M. Riad, S. Mestikawy, D. Vergé, H. Gozlan, and M. Hamon, Visualization and quantification of central 5-HT1A receptors with specific antibodies, Neurochemistry International, vol.19, issue.4, p.413, 1991.
DOI : 10.1016/0197-0186(91)90058-L

H. Gozlan, S. Mestikawy, L. Pichat, J. Glowinski, and M. Hamon, Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT, Nature, vol.77, issue.5930, p.140, 1983.
DOI : 10.1038/305140a0

P. C. Moser, M. D. Tricklebank, D. N. Middlemiss, A. K. Mir, M. F. Hibert et al., Characterization of MDL 73005EF as a 5-HT1A selective ligand and its effects in animal models of anxiety: comparison with buspirone, 8-OH-DPAT and diazepam, British Journal of Pharmacology, vol.21, issue.2, pp.343-349, 1990.
DOI : 10.1111/j.1476-5381.1990.tb14706.x

P. R. Hartig, T. A. Branchek, and R. L. Weinshank, A subfamily of 5-HT1D receptor genes, Trends in Pharmacological Sciences, vol.13, p.152, 1992.
DOI : 10.1016/0165-6147(92)90053-9

M. W. Hamblin, R. W. Mcguffin, M. A. Metcalf, D. M. Dorsa, and K. M. Merchant, Distinct 5-HT1B and 5-HT1D serotonin receptors in rat: Structural and pharmacological comparison of the two cloned receptors, Molecular and Cellular Neuroscience, vol.3, issue.6, p.578, 1992.
DOI : 10.1016/1044-7431(92)90070-I

F. Libert, E. Passage, M. Parmentier, M. J. Simons, G. Vassart et al., Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor, Genomics, vol.11, issue.1, p.225, 1991.
DOI : 10.1016/0888-7543(91)90125-X

E. Weisberg and M. Teitler, Novel high-affinity3H-serotonin binding sites in rat and bovine brain tissue, Drug Development Research, vol.57, issue.3, p.225, 1992.
DOI : 10.1002/ddr.430260303

J. E. Leysen, C. J. Niemegeers, J. P. Tollemaere, and P. H. Laduron, Serotonergic component of neuroleptic receptors, Nature, vol.55, issue.5649, p.168, 1978.
DOI : 10.1016/0024-3205(77)90323-X

J. C. Chambard, . Van-obberghen, E. Schilling, R. J. Haslam, V. Vouret et al., Chinese hamster serotonin (5-HT) type 2 receptor cDNA sequence, Nucleic Acids Research, vol.18, issue.17, p.5282, 1990.
DOI : 10.1093/nar/18.17.5282

R. S. Sparkes, N. Lan, I. Klisak, T. Mohandas, A. Diep et al., Assignment of a serotonin 5HT-2 receptor gene (HTR2) to human chromosome 13q14???q21 and mouse chromosome 14, Genomics, vol.9, issue.3, p.461, 1991.
DOI : 10.1016/0888-7543(91)90411-7

A. Pazos, D. Hoyer, and J. M. Palacios, The binding of serotonergic ligands to the porcine choroid plexus: Characterization of a new type of serotonin recognition site, European Journal of Pharmacology, vol.106, issue.3, p.539, 1984.
DOI : 10.1016/0014-2999(84)90057-8

D. Hoyer, Molecular pharmacology and biology of 5-HT1C receptors, Trends in Pharmacological Sciences, vol.9, issue.3, p.89, 1988.
DOI : 10.1016/0165-6147(88)90174-5

C. J. Grossman, G. J. Kilpatrick, and K. T. Bunce, Development of a radioligand binding assay for 5-HT4 receptors in guinea-pig and rat brain, British Journal of Pharmacology, vol.100, issue.3, p.618, 1993.
DOI : 10.1111/j.1476-5381.1993.tb13617.x

M. Hibert and P. Moser, MDL 72832 and MDL 73005EF: Novel, potent and selective 5-HT1A receptor ligands with different pharmacological properties, Drugs of the Future, vol.15, issue.2, p.159, 1990.
DOI : 10.1358/dof.1990.015.02.114544

B. J. Van-steen, I. Van-wijngaarden, M. T. Tulp, and W. Soudijn, Structure-Affinity Relationship Studies on 5-HT1A receptor Ligands. 2. Heterobicyclic Phenylpiperazines with N4-Aralkyl Substituents, Journal of Medicinal Chemistry, vol.37, issue.17, pp.2761-2773, 1994.
DOI : 10.1021/jm00043a015

A. Orjales, L. Alonso-cires, L. Labeaga, and R. Corcostegui, New (2-Methoxyphenyl)piperazine Derivatives as 5-HT1A Receptor Ligands with Reduced .alpha.1-Adrenergic Activity. Synthesis and Structure-Affinity Relationships, Journal of Medicinal Chemistry, vol.38, issue.8, pp.1273-1277, 1995.
DOI : 10.1021/jm00008a005

B. J. Van-steen, I. Van-wijngaarden, M. T. Tulp, and W. Soudijn, Structure-affinity relationship studies on 5-HT1A receptor ligands. 1. Heterobicyclic phenylpiperazines with N4-alkyl substituents, Journal of Medicinal Chemistry, vol.36, issue.19, pp.2751-2760, 1993.
DOI : 10.1021/jm00071a006

Z. P. Zhuang, M. P. Kung, and H. F. Kung, Synthesis And Evaluation of 4-(2'-Methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)- p-iodobenzamido]ethyl]piperazine (p-MPPI): A New Iodinated 5-HT1A Ligand, Journal of Medicinal Chemistry, vol.37, issue.10, pp.1406-1407, 1994.
DOI : 10.1021/jm00036a003

