Discovery of pyrroloimidazoles as agents stimulating neurite outgrowth

QSAR and Combinatorial Science

Volumn 25, Issue 5-6, 2006, Pages 527-535

  Beck, Barbara ^a   Leppert, Christian A ^b   Mueller, Bernhard K ^b   Dömling, Alexander ^a,c  

^a Biovertis AG   (Germany)

^b MAX PLANCK INST FÜR BIOLOGIE   (Germany)

^c ABC Pharma   (Germany)

Author keywords

Isocyanide; Multicomponent reaction; Neurite outgrowth; Phenotype assay

Indexed keywords

REACTION KINETICS; SCAFFOLDS;

CARBALDEHYDES; COMBINATORIAL SYNTHESIS; ISOCYANIDES; MULTICOMPONENT REACTION; MULTICOMPONENTS; NEURITE OUTGROWTH; PHENOTYPE ASSAY; PRIMARY AMINES; SMALL MOLECULES; VAN LEUSEN REACTIONS;

CYANIDES;

3 (3 BENZYL 3H IMIDAZOL 4 YL) INDOLE 1 CARBOXYLIC TERT BUTYL ESTER; 3 (3 CYCLOHEXYL 3H IMIDAZOL 4 YL) INDOLE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 3 (3 METHYL 3H IMIDAZOL 4 YL) INDOLE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 3 (4 BENZYLPIPERIDIN 1H 5 YL) 2 METHYL 1H INDOLE; 3 [3 (IMIDAZOL 1 YL PROPYL) 3H IMIDAZOL 4 YL] INDOLE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 5 (BENZYLOXY) 3 (1 TETRAHYDRONAPHTHALIN 1H IMIDAZOL 5 YL) 1H PYRROL[2,3 C]PYRIDINE; IMIDAZOLE DERIVATIVE; PYRROLOIMIDAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CHEMICAL REACTION; CONTROLLED STUDY; DRUG SYNTHESIS; HUMAN; NERVE FIBER GROWTH; NERVE FIBER REGENERATION; NONHUMAN; PRIORITY JOURNAL; SPINAL CORD LESION; VERO CELL;

EID: 33745769257     PISSN: 1611020X     EISSN: 16110218     Source Type: Journal    
DOI: 10.1002/qsar.200540300     Document Type: Article

References (20)

1. T. J. Mitchison, Chem. Biol. 1994, 1, 3-6.
2. S. L. Schreiber, Bioorg. Med. Chem. 1998, 6, 1127-1152.
3. P. J. Horner, F. H. Gage, Nature 2000, 407, 963-970.
4. For a chondroitin sulfate small molecule stimulating neuronal growth: S. E. Tully, R. Mabon, C. I. Gama, S. M. Tsai, X. Liu, L. C. Hsieh-Wilson, J. Am. Chem. Soc. 2004, 126, 7736-7737.
5. B. K. Mueller, Annu. Rev. Neurosci. 1999, 22, 351-388.
6. P. P. Monnier, A. Sierra, J. M. Schwab, S. Henke-Fahle, B. K. Mueller, Mol. Cell. Neurosci. 2003, 22, 319-330.
7. A. Dömling, Chem. Rev. 2006, 126, 17-89.
8. C. Hulme, V. Gore, Curr. Med. Chem. 2003, 10, 51-80.
9. For a recent report on neurite-outgrowth activity of the proteasome inhibitor TMC-95A see: M. Inoue, H. Zhai, H. Furuyama, Y. Fukuyama, M. Hirama, Bioorg. Med. Chem. Lett. 2004, 14, 663-665.
10. D. van Leusen, A. van Leusen, Organic Reactions 2001, 57, 419-659.
11. J. Sisko, A. J. Kassick, M. Mellinger, J. J. Filan, A. Allen, M. A. Olsen, J. Org. Chem. 2000, 65, 1516-1524.
12. J. Sisko, M. Mellinger, M. Pure Appl. Chem. 2002, 74, 1349-1357.
13. Leading reviews in this area: a) L. Weber, K. Illgen, M. Almstetter, Synlett 1999, 366-374.
14. b) H. Bienaymé, C. Hulme, G. Oddon, P. Schmitt, Chem. Eur. J. 2000, 6, 3321-3329.
15. c) A. Dömling, I. Ugi, Angew. Chem. Intl. Ed. Engl. 2000, 39, 3168-3210.
16. B. Beck, A. Dömling, WO0125213
17. a) J. Sisko, M. Mellinger, P. W. Sheldrake, N. H. Baine, Tetrahedron Lett. 1996, 37, 8113-8116;
18. b) J. Sisko, M. Mellinger, P. W. Sheldrake, N. H. Baine, Org. Synth. 2002, 77, 198-202.
19. A diversity of α-substituted TOSMICs is available form several sources, e.g. www.synthatex.com.
20. A common target of many neurite outgrowth inhibitors is the rho family of small GTPases. For a recent review: K. L. Guan, Y. Rao, Nat. Rev. Neurosci. 2003, 4, 941-956.