Camille G. Wermuth

Prestwick Chemical, Illkirch, Alsace, France

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Publications (125)430.19 Total impact

  • Camille G. Wermuth · Serge Grisoni · Bruno Villoutreix · J.-P. Rocher
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    ABSTRACT: This chapter describes a panel of strategies used by medicinal chemists to establish the preliminary Structure-Activity Relationship (SAR) of biologically relevant starting points. These approaches depend on the level of information on the target and on the profile of the hit molecule. Seven rules are proposed as guidelines leading to the identification of a proof of concept molecule having a suitable profile for in vivo pharmacological validation and a potential to progress towards a clinical candidate.
    No preview · Article · Jan 2015
  • Y.M. Choi-Sledeski · C.G. Wermuth
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    ABSTRACT: The subsequent section describes the prodrug concept, the problems of the parent drug that prodrugs can overcome, the design aspects, and the difficulties associated with the clinical development of a prodrug. The chapter expands on the recent development of sophisticated prodrug conjugates that target the drug molecule to the site of action by molecular addresses specific to cell/tissue type or by unique microenvironment cleavage conditions to release the drug. Despite the difficulties of progressing a prodrug through clinical development, there are many marketed prodrugs, and the recent macromolecular prodrugs that have been approved suggest that the trend of increasing approvals will continue and that prodrugs will remain an important tool for drug discovery.
    No preview · Article · Jan 2015
  • Camille G. Wermuth
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    ABSTRACT: This chapter concerns the bioactive compounds bearing on their skeleton one or more asymmetric carbon atom(s). Enantiomers may elicit differentiated biological responses and thus provide useful information on drug-receptor interactions and on receptor characteristics. A drug is subjected to a variety of physiological processes: absorption, distribution metabolism, uptake at storage sites, and excretion. Toward a biological target, the potency of two enantiomers can sometimes differ considerably, or sometimes be very similar. The biological response induced by a pair of enantiomers can differ in potency (quantitative difference) or in nature (qualitative difference). It is assumed that one enantiomer acts at one receptor site, whereas its antipode is recognized by other sites and possesses a different activity and toxicity profile. Besides the difference in potency, two enantiomers show differences in their pharmacological profile. Racemates and both enantiomers are usually three different pharmacological entities, and extensive pharmacological, toxicological, and clinical pharmacological research is required before it can be decided whether it is advantageous to use racemates or enantiomers in clinical practice.
    No preview · Chapter · Jan 2015
  • Camille G. Wermuth · Bruno Villoutreix · Serge Grisoni · Anne Olivier · J.-P. Rocher
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    ABSTRACT: This chapter is presenting the various strategies used to find pertinent compounds as starting points for optimization up to a drug. The discovery strategies from the historical ones to the most modern approaches are reviewed. They consist into mainly five approaches: the improvement of already existing drugs, the systematic screening, the exploitation of observed biological activities, the attempts towards rational design and the target protein structure-based approaches. These strategies are not mutually exclusive and can be appropriately applied and combined.
    No preview · Article · Jan 2015
  • Camille G. Wermuth
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    ABSTRACT: One can estimate that about 50% of all the drug molecules used in medicine contain a phenyl ring which can be substituted or not. The bioisosteric replacement of these phenyl rings by the corresponding pyridazine rings opens an access to several thousands of diaza analogues presenting more interaction possibilities, lower Log P values and improved crystalline salts. The use of pyridazine scaffolds in place of phenyl scaffolds entails additional interaction possibilities. Another interest of pyridazines is their capacity to act as original functional surrogates. Thus, aminopyridazines can be used as carboxamide, as well as amine surrogates. Finally, the many examples of pyridazines used either as a structural element or as a main scaffold, justify largely their status as privileged structures
    No preview · Article · Oct 2011 · Medicinal Chemistry Communication
  • Isabelle Parrot · Guillaume Ritter · Camille G. Wermuth · Marcel Hibert

