3D-QSAR studies on cannabinoid CB1 receptor agonists: G-protein activation as biological data

Journal of Medicinal Chemistry

Volumn 49, Issue 2, 2006, Pages 554-566

  Salo, Outi M H ^a   Savinainen, Juha R ^a   Parkkari, Teija ^a   Nevalainen, Tapio ^a   Lahtela Kakkonen, Maija ^a   Gynther, Jukka ^a   Laitinen, Jarmo T ^a   Järvinen, Tomi ^a   Poso, Antti ^a  

^a UNIVERSITY OF EASTERN FINLAND   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR AGONIST; CANNABINOID RECEPTOR AGONIST; ENDOCANNABINOID; GUANINE NUCLEOTIDE BINDING PROTEIN; RIMONABANT; UNCLASSIFIED DRUG;

ARTICLE; AUTOMATION; COMPARATIVE MOLECULAR FIELD ANALYSIS; COMPARATIVE MOLECULAR SIMILARITY INDICES ANALYSIS; DRUG ACTIVITY; DRUG BINDING SITE; DRUG RECEPTOR BINDING; DRUG STRUCTURE; ENZYME ACTIVATION; PREDICTION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; VALIDATION PROCESS;

ANIMALS; CEREBELLUM; ENDOCANNABINOIDS; GTP-BINDING PROTEINS; LIGANDS; MALE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RADIOLIGAND ASSAY; RATS; RATS, WISTAR; RECEPTOR, CANNABINOID, CB1;

EID: 31544434659     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0505157     Document Type: Article

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101. Ernst, J.; Sheldrick, W. S.; Fahrhop, J.-H. The structures of the essential unsaturated fatty acids. Crystal structure of linoleic acid and evidence for the crystal structures of alpha-linolenic and arachidonic acid. Z. Naturforsch. 1979, 34h, 706-711.
102. Rich, M. U. Conformational analysis of arachidonic and related fatty acids using molecular dynamics simulations. Biochim. Biophys. Acta 1993, 1178, 87-96.
103. Corey, E. J.; Iguchi, S.; Albright, J.; De, B. Studies on the conformational mobility of arachidonic acid. Facile macrolactonization of 20-hydroxyarachidonic acid. Tetrahedron Lett. 1983, 24, 37-40.
104. Leach, A. R.; Prout, K. Automated conformational analysis: directed conformational search using the A* algorithm. J. Comput. Chem, 1990, 11, 1193-1205.
105. Reggio, P. H.; Traore, H, Conformational requirements for eadocannabinoid nabinoid with the cannabinoin receptors, the anandamide transporter and fatty acid amidohydrolase. Chem. Phys. Lipids 2000, 108, 15-35.
106. Atom pairs fur distance constrainls: U-shaped = 1-19, 3-17, 4-9, 12-14; J-shaped = 2-8, 3-11, 9-15, 7-20; extended = 2-19, 4-11; helical = 1-8, 7-13, 9-20. See Table 1 (molecule 19) for atom numbering. Constrain constant = 100.00 for all shapes except for extended = 200.00.
107. MD parameters: Tripos force field, charges = none, length = 100 ps, temperature = 500 K, step sine = 2 fs, Bonds to SHAKE applied on hydrogen atoms, snapshot every 1 ps.
108. Gaussian 98, Gaussian, Inc.: Wallingford, CT, 1998.
109. Gaussifin parameters: multiplicity = singlet; charges = Merz-Kollman; theory = Hartree-Fock; basis set = 3-21G*, geometry optimization = FULL; constrain charges to match dipole = YES.
110. PM3, AM1, MNDO (ESP fit); computed via MOPAC v. 6.0 (QCPE No. 455) interface in SYBYL.
111. Gasteiger, Gasteiger-Hückel, Pullman, Del-Re; computed as implemented in SYBYL.
112. Dewar, M. J. S.; Thiel, W. Ground States of Molecules, 38. The MNDO Method, Approximations and Parameters, J. Am. Chem. Soc. 1977, 99, 4899-4907.
113. Besler, B. H.; Merz, K. M.; Kollman, P. A, Atomic charges derived from semiempirical methods. J. Comput. Chem. 1990, 11, 431-439.
114. Ballesteros, J. A.; Weinstein, H. W. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G-protein coupled receptors. In Methods in Neuroscience; Conn, P. M., Sealfon, S. C., Eds.; Academic Press: San Diego, 1995; Vol. 25, pp 366-428.
115. Hurst, D. P.; Lynch, D. L.; Barnett-Norris, J.; Hyatt, S. M.; Seltzman, H. H.; Zhong, M.; Song, Z. H.; Nie, J.; Lewis, D.; Reggio, P. H. N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H- pyrazole-3-carboxnmide (SR141716A) interaction with LYS 3.28(192) is crucial for its inverse agonism at the cannabinoid CB1 receptor. Mol. Pharmacol. 2002, 62, 1274-1287.