R. K. Raghupathi, L. Fitzgerald, M. Teiler, and R. A. Glennon, Analogs of the 5-HT1A serotonin antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine with reduced .alpha.1-adrenergic affinity, Journal of Medicinal Chemistry, vol.34, issue.8, pp.2633-2638, 1991.
DOI : 10.1021/jm00112a043

A. Orjales, L. Alonso-cires, L. Labeaga, and R. Corcostegui, New (2-Methoxyphenyl)piperazine Derivatives as 5-HT1A Receptor Ligands with Reduced .alpha.1-Adrenergic Activity. Synthesis and Structure-Affinity Relationships, Journal of Medicinal Chemistry, vol.38, issue.8, pp.1273-1277, 1995.
DOI : 10.1021/jm00008a005

J. L. Mokrosz, M. H. Paluchowska, E. Wojcik, M. Filip, S. Harakchieva-minol et al., Structure-Activity Relationship Studies of Central Nervous System Agents. 13.4-[3-(Benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)piperazine, a New Putative 5-HT1A Receptor Antagonist, and Its Analogs, Journal of Medicinal Chemistry, vol.37, issue.17, pp.2754-2760, 1994.
DOI : 10.1021/jm00043a014

I. Van-wijngaarden, M. T. Tulp, and W. Soudijn, The concept of selectivity in 5-HT receptor research, European Journal of Pharmacology: Molecular Pharmacology, vol.188, issue.6, pp.301-312, 1990.
DOI : 10.1016/0922-4106(90)90190-9

L. E. Arvidsson, U. Hacksell, J. L. Nilsson, S. Hjorth, A. Carlsson et al., 8-Hydroxy-2-(dipropylamino)tetralin, a new centrally acting 5-hydroxytryptamine receptor agonist, Journal of Medicinal Chemistry, vol.24, issue.8, pp.921-935, 1981.
DOI : 10.1021/jm00140a002

J. Vallgarda, L. E. Arvidsson, B. E. Svensson, C. J. Fowler, and U. Hacksell, Phenolic derivatives of 1,2-methano-N,N-dipropyl-1,2,3,4-tetrahydronaphth-2-ylamine. Structural hybrids of 2-aminotetralin- and phenylcyclopropylamine-derived 5-HT1A-receptor agonists, European Journal of Medicinal Chemistry, vol.28, issue.5, pp.399-406, 1993.
DOI : 10.1016/0223-5234(93)90126-Y

C. Sonesson, T. Barf, J. Nilsson, D. Dijkstra, A. Carlsson et al., Synthesis and Evaluation of Pharmacological and Pharmacokinetic Properties of Monopropyl Analogs of 5-, 7-, and 8-[[(Trifluoromethyl)sulfonyl]oxy]-2-aminotetralins: Central Dopamine and Serotonin Receptor Activity, Journal of Medicinal Chemistry, vol.38, issue.8, pp.1319-1329, 1995.
DOI : 10.1021/jm00008a010

A. N. Jain, N. L. Harris, and J. Y. Park, Quantitative Binding Site Model Generation: Compass Applied to Multiple Chemotypes Targeting the 5-HT1A Receptor, Journal of Medicinal Chemistry, vol.38, issue.8, pp.1295-1308, 1995.
DOI : 10.1021/jm00008a008

Y. Liu, L. Cortizo, H. Yu, B. E. Svensson, T. Lewander et al., C8-Substituted derivatives of 2-(dipropylamino)tetralin: exploration of the effect of C8-aryl and heteroaryl substituents on the interaction with 5-HT1A-receptor, European Journal of Medicinal Chemistry, vol.30, issue.4, pp.277-286, 1995.
DOI : 10.1016/0223-5234(96)88236-5

C. G. Chidester, C. H. Lin, R. A. Lahti, S. R. Haadsma-svensson, and M. W. Smith, Comparison of 5-HT1A and dopamine D2 pharmacophores. X-ray structures and affinities of conformationally constrained ligands, Journal of Medicinal Chemistry, vol.36, issue.10, pp.1301-1315, 1993.
DOI : 10.1021/jm00062a001

Z. P. Zhuang, M. P. Kung, and H. F. Kung, Synthesis of (R,S)-trans-8-hydroxy-2-[N-n-propyl-N-(3'-iodo-2'-propenyl)amino]tetralin (trans 8-OH-PIPAT): a new 5-HT1A receptor ligand, Journal of Medicinal Chemistry, vol.36, issue.21, pp.3161-3165, 1993.
DOI : 10.1021/jm00073a016

A. G. Romero, J. A. Leiby, R. B. Mc-call, M. Piercey, and F. Han, Novel 2-substituted tetrahydro-3H-benz[e]indolamines: highly potent and selective agonists acting at the 5-HT1A receptor as possible anxiolytics and antidepressants, Journal of Medicinal Chemistry, vol.36, issue.15, pp.2066-2074, 1993.
DOI : 10.1021/jm00067a003

P. Stjernlof, M. Gullme, T. Elebring, B. Andersson, H. Wikstrom et al., (S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde: a new class of orally active 5-HT1A-receptor agonists, Journal of Medicinal Chemistry, vol.36, issue.15, pp.2059-2065, 1993.
DOI : 10.1021/jm00067a002

T. Podona, Thèse soutenue le 2/12/1992 à l'université d'Orléans. 3-amino-3,4- dihydro-2H-1-benzopyranes diversement substitués : Synthèses et propriétés pharmacologiques

R. J. Loncharich and B. R. Brooks, The effects of truncating long-range forces on protein dynamics, Proteins: Structure, Function, and Genetics, vol.80, issue.1, pp.32-45, 1989.
DOI : 10.1002/prot.340060104

W. F. Van-gunsteren and H. J. Berendsen, Computer Simulation of Molecular Dynamics: Methodology, Applications, and Perspectives in Chemistry, Angewandte Chemie International Edition in English, vol.29, issue.9, pp.992-1023, 1990.
DOI : 10.1002/anie.199009921

D. Van-belle, I. Couplet, M. Prevost, and S. Wodak, Calculations of electrostatic properties in proteins, Journal of Molecular Biology, vol.198, issue.4, pp.721-735, 1987.
DOI : 10.1016/0022-2836(87)90213-0

W. Van-gunsteren, On the interpretation of biochemical data by molecular dynamics computer simulation, European Journal of Biochemistry, vol.19, issue.3, pp.947-961, 1992.
DOI : 10.1016/0014-5793(90)80143-7

M. Karplus and G. A. Petsko, Molecular dynamics simulations in biology, Nature, vol.347, issue.6294, pp.631-639, 1990.
DOI : 10.1038/347631a0

W. H. Press, B. P. Flannery, S. A. Teukolsky, W. T. Vetterling, and . Ed, Numerical Recipes In Pascal : The Art of Scientific Computing, 1989.

