Synthesis and evaluation of 4-(1-aminoalkyl)-N-(4-pyridyl) cyclohexanecarboxamides as Rho kinase inhibitors and neurite outgrowth promoters

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 19, 2004, Pages 4931-4934

  Gingras, Karine ^a   Avedissian, Hovsep ^b   Thouin, Eryk ^a   Boulanger, Véronique ^a   Essagian, Charles ^a   McKerracher, Lisa ^a,b   Lubell, William D ^b  

^a C   (Canada)

^b UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

Enzyme inhibitor; Kinase; Rho; Synthesis

Indexed keywords

4 (1 AMINOETHYL) N (4 PYRIDYL)CYCLOHEXANECARBOXAMIDE; OCTANE; PHOSPHOTRANSFERASE INHIBITOR; PROPANE; RHO KINASE;

ANIMAL CELL; ARTICLE; CELL ASSAY; CONTROLLED STUDY; DRUG ACTIVITY; DRUG SCREENING; DRUG SYNTHESIS; ENZYMATIC ASSAY; ENZYME INHIBITION; EXAMINATION; MOUSE; NERVE FIBER GROWTH; NEUROBLASTOMA CELL; NONHUMAN; STEREOCHEMISTRY;

AMIDES; CELL LINE; ENZYME INHIBITORS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; NEURITES; PROTEIN-SERINE-THREONINE KINASES; PYRIDINES; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 4444283128     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.07.025     Document Type: Article

References (30)

1. M.E.M. Noble, J.A. Endicott, and L.N. Johnson Science 303 2004 1800
2. H. Shimokawa, H. Iinuma, H. Kishida, M. Nakashima, and K. Kato Circulation 104 2001 2843
3. T. Ishizaki, M. Uehata, I. Tamechika, J. Keel, K. Nonomura, M. Maekawa, and S. Narumiya Mol. Pharmacol. 57 2000 976
4. S.P. Davies, H. Reddy, M. Caivano, and P. Cohen Biochem. J. 351 2000 95
5. L. McKerracher, and M.J. Winton Neuron 36 2002 345
6. P. Dergham, B. Ellezam, C. Essagian, H. Avedissian, W.D. Lubell, and L. McKerracher J. Neurosci. 22 2002 6570
7. Arita, M.; Saito, T.; Okuda, H.; Sato, H.; Uehata, M. U.S. Patent 5,478,838, 1995
8. Muro, T.; Seki, T.; Abe, M.; Inui, J.; Sato, H. U.S. Patent 4,997,834, 1991
9. H.-J. Cristau, J. Monbrun, M. Tillard, and J.-L. Pirat Tetrahedron Lett. 44 2003 3183
10. R. Bloch Chem. Rev. 98 1998 1407
11. The 9:1 diastereomeric ratio observed after coupling 1 to N-(toluenesulfonyl)prolyl chloride was in close agreement with the 93:7 dr obtained in the addition of MeMgBr to α-methylbenzyl cyclohexylaldimines: G. Alvaro, D. Savoia, and M.R. Valentinetti Tetrahedron 52 1996 571
12. C. Boga, D. Savoia, and A. Umani-Ronchi Tetrahedron: Asymmetry 1 1990 291
13. G. Alvaro, C. Boga, D. Savoia, and A. Umani-Ronchi J. Chem. Soc., Perkin Trans. 1 1996 875
14. +])
15. G. Bringmann, J.-P. Geisler, T. Geuder, G. Künkel, and L. Kinzinger Liebigs Ann. Chem. 1990 795
16. M. Zhao, J. Li, E. Mano, Z. Song, D.M. Tschaen, E.J.J. Grabowski, and P.J. Reider J. Org. Chem. 64 1999 2564
17. J.E. Dettwiler, and W.D. Lubell J. Org. Chem. 68 2003 177
18. A. Avenoza, J.H. Busto, J.M. Peregrina, and F. Rodriguez J. Org. Chem. 67 2002 4241
19. R.F. Poulain, A.L. Tartar, and B.P. Déprez Tetrahedron Lett. 42 2001 1495
20. J. Cluzeau, and W.D. Lubell J. Org. Chem. 69 2004 1504
21. Stereochemical assignment for the alcohol 12 was made based on the product from the addition of (R,R)-diisopropyl-2-allyl-1,3,2-dioxaborolane-4,5- dicarboxylate to cyclohexane carboxaldehyde, which produced predominantly the (S)-alcohol (dr 93:7): W.R. Roush, L.K. Hoong, M.A.J. Palmer, and J.C. Park J. Org. Chem. 55 1990 4109
22. W.R. Roush, A.E. Walts, and L.K. Hoong J. Am. Chem. Soc. 107 1985 8186
23. W.R. Roush, A.D. Palkowitz, and K. Ando J. Am. Chem. Soc. 112 1990 6248
24. K.C. Nicolaou, T. Caulfield, H. Kataoka, and T. Kumazawa J. Am. Chem. Soc. 110 1988 7910
25. H.E. Blackwell, D.J. O'Leary, A.K. Chatterjee, R.A. Washenfelder, D.A. Bussmann, and R.H. Grubbs J. Am. Chem. Soc. 122 2000 58
26. T.M. Trnka, and R.H. Grubbs Acc. Chem. Res. 34 2001 18
27. S. Randl, and S. Blechert J. Org. Chem. 68 2003 8879
28. The isomeric ratio 75:25 trans:cis was assigned by integration of isomeric signals at 5.26 and 5.35 and 5.47 and 5.57 ppm. The major isomer was assigned the trans isomer based on the 15.3 Hz coupling constant for the olefin protons
29. In the case of 2 the Boc group was removed before hydrogenation; with 3 the hydrogenation preceded Boc deprotection
30. +])