54610-49-0Relevant articles and documents
Efficient synthesis of novel 2,3-dihydro-1,3,5,4-thiadiazaphosphole derivatives
Balti, Monaem,Efrit, Mohamed Lotfi
, p. 466 - 475 (2016/07/23)
ABSTRACT: The condensation of various thiosemicarbazones with methyl thiophene-2-carboximidate afforded the corresponding intermediates 2a–2h. Subsequent cyclization of the latter compounds with hexamethylphosphorous triamide constitutes a new route to the synthesis of novel highly functionalized thiadiazaphosphole derivatives 4a–4h. This method offers significant advantages such as efficiency, high yields and mild reaction conditions.
1,2-disubstituted hexahydro-1 H -benzo[d]imidazoles: Synthesis, characterization, and stability
Tydlitat, Jiri,Bures, Filip,Kulhanek, Jiri,Ruzicka, Ales
scheme or table, p. 3934 - 3940 (2010/12/29)
Starting from commercially available (hetero)aromatic nitriles and (1R,2R)-cyclohexane-1,2-diamine, nine NH-imidazolines (hexahydro-1H-benzo[d] imidazoles) were synthesized in good yields. The molecular structures of three imidazolines were confirmed by X-ray analysis. N-Benzylation afforded some of the desired N-benzylimidazolines, but was incompatible with imidazolines that possessed strong electron-accepting heteroaromatic groups at C2. In the latter cases, the products decomposed during column chromatography to form N,N-disubstituted cyclohexane-1,2-diamines. Georg Thieme Verlag Stuttgart · New York.
Synthesis and Histamine H1 Receptor Agonist Activity of a Series of 2-Phenylhistamines, 2-Heteroarylhistamines, and Analogues
Leschke, Christian,Elz, Sigurd,Garbarg, Monique,Schunack, Walter
, p. 1287 - 1294 (2007/10/02)
New histamine derivatives characterized by a (substituted) aryl, heteroaryl, benzyl, or hetroarylmethyl substituent in the C2 position of the imidazole ring have been prepared from appropriate imidates or amidines, respectively, and 2-oxo-4-phthalimido-1-butyl acetate (1).The compounds were screened as potential H1 receptor agonist on the isolated guinea pig ileum.The 3-halogenated 2-phenylhistamines (halogen = Br (35) and I (36) were equipotent with histamine, while 2-(3-(trifluoromethyl)phenyl)histamine (2-ethanamine (39)) was significantly more potent than histamine (39: pD2 = 6.81, relative activity = 128percent).The 2-substituted histamine analogues were potential H1 receptor agonists on the endothelium-denuded isolated guinea pig aorta with pEC50 values generally smaller than observed on the guinea pig ileum, but the rank order of potency was found to be similar.The contractile effects on guinea pig ileum and aorta, respectively, could be blocked concentraction-dependently by the H1 receptor antagonist mepyramine, yielding KB values for mepyramine in the nanomolar range.In vitro compounds 35 and 39 bound to mepyramine-labeled guinea pig cerebellar membranes with a pKi of 6.1 and 5.9, respectively.However, upon iv administration, 35 (3-100 mg/kg) and 39 (3-300 mg/kg) failed to inhibit the binding of mepyramine to mouse cerebral cortex in vivo , thereby indicating that these histamine derivatives are not able to penetrate the blood-brain berrier.In functional in vitro studies on histamine H2, H3, and other neurotransmitter receptors the selectivity of 39 was found to be 2138 (H1:H2), >64 (H1:H3), 1000 (H1:M3, 105 (H1:α1), 708 (H1:β1) and 71 (H1:5HT2A).Thus compound 39 is the most potent and selective H1 receptor agonist reported so far .These results make meta- substituted 2-phenylhistamines, especially 2-(3-(trifluoromethyl)phenyl)- and 2-(3-bromophenyl)histamine (39 and 35, respectively) valuable experimental tools for the selective stimulation of histamine H1 receptors and the study of H1 receptor-mediated functions.
