Zetidoline metabolism by rat liver microsomes

Assandri, Alessandro; Galliani, Glulio; Zerilli, L. F.; Tuan, G.; Tarzia, Giorgio; Barone, Domenico

doi:10.1016/0006-2952(86)90110-3

Cited by 6 publications

(2 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Asahi Chemical Industry Co., Ltd., Asahi-machi, Nobeoka-shi, Miyazaki 882, Japan. Received April 7,1988 Two novel series of jV-(2-guanidinoalkyl)-5-isoquinolinesulfonamides, 2 and 3, were prepared. Many of the compounds possessed vasodilatory activity when injected locally into the femoral artery of dogs.…”

Section: Methodsmentioning

confidence: 99%

“…piquindone (2) and molindone (3)), and zetidoline (4). [5][6][7] In previous studies, some of us have demonstrated close structural analogies among orthopramides. In particular, their molecular electrostatic potential (MEP) could be rationalized in terms of a pharmacophore8 which has been found to be similar to that displayed by molindone and piquindone.9 Recently, this pharmacophoric model has received independent validation by being proven congruent with the results of a traditional quantitative structureactivity relationship (QSAR) analysis of 20 orthopramide derivatives.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Stereoelectronic study of zetidoline, a dopamine D2 receptor antagonist

Collin¹,

Evrard²,

Vercauteren³

et al. 1989

J. Med. Chem.

View full text Add to dashboard Cite

A combination of experimental and theoretical methods were used to investigate the stereoelectronic structure of zetidoline, a dopamine D2 receptor antagonist showing Na+-dependent binding. The solid-state conformation of zetidoline is characterized by synplanarity (coplanarity of the two rings with the chloro substituent and the carbonyl group on the same side). The side chain in the crystal adopts a folded conformation which places the azetidine nitrogen atom at about 8 A from the center of the aromatic ring. Quantum mechanical calculations indicate the synperiplanar and antiperiplanar conformations of the ring system to be of approximately equal energies. The molecular electrostatic potential of zetidoline in a nearly extended conformation shows a remarkable similarity with that of orthopramides (e.g. metoclopramide) and indolones (e.g. piquindone), i.e. two groups of drugs displaying the same D2 selectivity and Na+-dependent binding. We postulate that the close stereoelectronic similarity between zetidoline, orthopramides, and indolones accounts for their identical mechanism of action in the molecular level.

show abstract

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%