Solution-phase parallel synthesis and evaluation of anticonvulsant activity of N-substituted-3,4-dihydroisoquinoline-2(1H)-carboxamides

European Journal of Medicinal Chemistry

Volumn 44, Issue 3, 2009, Pages 1349-1354

  Gitto, Rosaria ^a   Pagano, Benedetta ^a   Citraro, Rita ^b   Scicchitano, Francesca ^b   De Sarro, Giovanbattista ^b   Chimirri, Alba ^a  

^a UNIVERSITY OF MESSINA   (Italy)

^b UNIVERSITY MAGNA GRAECIA OF CATANZARO   (Italy)

Author keywords

Anticonvulsant; DBA 2 mice; Isoquinoline; Solution phase parallel synthesis (SPPS)

Indexed keywords

1 (4' BROMOPHENYL) 6,7 DIMETHOXY N PROPYL 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' BROMOPHENYL) N BUTYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' BROMOPHENYL) N CYCLOHEXYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' BROMOPHENYL) N CYCLOPENTYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' BROMOPHENYL) N ETHYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' BROMOPHENYL) N ISOPROPYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' CHLOROPHENYL) 6,7 DIMETHOXY N PROPYL 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' CHLOROPHENYL) N CYCLOHEXYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' CHLOROPHENYL) N CYCLOPENTYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' CHLOROPHENYL) N ETHYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' CHLOROPHENYL) N ISOPROPYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' CHLOROPHENYL) N TERY BUTYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' FLUOROOPHENYL) N ETHYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' FLUOROPHENYL) 6,7 DIMETHOXY N PROPYL 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 (4' FLUOROPHENYL) N ISOPROPYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 N BUTYL (4' CHLOROPHENYL) 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 1 N BUTYL (4' FLUOROPHENYL) 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; 6'7 DIMETHOXY 1 PHENYL N PROPYL 3,4 DIHYDROISOQUINOLIN 2(IH) CARBOXAMIDE; 6'7 DIMETHOXY N ISOPROPYL 1 PHENYL 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; ANTICONVULSIVE AGENT; GABAPENTIN; N BUTYL 6,7 DIMETHOXY 1 PHENYL 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; N CYCLOHEXYL 6'7 DIMETHOXY 1 PHENYL 3,4 DIHYDROISOQUINOLINE 2(1H) CARBOXAMIDE; N CYCLOPENTYL 6'7 DIMETHOXY 1 (4' FLUOROPHENYL) 3,4 DIHYDROISOQUINOLINE 2(1H) CARBOXAMIDE; N CYCLOPENTYL 6'7 DIMETHOXY 1 PHENYL 3,4 DIHYDROISOQUINOLINE 2(1H) CARBOXAMIDE; N ETHYL 1 PHENYL 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; N TERT BUTYL 1 (4' CHLOROPHENYL) 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; N TERT BUTYL 1 (4' FLUOROPHENYL) 6,7 DIMETHOXY 3,4 DIHYDROISOQUINOLIN 2(1H) CARBOXAMIDE; N TERT BUTYL 6'7 DIMETHOXY 1 PHENYL 3,4 DIHYDROISOQUINOLINE 2(1H) CARBOXAMIDE; UNCLASSIFIED DRUG; VALPROIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICONVULSANT ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; MALE; MOUSE; NONHUMAN; SEIZURE; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTICONVULSANTS; ISOQUINOLINES; MAGNETIC RESONANCE SPECTROSCOPY; MICE; MICE, INBRED DBA; SEIZURES;

EID: 60549099775     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2008.02.025     Document Type: Article

References (21)

