Pure &App/. Chem., Vol. 70, No. 5, pp. 1129-1143,1998.
`Printed in Great Britain.
`Q 1998 IUPAC
`
`INTERNATIONAL UNION OF PURE
`AND APPLIED CHEMISTRY
`
`CHEMISTRY AND HUMAN HEALTH DIVISION
`MEDICINAL CHEMISTRY SECTION
`
`GLOSSARY OF TERMS USED IN
`MEDICINAL CHEMISTRY
`(IUPAC Recommendations 1998)
`
`Prepared for publication by
`C. G. WERMUTH' (CHAIRMAN),
`C. R. GANELLIN2, P. LINDBERG3 AND L. A. MITSCHER4
`'Facultt de Pharmacie, Universitt Louis Pasteur, Strasbourg, France
`2University College London, London, UK
`3Astra Hassle AB, Molndal, Sweden
`4School of Pharmacy, University of Kansas, Lawrence, Kansas, USA
`
`Membership of the Section during the period (1992-1995) when this report was prepared was as
`follows:
`President: J. G. Topliss (USA); Vice-President: N. Koga (Japan); Past-President: C. G. Wermuth
`(France); Secretary: W. D. Busse (Germany); Titular members: C. R. Ganellin (U.K.); L. A. Mitscher
`(USA); Co-opted members: P. Anderson (USA); P. R. Andrews (Australia); W. A. Denny (New
`Zealand); W. Granick (Russia); Y. Guindon (Canada); C. A. G. Haasnoot (The Netherlands); J. Ide
`(Japan); R. Imhof (Switzerland); P. Lindberg (Sweden); G. Tarzia (Italy); R. S . Xu (China); National
`Representatives: A. 0. M. Stoppani (Argentina); E. J. Barreiro (Brazil); A. Again (Bulgaria);
`J. Krepelka (Czechoslovakia); E. K. Pohjala (Finland); A. Monge Vega (Spain).
`
`Republication or reproduction of this report or its storage and/or dissemination by electronic means is permitted
`without the need for formal IUPACpermission on condition that an acknowledgement, with full reference to the
`source along with use of the copyright symbol 0, the name IUPAC and the year of publication are prominently
`visible. Publication of a translation into another language is subject to the additional condition of prior approval
`from the relevant IUPAC National Adhering Organization.
`
`AstraZeneca Exhibit 2089
`Mylan v. AstraZeneca
`IPR2015-01340
`
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`
`Glossary of terms used in medicinal chemistry
`(IUPAC Recommendations 1998)
`
`Abstract: The objective of the glossary is to provide in a single document a consistent terminology
`and concise definitions of terms covering the various aspects of medicinal chemistry. This was felt
`necessary with regard to the rapid changes occuring in medicinal chemistry and also by the need
`to establish international definition standards. Effectively the possibility exists that in different
`countries certain terms may not have the same meaning, in such a case the creation of an
`internationally accepted definition is particularly justified.
`A Working Party belonging to the IUPAC Section on Medicinal Chemistry has therefore been
`assembled which prepared the present glossary. Concise but sufficiently explanatory definitions
`have been formulated for about one hundred commonly employed terms which can be considered
`of particular interest to the medicinal chemistry community. The glossary has been compiled in
`part from definitions proposed by the Working Party in part from earlier IUPAC glossaries and in
`part from well-accepted definitions taken from the literature but which were sometimes published
`in journals or books that may not be readily accessible.
`
`ALPHABETICAL ORDERED ENTRIES
`The glossary has been compiled in part from definitions proposed by the Working Party and in part from
`well-accepted definitions taken from the literature. In most cases, definitions given here are for specific
`areas of medicinal chemistry. Some definitions taken from the Glossary for Chemists of Terms Used in
`Biotechnology (Pure Appl. Chem., 1992, 64, 143-168) were also included, eventually in a slightly
`modified form; they are identified by an asterisk*. Others, which appear in the Glossary on Computational
`Drug Design (Pure Appl. Chem., 1997, 69, 1137-1 152) and in Glossary for Chemists of terms used in
`Toxicology (Pure Appl. Chem. 1993,65,2003-2122), are identified by a double** and a triple*** asterisk
`respectively.
