Journal ArticleDOI
Synthesis and Pharmacology of Combined Histamine H1‐/H2‐Receptor Antagonists Containing Diphenhydramine and Cyproheptadine Derivatives
Cornelia Wolf,Schunack Walter G +1 more
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TLDR
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.Abstract:
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.read more
Citations
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Journal ArticleDOI
Clinical pharmacology of new histamine H1 receptor antagonists.
Simons Fe,Keith J. Simons +1 more
TL;DR: Most orally administered new H1 receptor antagonists are well absorbed and appear to be extensively distributed into body tissues; many are highly protein-bound.
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Synthesis and applications of chiral organoboranes generated from sulfonium ylides.
TL;DR: The ylide-borane reaction was applied to short syntheses of the anti-inflammatory agents neobenodine and cetirizine, both of which contain a chiral diarylmethylalkoxy and diarylmethylamino moiety, respectively.
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The pharmacological profile of ovalbumin-induced paw oedema in rats.
Regina Fátima Gonçalves Feitosa,G B Melcíades,Ana Maria Sampaio Assreuy,Marcos Fábio Gadelha Rocha,Ronaldo A. Ribeiro,Aldo A. M. Lima +5 more
TL;DR: Data indicate that allergic oedema is more sensitive to anti-serotonin drugs, mainly anti-5-HT2, suggesting that the principal mediator of this inflammatory response is serotonin.
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Reduction of tinnitus severity by the centrally acting muscle relaxant cyclobenzaprine: an open-label pilot study.
Claudia Coelho,Ricardo Rodrigues Figueiredo,Elmar Frank,Julia Burger,Martin Schecklmann,Michael Landgrebe,Berthold Langguth,Ana Belén Elgoyhen +7 more
TL;DR: High-dose cyclobenzaprine resulted in a significant reduction in the Tinnitus Handicap Inventory (THI) score between baseline and week 12 in the intention-to-treat sample, and other treatments were not effective.
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Step Forward to Stronger Neutral Organic Superbases: Fused Troponimines.
TL;DR: NICS and anisotropy of the induced current density (ACID) were utilized in this study to probe into the aromaticity-related parameters of the proposed molecules and revealed the highest GB/PA values for the molecules having cyclobutadiene in between two troponimines.
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Journal ArticleDOI
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