T. Noguti and N. Go, Efficient monte carlo method for simulation of fluctuating conformations of native proteins, Biopolymers, vol.52, issue.3, pp.527-546, 1985.
DOI : 10.1002/bip.360240308

J. A. Mc-cammon, B. R. Gelin, and M. Karplus, Dynamics of folded proteins, Nature, vol.58, issue.5612, p.585, 1977.
DOI : 10.1038/267585a0

L. Verlet, Computer "Experiments" on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules, Physical Review, vol.159, issue.1, pp.98-103, 1967.
DOI : 10.1103/PhysRev.159.98

R. W. Hockney and J. W. Eastwood, Computer Simulation Using Particles, 1981.
DOI : 10.1201/9781439822050

J. P. Ryckaert, G. Ciccotti, and H. J. Berendsen, Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes, Journal of Computational Physics, vol.23, issue.3, pp.327-341, 1977.
DOI : 10.1016/0021-9991(77)90098-5

E. E. Abola, F. C. Bernstein, T. F. Koetzle, G. Marshall, C. Humblet et al., The Protein Data Bank. 47 a) Humblet, C Annu. Rep. Med. Chem. Drug. Dev. Res. J. R. J. Med. Chem. Eur. J. Med. Chem, vol.15, issue.24, pp.1087-1118, 1980.

C. Mellin, J. Vallgarda, D. L. Nelson, L. Björk, H. Yu et al., A 3 dimensional model for 5-HT1A-receptor agonists based on stereoselective methyl-substituted and conformationally restricted analogs of 8-hydroxy-2-(dipropylamino)tetralin, Journal of Medicinal Chemistry, vol.34, issue.2, pp.497-510, 1991.
DOI : 10.1021/jm00106a004

R. A. Glennon, R. B. Westkaemper, and P. Bartyzel, Serotonin Receptor Subtypes: basic and Clinical Aspects, pp.19-64, 1991.

C. G. Chidester, C. H. Lin, R. A. Lahti, S. R. Haadsma-svensson, and M. W. Smith, Comparison of 5-HT1A and dopamine D2 pharmacophores. X-ray structures and affinities of conformationally constrained ligands, Journal of Medicinal Chemistry, vol.36, issue.10, pp.1301-1315, 1993.
DOI : 10.1021/jm00062a001

M. J. Mokrosz, B. Duszynska, A. J. Bojarski, J. L. Mokrosz, and . Bio, Structure-activity relationship studies of CNS agents-XVII. Spiro[piperidine-4???,1-(1,2,3,4-tetrahydro-??-carboline)] as a probe defining the extended topographic model of 5-HT1A receptors, Bioorganic & Medicinal Chemistry, vol.3, issue.5, pp.533-538, 1995.
DOI : 10.1016/0968-0896(95)00039-J

H. Kubinyi, QSAR : Hansch Analysis and Related Approaches
DOI : 10.1002/9783527616824

T. C. Bruice, N. Kharasch, and R. J. Winzler, A correlation of thyroxine-like activity and chemical structure, Archives of Biochemistry and Biophysics, vol.62, issue.2, pp.305-317, 1956.
DOI : 10.1016/0003-9861(56)90129-1

O. R. Hansen, Hammett Series with Biological Activity., Acta Chemica Scandinavica, vol.16, pp.1593-1600, 1962.
DOI : 10.3891/acta.chem.scand.16-1593

C. Hansch and T. Fujita, -??-?? Analysis. A Method for the Correlation of Biological Activity and Chemical Structure, Journal of the American Chemical Society, vol.86, issue.8, pp.1616-1626, 1964.
DOI : 10.1021/ja01062a035

S. Wold, A. Ruhe, H. Wold, I. Dunn, and W. , The Collinearity Problem in Linear Regression. The Partial Least Squares (PLS) Approach to Generalized Inverses, SIAM Journal on Scientific and Statistical Computing, vol.5, issue.3, pp.735-743, 1984.
DOI : 10.1137/0905052

I. Cramer, R. D. Patterson, D. E. Bunce, and J. D. , Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins, Journal of the American Chemical Society, vol.110, issue.18, pp.5959-5967, 1988.
DOI : 10.1021/ja00226a005

L. H. Hall and L. B. Kier, The Molecular Connectivity chi Indexes and Kappa Shape Indexes in Structure-Property Modeling, Rewiews in Computational Chemistry, 1991.