`
`Active transport*
`Active transport is the carriage of a solute across a biological membrane from low to high concentration
`that requires the expenditure of (metabolic) energy.
`
`Address-message concept
`Address-message concept refers to compounds in which part of the molecule is required for binding
`(address) and part for the biological action (message).
`
`ADME
`Abbreviation for Absorption, Distribution, Metabolism, Excretion. (See also Pharmacokinetics; Drug
`disposition).
`
`Affinity
`Affinity is the tendency of a molecule to associate with another. The affinity of a drug is its ability to bind
`to its biological target (receptor, enzyme, transport system, etc.) For pharmacological receptors it can be
`thought of as the frequency with which the drug, when brought into the proximity of a receptor by
`diffusion, will reside at a position of minimum free energy within the force field of that receptor.
`
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`For an agonist (or for an antagonist) the numerical representation of affinity is the reciprocal of the equilibrium
`dissociation constant of the ligand-receptor complex denoted KA, calculated as the rate constant for offset (k.1) divided by the
`rate constant for onset (kl).
`
`Agonist * * *
`An agonist is an endogenous substance or a drug that can interact with a receptor and initiate a
`physiological or a pharmacological response characteristic of that receptor (contraction, relaxation,
`secretion, enzyme activation, etc.).
`
`Allosteric binding sites
`Allosteric binding sites are contained in many enzymes and receptors. As a consequence of the binding
`to allosteric binding sites, the interaction with the normal ligand may be either enhanced or reduced.
`
`Allosteric enzyme*
`An allosteric enzyme is an enzyme that contains a region to which small, regulatory molecules
`("effectors") may bind in addition to and separate from the substrate binding site and thereby affect the
`catalytic activity.
`On binding the effector, the catalytic activity of the enzyme towards the substrate may be enhanced, in which case the
`effector is an activator, or reduced, in which case it is a de-activator or inhibitor.
`
`Allosteric regulation
`Allosteric regulation is the regulation of the activity of allosteric enzymes. (See also Allosteric binding
`sites; Allosteric enzymes).
`
`Analog
`An analog is a drug whose structure is related to that of another drug but whose chemical and biological
`properties may be quite different. (See also Congener).
`
`Antagonist* * *
`An antagonist is a drug or a compound that opposes the physiological effects of another. At the receptor
`level, it is a chemical entity that opposes the receptor-associated responses normally induced by another
`bioactive agent.
`
`Antimetabolite" * *
`An antimetabolite is a structural analog of an intermediate (substrate or coenzyme) in a physiologically
`occurring metabolic pathway that acts by replacing the natural substrate thus blocking or diverting the
`biosynthesis of physiologically important substances.
`
`Antisense molecule
`An antisense molecule is an oligonucleotide or analog thereof that is complementary to a segment of
`RNA (ribonucleic acid) or DNA (deoxyribonucleic acid) and that binds to it and inhibits its normal
`function.
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`Autacoid
`An autacoid is a biological substance secreted by various cells whose physiological activity is restricted to
`the vicinity of its release; it is often referred to as local hormone.
`
`Autoreceptor
`An autoreceptor, present at a nerve ending, is a receptor that regulates, via positive or negative feedback
`processes, the synthesis and/or release of its own physiological ligand. (See also Heteroreceptor).
`
`Bioassay* * *
`A bioassay is a procedure for determining the concentration, purity, and/or biological activity of a
`substance (e.g., vitamin, hormone, plant growth factor, antibiotic, enzyme) by measuring its effect on an
`organism, tissue, cell, enzyme or receptor preparation compared to a standard preparation.
`
`Bioisostere
`A bioisostere is a compound resulting from the exchange of an atom or of a group of atoms with another,
`broadly similar, atom or group of atoms. The objective of a bioisosteric replacement is to create a new
`compound with similar biological properties to the parent compound. The bioisosteric replacement may be
`physicochemically or topologically based. (See also Isostere)
`
`Bioprecursor prodrug
`A bioprecursor prodrug is a prodrug that does not imply the linkage to a carrier group, but results from
`a molecular modification of the active principle itself. This modification generates a new compound, able
`to be transformed metabolically or chemically, the resulting compound being the active principle.
