Trends in QSARand MolecularModelling 92Proceedings of the 9th European Symposium onStructure-Activity Relationships: QSAR andMolecular ModellingSeptember 7-11, 1992, Strasbourg, France

Edited by

C.G. WermuthLaboratory of Organic ChemistryFaculty of PharmacyUniversity Louis PasteurF-67401 Illkirch, France

ESCOM • Leiden • 1993

Contents

Preface v

Ninth European Symposium on Structure-Activity Relationships: viiQSAR and Molecular Modelling - Organization and Committees

Welcome Lecture

Activity in QSAR: From A major to A minor 3P.M. Laduron

Section I: De novo DesignX-ray and NMR-based Drug Design

Recent advances in de novo molecular design 11J.B. Moon and W.J. Howe

New strategies that improve the efficiency of the 3D design of 20bioactive molecules

Y.C. Martin, M.G. Bures, E.A. Danaher and J. DeLazzer

LUDI: A computer program for de novo ligand design 27H.-J. Bohm

Docking ligands in the receptor cavity: What have we learned? 35C. Humblet, E.A. Lunney and T. Mirzadegan

APOLLO pharmacophores and the pseudoreceptor concept 44J.P. Snyder, S.N. Rao, K.F. Koehler, A. Vedani and R. Pellicciari

Molecular modelling contributions to serine protease and serine 52esterase inhibitor design

K. Gubernator, H.J. Ammann, C. Broger, D. Bur, D.M. Doran,PR. Gerber, K. Miiller and T.M. Schaumann

Simple modifications of MD force fields for determination of 59peptide structures from NMR data

D.F. Mierke and H. Kessler

Section II: Parameters and Interactions

Multivariate data modeling of new steric, topological and CoMFA- 69derived substituent parameters

H. van de Waterbeemd, P.-A. Carrupt, B. Testa and L.B. Kier

A structural model for drug interactions with biological mem- 76branes: Hydrophobicity, hydrophilicity and amphiphilicity in drugstructures

L.G. Herbette

Relationships between structure and activity based on a partitioning 86of free energy contributions in the estimation of binding constants

M.S. Searle and D.H. Williams

2D and 3D lipophilicity parameters in QSAR 93J.P. Dubost

Polar intermolecular interactions encoded in partition coefficients 101and their interest in QSAR

N. El Tayar and B. Testa

Mechanism of retention of benzodiazepines in affinity, reversed- 109phase and adsorption high-performance liquid chromatography inview of quantitative structure-retention relationships

R. Kaliszan, A. Kaliszan, T.A.G. Noctor, W.P. Purcell and I.W.Waine

Analysis of enzyme-ligand interactions in organic solvents: A 112QSAR approach

CM. Compadre, R.I. Sanchez, C. Bhuvaneswaran, R.L.Compadre, D. Plunkett and S.G. Novick

QSAR H-bonding descriptions 116O. Raevsky, V. Grigor'ev and E. Mednikova

Methods and parameters to describe drug membrane interaction and 120their use in QSAR

J.K. Seydel, H.P. Cordes, M. Albores-Velasco, K. Visser and M.Wiese

Conformation calculations of peptides with polar amino acids: 124Differences by surrounding conditions and by modelling approaches

G. Krause and A. Koch

The use of neural networks for data analysis in QSAR: Chance 128effects

D.T. Manallack and D.J. Livingstone

A basic confrontation of Rekker's revised E/-system with HPLC 132retention data obtained on a mixed series of aliphatic and aromatichydrocarbons

R.F. Rekker and G. de Vries

QSTAR expressions for integral and differential biological response 137S. Baldz

Concept and features of EMIL, a system for lead evolution of bio- 143active compounds

T. Fujita

Interaction terms in Free-Wilson analysis: A QSAR of histamine 160H2-agonists

R. Franke and A. Buschauer

QSAR and environmental toxicology: A challenge for the 1990s 163J.C. Dearden

Section III: Molecular Modelling

Study of the recognition of the heparin-like pentasaccharides by 169antithrombin III

P.D.J. Grootenhuis, C.A.A. van Boeckel, A.M.M. Rood, A. Visser,T.G. van Dinther and D. Meuleman

Computer-aided modelling of G-protein coupled receptor: Applica- 175tion to cationic neurotransmitter and mammalian opsin receptors

