Benzyl prolinate derivatives as novel selective KCC2 blockers

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 8, 2010, Pages 2542-2545

  Pégurier, Cécile ^a   Bosman, Nathalie ^a   Collart, Philippe ^a   Delporte, Marie Laure ^a   Leclercq, Karine ^a   Lengelé, Sébastien ^a   Kanduluru, Ananda Kumar ^b   Meunier, Stéphane ^b   Pacico, Nathalie ^a   Vadali, Lakshmana Rao ^b   Wagner, Alain ^b   Wolff, Christian ^a   Provins, Laurent ^a  

^a UCB PHARMA   (Belgium)

^b CNRS   (France)

Author keywords

Epilepsy; Furosemide; KCC2

Indexed keywords

BENZYL 1 ACETYL 2 BENZYLPROLINATE; BENZYL PROLINATE DERIVATIVE; FUROSEMIDE; POTASSIUM CHLORIDE COTRANSPORTER; POTASSIUM CHLORIDE COTRANSPORTER KCC2 BLOCKING AGENT; PROLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CANCER CELL CULTURE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; RAT; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANIMALS; PROLINE; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SYMPORTERS;

EID: 77950065713     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.02.092     Document Type: Article

References (16)

1. Song L., Mercado A., Vazquez N., Xie Q., Desai R., George A.L., Gamba G., and Mount D.B. Mol. Brain Res. 103 (2002) 91
2. Rivera C., Voipio J., Payne J.A., Ruusuvuori E., Lahtinen H., Lamsa K., Pirvola U., Saarma M., and Kaila K. Nature 397 (1999) 251
3. De Koninck Y. Curr. Opin. Pharmacol. 7 (2007) 93
4. Gamba G. Physiol. Rev. 85 (2005) 423
5. Hesdorffer D.C., Stables J.P., Hauser W.A., Annegers J.F., and Cascino G. Ann. Neurol. 50 (2001) 458
6. Delpire E., Days E., Lewis L.M., Mi D., Kim K., Lindsley C.W., and Weaver C.D. PNAS 106 (2009) 5383
7. + is determined by atomic absorption spectroscopy.
8. + is determined by atomic absorption spectroscopy.
9. Confalone P.N., Huie E.M., Ko S.S., and Cole G.M. J. Org. Chem. 53 (1988) 482
10. Ghose A.K., and Crippen G.M. J. Comput. Chem. 7 (1986) 565
11. Leach A.G., Jones H.D., Cosgrove D.A., Kenny P.W., Ruston L., MacFaul P., Wood J.M., Colclough N., and Law B. J. Med. Chem. 49 (2006) 6672
12. Male genetically sound-sensitive mice, weighing 18-30 g, are used. They are submitted to a first challenge for selection of responding animals. An acoustic stimulus (85 dB, 10-20 kHz) is delivered for 30 s. The mice are observed and the presence of the three phases of the seizure activity (wild running, clonic and tonic convulsions) is noted. The next day, compounds are administered before induction of the acoustic stimulus and the proportion of animals protected against the three phases is calculated in each group (N = 10 animals/tested dose).
13. Reid K.H., Guo S.Z., and Iyer V.G. Brain Res. 864 (2000) 134
14. Margineanu D.G., and Klitgaard H. Epilepsy Res. 69 (2006) 93
15. Holtkamp M., Matzen J., Buchheim K., Walker M.C., and Meierkord H. Epilepsia 44 (2003) 1141
16. Luszczki J.J., Sawicka K.M., Kozinska J., Borowicz K.K., and Czuczwar S.J. Epilepsy Res. 76 (2007) 66