L. B. Kier and L. H. Hall, Derivation and Significance of Valence Molecular Connectivity, Journal of Pharmaceutical Sciences, vol.70, issue.6, p.583, 1981.
DOI : 10.1002/jps.2600700602

A. Bondi, van der Waals Volumes and Radii, The Journal of Physical Chemistry, vol.68, issue.3, p.441, 1964.
DOI : 10.1021/j100785a001

L. H. Hall, E. L. Maynard, and L. B. Kier, QSAR investigation of benzene toxicity to fathead minnow using molecular connectivity, Environmental Toxicology and Chemistry, vol.49, issue.9, p.783, 1989.
DOI : 10.1002/etc.5620080905

B. Hetnarski and R. D. O-'brien, Charge-transfer constant. New substituent constant for structure-activity relations, Journal of Medicinal Chemistry, vol.18, issue.1, pp.29-33, 1975.
DOI : 10.1021/jm00235a007

E. J. Lien, R. C. Liao, and H. G. Shinouda, Quantitative Structure-Activity Relationships and Dipole Moments of Anticonvulsants and CNS Depressants, Journal of Pharmaceutical Sciences, vol.68, issue.4, pp.463-465, 1979.
DOI : 10.1002/jps.2600680418

J. C. Dearden and R. M. Nicholson, The prediction of biodegradability by the use of quantitative structure-activity relationships: Correlation of biological oxygen demand with atomic charge difference, Pesticide Science, vol.VII, issue.3, pp.305-310, 1986.
DOI : 10.1002/ps.2780170314

A. K. Debnath, R. L. Lopez-de-compadre, G. Debnath, A. J. Shusterman, and C. Hansch, Structure-activity relationship of mutagenic aromatic and heteroaromatic nitro compounds. Correlation with molecular orbital energies and hydrophobicity, Journal of Medicinal Chemistry, vol.34, issue.2, pp.786-797, 1991.
DOI : 10.1021/jm00106a046

R. C. Young, R. C. Mitchell, T. H. Brown, C. R. Ganellin, R. Griffiths et al., Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists, Journal of Medicinal Chemistry, vol.31, issue.3, pp.656-671, 1988.
DOI : 10.1021/jm00398a028

R. F. Rekker and R. Mannhold, Calulation of Drug Lipophilicity : The Hydrophobic Fragmental Constant Approach, 1992.

A. K. Ghose and G. M. Crippen, Atomic Physicochemical Parameters for Three-Dimensional Structure-Directed Quantitative Structure-Activity Relationships I. Partition Coefficients as a Measure of Hydrophobicity, Journal of Computational Chemistry, vol.6, issue.4, pp.565-577, 1986.
DOI : 10.1002/jcc.540070419

T. Jr and R. W. , Steric Effects in Organic Chemistry, 1956.

C. Hansch and A. Leo, Substituent constants for correlation analysis, Journal of Medicinal Chemistry, vol.20, issue.2, 1979.
DOI : 10.1021/jm00212a024

A. K. Ghose and G. M. Crippen, Atomic physicochemical parameters for three-dimensional-structure-directed quantitative structure-activity relationships. 2. Modeling dispersive and hydrophobic interactions, Journal of Chemical Information and Modeling, vol.27, issue.1, pp.21-35, 1987.
DOI : 10.1021/ci00053a005

M. Calas, J. Bompart, L. Giral, and G. Grassy, Relation structure???activit?? dans la s??rie des quinolones, European Journal of Medicinal Chemistry, vol.26, issue.3, p.279, 1991.
DOI : 10.1016/0223-5234(91)90060-Z

M. Montagut, M. Saux, . Carpy, and G. Grassy, Analyse multidimensionnelle des RSA d'une s??rie de mol??cules apparent??es ?? la clonidine, European Journal of Medicinal Chemistry, vol.25, issue.5, pp.387-395, 1990.
DOI : 10.1016/0223-5234(90)90001-J

J. L. Stigliani, M. Bonnafous, and G. Grassy, Reconnaissance de forme et structure mol??culaire: ??tude comparative de quelques voies d'approche appliqu??es ?? l'??tude du pouvoir carcinog??ne d'hydrocarbures aromatiques polybenz??niques, European Journal of Medicinal Chemistry, vol.25, issue.2, pp.157-170, 1990.
DOI : 10.1016/0223-5234(90)90024-W

A. T. Balaban, Applications of graph theory in chemistry, Journal of Chemical Information and Modeling, vol.25, issue.3, p.334, 1985.
DOI : 10.1021/ci00047a033

A. Balaban, Chemical Applications of Graph Theory, 1976.

C. Chatfield and A. J. Collins, Introduction to Multivariate Analysis, 1980.
DOI : 10.1007/978-1-4899-3184-9

B. F. Manly, Multivariate Statistical Methods A Primer, 1986.

Y. C. Martin, J. B. Holland, C. H. Jarboe, and N. Plotnikoff, Discriminant analysis of the relation between physical properties and the inhibition of monoamine oxidase by aminotetralins and aminoindans, Journal of Medicinal Chemistry, vol.17, issue.4, pp.409-413, 1974.
DOI : 10.1021/jm00250a008

G. Prakash and E. M. Hodnett, Discriminant analysis and structure-activity relationships. 1. Naphthoquinones, Journal of Medicinal Chemistry, vol.21, issue.4, pp.369-374, 1978.
DOI : 10.1021/jm00202a011

C. Daniel and F. S. Wood, Fitting Equation to Data, 1980.

N. R. Draper and H. Smith, Applied Regression Analysis, 1981.
DOI : 10.1002/9781118625590

I. Dunn, W. J. Wold, S. Edlund, U. Hellberg, S. Gasteiger et al., Multivariate structure-activity relationships between data from a battery of biological tests and an ensemble of structure descriptors: The PLS method, Quantitative Structure-Activity Relationships, vol.22, issue.4, pp.131-137, 1984.
DOI : 10.1002/qsar.19840030402

A. J. Hopfinger, A QSAR investigation of dihydrofolate reductase inhibition by Baker triazines based upon molecular shape analysis, Journal of the American Chemical Society, vol.102, issue.24, pp.7196-7206, 1980.
DOI : 10.1021/ja00544a005

A. J. Hopfinger, Theory and application of molecular potential energy fields in molecular shape analysis: a quantitative structure-activity relationship study of 2,4-diamino-5-benzylpyrimidines as dihydrofolate reductase inhibitors, Journal of Medicinal Chemistry, vol.26, issue.7, pp.990-996, 1983.
DOI : 10.1021/jm00361a011