S. Trumpp-Kallmeyer, J. Hoflack, A. Bruinvels and M. Hibert

Molecular modelling studies on the digitalis binding site of the 180Na7K+-ATPase

H.-D. Holtje and S. Anzali

Molecular modeling of viral peptides bound to class I MHC pro- 186teins

D. Rognan and G. Folkers

Theoretical model for the metabolism of caffeine and its inhibition 193F. Sanz, E. Lopez de Brinas, J. Rodriguez and F. Manaut

The importance of a disulphide bond in the binding of dopamine to 197the D2 receptor: A molecular modelling study

H. Moereels and J.E. Ley sen

Section IV: Molecular Similarity

Molecular similarity 203W.G. Richards

Searching for molecular similarity between flexible molecules 207P.M. Dean and T.D.J. Perkins

Statistical analysis and shape recognition: Applications to MD 216simulations, conformational analysis and structure-activity relation-ships

G. Grassy and R. Lahana

Topological approaches to three-dimensional molecular shape 220/. Bradshaw, E.W. Wynn, D.W. Salt and M.G. Ford

Section V: 3D QSAR

Experience with comparative molecular field analysis 227P. Floersheim, J. Nozulak and H.P. Weber

CoMFA as a tool for active site modelling 233G. Folkers, A. Merz and D. Rognan

Use of the hydrogen-bond potential function in comparative mol- 245ecular field analysis (CoMFA): An extension of CoMFA

K.H. Kim

Experiences with conformationally flexible 3D databases 252J.S. Mason

GOLPE: An advanced chemometric tool for 3D QSAR problems 256M. Baroni, G. Costantino, G. Cruciani, D. Riganelli, R. Valigiand S. dementi

Three dimensional molecular modeling of the ocla-adrenoceptor: 260Direct 3D-QSAR modeling of selective antagonists

F. Fanelli, M. C. Menziani, M. Cocchi and P. G. De Benedetti

New methods for 3D SAR and lead generation in computer-aided 263drug design

A. Itai, N. Tomioka and Y. Nishibata

Posters

Conformational studies of immunologically active carbocyclic 271analogues of MDP

P. Pristovsek, J. Mavri, J. Kidric and D. Hadzi

Molecular modelling and high-field NMR techniques for interac- 273tions of cognition-activator drugs with cyclodextrins

M.E. Amato, F. Djeda'ini-Pilard, G.C. Pappalardo and B. Perly

Conformational analysis of C3'-substituted pyrimidine nucleosides 276by X-ray diffraction

D. Everaert, N.M. Blaton, O.M. Peeters and C.J. de Ranter

Conformational properties of pyranosyl nucleosides by X-ray dif- 278fraction and modelling techniques

H.L. de Winter, C.J. de Ranter, N.M. Blaton and O.M. Peeters

Conformational and lipophilic behaviour of 2-amino-2-oxazolines 280with antidepressant activity

C. Jarry, J.-J. Bosc, F. Demotes-Mainard, M. Laguerre and A.Carpy

Crystal and molecular structures of the calcium carbohydrates: 282Chloride salt of the lactobionic acid (C12H2,O12)"(Ca)2XCl)^4H2O,lactose complex with calcium chloride C|2H22OnCaCl2-7H2O andcalcium galactonate (C6HnO7)Ca1/2-2!/2H2O

J. Blaszcyk, M. W. Wieczorek and B. W. Krol

Comparison of ligands for the peripheral benzodiazepine receptors 285using ab initio molecular orbital calculations

G. Georges, M. Dory, F. Durant and D.P. Vercauteren

l-[[4-(Aminoalkoxy)phenyl]sulfonyl] indolizines, a novel class of 288calcium entry blockers: Relations between chemical structure, ste-roelectronic properties and anticalcic activity

V. Gibon, G. Evrard, D.P. Vercauteren, F. Durant, J. Gubin andP. Chatelain

Structural and theoretical study of 5-(7?)-(methoxymethyl)-3-aryl- 291oxazolidin-2-ones, reversible monoamine oxidase inhibitors

J. Wouters, F. Moureau, M. Dory, G. Evrard, J.J. Koenig, F.Ducrey, EX. Jarreau and F. Durant

Conformation-activity relationships in the verapamil class of cal- 294cium antagonists

M.N. Romanelli, E. Teodori, S. Dei, S. Scapecchi, F. Gualtieri,A. Chiarini and R. Mannhold

A QSAR evaluation of existing contact allergy database 297M.T.D. Cronin and D.A. Basketter

Drug-receptor dissociation time: Its dependence on the structure 299A. Miklavc and D. Kocjan

Biological systems for measuring mutagenicity and carcinogenicity, 301and 'average' properties of active compounds

