199007-50-6Relevant academic research and scientific papers
Intramolecular Diels-Alder chemistry of 4-vinylimidazoles
He, Yong,Krishnamoorthy, Pasupathy,Lima, Heather M.,Chen, Yingzhong,Wu, Haiyan,Sivappa, Rasapalli,Dias, H. V. Rasika,Lovely, Carl J.
scheme or table, p. 2685 - 2701 (2011/05/08)
An investigation of 4-vinylimidazoles as diene components in the intramolecular Diels-Alder reaction is described. In the course of these studies several parameters affecting the cycloaddition were evaluated including the nature of the imidazole protecting group, the type of dienophile and the linking group. These investigations established that amino linkers were generally more effective than either ethers or esters. In most cases, the cycloadditions were highly stereoselective, resulting in the formation of products derived from an anti transition state. The polysubstituted tetrahydrobenzimidazole core of the pyrrole-imidazole alkaloid ageliferin can be constructed through the use of pseudo dimeric 4-vinylimidazoles.
Synthesis and evaluation of potent, highly-selective, 3-aryl-piperazinone inhibitors of protein geranylgeranyltransferase-I
Peng, Hairuo,Carrico, Dora,Thai, Van,Blaskovich, Michelle,Bucher, Cynthia,Pusateri, Erin E.,Sebti, Said M.,Hamilton, Andrew D.
, p. 1768 - 1784 (2008/02/05)
A series of compounds based on the carboxyl-terminal CAAL sequence of PGGTase-I substrates was designed and synthesized. Using piperazin-2-one as a semi-rigid scaffold, we have introduced critical pharmacophores in a well-defined arrangement to mimic the CAAL sequence. High potency and exceptional selectivity were obtained for inhibition of PGGTase-I with structures such as 45 and 70. Potency of this series of GGTIs was dependent on the presence of an l-leucine residue with a free carboxyl terminus, as well as an S configuration of the 3-aryl group. The selectivity was significantly enhanced by 5-methyl substitution on the imidazole ring and fluorine substitution on the 3-aryl group. Modification of the 6-position of the piperazinone scaffold was found to be unfavorable. Compounds 44 and 69, the corresponding methyl esters of 45 and 70, were found to selectively block processing of Rap1A by PGGTase-I in whole cells with IC50 values of 0.4 M and 0.7 M respectively. The Royal Society of Chemistry 2006.
Imidazole derivatives having an inhibitory activity for farnesyl transferase and process for preparation thereof
-
, (2008/06/13)
The present invention relates to a novel imidazole derivative represented by formula (1) which shows an inhibitory activity against farnesyl transferase or pharmaceutically acceptable salts or isomers thereof, in which A, n1and Y are defined in the specification; to a process for preparation of the compound of formula (1); to intermediates which are used in the preparation of the compound of formula (1); and to a pharmaceutical composition comprising the compound of formula (1) as an active ingredient.
Development of FUB 181, a selective histamine H3-receptor antagonist of high oral in vivo potency with 4-(ω-(arylalkyloxy)alkyl)-1H-imidazole structure
Stark, Holger,Huels, Annette,Ligneau, Xavier,Purand, Katja,Pertz, Heinz,Arrang, Jean-Michel,Schwartz, Jean-Charles,Schunack, Walter
, p. 211 - 218 (2007/10/03)
A series of 4-(ω-(arylalkyloxy)alkyl)-1H-imidazoles and related sulphur-containing compounds have been prepared and evaluated for their histamine H3-autoreceptor antagonist in vitro potency in an assay on synaptosomes of rat cerebral cortex. In addition, the in vivo potency has been determined from the changes in N(τ)-methylhistamine levels in brain after p.o. administration to mice. Compounds with different alkyl chains and various aryl moities have been synthesized and tested to explore structure- activity azol-4-yl)methyl and 2-(1H-imidazol-4-yl)ethyl ether derivatives showed low to moderate H3-receptor antagonist potency, whereas the corresponding allyl and propyl derivatives were compounds with high antagonist in vitro potency. Corresponding thioether or sulphoxide derivatives also showed antagonist activity. Additionally, some ether derivatives possessed high in vivo potency as well. The most active ether derivatives under in vivo conditions were 4-(3-(3-(4- fluorophenyl)propyloxy)propyl)-1H-imidazole (11b) and the corresponding chloro compound 11c (FUB 181) with ED50 values of 0.76 and 0.80 mg/kg, respectively. On the other hand, all compounds tested showed weak activity at histamine H1 or H2 receptors. Furthermore, the most promising ether FUB 181 exhibited low activity at adrenergic α1, β(1/2), serotonergic 5-HT(2A), 5- HT3, and muscarinic M3 receptors. Time-course investigations of FUB 181 in mice showed a rapid mode of action with the highest value 3 h after p.o. application. Thus, FUB 181 appears to block histamine H3 receptors potently and selectively.
