17349-99-4Relevant academic research and scientific papers
Synthesis and pharmacology of combined histamine H1-/H2-receptor antagonists containing diphenhydramine and cyproheptadine derivatives
Wolf, Cornelia,Schunack, Walter
, p. 87 - 94 (2007/10/02)
The classical histamine H1-receptor antagonists diphenhydramine (3a) and cyproheptadine (9) and their derivatives (3b-d, 10) were connected with a 2-guanidinothiazole containing structure (28) derived from the H2-receptor antagonist tiotidine in order to obtain combined H1/H2-receptor antagonists. The two moieties were not directly linked together, but were separated by a polymethylene spacer and a polar group (nitroethenediamine or urea). Thus 12 compounds were obtained that proved in vitro to possess high H1- and H2-receptor antagonist activity at the isolated guinea-pig ileum (H1) and the isolated guinea-pig right atrium (H2), respectively. The incorporation of the diphenhydramine as well as the cyproheptadine component provides high affinity to H1-receptors. The tricyclic cyproheptadine and its 10,11-dihydro derivative (30-32, 34), however, cause a decrease of H2-receptor antagonist potency compared to the diphenhydramines (29a-d, 33a-d). Using nitroethenediamine as the polar group is apparently more favourable to H1- and H2-receptor affinity as the urea function. All compounds elicit a dual mode of competitive and noncompetitive antagonism. Among the novel compounds the nitroethenediamines with 4-fluoro- or 4-methyl-substituted diphenhydramine as H1-receptor antagonist moiety (29c, d) display the most potent H1- and H2-receptor antagonist effects. The presented concept is a very promising way to combine H1- and H2-receptor antagonist properties in one molecule.
Synthesis, Absolute Configuration and Circular Dichroism of Some Diarylmethane Derivatives
Stanchev, Stephan,Rakovska, Rosiza,Berova, Nikolina,Snatzke, Guenter
, p. 183 - 198 (2007/10/02)
Synthesis and assignment of the absolute configuration of different types of compounds bearing the diarylmethane moiety is presented.The absolute configuration was determined using chemical correlation and CD approaches based on the sign of the O-O vibronic transition within the α-aromatic (1Lb) band of the substituted phenyl chromophore.