R. Benigni, C. Andreoli, M. Cotta-Ramusino and A. Giuliani

Dipolar, hydrogen bonding and van der Waals forces and their 303contributions to the partition behaviour of drugs and chemicals

E.J. Lien, S. Banerjee, A. Khan, H. Gao and F. Wang

Molecular modelling of enzymes and receptors involved in 305carcinogenesis: QSARS and COMPACT-3D

D.F.V. Lewis, H. Moereels, B.G. Lake, C. Ioannides and D.V.Parke

The study of bioisosterism using molecular transform 310/. Csorvdssy

Structure-activity relationships of non-peptide Angiotensin II antag- 312onists

L. Belvisi, L. Bonati, G. Bravi, D. Pitea, A. Salimbeni, C.Scolastico, R. Todeschini and A. Vulpetti

Prediction of biological activity using continuum regression 314J.A. Malpass, D.W. Salt, E.W. Wynn, M.G. Ford and D.J.Livingstone

Hyperdimensionality in QSAR: Cutting problems to workable sizes 317J.W. McFarland and D.J. Gans

CARSO response surface modelling of para-substituted-/V-hetero- 319aryl benzylamines antimycotic activities

M. Biava, R. Fioravanti, G.C. Porretta, L. Caruso, G.Musumarra, N. Simonetti and A. Villa

Design of more informative molecules for QSAR study in a series 321of juvenile hormones

R. Carpignano, M. Dolci and D. Scarfi

Application of a robust method for detecting outliers in data used 324for antineoplastic activity prediction

I.K. Pajeva, N.M. Neykov and P.N. Neytchev

Application of computed atomic and molecular descriptors in 326QSAR modelling

R.L. Hilderbrandt and J. Frazer

Photoreactivity of coumarin derivatives: Pattern recognition and 328QSAR studies

A. Pozzan, M. Palumbo, F. Dall'Acqua and M. Mabilia

The use of molecular electrostatic potential in QSAR 331D.B. Kireev, O.A. Raevsky and V.I. Fetisov

Application of QSAR and molecular modelling in designing l-[4- 333arylpiperazin-l-yl]-3-thioarylpropanes: A new class of centrallyacting hypotensive agents

A.K. Saxena, J. Rao, R.C. Srimal, E. Audry and A. Carpy

Modelling the aquatic toxicity of reactive organic chemicals: Find- 336ing descriptors for SN2 reactivity

H.J.M. Verhaar, A. Goffin, E. Rorije and J.L.M. Hermens

Similarity of MEP distributions obtained using several semiempiri- 339cal and ab initio wave functions: A cluster analysis

J. Rodriguez, F. Manaut and F. Sanz

Electrostatic contributions to binding affinity for the enzyme thy- 341midylate synthase and a series of inhibitors

R.J. Bacquet

A simple method to calculate net atomic charges (EMIR): Rapid 344access to the charge-dependent properties of molecules

V.I. Fetisov

Incorporation of elimination can improve the pseudo-equilibrium 346description of bioactivity-hydrophobicity-acidity profiles

S. Baldz

Lipophilic and electronic factors influencing the activity of a series 349of urea ACAT inhibitors: Approaches to model specification

C.J. Blankley and A.D. White

Prediction of lipophilicity in peptide-like molecules 352H. Karajiannis and H. van de Waterbeemd

Topological lipophilicity potential: A new tool for a fast evaluation 354of lipophilicity distribution on a molecular graph

M.H. Langlois, E. Audry, F. Croizet, P. Dallet, A. Carpy andJ.P. Dubost

MEPSIM: An integrated computational system for molecular elec- 356trostatic potential analysis and comparison

F. Sanz, F. Manaut, J. Rodriguez, E. Lozoya and E. Lopez deBrinas

New van der Waals indicators of shape and size of substituents and 358molecules for quantitative treatment of steric effects

D. Ciubotariu, E. Deretey, M. Medeleanu, V. Gogonea, S.Muresan, A. Novae, C. Bologa and Z. Simon

Prediction of the logP of typical heteroaromatic compounds by 360reversed-phase liquid chromatography

C. Yamagami and N. Takao

Development of new molecular descriptors using conformational 362energies from quantum calculations and their application in QSAR-analysis

R.K. Joshi, T. Meister, L. Scapozza and T.-Ku Ha

Use of molecular modelling in the interpretation of conventional 364QSAR equations: Inclusion complexes of cyclodextrins withphenobarbital