`
`Biotransformation
`Biotransformation is the chemical conversion of substances by living organisms or enzyme preparations.
`
`CADD
`See Computer-assisted drug design
`
`Carrier-linked prodrug (Carrier prodrug)
`A carrier-linked prodrug is a prodrug that contains a temporary linkage of a given active substance with
`a transient carrier group that produces improved physicochemical or pharmacokinetic properties and that
`can be easily removed in vivo, usually by a hydrolytic cleavage.
`
`Cascade prodrug
`A cascade prodrug is a prodrug for which the cleavage of the carrier group becomes effective only after
`unmasking an activating group.
`
`Catabolism* * *
`Catabolism consists of reactions involving endogenous organic substrates to provide chemically available
`energy (e.g., ATP) and/or to generate metabolic intermediates used in subsequent anabolic reactions.
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`Catabolite
`A catabolite is a naturally occurring metabolite.
`
`Clone*
`A clone is a population of genetically identical cells produced from a common ancestor. Sometimes,
`"clone" is also used for a number of recombinant DNA (deoxyribonucleic acid) molecules all canying the
`same inserted sequence.
`
`Codon*
`A codon is the sequence of three consecutive nucleotides that occurs in mRNA which directs the
`incorporation of a specific amino acid into a protein or represents the starting or termination signals of
`protein synthesis.
`
`Coenzyme
`A coenzyme is a dissociable, low-molecular weight, non-proteinaceous organic compound (often
`nucleotide) participating in enzymatic reactions as acceptor or donor of chemical groups or electrons.
`
`Combinatorial synthesis
`Combinatorial synthesis is a process to prepare large sets of organic compounds by combining sets of
`building blocks.
`
`Combinatorial library
`A combinatorial library is a set of compounds prepared by combinatorial synthesis.
`
`CoMFA
`See Comparative Molecular Field Analysis
`
`Comparative Molecular Field Analysis (CoMFA)* *
`Comparative molecular field analysis (CoMFA) is a 3D-QSAR method that uses statistical correlation
`techniques for the analysis of the quantitative relationship between the biological activity of a set of
`compounds with a specified alignment, and their three-dimensional electronic and steric properties. Other
`properties such as hydrophobicity and hydrogen bonding can also be incorporated into the analysis. (See
`also Three-dimensional Quantitative Structure-Activity Relationship [3D-QSAR]).
`
`Computational chemistry* *
`Computational chemistry is a discipline using mathematical methods for the calculation of molecular
`properties or for the simulation of molecular behaviour.
`
`Computer-assisted drug design (CADD)* *
`Computer-assisted drug design involves all computer-assisted techniques used to discover, design and
`optimize biologically active compounds with a putative use as drugs.
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`Congener* * *
`A congener is a substance literally con- (with) generated or synthesized by essentially the same synthetic
`chemical reactions and the same procedures. Analogs are substances that are analogous in some respect to
`the prototype agent in chemical structure.
`Clearly congeners may be analogs or vice versa but not necessarily. The term congener, while most often a synonym for
`homologue, has become somewhat more diffuse in meaning so that the terms congener and analog are frequently used
`interchangeably in the literature.
`
`Cooperativity
`Cooperativity is the interaction process by which binding of a ligand to one site on a macromolecule
`(enzyme, receptor, etc.) influences binding at a second site, e.g. between the substrate binding sites of an
`allosteric enzyme. Cooperative enzymes typically display a sigmoid (S-shaped) plot of the reaction rate
`against substrate concentration. (See also Allosteric binding sites).
`
`3D-QSAR
`See Three-dimensional Quantitative Structure-Activity Relationship
`
`De novo design" *
`De novo design is the design of bioactive compounds by incremental construction of a ligand model within
`a model of the receptor or enzyme active site, the structure of which is known from X-ray or nuclear
`magnetic resonance (NMR) data.
`
`Disposition
`See Drug disposition
`
`Distomer
`A distomer is the enantiomer of a chiral compound that is the less potent for a particular action. This
`definition does not excude the possibility of other effect or side effect of the distomer (See also Eutomer).