G. Klebe, U. Abraham, and T. Mietzner, Molecular Similarity Indices in a Comparative Analysis (CoMSIA) of Drug Molecules to Correlate and Predict Their Biological Activity, Journal of Medicinal Chemistry, vol.37, issue.24, pp.4130-4146, 1994.
DOI : 10.1021/jm00050a010

A. C. Good, S. S. So, and W. G. Richards, Structure-activity relationships from molecular similarity matrices, Journal of Medicinal Chemistry, vol.36, issue.4, pp.433-438, 1993.
DOI : 10.1021/jm00056a002

R. Carbo, L. Leyda, and M. Arnau, How similar is a molecule to another? An electron density measure of similarity between two molecular structures, International Journal of Quantum Chemistry, vol.63, issue.Suppl., pp.1185-1189, 1980.
DOI : 10.1002/qua.560170612

A. Y. Meyer and W. G. Richards, Similarity of molecular shape, Journal of Computer-Aided Molecular Design, vol.50, issue.5, p.427, 1991.
DOI : 10.1007/BF00125663

A. C. Good, E. E. Hodgkin, and W. G. Richards, Utilization of Gaussian functions for the rapid evaluation of molecular similarity, Journal of Chemical Information and Modeling, vol.32, issue.3, pp.188-191, 1992.
DOI : 10.1021/ci00007a002

W. G. Richards, The dominant Role of Shape Similarity and Dissimilarity in QSAR, 10th European Symposium on SAR: QSAR and Molecular Modelling, pp.4-9, 1994.

G. E. Kellogg, S. F. Semus, and D. Abraham, HINT: A new method of empirical hydrophobic field calculation for CoMFA, Journal of Computer-Aided Molecular Design, vol.20, issue.6, pp.545-552, 1991.
DOI : 10.1007/BF00135313

T. G. Gantchev, H. Ali, and J. E. Van-lier, Quantitative Structure-Activity Relationships/Comparative Molecular Field Analysis (QSAR/CoMFA) for Receptor-Binding Properties of Halogenated Estradiol Derivatives, Journal of Medicinal Chemistry, vol.37, issue.24, pp.4164-4176, 1994.
DOI : 10.1021/jm00050a013

M. C. Nicklaus, G. W. Milne, and T. R. Burke-jr, QSAR of conformationally flexible molecules: Comparative Molecular Field Analysis of protein-tyrosine kinase inhibitors, Journal of Computer-Aided Molecular Design, vol.116, issue.5, pp.487-504, 1992.
DOI : 10.1007/BF00130399

B. J. Van-steen, I. Van-wijngaarden, M. T. Tulp, and W. Soudijn, Structure-Affinity Relationship Studies on 5-HT1A receptor Ligands. 2. Heterobicyclic Phenylpiperazines with N4-Aralkyl Substituents, Journal of Medicinal Chemistry, vol.37, issue.17, pp.2761-2773, 1994.
DOI : 10.1021/jm00043a015

M. Langlois, B. Bremont, D. Rousselle, and F. Gaudy, Structural analysis by the comparative molecular field analysis method of the affinity of ??-adrenoreceptor blocking agents for 5-HT1A and 5-HT1B receptors, European Journal of Pharmacology: Molecular Pharmacology, vol.244, issue.1, pp.77-87, 1993.
DOI : 10.1016/0922-4106(93)90061-D

A. Agarwal and E. W. Taylor, 3-D QSAR for intrinsic activity of 5-HT1A receptor ligands by the method of comparative molecular field analysis, Journal of Computational Chemistry, vol.40, issue.2, pp.237-245, 1993.
DOI : 10.1002/jcc.540140211

R. Henderson, J. Baldwin, T. H. Ceska, F. Zemlin, E. Beckmann et al., Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy, Journal of Molecular Biology, vol.213, issue.4, pp.899-929, 1990.
DOI : 10.1016/S0022-2836(05)80271-2

P. A. Hargrave and . Prog, Chapter 1 Rhodopsin chemistry, structure and topography, Progress in Retinal Research, vol.1, pp.1-51, 1982.
DOI : 10.1016/0278-4327(82)90003-7

J. L. Popot, D. M. Engelman, O. Gurel, and G. Zaccai, Tertiary structure of bacteriorhodopsin, Journal of Molecular Biology, vol.210, issue.4, pp.829-847, 1989.
DOI : 10.1016/0022-2836(89)90111-3

P. Tuffery, J. L. Popot, R. Lavery, . Ed, J. L. Rigaud et al., Structures and Functions of Retinal Proteins, Eurotext Ltd, vol.221, pp.13-16, 1992.

B. K. Kobilka, T. Frielle, S. Collins, T. L. Yang-feng, T. S. Kobilka et al., An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins, Nature, vol.329, issue.6134, pp.75-79, 1987.
DOI : 10.1038/329075a0

F. Jähnig and O. Edholm, Modeling of the structure of bacteriorhodopsin, Journal of Molecular Biology, vol.226, issue.3, pp.837-850, 1992.
DOI : 10.1016/0022-2836(92)90635-W

S. Trumpp-kallmeyer, J. Hoflack, A. Bruinvels, and M. Hibert, Modeling of G-protein-coupled receptors: application to dopamine, adrenaline, serotonin, acetylcholine, and mammalian opsin receptors, Journal of Medicinal Chemistry, vol.35, issue.19, pp.3448-3462, 1992.
DOI : 10.1021/jm00097a002

S. B. Needleman and C. D. Wunsch, A general method applicable to the search for similarities in the amino acid sequence of two proteins, Journal of Molecular Biology, vol.48, issue.3, pp.443-453, 1970.
DOI : 10.1016/0022-2836(70)90057-4