A. Lopata and K. Kddas

Comparison between RPHPLC capacity factors and octanol-water 367partition coefficients of 9H-xanthene and 9H-thioxanthene deriva-tives

E. Fillipatos, A. Tsantili-Kakoulidou and A. Papadaki-Valirake

The estimation of physicochemical properties by RP18-TLC 370K. Dross and C. Sonntag

Understanding the enantioselectivity of Mucor miehei lipase 373G. Ranghino, E. Battistel and S. Giovenco

Calculated logP values: Are they reliable? 379R. Mannhold, R.F. Rekker and A.M. ter Laak

Estimation of aqueous solubility from boiling point 381J. Altschuh and R. Briiggemann

Calculation of the topological invariants for the excised van der 384Waals' surface of a molecule

E.W. Wynn, D.W. Salt, M.G. Ford and J. Bradshaw

Measurement of pKa and logP of water-insoluble substances by 386potentiometric titration

A. Avdeef and J.E.A. Comer

Use of surface properties from ab initio calculations to characterize 388heterocycles

N.-A. Bergman and R.E. Carter

Length and alignment independent sequence-activity models 392S. Rdnnar, M. Sandberg, M. Sjb'strom and S. Wold

Grid-assisted similarity perception (GRASP): A new method of 394overlapping molecular structures

K.A. Mason, A.H. Katz and C.F. Shen

Use of neural networks to predict hydration sites in proteins 396R.C. Wade, H. Bohr and P.G. Wolynes

Role of the dipole moment during ligand receptor interaction: A 398hypothetic static model

T.I. Oprea, L. Kurunczi and E.E. Moret

The electroconformational space of the (3-adrenergic receptor: A 400molecular modelling study of f}-agonists

T.I. Oprea, T.I. Sulea, S. Muresan and Z. Simon

Determination of quantitative structure-activity relationships in 402antiviral metal complexes using molecular mechanics

PC. Yates

A novel automatic docking method for flexible molecules 404M. Yamada, N. Tomioka and A. Itai

Application of neural networks to the 3D-pharmacophore search 407problem

E. Feuilleaubois, V. Fabart and J.-P. Doucet

Comparative conformational analysis of pyrrolacetic compounds 409with antiinflammatory activity

/./. Vazquez, J.J. Lozano and R. Pouplana

Flexible docking of ligands to receptor sites using genetic 412algorithms

J.S. Dixon

Topological pharmacophore evaluation by interactive approach: A 414case study

S. Hubel

DIGFIT: A superposition generator for flexible molecules 416W.J. Streich

A combinatorial search of enzyme-ligand docking space using dis- 418tance geometry, cluster analysis and energy evaluation

M.A. Hermsmeier and W.F. Lau

Conformational properties of the transmembrane domains of the 420human D2-receptor: Comparison with bacteriorhodopsin

R. Kuhne and A. Koch

Topography of the huperzine A binding site in AChE: Ab initio 422docking of reversible inhibitors of AChE into the dynamic enzyme

Y.-P. Pang and A.P. Kozikowski

Characterization of the pharmacophoric pattern of acetylcholinester- 425ase inhibitors through conformational analysis

J.C. Pinto, J.J. Bourguignon and C.-G. Wermuth

Prolyl-endopeptidase inhibitors: Pharmacophore characterization via 427conformational analysis and pattern recognition

T. Langer and C.-G. Wermuth

Conformational search and transitional states study of arachidonic 429acid using molecular dynamics and AMI semiempirical calculations

M. Lopez, J-J. Lozano, J. Ruiz and R. Pouplana

Conformational analysis of some fentanyl derivatives in relation to 431the drug-receptor dissociation rate

D. Kocjan and A. Miklavc

Modelling of the 3D structure of Bacillus circulans var. alkalophi- 433lus cyclomaltodextrin glucanotransferase and comparison with a-amylase

E. Demchuk, M. Vihinen and T. Korpela

Rational approach towards the synthesis of new ALS-inhibitors 435K. Fischer, G. Hamprecht, E. Heistracher, G. Klebe, R. Kober,H. Mayer, N. Meyer, G. Paul, P. Plath, T. Saupe, N. Walker, H.Walter, K.O. Westphalen and B. Wtirzer

Molecular dynamics simulations of the complex of adenylate kinase 438from Escherichia coli and the inhibitor AP5A

P. Kern, R.M. Brunne, W.F. van Gunsteren and G. Folkers

Uncoupling of CD4 signal transduction with a rationally designed 441analog

J.M. McDonnel and B.A. Jameson

Modelling of noncompetitive antagonists of the TV-Methyl-D- 444Aspartate (NMDA) receptor

