Antihypertensive and antiarrhythmic properties of a para-hydroxy[bis(ortho-morpholinylmethyl)]phenyl-1,4-DHP compound: comparison with other compounds of the same kind and relationship with logP values.
A new para-hydroxy[bis(ortho-morpholinylmethyl)]phenyl-1,4-DHP substituted compound, (4-(4-hydroxy-3,5-bis(morpholin-4-ylmethyl)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester, LQM300), with antihypertensive and antiarrhythmic properties, has been synthesized. Four pKa values of this compound have been determined with the aid of the program SQUAD, at pseudo-physiological conditions (T = 37 degrees C and I = 0.15 M) by UV spectrophotometry and at T = 25 degrees C and I = 0.05 M by Capillary Zone Electrophoresis (CZE). The logP = 2.7 +/- 0.2 between n-octanol and water, has been estimated by UV spectrophotometry. The antihypertensive and antiarrhythmic efficacies as well as the logP values have been compared with other compounds of the same kind and related with their structure.
Abrego
Victor H
VH
Universidad Nacional Autónoma de México, FES-Cuautitlán, Laboratorio de Química Medicinal, Campo 1. Av. 1ero de mayo S/N. 54714 Estado de México, México.
Martínez-Pérez
Beatriz
B
Torres
Luis A
LA
Angeles
Enrique
E
Martínez
Luisa
L
Marroquín-Pascual
J Lorena
JL
Moya-Hernández
Rosario
R
Amaro-Recillas
Héctor Adrián
HA
Rueda-Jackson
Juan Carlos
JC
Rodríguez-Barrientos
Damaris
D
Rojas-Hernández
Alberto
A
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry* / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004095:Dihydropyridines / Q000737:chemistry* / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013056:Spectrophotometry, Ultraviolet
C554436:4-(4-hydroxy-3,5-bis(morpholin-4-ylmethyl)phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D004095:Dihydropyridines; D009025:Morpholines