J. Kyte and R. F. Doolittle, A simple method for displaying the hydropathic character of a protein, Journal of Molecular Biology, vol.157, issue.1, pp.105-132, 1982.
DOI : 10.1016/0022-2836(82)90515-0

M. F. Hibert, M. W. Gittos, D. N. Middlemiss, A. K. Mir, and J. R. Fozard, Graphics computer-aided receptor mapping as a predictive tool for drug design: development of potent, selective, and stereospecific ligands for the 5-HT1A receptor, Journal of Medicinal Chemistry, vol.31, issue.6, pp.1087-1093, 1988.
DOI : 10.1021/jm00401a007

M. F. Hibert, I. Mcdermott, D. N. Middlemiss, A. K. Mir, and J. R. Fozard, Radioligand binding study of a series of 5-HT1A receptor agonists and definition of a steric model of this site, European Journal of Medicinal Chemistry, vol.24, issue.1, pp.31-37, 1989.
DOI : 10.1016/0223-5234(89)90160-8

R. A. Glennon, Central serotonin receptors as targets for drug research, Journal of Medicinal Chemistry, vol.30, issue.1, pp.1-12, 1987.
DOI : 10.1021/jm00384a001

J. E. Macor, C. A. Burkhart, J. H. Heym, J. L. Ives, L. A. Lebel et al., 3-(1,2,5,6-Tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one: a potent and selective serotonin (5-HT1*) agonist and rotationally restricted phenolic analog of 5-methoxy-3-(1,2,5,6-tetrahydropyrid-4-yl)indole, Journal of Medicinal Chemistry, vol.33, issue.8, pp.2087-2093, 1990.
DOI : 10.1021/jm00170a007

J. E. Macor, C. B. Fox, C. Johnson, B. K. Koe, L. A. Lebet et al., 1-(2-Aminoethyl)-3-methyl-8,9-dihydropyrano[3,2-e]indole: a rotationally restricted phenolic analog of the neurotransmitter serotonin and agonist selective for serotonin (5-HT2-type) receptors, Journal of Medicinal Chemistry, vol.35, issue.20, pp.3625-3632, 1992.
DOI : 10.1021/jm00098a005

E. W. Taylor, S. Nikam, B. Weck, and A. Martin, Relative selectivity of some conformationally constrained tryptamine analogs at 5-HT1, 5-HT1A and 5-HT2 recognition sites, Life Sciences, vol.41, issue.16, pp.1961-1969, 1987.
DOI : 10.1016/0024-3205(87)90749-1

I. Van-wijngaarden, M. T. Tulp, and W. Soudijn, The concept of selectivity in 5-HT receptor research, European Journal of Pharmacology: Molecular Pharmacology, vol.188, issue.6, pp.301-312, 1990.
DOI : 10.1016/0922-4106(90)90190-9

M. D. Ennis, M. E. Baze, M. W. Smith, C. F. Lawson, R. B. Mc-call et al., Novel indolodioxanes with antihypertensive effects: potent ligands for the 5-HT1A receptor, Journal of Medicinal Chemistry, vol.35, issue.16, pp.3058-3066, 1992.
DOI : 10.1021/jm00094a021

P. Sternlöf, M. Gullme, T. Elebring, B. Andersson, H. Wikström et al., (S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde: a new class of orally active 5-HT1A-receptor agonists, Journal of Medicinal Chemistry, vol.36, issue.15, pp.2059-2065, 1993.
DOI : 10.1021/jm00067a002

S. E. Hillver, L. Björk, Y. L. Li, B. Svensson, S. Ross et al., (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin: a putative 5-HT1A-receptor antagonist, Journal of Medicinal Chemistry, vol.33, issue.6, pp.1541-1544, 1990.
DOI : 10.1021/jm00168a002

H. Wikström, B. Andersson, T. Elebring, J. Facyno, N. L. Allinger et al., Resolved cis-10-hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinoline: central serotonin stimulating properties, Journal of Medicinal Chemistry, vol.30, issue.9, pp.1567-1573, 1987.
DOI : 10.1021/jm00392a007

Y. Liu, B. E. Svensson, H. Yu, L. Cortizo, S. B. Ross et al., C8-substituted derivatives of 2-(dipropylamino)tetralin: Palladium-catalyzed synthesis and interactions with 5-HT1A-receptors, Bioorganic & Medicinal Chemistry Letters, vol.1, issue.5, pp.257-262, 1991.
DOI : 10.1016/S0960-894X(01)81038-6

Y. Liu, L. Cortizo, H. Yu, B. E. Svensson, T. Lewander et al., C8-Substituted derivatives of 2-(dipropylamino)tetralin: exploration of the effect of C8-aryl and heteroaryl substituents on the interaction with 5-HT1A-receptor, European Journal of Medicinal Chemistry, vol.30, issue.4, pp.277-286, 1995.
DOI : 10.1016/0223-5234(96)88236-5

A. N. Jain, N. L. Harris, and J. Y. Park, Quantitative Binding Site Model Generation: Compass Applied to Multiple Chemotypes Targeting the 5-HT1A Receptor, Journal of Medicinal Chemistry, vol.38, issue.8, pp.1295-1308, 1995.
DOI : 10.1021/jm00008a008

C. G. Chidester, C. H. Lin, R. A. Lahti, S. R. Haadsma-svensson, and M. W. Smith, Comparison of 5-HT1A and dopamine D2 pharmacophores. X-ray structures and affinities of conformationally constrained ligands, Journal of Medicinal Chemistry, vol.36, issue.10, pp.1301-1315, 1993.
DOI : 10.1021/jm00062a001

Z. P. Zhuang, M. P. Kung, and H. F. Kung, Synthesis of (R,S)-trans-8-hydroxy-2-[N-n-propyl-N-(3'-iodo-2'-propenyl)amino]tetralin (trans 8-OH-PIPAT): a new 5-HT1A receptor ligand, Journal of Medicinal Chemistry, vol.36, issue.21, pp.3161-3165, 1993.
DOI : 10.1021/jm00073a016

