TY - JOUR
T1 - Conformational evaluation and detailed 1H and 13C NMR assignments of flavoxate, a urinary tract antispasmodic agent
AU - Pérez-Hernández, Nury
AU - Morales-Ríos, Martha S.
AU - Cerda-García-Rojas, Carlos M.
AU - Joseph-Nathan, Pedro
PY - 2006/5/3
Y1 - 2006/5/3
N2 - 1H and 13C NMR chemical shift assignments for the urinary tract antispasmodic flavoxate (1) and flavoxate hydrochloride (2) were obtained from one- and two-dimensional measurements. A Monte Carlo random search using molecular mechanics, followed by geometry optimization of each minimum energy structure employing DFT calculations at the B3LYP/6-31G* level, and a Boltzmann analysis of the total energies, provided accurate molecular models which describe the conformational behavior of flavoxate (1). The electron density surfaces for the global minimum and the second minimum conformers 1a and 1b of this L-type Ca2+ channel inhibitor were calculated. The presence of both conformers in solution was demonstrated in full agreement with 2D NOESY data and NOE difference spectroscopy.
AB - 1H and 13C NMR chemical shift assignments for the urinary tract antispasmodic flavoxate (1) and flavoxate hydrochloride (2) were obtained from one- and two-dimensional measurements. A Monte Carlo random search using molecular mechanics, followed by geometry optimization of each minimum energy structure employing DFT calculations at the B3LYP/6-31G* level, and a Boltzmann analysis of the total energies, provided accurate molecular models which describe the conformational behavior of flavoxate (1). The electron density surfaces for the global minimum and the second minimum conformers 1a and 1b of this L-type Ca2+ channel inhibitor were calculated. The presence of both conformers in solution was demonstrated in full agreement with 2D NOESY data and NOE difference spectroscopy.
KW - 2D NMR
KW - Conformational analysis
KW - DFT calculations
KW - Flavoxate
KW - Molecular modeling
KW - NOEDS
KW - Urinary tract antispasmodic
UR - http://www.scopus.com/inward/record.url?scp=33645990661&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2005.11.042
DO - 10.1016/j.jpba.2005.11.042
M3 - Artículo
SN - 0731-7085
VL - 41
SP - 603
EP - 609
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
IS - 2
ER -