarke, Michele Coghlan, David Entwistle, David Fairman, Neil Feeder, Kim James, Rhys M. Jones, Nadia Laouar, Graham Lunn, Stuart Marshall, Sandra D. Newman, Sheena Patel, Matthew D. Selby, Fiona Spence, Emilio F. Stuart, Susan Summerhill, Michael A. Trevethick, Karen N. Wright, Michael Yeadon, David A. Price and Lyn H. Jones
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/c1md00140j

Matrix-based multiparameter optimisation of glucokinase activators: the discovery of AZD1092
Michael J. Waring, Craig Johnstone, Darren McKerrecher, Kurt G. Pike and Graeme Robb
Med. Chem. Commun., 2011, 2, 775-779
DOI: 10.1039/c1md00092f

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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MedChemmComm article on PAM in the press

27 Aug 2011

By Francesca Burgoyne.

MedChemComm has been making the headlines again!

The recently published article by Chris Easton and colleagues at the Australian National University entitled “Potent and selective inhibitors of human peptidylglycine α-amidating monooxygenase” was picked-up by several news outlets, including Medical News Today:

Love Hormone Oxytocin Inspires New Small-cell Lung Cancer Treatment Research
One in Every 28 Australians Are Diagnosed With Lung Cancer, Says Study
Lung cancer breakthrough yields new love hormone insights
Sex gives clues to new lung cancer treatment
Enzyme PAM Linked to Small Cell Lung Cancer: Study

Congratulations to Professor Easton and team!

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Designing CETP inhibitors for prevention of coronary heart disease

16 Aug 2011

By Francesca Burgoyne.

Coronary heart disease has been shown to be related to low levels of high-density lipoprotein cholesterol (HDL-C) in blood plasma, and consequently methods of controlling HDL-C levels are sought to reduce the risk of heart disease. Inhibition of the cholesteryl ester transfer protein (CETP) – the protein that transports cholesteryl esters from high-density lipoprotein (HDL) to low- and very low-density lipoproteins (LDLs and VLDLs) – has shown potential as a therapy.

Tarun Jha and a team from Jadavpur University have performed studies on a series of 2-arylbenzoxazoles to define the structural requirements of a good CETP inhibitor. The 2D QSAR study using using PCR, PLS and MLR techniques and kNN-MFA 3D QSAR results have generated a pharmacophore that they hope will provide a good scaffold for the design of future potent CETP inhibitors.

Download the paper today to read the details of their findings – it’s free to access until the end of 2011:

Chemometric modeling and pharmacophore mapping in coronary heart disease: 2-arylbenzoxazoles as cholesteryl ester transfer protein inhibitors
Dhritiman Jana, Amit Kumar Halder, Nilanjan Adhikari, Milan Kumar Maiti, Chanchal Mondal and Tarun Jha
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00135C

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Progress on lamellarins

01 Aug 2011

By Francesca Burgoyne.

This review article from Mercedes Álvarez and colleagues at The Center for Biomedical Research Network in Bioengineering, Biomaterials and Nanomedicine, Barcelona, have reviewed the recent developments in studies on lamellarins and their analogues.

Lamellarins are a family of marine pyrrole alkaloids, which have attracted interest as anti-tumour agents. The review encompasses synthetic strategies for total synthesis, structure–activity relationships and studies on mechanisms of biological action, mainly in the context of anti-tumor activity.

Download the full article here:

Progress on lamellarins
Daniel Pla, Fernando Albericio and Mercedes Álvarez
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00003A

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HOT: Reducing the prescription burden for COPD sufferers

14 Jul 2011

By .

Chronic obstructive pulmonary disease (COPD) is caused by emphysema and chronic bronchitis that damages the airways of the lungs leading to significantly reduced air flow and is predicted to be the third largest cause of death by 2030. Symptomatic relief is given by prescribing up to three different drugs for concurrent use, but the complexity of combining three different drugs that operate via three distinct mechanisms into a single device for inhalation dosing, such that patient compliance is high, is considerable.

Lyn Jones et al. from Pfizer have sought to facilitate the triple therapy concept by pursuing a strategy to incorporate muscarinic antagonism and β₂ agonism into a single molecule, such that combination with an inhaled corticosteroid could be achieved in a single dry powder inhaler device.

Compound 15 combined high metabolic clearance, low synthetic complexity, low oral bioavailability, desirable material properties and an impressive therapeutic index over haemodynamic effects, and these characteristics led to its nomination as a clinical candidate (PF-4348235).

This molecule has great potential to ease the medicines burden for COPD sufferers, so read about it now in MedChemComm.

This HOT article is free to access.