M. Laguerre, M. Elhalaoui and A. Carpy

Differentiation of a,- and a2-adrenoceptors agonists using the 446receptor mapping technique

P. Etcheto, M. Laguerre and A. Carpy

Modeling of a2-adrenoceptors agonists: Specificity of the oc2A-sub- 448type

P. Etcheto, M. Laguerre and A. Carpy

Computer modelling and structure-activity relationships of angio- 450tensin II-related compounds

M.-P. Joseph and B. Maigret

Molecular modelling studies of PCP binding by arylcyclohexylpi- 452peridines

C. Mercier, G. Canesi and J.-M. Kamenka

Molecular modeling and mutagenic activity of nitro- and amino- 454carbazoles

C. Mercier, S. Chemtob, V. Andre, P. Gauduchon and J.-C.Lancelot

GABAergic activity of triamino-pyridines and triamino-benzenes 456E.E. Polymeropoulos and B. Kutscher

Molecular modelling comparison of potent and selective K-agonists 461belonging to different chemical structures: A first attempt of K-receptor mapping

F. Bellucci and G. Dondio

Design and molecular modelling of antisense pyranosyl oligonu- 463cleotides

H.L. de Winter, C.J. de Ranter, N.M. Blaton and O.M. Peeters

Molecular modelling studies with CCK-B receptor antagonists 466G. Greco, E. Novellino, C. Silipo and A. Vittoria

A molecular modelling study of dianionic species extraction by 471dicationic extractants

C. Sella and D. Bauer

A molecular modeling study on the hormone binding site of the 473estrogen receptor

H.-D. Holtje and N. Dall

Theoretical investigations on the interaction of non-steroidal anti- 476phlogistics with a model of the active site of the human prostaglan-din endoperoxide synthase ('cyclooxygenase')

K. Kemmritz and H.-D. Holtje

Molecular modelling studies on the enzyme-substrate complex 478sialidase-iV-acetylneuraminic acid and the mechanism of catalysis

N.R. Taylor, A.K.J. Chong, M.S. Pegg and M. von Itzstein

Molecular determinants of the platelet aggregation inhibitory activ- 481ity of carbamoylpiperidines

Z. Feng, R. Gollamudi, E.O. Dillingham, S.E. Bond, B.A. Lyman,W.P. Purcell and R.J. Hill

Quantitative description of nucleic acid sequences based on chemi- 483cal characterization of the monomers

M. Sandberg, J. Jonsson, M. Sjb'strb'm, S. Wold and S. Rdnnar

3D Modelling of soybean glyoxysomal malate dehydrogenase 485N. Guex, F. Widmer, P. Gaillard, P.-A. Corrupt and B. Testa

Conformational requirements for interaction of L-glutamate with the 487metabotropic EAA receptor

G. Costantino, B. Natalini and R. Pellicciari

Molecular modelling of G-protein coupled receptors: The interac- 489tion between specific ligands and their putative binding sites

D.F.V. Lewis, I. Kitchen, D. Sugden, J. English and J. Arendt

Inductive reasoning in a QSAR intelligent system 495A.M. Sapegin

Development of QSARs from incomplete dose-response data using 497neural networks

M. Wiese

pKa prediction in multiply-substituted phenols: A comparison of 499multiple linear regression and back-propagation

VS. Rose, A.P. Hill, R.M. Hyde and A. Hersey

An approach to knowledge-based QSAR predictions using the 502MASCA model

H. Rothe and S. Boudon

Skin sensitisation structure-activity relationships for phenols and 504anilins and application of a qualitative rule-based system: DEREK

M.P. Payne, P.T. Walsh and J.J. Langowski

Expert system approach for predicting pKa 507F. Csizmadia, J. Szegezdi and F. Darvas

Molecular lipophilicity potential as a tool in 3D QSAR: Method 511development and applications

P. Gaillard, P.-A. Carrupt, B. Testa and A. Boundon

An active site model of phenylethanolamine JV-methyltransferase 513using CoMFA

G.L. Grunewald, N. Skjaerbaek and J.A. Monn

Use of the GRID program in the 3D QSAR of a series of calcium 517channel agonists

A.M. Davis, N.P. Gensmantel and D.P. Marriott

MLR and PLS: A comparison of the techniques applied to the 519QSAR analysis of a series of structurally diverse biologically activecompounds

I.M. McLay and J.S. Mason

Comparative molecular field analysis of CCK-A antagonists using 522field fit as alignment technique

