160073-02-9

Upstream product

• 67-56-1 methanol 
• 104-98-3 urocanic acid 
• 64407-67-6 methyl 3-(imidazol-4⁽⁵⁾-yl)-2-chloropropanoate 

Downstream Products

• 112606-55-0 C₂₆H₂₂N₂O₂ 
• 102676-60-8 3-(1-triphenylmethyl-1H-imidazol-4-yl)propanoic acid methyl ester 
• 1274939-79-5 Br^(1-)*C₅₃H₄₅N₆O₂⁽¹⁺⁾ 
• 1274939-78-4 Br^(1-)*C₅₃H₄₅N₆O₂⁽¹⁺⁾ 
• 1274939-77-3 Br^(1-)*C₅₃H₄₅N₆O₂⁽¹⁺⁾ 
• 1300748-92-8 (2E)-3-(1-benzyl-1H-imidazol-4-yl)prop-2-enyl 3-phenylpropynoate 
• 1300748-90-6 (2E)-3-(1-benzyl-1H-imidazol-4-yl)-2-propenyl (E)-3-acetylpropenoate 
• 1300748-88-2 ethyl (2E)-3-(1-benzyl-1H-imidazol-4-yl)-2-propenyl (2E)-2-butenedioate 
• 1300749-21-6 (2E)-3-(1-benzyl-1H-imidazol-4-yl)prop-2-enyl propynoate 
• 1300749-20-5 1-benzyl-4-[(1E)-3-(prop-2-ynyloxy)prop-1-enyl]-1H-imidazole 
• 1300749-19-2 (2E)-3-(1-benzyl-1H-imidazol-4-yl)prop-2-enyl (2E)-3-phenylpropenoate 
• 1300749-18-1 (2E)-3-(1-benzyl-1H-imidazol-4-yl)prop-2-enyl propenoate 
• 1300749-17-0 1-benzyl-4-((1E)-3-{[(2E)-3-phenylprop-2-enyl]oxy}-prop-1-enyl)-1H-imidazole 
• 1300749-16-9 4-[(1E)-3-(allyloxy)prop-1-enyl]-1-benzyl-1H-imidazole 

Relevant academic research and scientific papers

Antiviral effect of ribonuclease conjugated oligodeoxynucleotides targeting the IRES RNA of the hepatitis C virus

Hepatitis C virus (HCV) translation initiation is mediated by a highly structured and conserved RNA, termed the Internal Ribosome Entry Site (IRES), located at the 5′-end of its single stranded RNA genome. It is a key target for the development of new antiviral compounds. Here we made use of the recently developed HCV cell culture system to test the antiviral activity of artificial ribonucleases consisting of imidazole(s) linked to antisense oligodeoxynucleotides targeting the HCV IRES. Results from the cell culture model indicate that the naked antisense oligodeoxynucleotide displayed an efficient antiviral activity. Despite the increased activity observed with the addition of imidazole moieties when tested with the cell-free system, it appears that these improvements were not reproduced in the cellular model.

Intramolecular Diels-Alder chemistry of 4-vinylimidazoles

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.

Towards non-peptide ANG II AT1 receptor antagonists based on urocanic acid: Rational design, synthesis and biological evaluation

A series of o-, m- and p-benzyl tetrazole derivatives 11a-c has been designed, synthesized and evaluated as potential Angiotensin II AT1 receptor antagonists, based on urocanic acid. Compound 11b with tetrazole moiety at the m-position showed moderate, however, higher activity compared to the o- and p-counterpart analogues. Molecular modelling techniques were performed in order to extract their putative bioactive conformations and explore their binding modes.

Structure based design of novel inhibitors for histidinol dehydrogenase from Geotrichum candidum

Histidinol dehydrogenase, the product of the HisD gene, mediates the final step in the histidine biosynthetic pathway. This enzyme has captured attention for drug discovery studies in past few years. Recently, our group cloned and expressed Geotrichum candidum histidinol dehydrogenase and successful screening of substrate analog inhibitors of histidinol dehydrogenase led to some antifungal compounds with IC50 values in micromolar range. In this study, we have done docking analysis of these antifungal agents in G. candidum. Two new compounds were designed based on the docking results and these compounds turned out to be potent inhibitors of G. candidum histidinol dehydrogenase, showing IC50 values as low as 3.17 μM.

Efficient preparation of urocanic acid derivatives from histidine

Urocanic acid derivatives have served as useful starting materials in several total synthesis endeavors in our lab. This paper describes a convenient, large-scale synthesis of several derivatives of urocanic acid via the net elimination of ammonia from hi

N-benzyl imidazole derivatives and their use as aldosterone synthase inhibitors

The invention relates to the use of a N-benzyl 5-substituted imidazole derivative having the general formula I wherein R is (C1-3)alkyl, (C1-3)alkyloxy, halogen, nitro or cyano; R1 is (C1-6)alkyl, optionally substituted with OH, (C1-3)alkyloxy, (C1-3)alkylcarbonyloxy, (C1-3)alkyloxycarbonyl or halogen, or (C1-3)alkyloxycarbonyl; or R1 is phenyl, optionally substituted with 1-3 substituents independently selected from (C1-3)alkyl, (C1-3)alkyloxy, hydroxylmethyl and halogen; or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of a disorder or disease in a subject mediated by aldosterone synthase or responsive to inhibition of aldosterone synthase.

Acylguanidines as bioisosteres of guanidines: NG-acylated imidazolylpropylguanidines, a new class of histamine h2 receptor agonists

N1-Aryl(heteroaryl)alkyl-N2-[3-(1H-imidazol-4-yl) propyl]guanidines are potent histamine H2-receptor (H2R) agonists, but their applicability is compromised by the lack of oral bioavailability and CNS penetration. To improve pharmacokinetics, we introduced carbonyl instead of methylene adjacent to the guanidine moiety, decreasing the basicity of the novel H2R agonists by 4-5 orders of magnitude. Some acylguanidines with one phenyl ring were even more potent than their diaryl analogues. As demonstrated by HPLC-MS, the acylguanidines (bioisosteres of the alkylguanidines) were absorbed from the gut of mice and detected in brain. In GTPase assays using recombinant receptors, acylguanidines were more potent at the guinea pig than at the human H2R. At the hH1R and hH3R, the compounds were weak to moderate antagonists or partial agonists. Moreover, potent partial hH4R agonists were identified. Receptor subtype selectivity depends on the imidazolylpropylguanidine moiety (privileged structure), opening an avenue to distinct pharmacological tools including potent H4R agonists.

Synthesis and evaluation of potent, highly-selective, 3-aryl-piperazinone inhibitors of protein geranylgeranyltransferase-I

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.

2,3,4,5-TETRAHYDRO-1H-1,5-BENZODIAZEPINE DERIVATIVE AND MEDICINAL COMPOSITION

A 2,3,4,5-tetrahydro-1H-1,5-benzodiazepine derivative represented by the generalformula (1): [Chemical formula 1] (1) or a pharmaceutically acceptable saltthereof. They are useful as a therapeutic/preventive agent for diabetes, diabeticnephropathy, or glomerulosclerosis.