L. E. Arvidsson, U. Hacksell, A. M. Johansson, J. L. Nilsson, K. Svensson et al., (+)-cis-8-Hydroxy-1-methyl-2-(di-n-propylamino)tetralin: a potent and highly stereoselective 5-hydroxytryptamine receptor agonist, Journal of Medicinal Chemistry, vol.30, issue.11, pp.2105-2109, 1987.
DOI : 10.1021/jm00394a029

L. E. Arvidsson, A. Karlen, U. Norinder, L. Kenne, S. Sundell et al., Structural factors of importance for 5-hydroxytryptaminergic activity. Conformational preferences and electrostatic potentials of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and some related agents, Journal of Medicinal Chemistry, vol.31, issue.1, pp.212-221, 1988.
DOI : 10.1021/jm00396a034

C. H. Lin, S. R. Haadsma-svensson, G. Phillips, R. B. Mc-call, M. F. Piercey et al., Synthesis and biological activity of cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9-carboxamide: A potent and selective 5-HT1A receptor agonist with good oral availability, Journal of Medicinal Chemistry, vol.36, issue.15, pp.2208-2218, 1993.
DOI : 10.1021/jm00067a018

A. G. Romero, J. A. Leiby, R. B. Mc-call, M. Piercey, and F. Han, Novel 2-substituted tetrahydro-3H-benz[e]indolamines: highly potent and selective agonists acting at the 5-HT1A receptor as possible anxiolytics and antidepressants, Journal of Medicinal Chemistry, vol.36, issue.15, pp.2066-2074, 1993.
DOI : 10.1021/jm00067a003

C. Sonesson, T. Barf, J. Nilsson, D. Dijkstra, A. Carlsson et al., Synthesis and Evaluation of Pharmacological and Pharmacokinetic Properties of Monopropyl Analogs of 5-, 7-, and 8-[[(Trifluoromethyl)sulfonyl]oxy]-2-aminotetralins: Central Dopamine and Serotonin Receptor Activity, Journal of Medicinal Chemistry, vol.38, issue.8, pp.1319-1329, 1995.
DOI : 10.1021/jm00008a010

J. Vallgarda, L. E. Arvidsson, B. E. Svensson, C. J. Fowler, and U. Hacksell, Phenolic derivatives of 1,2-methano-N,N-dipropyl-1,2,3,4-tetrahydronaphth-2-ylamine. Structural hybrids of 2-aminotetralin- and phenylcyclopropylamine-derived 5-HT1A-receptor agonists, European Journal of Medicinal Chemistry, vol.28, issue.5, pp.399-406, 1993.
DOI : 10.1016/0223-5234(93)90126-Y

N. Naiman, R. Lyon, A. Bullock, L. Rydelek, L. Titeler et al., 2-(Alkylamino)tetralin derivatives: interaction with 5-HT1A serotonin binding sites, Journal of Medicinal Chemistry, vol.32, issue.1, pp.253-256, 1989.
DOI : 10.1021/jm00121a045

L. Björk, B. Höök, D. L. Nelson, N. E. Anden, and U. Hacksell, Resolved N,N-dialkylated 2-amino-8-hydroxytetralins: stereoselective interactions with 5-HT1A receptors in the brain, Journal of Medicinal Chemistry, vol.32, issue.4, pp.779-783, 1989.
DOI : 10.1021/jm00124a009

C. Mellin, J. Vallgarda, D. L. Nelson, L. Björk, ;. H. Yu et al., A 3 dimensional model for 5-HT1A-receptor agonists based on stereoselective methyl-substituted and conformationally restricted analogs of 8-hydroxy-2-(dipropylamino)tetralin, Journal of Medicinal Chemistry, vol.34, issue.2, pp.497-510, 1991.
DOI : 10.1021/jm00106a004

A. H. Thèse-de-benarab, 3-b] pyridines substituées sur l'hétérocycle oxygène : synthèse et propriétés pharmacologiques, p.4, 1992.

Z. P. Zhuang, M. P. Kung, and H. F. Kung, Synthesis And Evaluation of 4-(2'-Methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)- p-iodobenzamido]ethyl]piperazine (p-MPPI): A New Iodinated 5-HT1A Ligand, Journal of Medicinal Chemistry, vol.37, issue.10, pp.1406-1407, 1994.
DOI : 10.1021/jm00036a003

R. K. Raghupathi, L. Fitzgerald, M. Teitler, and R. A. Glennon, Analogs of the 5-HT1A serotonin antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine with reduced .alpha.1-adrenergic affinity, Journal of Medicinal Chemistry, vol.34, issue.8, pp.2633-2638, 1991.
DOI : 10.1021/jm00112a043

A. Hutchison, M. Williams, R. De-jesus, G. A. Stone, L. Sylvester et al., 2H-[1]Benzopyrano[3,4-b]pyridines. Synthesis and activity at central monoamine receptors, Journal of Medicinal Chemistry, vol.32, issue.3, pp.720-727, 1989.
DOI : 10.1021/jm00123a039

P. C. Moser, M. D. Tricklebank, D. N. Middlemiss, A. K. Mir, M. F. Hibert et al., Characterization of MDL 73005EF as a 5-HT1A selective ligand and its effects in animal models of anxiety: comparison with buspirone, 8-OH-DPAT and diazepam, British Journal of Pharmacology, vol.21, issue.2, pp.343-349, 1990.
DOI : 10.1111/j.1476-5381.1990.tb14706.x

J. L. Mokrosz, M. Pietrasiewicz, B. Duszynska, and M. T. Cegla, Structure-activity relationship studies of central nervous system (CNS) agents. 5. Effect of the hydrocarbon chain on the affinity of 4-substituted 1-(3-chlorophenyl)piperazines for 5-HT1A receptor sites, Journal of Medicinal Chemistry, vol.35, issue.13, pp.2369-2374, 1992.
DOI : 10.1021/jm00091a004

