Conformational studies on 2-guanidinylthiazole, famotidine and some analogues

Olea‐Azar, Claudio; Parra-Mouchet, Julia

doi:10.1016/s0166-1280(96)04779-3

Cited by 6 publications

(2 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…p interactions have relatively weak bond energies, they are large enough to be biologically significant [28]. Some authors suggested that famotidine binds to the H 2 -receptor via hydrogen bonds [29]. It is reasonable to suppose that various kinds of noncovalent p interactions could also be important for the binding of famotidine to the H 2 -receptor.…”

Section: The Other Intramolecular Interaction In Famotidinementioning

confidence: 99%

Interesting coordination abilities of antiulcer drug famotidine and antimicrobial activity of drug and its cobalt(III) complex

Miodragović

Bogdanović

Miodragović

et al. 2006

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

Section: The Other Intramolecular Interaction In Famotidinementioning

confidence: 99%

Interesting coordination abilities of antiulcer drug famotidine and antimicrobial activity of drug and its cobalt(III) complex

Miodragović

Bogdanović

Miodragović

et al. 2006

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

“…In the present work, ibuprofen (IBU) and famotidine (FMT) (Figure A(a,b), respectively) were selected to prepare a CAM system to probe that a rational design, leading to a desired structural motif constructed by specific N–H···O and O–H···N intermolecular interactions, can be performed. Multiple H-bond donors and acceptors are observed in the chemical structure of FMT, the imine nitrogen atom (N3) being the most basic , and therefore the most appropriate to participate in H-bond interactions with a given donor group. On the other hand, the hydroxyl group (H–O1) of the carboxylic moiety is the main H-bond donor in IBU .…”

Section: Introductionmentioning

confidence: 99%

Rational Design of a Famotidine–Ibuprofen Coamorphous System: An Experimental and Theoretical Study

et al. 2018

View full text Add to dashboard Cite

Famotidine (FMT) and ibuprofen (IBU) were used as model drugs to obtain coamorphous systems, where the guanidine moiety of the antacid and the carboxylic group of the nonsteroidal anti-inflammatory drug could potentially participate in H-bonds leading to a given structural motif. The systems were prepared in 3:7, 1:1, and 7:3 FMT and IBU molar ratios, respectively. The latter two became amorphous after 180 min of comilling. FMT-IBU (1:1) exhibited a higher physical stability in assays at 4, 25, and 40 °C up to 60 days. Fourier transform infrared spectroscopy accounted for important modifications in the vibrational behavior of those functional groups, allowing us to ascribe the skill of 1:1 FMT-IBU for remaining amorphous to equimolar interactions between both components. Density functional theory calculations followed by quantum theory of atoms in molecules analysis were then conducted to support the presence of the expected FMT-IBU heterodimer with consequent formation of a R8 structural motif. The electron density (ρ) and its Laplacian (∇ρ) values suggested a high strength of the specific intermolecular interactions. Molecular dynamics simulations to build an amorphous assembly, followed by radial distribution function analysis on the modeled phase were further employed. The results demonstrate that it is a feasible rational design of a coamorphous system, satisfactorily stabilized by molecular-level interactions leading to the expected motif.

show abstract

Solution-state NMR spectroscopy of famotidine revisited: spectral assignment, protonation sites, and their structural consequences

et al. 2011

View full text Add to dashboard Cite

Multinuclear one (1D-) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopic investigations of famotidine, the most potent and widely used histamine H(2)-receptor antagonist, were carried out in dimethyl sulfoxide-d(6) (DMSO-d(6)) and water. Previous NMR assignments were either incomplete or full assignment was based only on 1D spectra and quantum-chemical calculations. Our work revealed several literature misassignments of the (1)H, (13)C, and (15)N NMR signals and clarified the acid-base properties of the compound at the site-specific level. The erroneous assignment of Baranska et al. (J. Mol. Struct. 2001, 563) probably originates from an incorrect hypothesis about the major conformation of famotidine in DMSO-d(6). A folded conformation similar to that observed in the solid-state was also assumed in solution, stabilized by an intramolecular hydrogen bond involving one of the sulphonamide NH(2) protons and the thiazole nitrogen. Our detailed 1D and 2D NMR experiments enabled complete ab initio (1)H, (13)C, and (15)N assignments and disproved the existence of the sulphonamide NH hydrogen bond in the major conformer. Rather, the molecule is predominantly present in an extended conformation in DMSO-d(6). The aqueous acid-base properties of famotidine were studied by 1D (1)H- and 2D (1)H/(13)C heteronuclear multiple-bond correlation (HMBC) NMR-pH titrations. The experiments identified its basic centers including a new protonation step at highly acidic conditions, which was also confirmed by titrations and quantum-chemical calculations on a model compound, 2-[4-(sulfanylmethyl)-1,3-thiazol-2-yl]guanidine. Famotidine is now proved to have four protonation steps in the following basicity order: the sulfonamidate anion protonates at pH = 11.3, followed by the protonation of the guanidine group at pH = 6.8, whereas, in strong acidic solutions, two overlapping protonation processes occur involving the amidine and thiazole moieties.

show abstract

Conformational studies on 2-guanidinylthiazole, famotidine and some analogues

Cited by 6 publications

References 11 publications

Interesting coordination abilities of antiulcer drug famotidine and antimicrobial activity of drug and its cobalt(III) complex

Interesting coordination abilities of antiulcer drug famotidine and antimicrobial activity of drug and its cobalt(III) complex

Rational Design of a Famotidine–Ibuprofen Coamorphous System: An Experimental and Theoretical Study

Solution-state NMR spectroscopy of famotidine revisited: spectral assignment, protonation sites, and their structural consequences

Contact Info

Product

Resources

About