Journal of medicinal chemistry, 1999-04, Vol.42 (7), p.1115-1122
1999
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Details
- Autor(en) / Beteiligte
- Titel
- Characterization of the Binding Site of the Histamine H3 Receptor. 1. Various Approaches to the Synthesis of 2-(1H-Imidazol-4-yl)cyclopropylamine and Histaminergic Activity of (1R,2R)- and (1S,2S)-2-(1H-Imidazol-4-yl)- cyclopropylamine
- Ist Teil von
- Journal of medicinal chemistry, 1999-04, Vol.42 (7), p.1115-1122
- Ort / Verlag
- Washington, DC: American Chemical Society
- Erscheinungsjahr
- 1999
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Various approaches to the synthesis of all four stereoisomers of 2-(1H-imidazol-4-yl)cyclopropylamine (cyclopropylhistamine) are described. The rapid and convenient synthesis and resolution of trans-cyclopropylhistamine is reported. The absolute configuration of its enantiomers was determined by single-crystal X-ray crystallographic analysis. The distinct trans-cyclopropylhistamine enantiomers were tested for their activity and affinity on the histamine H3 receptor. (1S,2S)-Cyclopropylhistamine (VUF 5297) acts as an agonist both on the rat cortex (pD 2 = 7.1; α = 0.75) and on guinea pig jejunum (pD 2 = 6.6; α = 0.75). Its enantiomer, (1R,2R)-cyclopropylhistamine (VUF 5296), is about 1 order of magnitude less active. Both enantiomers show weak activity on H1 and H2 receptors. All synthetic attempts to cis-cyclopropylhistamine were unsuccessful. Nevertheless, the results of this study provide an ideal template for molecular modeling studies of histamine H3 receptor ligands.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-2623eISSN: 1520-4804DOI: 10.1021/jm9810912Titel-ID: cdi_proquest_miscellaneous_69681223
- Format
- –
- Schlagworte
- Animals, Binding Sites, Binding, Competitive, Biological and medical sciences, Cerebral Cortex - metabolism, Crystallography, X-Ray, Cyclopropanes - chemical synthesis, Cyclopropanes - chemistry, Cyclopropanes - metabolism, Cyclopropanes - pharmacology, Guinea Pigs, Heart Rate - drug effects, Histamine - analogs & derivatives, Histamine - chemical synthesis, Histamine - chemistry, Histamine - metabolism, Histamine - pharmacology, Histamine Agonists - chemical synthesis, Histamine Agonists - chemistry, Histamine Agonists - metabolism, Histamine Agonists - pharmacology, Ileum - drug effects, Ileum - physiology, In Vitro Techniques, Jejunum - drug effects, Jejunum - physiology, Medical sciences, Miscellaneous, Models, Molecular, Muscle Contraction - drug effects, Muscle, Smooth - drug effects, Muscle, Smooth - physiology, Neuropharmacology, Neurotransmitters. Neurotransmission. Receptors, Norepinephrine - metabolism, Pharmacology. Drug treatments, Rats, Receptors, Histamine H1 - drug effects, Receptors, Histamine H2 - drug effects, Receptors, Histamine H3 - metabolism, Stereoisomerism, Structure-Activity Relationship