`
`Docking studies
`Docking studies are molecular modeling studies aiming at finding a proper fit between a ligand and its
`binding site.
`
`Double-blind study
`A double-blind study is a clinical study of potential and marketed drugs, where neither the investigators
`nor the subjects know which subjects will be treated with the active principle and which ones will receive a
`placebo.
`
`Double prodrug (or pro-prodrug)
`A double prodrug is a biologically inactive molecule which is transformed in vivo in two steps
`(enzymatically and/or chemically) to the active species.
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`Drug
`A drug is any substance presented for treating, curing or preventing disease in human beings or in animals.
`A drug may also be used for making a medical diagnosis or for restoring, correcting, or modifying
`physiological functions (e.g., the contraceptive pill).
`
`Drug disposition
`Drug disposition refers to all processes involved in the absorption, distribution metabolism and excretion
`of drugs in a living organism.
`
`Drug latentiation
`Drug latentiation is the chemical modification of a biologically active compound to form a new
`compound, which in vivo will liberate the parent compound. Drug latentiation is synonymous with
`prodrug design.
`
`Drug targeting
`Drug targeting is a strategy aiming at the delivery of a compound to a particular tissue of the body.
`
`Dual action drug
`A dual action drug is a compound which combines two desired different pharmacological actions at a
`similarly efficacious dose.
`
`Efficacy
`Efficacy describes the relative intensity with which agonists vary in the response they produce even when
`they occupy the same number of receptors and with the same affinity. Efficacy is not synonymous to
`Intrinsic activity.
`Efficacy is the property that enables drugs to produce responses. It is convenient to differentiate the properties of drugs into
`two groups, those which cause them to associate with the receptors (affinity) and those that produce stimulus (efficacy). This
`term is often used to characterize the level of maximal responses induced by agonists. In fact, not all agonists of a receptor are
`capable of inducing identical levels of maximal responses. Maximal response depends on the efficiency of receptor coupling,
`i.e., from the cascade of events, which, from the binding of the drug to the receptor, leads to the observed biological effect.
`
`Elimination
`Elimination is the process achieving the reduction of of the concentration of a xenobiotic including its
`metabolism.
`
`Enzyme"
`An enzyme is a macromolecule, usually a protein, that functions as a (bio) catalyst by increasing the
`reaction rate.
`In general, an enzyme catalyzes only one reaction type (reaction selectivity) and operates on only one type of substrate
`(substrate selectivity). Substrate molecules are transformed at the same site (regioselectivity) and only one or preferentially one
`of chiral a substrate or of a racemate is transformed (enantioselectivity[special form of stereoselectivity]).
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`Enzyme induction*
`Enzyme induction is the process whereby an (inducible) enzyme is synthesized in response to a specific
`inducer molecule. The inducer molecule (often a substrate that needs the catalytic activity of the inducible
`enzyme for its metabolism) combines with a repressor and thereby prevents the blocking of an operator by
`the repressor leading to the translation of the gene for the enzyme.
`
`Enzyme repression*
`Enzyme repression is the mode by which the synthesis of an enzyme is prevented by repressor molecules.
`In many cases, the end product of a synthesis chain (e.g., an amino acid) acts as a feed-back corepressor by combining with
`an intracellular aporepressor protein, so that this complex is able to block the function of an operator. As a result, the whole
`operation is prevented from being transcribed into mRNA, and the expression of all enzymes necessary for the synthesis of the
`end product enzyme is abolished.
`
`Eudismic ratio
`Eudismic ratio is the potency of the eutomer relative to that of the distomer.
`
`Eutomer
`The Eutomer is the enantiomer of a chiral compound that is the more potent for a particular action (See
`also Distomer).
`
`Genome*
`A genome is the complete set of chromosomal and extrachromosomal genes of an organism, a cell, an
`organelle or a virus; the complete DNA (deoxyribonucleic acid) component of an organism.
`
`Hansch analysis* *
`Hansch analysis is the investigation of the quantitative relationship between the biological activity of a
`series of compounds and their physicochemical substituent or global parameters representing hydrophobic,
`electronic, steric and other effects using multiple regression correlation methodology.