Optimized glucuronidation of dual pharmacology β-2 agonists/M3 antagonists for the treatment of COPD
Laura Hilton, Rachel Osborne, Amy S. Kenyon, Helen Baldock, Mark E. Bunnage, Jane Burrows, Nick Clarke, Michele Coghlan, David Entwistle, David Fairman, Neil Feeder, Kim James, Rhys M. Jones, Nadia Laouar, Graham Lunn, Stuart Marshall, Sandra D. Newman, Sheena Patel, Matthew D. Selby, Fiona Spence, Emilio F. Stuart, Susan Summerhill, Michael A. Trevethick, Karen N. Wright, Michael Yeadon, David A. Price and Lyn H. Jones
Med. Chem. Commun., 2011, Advance Article

DOI: 10.1039/C1MD00140J

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HOT: self-cleaving chemical nucleases with unprecedented in vitro cytotoxicity

05 Jul 2011

By Francesca Burgoyne.

A challenge for the development of redox active metal-based chemotherapeutics is producing chemical nucleases capable of self-cleaving, so that they do not require a reducing agent to initiate DNA cleavage (which obviously limits their viability in vivo). In this HOT paper water soluble Cu²⁺ and Mn²⁺ bis-phenanthroline octanedioate complexes have been developed which are capable of doing just that – with very promising results.

The self-cleaving chemical nucleases have been developed by Andrew Kellett and Michael Devereux from Dublin Institute of Technology and colleagues from the National University of Ireland, DuPont and Penn State University. The complexes show nano and picomolar in vitro cytotoxicity towards cancer cells and better drug tolerance in vivo than cisplatin.

To find out more, download the paper. This article is currently free to access and is on the cover of Issue 7.

Water-soluble bis(1,10-phenanthroline) octanedioate Cu2+ and Mn2+ complexes with unprecedented nano and picomolar in vitro cytotoxicity: promising leads for chemotherapeutic drug development
Andrew Kellett, Mark O’Connor, Malachy McCann, Orla Howe, Alan Casey, Pauraic McCarron, Kevin Kavanagh, Mary McNamara, Sean Kennedy, Donald D. May, Philip S. Skell, Denis O’Shea and Michael Devereux
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C0MD00266F

For the authors’ previous work why not also see:

Bis-phenanthroline copper(II) phthalate complexes are potent in vitro antitumour agents with ‘self-activating’ metallo-nuclease and DNA binding properties
Andrew Kellett, Mark O’Connor, Malachy McCann, Mary McNamara, Patrick Lynch, Georgina Rosair, Vickie McKee, Bernie Creaven, Maureen Walsh, Siobhan McClean, Agnieszka Foltyn, Denis O’Shea, Orla Howe and Michael Devereux
Dalton Trans., 2011, 40, 1024-1027
DOI: 10.1039/C0DT01607A

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Are pyridazines privileged structures?

04 Jul 2011

By Francesca Burgoyne.

Camille Wermuth, Prestwick Chemical Inc., France, presents an interesting account of the use, and potential, of pyridazine scaffolds in medicinal chemistry in this hot review. He suggests that the pyridazine scaffold is a privileged structure, i.e. it is capable of providing useful ligands for more than one receptor, and has several advantages over the commonly used phenyl ring.

This article is part of the collection: 21st International Symposium on Medicinal Chemistry (EFMC-ISMC 2010) and is free to access:

Are pyridazines privileged structures?
Camille G. Wermuth
Med. Chem. Commun., 2011, Advance Article
DOI: 10.1039/C1MD00074H

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Call for papers – MedChemComm Natural Products themed issue

23 Jun 2011

By Richard Kelly.

We are delighted to announce a special themed issue of MedChemComm on Natural Products, due for publication in summer 2012

This themed issue, guest edited by Professor Christopher T. Walsh and Dr Sylvie Garneau-Tsodikova will collect together in one place some of the latest exciting research natural products chemistry, including, but not limited to: biosynthesis, novel natural products as drug or drug leads, novel technologies for natural products discovery, novel chemical transformations in natural product biosynthesis, as well as chemical and chemoenzymatic synthesis of natural products. Authors will benefit from increased exposure of their research alongside similar high level and cutting edge work.

Deadline for Submission: January 31, 2012. Although publication of the issue is scheduled for summer 2012, web publication of the Advance Article versions of each manuscript will proceed as soon as the article is ready, ensuring that research is disseminated without delay.

Manuscripts can be submitted using the online web submissions service at http://mc.manuscriptcentral.com/mcc. Please indicate on submission in the comments to editor section that your manuscript is invited and intended for the Natural Products themed issue.

For more information please contact the Editorial Office.

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RSC Medicinal Chemistry Blog

Top ten most accessed articles in July

MedChemmComm article on PAM in the press

Top ten most accessed articles in June

Designing CETP inhibitors for prevention of coronary heart disease

Progress on lamellarins

Top ten most accessed articles in May

HOT: Reducing the prescription burden for COPD sufferers

HOT: self-cleaving chemical nucleases with unprecedented in vitro cytotoxicity

Are pyridazines privileged structures?

Call for papers – MedChemComm Natural Products themed issue

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