J. L. Mokrosz, M. H. Paluchowska, E. Wojcik, M. Filip, S. Charakchieva-minol et al., Structure-Activity Relationship Studies of Central Nervous System Agents. 13.4-[3-(Benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)piperazine, a New Putative 5-HT1A Receptor Antagonist, and Its Analogs, Journal of Medicinal Chemistry, vol.37, issue.17, pp.2754-2760, 1994.
DOI : 10.1021/jm00043a014

B. J. Van-steen, I. Van-wijngaarden, M. T. Tulp, and W. Soudijn, Structure-Affinity Relationship Studies on 5-HT1A receptor Ligands. 2. Heterobicyclic Phenylpiperazines with N4-Aralkyl Substituents, Journal of Medicinal Chemistry, vol.37, issue.17, pp.2761-2773, 1994.
DOI : 10.1021/jm00043a015

M. D. Meyer, J. F. De-bernardis, and A. A. Hancok, Synthesis and structure activity relationships of cis- and trans-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-c]pyridines for 5-HT receptor subtypes, Journal of Medicinal Chemistry, vol.37, issue.1, pp.105-112, 1994.
DOI : 10.1021/jm00027a013

D. Zhang and H. Weinstein, Signal transduction by a 5-HT2 receptor: a mechanistic hypothesis from molecular dynamics simulations of the three-dimensional model of the receptor complexed to ligands, Journal of Medicinal Chemistry, vol.36, issue.7, pp.934-938, 1993.
DOI : 10.1021/jm00059a021

S. Trumpp-kallmeyer, J. Hoflack, A. Bruinvels, and M. Hibert, Modeling of G-protein-coupled receptors: application to dopamine, adrenaline, serotonin, acetylcholine, and mammalian opsin receptors, Journal of Medicinal Chemistry, vol.35, issue.19, pp.3448-3462, 1992.
DOI : 10.1021/jm00097a002

B. K. Kobilka, T. Frielle, S. Collins, T. Yang-feng, T. S. Kobilka et al., An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins, Nature, vol.329, issue.6134, pp.75-79, 1987.
DOI : 10.1038/329075a0

J. M. Baldwin, R. Henderson, E. Beckman, and F. Zemlin, Images of purple membrane at 2.8 ?? resolution obtained by cryo-electron microscopy, Journal of Molecular Biology, vol.202, issue.3, pp.585-591, 1988.
DOI : 10.1016/0022-2836(88)90288-4

R. Henderson and P. N. Unwin, Three-dimensional model of purple membrane obtained by electron microscopy, Nature, vol.181, issue.5521, pp.28-32, 1975.
DOI : 10.1038/257028a0

R. J. Lefkowitz, J. L. Benovic, B. Kobilka, and M. G. Caron, ??-Adrenergic receptors and rhodopsin: shedding new light on an old subject, Trends in Pharmacological Sciences, vol.7, pp.444-448, 1986.
DOI : 10.1016/0165-6147(86)90417-7

J. Deisenhofer and H. Michel, The Photosynthetic Reaction Center from the Purple Bacterium Rhodopseudomonas viridis, Science, vol.245, issue.4925, pp.1463-1467, 1989.
DOI : 10.1126/science.245.4925.1463

J. Deisenhofer, O. Epp, K. Miki, R. Hubert, and M. Michel, Structure of the protein subunits in the photosynthetic reaction centre of Rhodopseudomonas viridis at 3??? resolution, Nature, vol.216, issue.6047, pp.618-624, 1985.
DOI : 10.1038/318618a0

W. Kühlbrandt and D. N. Wang, Three-dimensional structure of plant light-harvesting complex determined by electron crystallography, Nature, vol.350, issue.6314, pp.130-134, 1991.
DOI : 10.1038/350130a0

R. A. Dixon, I. S. Sigal, E. Rands, R. B. Register, M. R. Candelore et al., Ligand binding to the ??-adrenergic receptor involves its rhodopsin-like core, Nature, vol.326, issue.6108, pp.73-77, 1987.
DOI : 10.1038/326073a0

P. R. Hartig, Molecular biology of 5-HT receptors, Trends in Pharmacological Sciences, vol.10, issue.2, pp.64-69, 1989.
DOI : 10.1016/0165-6147(89)90080-1

R. J. Lefkowitz, B. K. Kobilka, and M. G. Caron, The new biology of drug receptors, Biochemical Pharmacology, vol.38, issue.18, pp.2941-2948, 1989.
DOI : 10.1016/0006-2952(89)90001-4

L. Oxford-molecular, The Magdalen Centre

J. Kyte and R. Doolittle, A simple method for displaying the hydropathic character of a protein, Journal of Molecular Biology, vol.157, issue.1, pp.105-132, 1982.
DOI : 10.1016/0022-2836(82)90515-0

W. F. Van-gunsteren and H. J. Berendsen, Groningen Molecular Simulation (GROMOS) Library Manual, 1987.

J. J. Stewart, MOPAC: A semiempirical molecular orbital program, Journal of Computer-Aided Molecular Design, vol.7, issue.1, pp.1-105, 1990.
DOI : 10.1007/BF00128336

W. F. Van-gunsteren and H. J. Berendsen, Algorithms for macromolecular dynamics and constraint dynamics, Molecular Physics, vol.34, issue.5, pp.1311-1327, 1977.
DOI : 10.1107/S0567740875002415

X. Luo, D. Zhang, and H. Weinstein, Ligand-induced domain motion in the activation mechanism of a G-protein-coupled receptor, "Protein Engineering, Design and Selection", vol.7, issue.12, pp.1441-1448, 1994.
DOI : 10.1093/protein/7.12.1441