1. Perucca E., French C., and Bialer M. Development of new antiepileptic drugs: challenges, incentives, and recent advances. Lancet Neurol. 6 (2007) 793-804
2. Rogawski M.A. Molecular targets versus models for new antiepileptic drug discovery. Epilepsy Res. 68 (2006) 22-28
3. Rogawski M.A. Diverse mechanisms of antiepileptic drugs in the development pipeline. Epilepsy Res. 69 (2006) 273-294
4. De Sarro G., Gitto R., Russo E., Ibbadu G.F., Barreca M.L., De Luca L., and Chimirri A. AMPA receptor antagonists as potential anticonvulsant drugs. Curr. Top. Med. Chem. 5 (2005) 31-42
5. Barreca M.L., Gitto R., Quartarone S., De Luca L., De Sarro G., and Chimirri A. Pharmacophore modeling as an efficient tool in the discovery of novel noncompetitive AMPA receptor antagonists. J. Chem. Inf. Comput. Sci. 43 (2003) 651-655
6. De Luca L., Gitto R., Barreca M.L., Caruso R., Quartarone S., Citraro R., De Sarro G., and Chimirri A. 3D pharmacophore models for 1,2,3,4-tetrahydroisoquinoline derivatives acting as anticonvulsant agents. Arch. Pharm. (Weinheim) 339 (2006) 388-400
7. Gitto R., Barreca M.L., De Luca L., De Sarro G., Ferreri G., Quartarone S., Russo E., Constanti A., and Chimirri A. Discovery of a novel and highly potent noncompetitive AMPA receptor antagonist. J. Med. Chem. 46 (2003) 197-200
8. Gitto R., Barreca M.L., Francica E., Caruso R., De Luca L., Russo E., De Sarro G., and Chimirri A. Synthesis and anticonvulsant properties of 1,2,3,4-tetrahydroisoquinolin-1-ones. Arkivoc (2004) 170-180
9. Gitto R., Caruso R., Orlando V., Quartarone S., Barreca M.L., Ferreri G., Russo E., De Sarro G., and Chimirri A. Synthesis and anticonvulsant properties of tetrahydroisoquinoline derivatives. Farmaco 59 (2004) 7-12
10. Gitto R., Caruso R., Pagano B., De Luca L., Citraro R., Russo E., De Sarro G., and Chimirri A. Novel potent anticonvulsant agent containing a tetrahydroisoquinoline skeleton. J. Med. Chem. 49 (2006) 5618-5622
11. Arstad E., Gitto R., Chimirri A., Caruso R., Constanti A., Turton D., Hume S.P., Ahmad R., Pilowsky L.S., and Luthra S.K. Closing in on the AMPA receptor: Synthesis and evaluation of 2-acetyl-1-(4′-chlorophenyl)-6-methoxy-7-[(11)C]methoxy-1,2,3,4-tetrahydro isoquinoline as a potential PET tracer. Bioorg. Med. Chem. 14 (2006) 4712-4717
12. Ferreri G., Chimirri A., Russo E., Gitto R., Gareri P., De Sarro A., and De Sarro G. Comparative anticonvulsant activity of N-acetyl-1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives in rodents. Pharmacol. Biochem. Behav. 77 (2004) 85-94
13. DeSarro G., Chimirri A., DeSarro A., Gitto R., Grasso S., Giusti P., and Chapman A.G. GYKI 52466 and related 2,3-benzodiazepines as anticonvulsant agents in DBA/2 mice. Eur. J. Pharmacol. 294 (1995) 411-422
14. Donevan S.D., and Rogawski M.A. GYKI 52466, a 2,3-benzodiazepine, is a highly selective, noncompetitive antagonist of AMPA/kainate receptor responses. Neuron 10 (1993) 51-59
15. Gitto R., Barreca M.L., De Luca L., and Chimirri A. New trends in the development of AMPA receptor antagonists. Expert Opin. Ther. Pat. 14 (2004) 1199-1213
16. Chapman A.G., Croucher M.J., and Meldrum B.S. Evaluation of anticonvulsant drugs in DBA/2 mice with sound-induced seizures. Arzneimittelforschung 34 (1984) 1261-1264
17. Borowicz K.K., Duda A.M., Kleinrok Z., and Czuczwar S.J. Interaction of GYKI 52466, a selective non-competitive antagonist of AMPA/kainate receptors, with conventional antiepileptic drugs in amygdala-kindled seizures in rats. Pol. J. Pharmacol. 53 (2001) 101-108
18. Jakus R., Graf M., Ando R.D., Balogh B., Gacsalyi I., Levay G., Kantor S., and Bagdy G. Effect of two noncompetitive AMPA receptor antagonists GYKI 52466 and GYKI 53405 on vigilance, behavior and spike-wave discharges in a genetic rat model of absence epilepsy. Brain Res. 1008 (2004) 236-244
19. Donato Di Paola E., Gareri P., Davoli A., Gratteri S., Scicchitano F., Naccari C., and De Sarro G. Influence of levetiracetam on the anticonvulsant efficacy of conventional antiepileptic drugs against audiogenic seizures in DBA/2 mice. Epilepsy Res. 75 (2007) 112-121
20. Advanced Chemistry and Development, ACD/Lab, 2004, .
21. Litchfield Jr. J.T. A method for rapid graphic solution of time-percent effect curves. J. Pharmacol. Exp. Ther. 97 (1949) 399-408