    No preview · Article · Nov 2010 · ChemInform
  • Isabelle Parrot · Yveline Rival · Camille G. Wermuth
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Oct 2010 · ChemInform
  • Sebastien Guery · Yveline Rival · Camille G. Wermuth
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    ABSTRACT: For Abstract see ChemInform Abstract in Full Text.
    No preview · Article · Oct 2010 · ChemInform
  • Camille G. Wermuth
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    ABSTRACT: Analog design is usually defined as the modification of a drug molecule or of any bioactive compound in order to prepare a new molecule showing chemical and biological similarity with the original model compound. Excellent descriptions of the various possibilities of bioisosteric replacement are found in Cannon's chapter “Analog Design” published in the previous edition of this book. As a rule, it is expected that the analog exhibits some improvements over the original drug molecule, but sometimes financial motivations are predominant and justify the decision to prepare an analog in order to share market parts. Analog design is a fruitful procedure, easy to practice, and very popularly employed in pharmaceutical research from the beginning. Particularly, from the second half of the twentieth century, the production of very sophisticated molecules such as steroids, prostaglandins, anticancer drugs, and antibiotics became available and considerable advances could be made in medicinal chemistry. Analog design represents two-third of all small molecule sales. Among the 29 new drugs launched in 2000, 24 were copies.Keywords:analog design;analogs of metabolites;functional analogs;scaffold hopping;structural analogs
    No preview · Chapter · Sep 2010
  • Yveline Rival · Camille G. Wermuth
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Aug 2010 · ChemInform
  • Sebastien Guery · Isabelle Parrot · Yveline Rival · Camille G. Wermuth
    [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Aug 2010 · ChemInform
  • Sebastien Guery · Isabelle Parrot · Yveline Rival · Camille G. Wermuth
    [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Jun 2010 · ChemInform
  • Christophe Morice · Camille G. Wermuth
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    ABSTRACT: Noncyclic molecules can be cyclized, attached to, or included in ring systems. In medicinal chemistry three kinds of approaches are currently used. The first approach, the analogical approach. , consists of ring-chain transformations, ring contractions or expansions, and various other ring transformations. The second strategy, called the disjunctive approach, aims at the progressive simplification of the original active principle (which is often a natural compound). The objective is to extract information about the minimal structure that is required for activity. Finally, the conjunctive approach is based on the creation or addition of supplementary rings. The objective is to constrain an originally flexible compound and to impose precise conformations and configurations. The preparation of such molecules is of prime importance in the exploration of ligand-receptor interaction and for molecular modeling studies. Molecular variations involving the study of homologous series or the application of the vinylogy concept induce relatively minor changes of the pharmacological profile and result in optimizing the potency. Modifying ring systems-ring-chain transformation, ring contractions and expansions, and reorganization of cyclic systems-represents a highly productive approach in the design of new drug analogs and in the exploration of the drug-receptor interactions.
    No preview · Chapter · Dec 2008
  • Susheel Nara · Jean Martinez · Camille‐Georges Wermuth · Isabelle Parrot
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
    No preview · Article · Mar 2007 · ChemInform
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    ABSTRACT: In order to develop a fluorescence polarization (FP) assay for calcium binding proteins, a fluorescent peptides based library of 1328 compounds has been synthesized. The use of this library has been validated by setting up a FP-high-throughput screening (FP-HTS) assay for calmodulin using the synthetic gene product (synCaM). With this assay, a set of 880 FDA approved compounds was screened. Besides the promazine class, we discovered two new classes of compounds that interact with calmodulin in a calcium dependent manner. One class has compounds with anti-histaminic/spasmolytic activities, and the other one are detergents with antibacterial activities.
    Full-text · Article · Dec 2006 · Biochimica et Biophysica Acta
  • Camille G. Wermuth
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    ABSTRACT: Definitions Functional Groups Considered as Pharmacophores: the Privileged Structure ConceptHistorical Perspective Early Considerations About Structure-Activity RelationshipsEarly Considerations About the Concept of ReceptorsEhrlichs “Magic Bullet”Fischers “Lock and Key”Pharmacophores: the Viewpoint of a Medicinal Chemist Two-dimensional Pharmacophores Sulfonamides and PABAEstrogensAn Early Three-dimensional Approach: the Three-point Contact Model Clonidine and Its Interaction with the α-Adrenergic ReceptorCriteria for a Satisfactory Pharmacophore ModelCombination of PharmacophoresConclusion References Functional Groups Considered as Pharmacophores: the Privileged Structure Concept Early Considerations About Structure-Activity RelationshipsEarly Considerations About the Concept of ReceptorsEhrlichs “Magic Bullet”Fischers “Lock and Key” Two-dimensional Pharmacophores Sulfonamides and PABAEstrogensAn Early Three-dimensional Approach: the Three-point Contact Model Clonidine and Its Interaction with the α-Adrenergic ReceptorCriteria for a Satisfactory Pharmacophore ModelCombination of Pharmacophores Sulfonamides and PABAEstrogens Clonidine and Its Interaction with the α-Adrenergic Receptor
    No preview · Chapter · Aug 2006
  • Camille G. Wermuth

    No preview · Chapter · Jun 2006
  • Camille G. Wermuth

    No preview · Chapter · May 2006
  • Camille G Wermuth
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    ABSTRACT: A survey of novel small-molecule therapeutics reveals that the majority of them result from analogue design and that their market value represents two-thirds of all small-molecule sales. In natural science, the term analogue, derived from the Latin and Greek analogia, has always been used to describe structural and functional similarity. Extended to drugs, this definition implies that the analogue of an existing drug molecule shares structural and pharmacological similarities with the original compound. Formally, this definition allows the establishment of three categories of drug analogues: analogues possessing chemical and pharmacological similarities (direct analogues); analogues possessing structural similarities only (structural analogues); and chemically different compounds displaying similar pharmacological properties (functional analogues).
    No preview · Article · May 2006 · Drug Discovery Today
  • Camille G Wermuth
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    ABSTRACT: Selective optimization of side activities of drug molecules (the SOSA approach) is an intelligent and potentially more efficient strategy than HTS for the generation of new biological activities. Only a limited number of highly diverse drug molecules are screened, for which bioavailability and toxicity studies have already been performed and efficacy in humans has been confirmed. Once the screening has generated a hit it will be used as the starting point for a drug discovery program. Using traditional medicinal chemistry as well as parallel synthesis, the initial 'side activity' is transformed into the 'main activity' and, conversely, the initial 'main activity' is significantly reduced or abolished. This strategy has a high probability of yielding safe, bioavailable, original and patentable analogues.
    No preview · Article · Mar 2006 · Drug Discovery Today

Publication Stats

4k Citations
430.19 Total Impact Points

Institutions

  • 2004-2011
    • Prestwick Chemical
      Illkirch, Alsace, France
  • 1982-2010
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1973-1999
    • University of Strasbourg
      • Faculty of pharmaceutical sciences
      Strasburg, Alsace, France
  • 1998
    • National Academy of Sciences of Ukraine
      Kievo, Kyiv City, Ukraine
  • 1991
    • Notre Dame de Namur University
      Indiana, United States