A peptidic binding site model for PDE 4 inhibitors

Quantitative Structure-Activity Relationships

Volumn 18, Issue 6, 1999, Pages 543-547

  Polymeropoulos, Emmanuel E ^a   Höfgen, Norbert ^a  

^a ASTA MEDICA AG   (Germany)

Author keywords

Modelling; Phosphodiesterase 4; PrGen; Receptor

Indexed keywords

BINDING ENERGY; FORECASTING;

AMINO ACID RESIDUES; BINDING SITE MODELS; BINDING-SITES; MODEL PROGRAMS; MODELING; PHOSPHODIESTERASE-4; PRGEN; PSEUDORECEPTOR MODEL; RECEPTOR; TRAINING SETS;

ESTERS;

4 (3 BUTOXY 4 METHOXYBENZYL) 2 IMIDAZOLIDINONE; 4 [2 [3 (CYCLOPENTYLOXY) 4 METHOXYPHENYL] 2 PHENYLETHYL]PYRIDINE; AMINO ACID; AROFYLLINE; CILOMILAST; GW 3600; INDOLE DERIVATIVE; NITRAQUAZONE; PDA 641; PHOSPHODIESTERASE IV INHIBITOR; PICLAMILAST; PYRAZINE DERIVATIVE; ROLIPRAM; UNCLASSIFIED DRUG; XANTHINE DERIVATIVE; ZINC ION;

ANALYTICAL ERROR; ARTICLE; BINDING SITE; COMPUTER MODEL; DRUG BINDING; PREDICTION; PRIORITY JOURNAL;

EID: 0343339896     PISSN: 09318771     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1521-3838(199912)18:6<543::AID-QSAR543>3.0.CO;2-V     Document Type: Article

References (16)

1. Palfreyman, M.N., Phosphodiesterase type IV inhibitors as antiinflammatory agents, Drugs Future 20, 793-804 (1995).
2. Karlsson, J.A., Aldous, D., Phosphodiesterase 4 inhibitors for the treatment of asthma, Exp. Opin. Ther. Patents 7, 989-1003 (1997).
3. Polymeropoulos, E.E., Höfgen, N., A pharmacophore model for PDE 4 inhibitors, Quant. Struct.-Act. Relat. 16, 231-234 (1997).
4. Zbinden, P., Dobler, M., Folkers, G., Vedani, A, Pseudo-receptor modeling using receptor-mediated ligand alignment and pharmacophore equilibration, Quant. Struct.-Act. Relat. 17, 122-130 (1998).
5. Höfgen, N. et al., EP 736532.
6. Höfgen, N. et al., DE 198 18 964.8 (reg. nr.)
7. AM1; MOPAC v.6.0, QCPE, No. 455, 1989.
8. Marengo, E., Todeschini, R., A new algorithm for optimal, distance-based experimental design, Chemom. Intell. Lab. Syst. 16, 37-44 (1992).
9. Goodford, P.J., A computational procedure for determining energetically favourable binding sites on biologically important macromolecules, J. Med. Chem. 28, 849-857 (1985).
10. Bou, J. et al., Third International Conference on Cyclic Nucleotide Phosphodiesterases: From Genes to Therapies, Glasgow, July 1996.
11. Cavalla, D., Frith, R., Phosphodiesterase IV inhibitors: Structural diversity and therapeutic potential in asthma, Curr. Med. Chem. 2, 561-572 (1995).
12. Inhibition of PDE IV in human PMNL. Assay established at ASTA/AWD.
13. Stafford, J.A., Veal, J.M., Feldman, P.L., Valvano, N.L., Baer, P.G., Brackeen, M.F., Sloan Brawley, E., Connolly, K.M., Domanico, P.L., Han, B., Rose, D.A., Rutkowske, R.D., Sekut, L., Stimpson, S.A., Strickland, A.B., Verghese, M.W., Introduction of a conformational switching element on a pyrrolidine ring. Synthesis and evaluation of (R,R)-(+/-)-methyl 3-acetyl-4-(3-cyclopentoxy) 4-methoxyphenyl)-3-methyl 1-pyrrolidine carboxylate, a potent and selective inhibitor of cAMP-specific phosphodiesterase, J. Med. Chem. 38, 4972-4975 (1995).
14. Cavalla, D. et al., XIVth International Symposium on Medicinal Chemistry, Maastricht 1996, P-5.11.
15. 3H]rolipram binding activity and their relationship to emetic behavior in the ferret, J. Med. Chem. 39, 120-125 (1996).
16. Francis, S.H., Colbran, J.L., McAllister-Lucas, L.M., Corbin, J.D., Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase, J. Biol. Chem. 269, 22477-22480 (1994).