The hypothesis that the activity of cimetidine, a member of a family of anti-ulcer drugs, may depend on the protonation ability of the unsaturated nitrogens of its guanidine arm is studied quantitatively on the basis of energies and charge distributions determined by the PM3 method. At variance of histamine, whose two sites susceptible of proton activity are more or less energetically equivalent, in cimetidine protonation at the imidazole cycle is favoured. However, the ability of the cyano-guanidine arm to fur a proton depends on the conformation of the whole molecule and, in certain cases, it becomes comparable with that of the imidazole nitrogen. These points may provide a key to a better understanding of the mechanism of action of drugs of the cimetidine group.
On the protonation of the guanidine arm of cimetidine: A theoretical study
PELUSO, Andrea
1996-01-01
Abstract
The hypothesis that the activity of cimetidine, a member of a family of anti-ulcer drugs, may depend on the protonation ability of the unsaturated nitrogens of its guanidine arm is studied quantitatively on the basis of energies and charge distributions determined by the PM3 method. At variance of histamine, whose two sites susceptible of proton activity are more or less energetically equivalent, in cimetidine protonation at the imidazole cycle is favoured. However, the ability of the cyano-guanidine arm to fur a proton depends on the conformation of the whole molecule and, in certain cases, it becomes comparable with that of the imidazole nitrogen. These points may provide a key to a better understanding of the mechanism of action of drugs of the cimetidine group.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.