R. Bureau, S. Rault, J.-C. Pilo and M. Robba

3D QSAR of insecticidal dioxatricycloalkene and its related com- 525pounds

M. Akamatsu, T. Fujita, Y. Ozoe, K. Mochida, T. Nakamura andF. Matsumura

Use of advanced chemometric tools and comparison of different 3D 527descriptors in QSAR analysis of prazosin analog oc,-adrenergicantagonists

M. Cocchi, G. Cruciani, M.C. Menziani and P.G. De Benedetti

Pharmacophore development of (-)-cocaine analogs for the 530dopamine, serotonin, and norepinephrine uptake sites using aQSAR and CoMFA approach

F.I. Carroll, P. Abraham, A.H. Lewin, J.W. Boja and M.J. Kuhar

Partitioning behaviour of piracetam-type cogniton enhancers 532C Altomare, A. Carotti, S. Cellamare, P.-A. Carrupt and B.Testa

Partition behavior of solvents, drugs and chemicals 534E.J. Lien, H. Gao, F. Wang and H.G. Shinouda

Use of molecular electrostatic potentials for analysis of anti- 536convulsant activities of phenylsuccinimides

W. Kwiatkowski and J. Karolak-Wojciechowska

Application of molecular orbital calculations to the QSAR analysis 538of enzyme-ligand interactions

R.L. Compadre, CM. Compadre, M.A. Belmont and J.K. Sims

QSARs of fathead minnow and Microtox toxicity data using canon- 541ical correlation analysis

M.T.D. Cronin and J.C Dearden

The Hypersurface Iterative Projection (HIP) method and its applica- 543tion to bicyclic pyrazolidinone antibacterial agents

D.B. Boyd

QSAR analysis of time- and dose-dependent in vivo drug effects 546using artificial neural networks

K.-J. Schapper, M. Wiese, R. Dieter, P. Emig, J. Engel, B.Kutscher and E.E. Polymeropoulos

Brain penetration and H-bonding capacity 550H. van de Waterbeemd and M. Kansy

Antiserotoninergic activity of 2-aminoethylbenzocyclanones in rat 552aorta: Structure-activity relationships

F. Sanz, J. Rodriguez, E. Lozoya, F. Manaut, T.G. Ferreiro, M.I.Loza, J.A. Fontela, I. Cadavid and E. Ravina

Estrogenic activity: An example of considering effectuation models 554in biological data interpretation and QSAR

S. Dove and H. Schonenberger

QSAR and quantum-mechanical studies in cytotoxic series of nitro- 556and aminocarbazoles

C. Mercier and S. Chemtob

QSAR analysis of the toxicological activity of /V,N-(dimethylami- 558no)ethyl-benzoate hydrochlorides

A.T. do Amaral, Y. Miyazaki, G. Capobianco, B.Y. Frey, A.S.Stachissini, S.M. Miguel, A.B. Kawabe, L.C Tavares, M.Galacci, L. Caprara and A.C. Oliveira

QSAR in the nonsteroidal anti-inflammatory agents: The fenamic 560acids

J.J. Lozano, M. Lopez, J. Ruiz, IJ. Vazquez and R. Pouplana

Application of QSAR of substituted benzamides for prediction of 562their biodistribution as tracer radioligands in the brain

T. de Paulis, D.E. Schmidt, S. Ansari, J.R. Votaw, R.G. Manning,J.A. Clanton, N.S. Mason and R.M. Kessler

QSAR by MTD for inhibition of keratinization of tracheal cells in 568organ culture by retinoids

T.I. Oprea, T.I. Sulea, D. Ciubotariu, I. Niculescu-Duvaz and Z.Simon

QSAR of some antibacterial active isosteric heterocyclic com- 570pounds against an enterobacter

/. Yalcin, E. Sener and /. Oren

The effect of ortho substitution of the 2,4-diamino-5-(x-benzyl) 573pyrimidine nucleus on the inhibition of avian and bacterial dihydro-folate reductase

CD. Selassie

A note on excess toxicity of acetylenic alcohols to ciliate Tetrahy- 575mena pyriformis

M. Tichy and T. W. Schultz

Different structural requirements for the inhibitory activity of furan 577carboxanilide derivatives against SDC for either wild or mutantstrains of Ustilago maydis

A. Aghazadeh and M. Mahmoudian

The value of the local lymph node assay in the development of 580QSARs for skin sensitization potential

D.A. Basketter, D. Roberts, M.T.D. Cronin and E. Scholes

Author index 585

Subject index 591