`
`Hapten" * *
`A hapten is a low molecular weight molecule that contains an antigenic determinant but which is not itself
`antigenic unless combined with an antigenic carrier.
`
`Hard drug
`A hard drug is a nonmetabolizable compound, characterized either by high lipid solubility and
`accumulation in adipose tissues and organelles, or by high water solubility.
`In the lay press the term "Hard Drug" refers to a powerful drug of abuse such as cocaine or heroin.
`
`Heteroreceptor
`A heteroreceptor is a receptor regulating the synthesis and/or the release of mediators other than its own
`ligand (See also Autoreceptor).
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`Homo I o g u e
`The term homologue is used to describe a compound belonging to a series of compounds differing from
`each other by a repeating unit, such as a methylene group, a peptide residue, etc.
`
`Hormone* * *
`A hormone is a substance produced by endocrine glands, released in very low concentration into the
`bloodstream, and which exerts regulatory effects on specific organs or tissues distant from the site of
`secretion.
`
`Hydrophilicity" *
`Hydrophilicity is the tendency of a molecule to be solvated by water.
`
`Hydrophobicity* *
`Hydrophobicity is the association of non-polar groups or molecules in an aqueous environment which
`arises from the tendency of water to exclude non polar molecules. (See also Lipophilicity).
`
`IND
`Abbreviation for Investigational New Drug.
`
`Intrinsic activity
`Intrinsic activity is the maximal stimulatory response induced by a compound in relation to that of a given
`reference compound (See also Partial agonist)
`This term has evolved with common usage. It was introduced by Ariens as a proportionality factor between tissue response
`and receptor occupancy. The numerical value of intrinsic activity'(a1pha) could range from unity (for full agonists, i.e.,
`agonist inducing the tissue maximal response) to zero (for antagonists), the fractional values within this range denoting partial
`agonists. Aritms' original definition equates the molecular nature of alpha to maximal response only when response is a linear
`function of receptor occupancy. This function has been verified. Thus, intrinsic activity, which is a drug and tissue parameter,
`cannot be used as a characteristic drug parameter for classification of drugs or drug receptors. For this purpose, a
`proportionality factor derived by null methods, namely, relative efficacy, should be used. Finally, "intrinsic activity" should
`not be used instead of "intrinsic efficacy". A "partial agonist" should be termed "agonist with intermediate intrinsic efficacy"
`in a given tissue.
`
`Inverse agonist
`An inverse agonist is a drug which acts at the same receptor as that of an agonist, yet produces an
`opposite effect. Also called negative antagonists.
`
`lsosteres
`Isosteres are molecules or ions of similar size containing the same number of atoms and valence electrons,
`e.g., 0 2 - , F-, Ne (See also Bioisostere).
`
`Latentiated drug
`See Drug Latentiation.
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`Lead discovery
`Lead discovery is the process of identifying active new chemical entities, which by subsequent
`modification may be transformed into a clinically useful drug.
`
`Lead generation
`Lead generation is the term applied to strategies developed to identify compounds which possess a
`desired but non-optimized biological activity.
`
`Lead optimization
`Lead optimization is the synthetic modification of a biologically active compound, to fulfill all
`stereoelectronic, physicochemical, pharmacokinetic and toxicologic requirements for clinical usefulness.
`
`Lipophilicity* *
`Lipophilicity represents the affinity of a molecule or a moiety for a lipophilic environment. It is
`commonly measured by its distribution behaviour in a biphasic system, either liquid-liquid (e.g., partition
`coefficient in octan- 1 -ol/water) or solidliquid (retention on reversed-phase high performance liquid
`chromatography (RP-HPLC) or thin-layer chromatography (TLC) system). (See also Hydrophobicity).
`
`Medicinal chemistry
`Medicinal chemistry is a chemistry-based discipline, also involving aspects of biological, medical and
`pharmaceutical sciences. It is concerned with the invention, discovery, design, identification and
`preparation of biologically active compounds, the study of their metabolism, the interpretation of their
`mode of action at the molecular level and the construction of structure-activity relationships.
`
`Metabolism*
`The term metabolism comprises the entire physical and chemical processes involved in the maintenance
`and reproduction of life in which nutrients are broken down to generate energy and to give simpler
`molecules (catabolism) which by themselves may be used to form more complex molecules (anabolism).
