July 2011 – RSC Medicinal Chemistry Blog

Archive for July, 2011

Top ten most accessed articles in May

26 Jul 2011

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

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

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

Synthesis and biological evaluation of tetrazole containing compounds as possible anticancer agents
Chebolu Naga Sesha Sai Pavan Kumar, Dusmant Kumar Parida, Amlipur Santhoshi, Anil Kumar Kota, Balasubramanian Sridhar and Vaidya Jayathirtha Rao
Med. Chem. Commun., 2011, 2, 486-492, DOI: 10.1039/C0MD00263A

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

Computational ligand-based rational design: role of conformational sampling and force fields in model development
Jihyun Shim and Alexander D. MacKerell, Jr.
Med. Chem. Commun., 2011, 2, 356-370, DOI: 10.1039/C1MD00044F

N1-Benzyl substituted cambinol analogues as isozyme selective inhibitors of the sirtuin family of protein deacetylases
Federico Medda, Thomas L. Joseph, Lisa Pirrie, Maureen Higgins, Alexandra M. Z. Slawin, Sonia Lain, Chandra Verma and Nicholas J. Westwood
Med. Chem. Commun., 2011, 2, 611-615, DOI: 10.1039/C1MD00023C

Antimycobacterial activity of spirooxindolo-pyrrolidine, pyrrolizine and pyrrolothiazole hybrids obtained by a three-component regio- and stereoselective 1,3-dipolar cycloaddition
Stephen Michael Rajesh, Subbu Perumal, J. Carlos Menéndez, Perumal Yogeeswari and Dharmarajan Sriram
Med. Chem. Commun., 2011, 2, 626-630, DOI: 10.1039/C0MD00239A

Synthesis and SAR studies of benzimidazole derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: Focus to detune hERG inhibition
Pradip K. Sasmal, Sanjita Sasmal, Chandrasekhar Abbineni, B. Venkatesham, P. Tirumala Rao, M. Roshaiah, Ish Khanna, V. J. Sebastian, J. Suresh, Manvendra P. Singh, Rashmi Talwar, Dhanya Shashikumar, K. Harinder Reddy, Thomas M. Frimurer, Øystein Rist, Lisbeth Elster and Thomas Högberg
Med. Chem. Commun., 2011, 2, 385-389, DOI: 10.1039/C1MD00015B

Glycosylated porphyrin derivatives and their photodynamic activity in cancer cells
Seenuvasan Vedachalam, Bo-Hwa Choi, Kalyan Kumar Pasunooti, Kun Mei Ching, Kijoon Lee, Ho Sup Yoon and Xue-Wei Liu
Med. Chem. Commun., 2011, 2, 371-377, DOI: 10.1039/C0MD00175A

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

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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HOT: Reducing the prescription burden for COPD sufferers

14 Jul 2011

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

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

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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RSC Medicinal Chemistry Blog

Archive for July, 2011

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?

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