Parallel synthesis of a series of potentially brain penetrant aminoalkyl benzoimidazoles

Bioorganic and Medicinal Chemistry

Volumn 16, Issue 5, 2008, Pages 2313-2328

  Micco, Iolanda ^a   Nencini, Arianna ^a   Quinn, Joanna ^a   Bothmann, Hendrick ^a   Ghiron, Chiara ^a   Padova, Alessandro ^a   Papini, Silvia ^a  

^a Siena Biotech SpA   (Italy)

Author keywords

Alpha7; Alzheimer's disease; Benzoimidazole

Indexed keywords

1 [3 (2 PYRIDIN 3 YLMETHYL BENZOIMIDAZOL 1 YL)PROPYL]PYRROLIDIN 2 ONE; 1 [3 [2 (2 METHOXYBENZYL)BENZOIMIDAZOL 1 YL]PROPYL]PYRROLIDIN 2 ONE; 1 [3 [2 (3 CHLOROPHENOXYMETHYL)BENZOIMIDAZOL 1 YL]PROPYL]PYRROLIDIN 2 ONE; 2 (2 CHLORO[HENOXYMETHYL) 1 [3 (2 METHYLPIPERIDIN 1 YL)PROPYL] 1H BENZOIMIDAZOLE; 2 (2 CHLOROPHENOXYMETHYL) 1 (3 MORPHOLIN 4 YL PROPYL) 1H BENZOIMIDAZOLE; 2 (2 FLUOROBENZYL) 1 [3 (4 METHYLPIPERAZIN 1 YL)PROPYL] 1H BENZOIMIDAZOLE; 2 (2 METHOXYBENZYL) 1 [3 (2 METHYLPIPERIDIN 1 YL)PROPYL] 1H BENZOIMIDAZOLE; 2 (2 METHOXYPHENOXYMETHYL) 1 (3 MORPHOLIN 4 YLPROPYL) 1H BENZOIMIDAZOLE; 2 (2 METHOXYPHENOXYMETHYL) 1 [3 (4 METHYLPIPERAZIN 1 YL)PROPYL] 1H BENZOIMIDAZOLE; 2 (3 CHLOROPHENOXYMETHYL) 1 [3 (4 METHYLPIPERAZIN 1 YL)PROPYL] 1H BENZOIMIDAZOLE; 2 (4 FLUOROPHENOXYMETHYL) 1 [2 (1 METHYLPYRROLIDIN 2 YL)ETHYL] 1H BENZOIMIDAZOLE; 2 BENZYL 1 [3 (2 METHYLPIPERIDIN 1 YL)PROPYL] 1H BENZOIMIDAZOLE; [3 [2 (2 CHLOROPHENOXYMETHYL)BENZOIMIDAZOL 1 YL]PROPYL]DIMETHYLAMINE; [3 [2 (4 BROMOBENZYL) 5 FLUOROBENZOIMIDAZOL 1 YL]PROPYL]DIMETHYLAMINE; [3 [2 (4 BROMOBENZYL)BENZOIMIDAZOL 1 YL]PROPYL]DIETHYLAMINE; [3 [2 (4 FLUOROPHENOXYMETHYL) 5 METHYLBENZOIMIDAZOL 1 YL]PROPYL]DIMETHYLAMINE; BENZOIMIDAZOLE DERIVATIVE; BUNGAROTOXIN RECEPTOR; DIETHYL [3 [2 (2 METHOXYPHENOXYMETHYL)BENZOIMIDAZOL 1 YL]PROPYL]AMINE; DIETHYL [3 [2 4 TOLYLOXYMETHYL BENZOIMIDAZOL 1 YL)PROPYL]AMINE; DIMETHYL [3 (2 PHENOXYMETHYL BENZOIMIDAZOL 1 YL)PROPYL]AMINE; DIMETHYL [4 [1 (3 MORPHOLIN 4 YL) 1H BENZOIMIDAZOL 2 YLMETHYL]PHENYL]AMINE; IMIDAZOLE DERIVATIVE; NICOTINIC AGENT; UNCLASSIFIED DRUG;

ACYLATION; ALKYLATION; ANIMAL CELL; ARTICLE; BINDING SITE; CALCIUM TRANSPORT; CONTROLLED STUDY; CYCLIZATION; DRUG PURIFICATION; DRUG STRUCTURE; DRUG SYNTHESIS; NONHUMAN; PROTON NUCLEAR MAGNETIC RESONANCE; PROTON TRANSPORT; RAT; THIN LAYER CHROMATOGRAPHY;

ALKYLATION; AMINATION; ANIMALS; BENZIMIDAZOLES; BRAIN; CALCIUM; CELL LINE; CHEMISTRY, PHYSICAL; CHICKENS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; RATS; RECEPTORS, NICOTINIC; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 40749163074     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2007.11.068     Document Type: Article

References (39)

