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Perspectives in Medicinal Chemistry

Synopsis: An open access, peer reviewed electronic journal that covers drug design in the form of commentaries and reviews which do not require disclosure of proprietary information.


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About this journal

Aims:

Perspectives in Medicinal Chemistry (PMC) is an exciting peer-reviewed open access on-line journal. It was developed to help medicinal chemists keep apace with the expanding volume of information published in their field. Rather than providing exhaustive reviews of published work, PMC calls upon leading researchers to succinctly summarize observations from numerous original publications as hybrid review-commentaries. These articles are published continually on the website and are often commissioned by the Editor in Chief. While the submission of completed manuscripts is acceptable, we encourage proposals for future articles sent to the Managing Editor. These proposals should provide a rationale and brief outline (<250 words) for the article.

Scope:

Articles published in PMC are succinct and carefully-illustrated works intending to provide a thoughtful overview of a significant research area in medicinal chemistry. Importantly, these articles provide a representative but not exhaustive overview of recent advances in a particular research field. Articles in PMC provide insight on the implications of the new developments and provide an opportunity for authors to discuss their ideas of 'the road ahead' in their research areas. These articles are carefully peer-reviewed to ensure a balanced representation of the literature.

Perspectives in Medicinal Chemistry will publish articles that combine aspects of commentaries and reviews, allowing medicinal chemists to discuss drug design without the necessity of revealing proprietary information. Authors are encouraged to submit review-type manuscripts which go beyond conventional reviews by incorporating a sense of perspective to enhance articles' value to readers and to allow authors to demonstrate and share their perspectives in drug discovery.

Editorial standards and procedures:

Submissions, excluding editorials, letters to the editor and dedications, will be peer reviewed by two reviewers.  Reviewers are required to provide fair, balanced and constructive reports.  

Under our Fairness in Peer Review Policy authors may appeal against reviewers' recommendations which are ill-founded, unobjective or unfair.  Appeals are considered by the Editor in Chief or Associate Editor.

Papers are not sent to peer reviewers following submission of a revised manuscript. Editorial decisions on re-submitted papers are based on the author's response to the initial peer review report.

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This journal is indexed by the following services:

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This journal has been awarded a SPARC Europe Seal. The Seal is an initiative of SPARC Europe (Scholarly Publishing and Academic Resources Coalition) and the Directory of Open Access Journals (DOAJ) which is awarded to journals applying a Creative Commons CC-BY copyright license and that make journal metadata accessible to DOAJ.  

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National Institutes of Health Public Access Policy compliant:

As of April 7 2008, the US NIH Public Access Policy requires that all peer reviewed articles resulting from research carried out with NIH funding be deposited in the Pubmed Central archive.

If you are an NIH employee or grantee Libertas Academica will ensure that you comply with the policy by depositing your paper at Pubmed Central on your behalf. 

ISSN: 1177-3910


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The pKa Distribution of Drugs: Application to Drug Discovery

Authors: David T. Manallack
Publication Date: 17 Sep 2007
Perspectives in Medicinal Chemistry 2007:1 25-38

David T. Manallack

Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, 3052, Australia.

Dedication: Dedicated to the memory of Professor Martyn Ford

Abstract: The acid-base dissociation constant (pKa) of a drug is a key physicochemical parameter influencing many biopharmaceutical characteristics. While this has been well established, the overall proportion of non-ionizable and ionisable compounds for drug-like substances is not well known. Even less well known is the overall distribution of acid and base pKa values. The current study has reviewed the literature with regard to both the proportion of ionizable substances and pKa distributions. Further to this a set of 582 drugs with associated pKa data was thoroughly examined to provide a representative set of observations. This was further enhanced by delineating the compounds into CNS and non-CNS drugs to investigate where differences exist. Interestingly, the distribution of pKa values for single acids differed remarkably between CNS and non-CNS substances with only one CNS compound having an acid pKa below 6.1. The distribution of basic substances in the CNS set also showed a marked cut off with no compounds having a pKa above 10.5.

The pKa distributions of drugs are infl uenced by two main drivers. The fi rst is related to the nature and frequency of occurrence of the functional groups that are commonly observed in pharmaceuticals and the typical range of pKa values they span. The other factor concerns the biological targets these compounds are designed to hit. For example, many CNS targets are based on seven transmembrane G protein-coupled receptors (7TM GPCR) which have a key aspartic acid residue known to interact with most ligands. As a consequence, amines are mostly present in the ligands that target 7TM GPCR’s and this influences the pKa profi le of drugs containing basic groups. For larger screening collections of compounds, synthetic chemistry and the working practices of the chemists themselves can influence the proportion of ionizable compounds and consequent pKa distributions. The findings from this study expand on current wisdom in pKa research and have implications for discovery research with regard to the composition of corporate databases and collections of screening compounds. Rough guidelines have been suggested for the profile of compound collections and will evolve as this research area is expanded.

Categories: Pharmacology


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Posted by
bhushan kalbande
10:15,February 24, 2009

nice work and it gives lot of idea regarding desining of new chemical entity thank you


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