`In case of heterotrophic organisms, the energy evolving from catabolic processes is made available for
`use by the organism.
`In medicinal chemistry the term metabolism refers to the biotransformation of xenobiotics and
`particularly drugs, (See also Biotransformation; Xenobiotic).
`
`Metabolite
`A metabolite is any intermediate or product resulting from metabolism.
`
`Me-too drug
`A me-too drug is a compound that is structurally very similar to already known drugs, with only minor
`pharmacological differences.
`
`Molecular graphics* *
`Molecular graphics is the visualization and manipulation of three-dimensional representations of
`molecules on a graphical display device.
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`Molecular modeling* *
`Molecular modeling is a technique for the investigation of molecular structures and properties using
`computational chemistry and graphical visualization techniques in order to provide a plausible three-
`dimensional representation under a given set of circumstances.
`
`Mutagen* * *
`A mutagen is an agent that causes a permanent heritable change (i.e., a mutation) into the DNA
`(deoxyribonucleic acid) of an organism.
`
`Mutual prodrug
`A mutual prodrug is the association in a unique molecule of two, usually synergistic, drugs attached to
`each other, one drug being the carrier for the other and vice versa.
`
`NCE
`See New Chemical Entity.
`
`NDA
`Abbreviation for New Drug Application.
`
`New Chemical Entity.
`A new chemical entity (NCE) is a compound not previously described in the literature.
`
`Non-classical isostere
`Same meaning as Bioisostere.
`
`Nucleic acid*
`A nucleic acid is a macromolecule composed of linear sequences of nucleotides that perform several
`functions in living cells, e.g., the storage of genetic information and its transfer from one generation to the
`next DNA (deoxyribonucleic acid), the expression of this information in protein synthesis (mRNA, tRNA)
`and may act as functional components of subcellular units such as ribosomes (rRNA).
`RNA (ribonucleic acid) contains D-ribose, DNA contains 2-deoxy-~-ribose as the sugar component.
`
`Nucleoside"
`A nucleoside is a compound in which a purine or pyrimidine base is bound via a N-atom to C-1 replacing
`the hydroxy group of either 2-deoxy-~-ribose or of D-ribose, but without any phosphate groups. (See also
`nucleotide).
`The common nucleosides in biological systems are adenosine, guanosine, cytidine, and uridine (which contain ribose) and
`deoxyadenosine, deoxyguanosine, deoxycytidine and thymidine (which contain deoxyribose).
`
`Nucleotide
`A nucleotide is a nucleoside in which the primary hydroxy group of either 2-deoxy-~-ribose or of D-
`ribose is esterified by orthophosphoric acid. (See also nucleoside).
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`Oligonucleotide
`An oligonucleotide is an oligomer resulting from a linear sequences of nucleotides.
`
`Oncogene* * *
`An oncogene is a normal cellular gene which, when inappropriately expressed or mutated, can transform
`eukaryotic cells into tumour cells.
`
`Orphan drug
`An orphan drug is a drug for the treatment of a rare disease for which reasonable recovery of the
`sponsoring firm's research and development expenditure is not expected within a reasonable time. The term
`is also used to describe substances intended for such uses.
`
`Partial agonist
`A partial agonist is an agonist which is unable to induce maximal activation of a receptor population,
`regardless of the amount of drug applied (See also Intrinsic activity).
`
`Pattern recognition* *
`Pattern recognition is the identification of patterns in large data sets using appropriate mathematical
`methodologies.
`
`Peptidomimetic
`A peptidomimetic is a compound containing non-peptidic structural elements that is capable of mimicking
`or antagonizing the biological action(s) of a natural parent peptide. A peptidomimetic does no longer have
`classical peptide characteristics such as enzymatically scissille peptidic bonds. (See also peptoids).
`
`Peptoid
`A peptoid is a peptidomimetic that results from the oligomeric assembly of N-substituted glycines.
`
`Pfeiffer's rule
`Pfeiffer's rule states that in a series of chiral compounds the eudismic ratio increases with increasing
`potency of the eutomer.
