Die Struktur von Cimetidin (N″‐Cyan‐N‐Methyl‐N′‐[2‐[(5‐methyl‐1H‐imidazol‐4‐yl)methylthio]ethyl]guanidin), einem Histamin H₂‐Rezeptor‐Antagonist

Abstract

Cimetidin Kristallisiert monoklin (Raumgruppe P21/c). Seine Struktur wurde röntgenographisch bestimmt und bis R = 0.035 verfeinert. Im Einzelmolekül entsteht durch eine intramolekulare N…HN‐Wasserstoffbrückenbindung zwischen Imidazolring und Guanidingruppe ein stabiler zehngliedriger Ring. Intermolekulare Wasserstoffbrückenbindungen, die von der Cyanguanidingruppe ausgehen, verbinden zwei Nachbarmoleküle paarweise in einer Kopf‐Schwanz‐Anordnung zu einem Zwölfring. Diese Molekülpaare verknüpfen sich über Wasserstoffbrücken zwischen Imidazolring und Cyangruppe zu gewellten Schichten.

Modelling of H2 antagonists and tridimensional modelling of H2 receptor interactions. Part 2

“…The crystallographic structures of the H2 antagonists cimetidine [15], ranitidine [16], and famotidine [17] were obtained from the Cambridge Structural Data Base. These were minimised using a refined parametrisation of the MNDO Hamiltonian, the PM3 method [ 181, which gives very good agreement between calculated conformational structures and experimental data [18, 191. The atomic charges for cimetidine, ranitidine and famotidine obtained by the AM1 method [20] were used in the MM (Molecular Mechanics) and MD (Molecular Dynamics) calculations.…”

“…Finally, the potential energies calculated for these complexes reflect the nature of the stabilizing interactions. Previous conformational studies of cimetidine derivatives using X-ray crystallography [15,22] and NMR techniques [23] have assumed that the E, 2 conformation of the cyanoguanidine moiety is associated with histamine H2 antagonist activity. The crystallographic structure of E, Z ring protonated cimetidine [15] was optimised using the PM3 method and its energy compared with the other isomeric conformations.…”

“…Previous conformational studies of cimetidine derivatives using X-ray crystallography [15,22] and NMR techniques [23] have assumed that the E, 2 conformation of the cyanoguanidine moiety is associated with histamine H2 antagonist activity. The crystallographic structure of E, Z ring protonated cimetidine [15] was optimised using the PM3 method and its energy compared with the other isomeric conformations. The E, Z form was found to be most stable, and was therefore, the only form considered in this study, and docked into the H2 receptor model active site.…”

A PCA-based chemometrics-assisted ATR-FTIR approach for the classification of polymorphs of cimetidine: Application to physical mixtures and tablets

“…The different polymorphs of CIM and their mixtures have been studied and characterized by X-ray crystallography [25][26][27][28], synchrotron X-ray powder diffraction [29] and vibrational (IR, Raman, NIR) spectroscopy [30][31][32]. The literature also contains other approaches, including calorimetry [24,33], atomic force microscopy [34] and solid-state NMR spectrometry [35,36].…”

Low temperature structure and dynamics of β-chloropivalic acid

“…Prominent members of ordered-disordered phase transitions are neopentane 1 and pivalic acid 2 . The shape of neopentane (CH 3 ) 4 C can be regarded as a sphere, where as pivalic acid CH 2 Cl(CH 3 ) 2 CCOOH forms dimers and therefore is cigar-like shaped.…”