223419-72-5Relevant academic research and scientific papers
Design, synthesis, and structure-activity relationships of acetylene- based histamine H3 receptor antagonists
Ali, Syed M.,Tedford, Clark E.,Gregory, Rosilyn,Handley, Michael K.,Yates, Stephen L.,Hirth, Walter W.,Phillips, James G.
, p. 903 - 909 (2007/10/03)
New, potent, and selective histamine H3 receptor antagonists have been synthesized by employing the use of (1) an appropriately positioned nonpolar acetylene spacer group, (2) either a two-carbon straight chain linker or a conformationally restricting trans-cyclopropane ring between the C-4 position of an imidazole headgroup and the acetylene spacer, and (3) a Topliss operational scheme for side-chain substitution for optimizing the hydrophobic domain. Compounds 9-18 are examples synthesized with the two-carbon straight chain linker, whereas 26-31 are analogues prepared by incorporation of the trans-(±)-cyclopropane at the C-4 position of an imidazole headgroup. Synthesis of both the (1R,2R)- and (1S,2S)-cyclopropyl enantiomers of the most potent racemic compound 31 (K(i) = 0.33 ± 0.13 nM) demonstrated a stereopreference in H3 receptor binding affinity for the (1R,2R) enantiomer 32 (K(i) = 0.18 ± 0.04 nM) versus the (1S,2S) enantiomer 33 (K(i) = 5.3 ± 0.5 nM). (1R,2R)-4-(2-(5,5-Dimethylhex-1-ynyl)cyclopropyl)-imidazole (32) is one of the most potent histamine H3 receptor antagonists reported to date.
New acetylene based histamine H3 receptor antagonists derived from the marine natural product verongamine
Ali, Syed M.,Tedford, Clark E.,Gregory, Rosilyn,Yates, Stephen L.,Phillips, James G.
, p. 1133 - 1138 (2007/10/03)
New histamine H3 receptor antagonists were developed using an acetylene moiety as a replacement for the amide-oxime functionality of verongamine 5. Optimization of receptor binding was performed by following aliphatic Topliss tree guidelines. These new H3 ligands demonstrate excellent blood-brain barrier penetration.