`
`Pharmacokinetics* * *
`Pharmacokinetics refers to the study of absorption, distribution, metabolism and excretion (ADME) of
`bioactive compounds in a higher organism. (See alsoDrug disposition).
`
`Pharmacophore (pharmacophoric pattern)
`A pharmacophore is the ensemble of steric and electronic features that is necessary to ensure the optimal
`supramolecular interactions with a specific biological target structure and to trigger (or to block) its
`biological response.
`A pharmacophore does not represent a real molecule or a real association of functional groups, but a purely abstract concept
`that accounts for the common molecular interaction capacities of a group of compounds towards their target structure. The
`pharmacophore can be considered as the largest common denominator shared by a set of active molecules. This definition
`
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`discards a misuse often found in the medicinal chemistry literature which consists of naming as pharmacophores simple
`chemical functionalities such as guanidines, sulfonamides or dihydroimidazoles (formerly imidazolines), or typical structural
`skeletons such as flavones, phenothiazines, prostaglandins or steroids.
`
`Pharrnacophoric descriptors
`Pharmacophoric descriptors are used to define a pharmacophore, including H-bonding, hydrophobic
`and electrostatic interaction sites, defined by atoms, ring centers and virtual points.
`
`Placebo
`A placebo is an inert substance or dosage form which is identical in appearance, flavor and odour to the
`active substance or dosage form. It is used as a negative control in a bioassay or in a clinical study.
`
`Potency* * *
`Potency is the dose of drug required to produce a specific effect of given intensity as compared to a
`standard reference.
`Potency is a comparative rather than an absolute expression of drug activity. Drug potency depends on both affinity and
`efficacy. Thus, two agonists can be equipotent, but have different intrinsic efficacies with compensating differences in affinity.
`
`Prodrug
`A prodrug is any compound that undergoes biotransformation before exhibiting its pharmacological
`effects. Prodrugs can thus be viewed as drugs containing specialized non-toxic protective groups used in
`a transient manner to alter or to eliminate undesirable properties in the parent molecule . (See also Double
`prodrug).
`
`QSAR
`See Quantitative Structure-Activity Relationships
`
`Quantitative Structure-Activity Relationships (QSAR)" *
`Quantitative structure-activity relationships are mathematical relationships linking chemical structure
`and pharmacological activity in a quantitative manner for a series of compounds. Methods which can be
`used in QSAR include various regression and pattern recognition techniques.
`
`Receptor*
`A receptor is a molecule or a polymeric structure in or on a cell that specifically recognizes and binds a
`compound acting as a molecular messenger (neurotransmitter, hormone, lymphokine, lectin, drug, etc.).
`
`Receptor mapping* *
`Receptor mapping is the technique used to describe the geometric and/or electronic features of a binding
`site when insufficient structural data for this receptor or enzyme are available. Generally the active site
`cavity is defined by comparing the superposition of active to that of inactive molecules.
`
`0 1998 IUPAC, Pure and Applied Chemistry 70, 1 129-1 143
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`Second messenger
`A second messenger is an intracellular metabolite or ion increasing or decreasing as a response to the
`stimulation of receptors by agonists, considered as the "first messenger". This generic term usually does
`not prejudge the rank order of intracellular biochemical events.
`
`Site-specific delivery
`Site-specific delivery is an approach to target a drug to a specific tissue, using prodrugs or antibody
`recognition systems.
`
`Soft drug
`A soft drug is a compound that is degraded in vivo to predictable non-toxic and inactive metabolites, after
`having achieved its therapeutic role.
`
`SPC
`See Structure-property correlations
`
`Structure-activity relationship (SARI
`Structure-activity relationship is the relationship between chemical structure and pharmacological
`activity for a series of compounds.
`
`Structure-based design* *
`Structure-based design is a drug design strategy based on the 3D structure of the target obtained by X-
`ray or NMR.
`
`Structure-property correlations (SPCI * *
`Structure-property correlations refers to all statistical mathematical methods used to correlate any
`structural property to any other property (intrinsic, chemical or biological), using statistical regression and
`pattern recognition techniques.
`
`Systemic* * *
`Systemic means relating to or affecting the whole body.
`
`Teratogen * * *
`