1. Picciotto M.R., Caldarone B.J., King S.L., and Zachariou V. Neuropsychopharmacology 22 (2000) 451-465
2. Davis K.L., and Yamamura H.I. Life Sci. 23 (1978) 1729-1734
3. Holladay M.W., Dart M.J., and Lynch J.K. J. Med. Chem. 40 (1997) 4169-4194
4. Abreo M.A., Lin N.-H., Garvey D.S., Gunn D.E., Hettinger A.-M., Wasicak J.T., Pavlik P.A., Martin Y.C., Donnelly-Roberts D.L., Anderson D.J., Sullivan J.P., Williams M., Arneric S.P., and Holladay M.W. J. Med. Chem. 39 (1996) 817-825
5. Tatsumi R., Seio K., Fujio M., Katayama J., Horikawa T., Hashimoto K., and Tanaka H. Bioorg. Med. Chem. Lett. 16 (2004) 3781-3784
6. Bodnar A.L., Cortes-Burgos L.A., Cook K.K., Dinh D.M., Groppi V.E., Hajos M., Higdon N.R., Hoffmann W.E., Hurst R.S., Myers J.K., Rogers B.N., Wall T.M., Wolfe M.L., and Wong E. J. Med. Chem. 48 (2005) 905-908
7. Bunnelle W.H., Dart M.J., and Schrimpf M.R. Curr. Med. Chem. 4 (2004) 299-334
8. Tatsumi R., Fujio M., Takanashi S., Numata A., Katayama J., Satoh H., Shiigi Y., Maeda J., Kuriyama M., Horikawa T., Murozono T., Hashimoto K., and Tanaka H. J. Med. Chem. 49 (2006) 4374-4383
9. CCDC, GOLD version 2.2 2005.
10. Leonik F.M., Papke R.L., and Horenstein N.A. Bioorg. Med. Chem. Lett. 17 (2007) 1520-1522
11. Mazurov A., Klucik J., Miao L., Phillips T.Y., Seamans A., Schmitt J.D., Hauser T.A., Johnson Jr. R.T., and Miller C. Bioorg. Med. Chem. Lett. 15 (2005) 2073-2077
12. Macor J.E., Gurley D., Lanthorn T., Loch J., Mack R.A., Mullen G., Tran O., Wright N., and Gordon J.C. Bioorg. Med. Chem. Lett. 11 (2001) 319-321
13. Lanzafame A.A., Sexton P.M., and Christopoulos A. Mol. Pharmacol. 70 (2006) 736-746
14. Schmitz W.D., Denhart D.J., Brenner A.B., Ditta J.L., Mattson R.J., Mattson G.K., Molski T.F., and Macor J.E. Bioorg. Med. Chem. Lett. 15 (2005) 1619-1621
15. http://www.accelrys.com.
16. Lipinski C.A., Lombardo F., Dominy B.W., and Feeney P.J. Adv. Drug Del. Rev. 23 (1997) 3-25
17. Lipinski C.A. J. Pharm. Tox. Meth. 44 (2000) 235
18. Norinder U., and Haeberlein M. Adv. Drug Del. Rev. 54 (2002) 291-313
19. Veber D.F., Johnson S.R., Cheng H.-Y., Smith B.R., Ward K.W., and Kopple K.D. J. Med. Chem. 45 (2002) 2615
20. Mahar Doan K.M., Humphreys J.E., Webster L.O., Wring S.A., Shampine L.J., Serabjit-Singh J.C., Adkison K.K., and Polli J.W. J. Pharmacol. Exp. Ther. 303 (2002) 1029-1037
21. http://www.spotfire.com.
22. Nakane M., Cowart M.D., Hsieh G.C., Miller L., Uchic M.E., Chang R., Terranova M.A., Donnelly-Roberts D.L., Namovic M.T., Miller T.R., Wetter J.M., Marsh K., Stewart A.O., Brioni J.D., and Moreland R.B. Neuropharmacology 49 (2005) 112-121
23. Huang S., Lin R., Yu Y., Lu Y., Connolly P.J., Chiu G., Li S., Emanuel S.L., and Middleton S.A. Bioorg. Med. Chem. Lett. 17 (2007) 1243-1245
24. Ng R.A., Lanter J.C., Alford V.C., Allan G.F., Sbriscia T., Lundeen S.G., and Sui Z. Bioorg. Med. Chem. Lett. 17 (2007) 1784-1787
25. Karlin A., and Akabas M.H. Neuron 15 (1995) 1231-1244
26. Le Novere N., Grutter T., and Changeux J.P. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 3210-3215
27. Schapiro M., Abagyan R., and Totrov M. BMC Struct. Biol. 2 (2002) 1-9
28. Brejc K., van Dijk W.J., Klaassen R.V., Schuurmans M., van Der Oost J., Smit A.B., and Sixma T.K. Nature 411 (2001) 269-276
29. a7gg_nic.pdb available from http://www.ebi.ac.uk/compneur-srv/LGICdb/HTML/ACHa7gaga.php.
30. http://www.maybridge.com; http://www.specs.net.
31. Corina version 3.2 2005. Molecular Networks GmbH.
32. LigPrep version 1.6 2005. Schrödinger, LLC.
33. Lester H.A., Dibas M.I., Dahan D.S., Leite J.F., and Dougherty D.A. Trends in Neurosciences 27 (2004) 329-336
34. Poulain R., Horvath D., Bonnet B., Eckhoff C., Chapelain B., Bodinier M.-C., and Déprez B. J. Med. Chem. 21 (2001) 3378-3390
35. Bellamy F.D., and Ou K. Tetrahedron Lett. 25 (1984) 839-842
36. Elderfield R.C., and Meyer V.B. J. Am. Chem. Soc. 76 (1954) 1883-1886
37. White W., Almassy R., Calvert A.H., Curtin N.J., Golding B.T., Griffin R.J., Maegley K., Newell D.R., and Srinivasan S. J. Med. Chem. 43 (2000) 4084-4097
38. http://www.zinsser.com.
39. Dunlop J., Roncarati R., Jow B., Bothmann H., Lock T., Kowal D., Bowlby M., and Terstappen G.C. Biochemical Pharmacology 74 (2007) 1172-1181