53704-79-3

Upstream product

• 38622-91-2 [(p-methylphenyl)sulfonylmethyl]isonitrile 
• 100-52-7 benzaldehyde 
• 100-46-9 benzylamine 
• 100843-80-9 9-Benzyl-1-((Z)-2-benzylamino-2-phenyl-vinyl)-6-[(E)-benzylimino]-6,9-dihydro-1H-purine 
• 95633-81-1 1-phenacyl-9-benzylhypoxanthine 
• 100843-80-9 9-Benzyl-1-((Z)-2-benzylamino-2-phenyl-vinyl)-6-[(Z)-benzylimino]-6,9-dihydro-1H-purine 
• 71333-60-3 (E)-1-Isocyano-2-phenyl-1-tosylethene 
• 60007-51-4 3-(2-oxo-2-phenylethyl)quinazolin-4(3H)-one 
• 119825-78-4 (E)-methyl β-bromo-α-formylaminocinnamate 
• 130740-17-9 (E)-Methyl 3-bromo-2-isocyano-3-phenylacrylate 
• 4238-71-5 1-benzylimidazole 
• 108-86-1 bromobenzene 
• 70-11-1 α-bromoacetophenone 
• 71333-72-7 N-[(E)-2-phenyl-1-(toluene-4-sulfonyl)-vinyl]-formamide 

Downstream Products

• 1027497-21-7 [2-(1-Benzyl-5-phenyl-1H-imidazol-2-ylsulfanylmethyl)-phenyl]-dimethyl-amine 
• 1041845-48-0 1-benzyl-2-(2-naphthyl)-5-phenyl-1H-imidazole 
• 1041845-46-8 1-benzyl-2-(4-methoxyphenyl)-5-phenyl-1H-imidazole 
• 1041845-53-7 1-benzyl-4-bromo-5-phenyl-1H-imidazole 
• 670-95-1 4-phenyl-1H-imidazole 
• 1401316-08-2 2-(4-methoxyphenyl)-5-phenyl-4-(4-trifluoromethylphenyl)-1H-imidazole 
• 1401316-07-1 N-benzyl-2-(4-methoxyphenyl)-4-(4-trifluoromethylphenyl)-5-phenylimidazole 

Relevant academic research and scientific papers

IMIDAZOLE SYNTHESYS ON A SOLID SUPPORT

Imidazole synthesis has been demonstrated using polymer supported 4-carboxamido-5-aminoimidazole and hypoxanthine.

An imidazole based H-Phe-Phe-NH2 peptidomimetic with anti-allodynic effect in spared nerve injury mice

The dipeptide amide H-Phe-Phe-NH2 (1) that previously was identified as a ligand for the substance P 1–7 (SP1–7) binding site exerts intriguing results in animal models of neuropathic pain after central but not after peripheral administration. The dipeptide 1 is derived from stepwise modifications of the anti-nociceptive heptapeptide SP1–7 and the tetrapeptide endomorphin-2 that is also binding to the SP1–7 site. We herein report a strong anti-allodynic effect of a new H-Phe-Phe-NH2 peptidomimetic (4) comprising an imidazole ring as a bioisosteric element, in the spare nerve injury (SNI) mice model after peripheral administration. Peptidomimetic 4 was stable in plasma, displayed a fair membrane permeability and a favorable neurotoxic profile. Moreover, the effective dose (ED50) of 4 was superior as compared to gabapentin and morphine that are used in clinic.

Repetitive Imidazole Synthesis Using an Immobilized Imidazole Template

A model representing the chemical simulation of the ATP-imidazole cycle programmed to continuous production of the daughter imidazoles from the immobilized parent imidazole template is presented. 6-Chloropurine was anchored to polystyrene by reaction with

Structure-guided optimization of 1H-imidazole-2-carboxylic acid derivatives affording potent VIM-Type metallo-β-lactamase inhibitors

Production of metallo-β-lactamases (MBLs) in bacterial pathogens is an important cause of resistance to the ‘last-resort’ carbapenem antibiotics. Development of effective MBL inhibitors to reverse carbapenem resistance in Gram-negative bacteria is still needed. We herein report X-ray structure-guided optimization of 1H-imidazole-2-carboxylic acid (ICA) derivatives by considering how to engage with the active-site flexible loops and improve penetration into Gram-negative bacteria. Structure-activity relationship studies revealed the importance of appropriate substituents at ICA 1-position to achieve potent inhibition to class B1 MBLs, particularly the Verona Integron-encoded MBLs (VIMs), mainly by involving ingenious interactions with the flexible active site loops as observed by crystallographic analyses. Of the tested ICA inhibitors, 55 displayed potent synergistic antibacterial activity with meropenem against engineered Escherichia coli strains and even intractable clinically isolated Pseudomonas aeruginosa producing VIM-2 MBL. The morphologic and internal structural changes of bacterial cells after treatment further demonstrated that 55 crossed the outer membrane and reversed the activity of meropenem. Moreover, 55 showed good pharmacokinetic and safety profile in vivo, which could be a potential candidate for combating VIM-mediated Gram-negative carbapenem resistance.

Aminocarbonylation of 4-iodo-1H-imidazoles with an amino acid amide nucleophile: Synthesis of constrained H-Phe-Phe-NH2 analogues

A simple and an expedient process to prepare 5-aryl-1-benzyl-1H-imidazole- 4-carboxamides by the aminocarbonylation of 5-aryl-4-iodo-1H-imidazoles using ex situ generation of CO from Mo(CO)6 with an amino acid amide nucleophile is reported. Furthermore, a microwave-assisted protocol for the direct C-5 arylation of 1-benzyl-1H-imidazole and a regioselective C-4 iodination method to acquire starting material for our aminocarbonylation are presented. The method can be used to prepare imidazole based peptidomimetics, herein exemplified by the synthesis of constrained H-Phe-Phe-NH2 analogues.

One-pot sequential direct C-H bond arylation of azoles catalyzed by [Pd(phen)2](PF6)2: Synthetic methods for triarylated azoles

Synthetic methods for triarylated azoles containing three different aryl groups via one-pot sequential multiple C-H bond arylations are described. The one-pot sequential diarylation of C5-monoarylated azoles was achieved by the simple sequential addition of two different aryl iodides with a [Pd(phen) 2]PF6 catalytic system. The one-pot triarylation of N-methylimidazole was achieved by the combination of a previously reported Pd(OAc)2-P(2-furyl)3 system and the present [Pd(phen) 2]PF6 system. In this case, portionwise addition of aryl halide, base and the catalyst in the final step significantly improved the overall yield of the desired triarylated product. These protocols led to triarylated azoles without a loss of efficiency compared to the corresponding previously reported stepwise syntheses via direct C-H bond arylation.

Synthesis, Biological Evaluation, and Molecular Modeling of 1 -Benzyl-1H-imidazoles as Selective Inhibitors of Aldosterone Synthase (CYP11B2)

Reducing aldosterone action is beneficial in various major diseases such as heart failure. Currently, this is achieved, with mineralocorticoid, receptor antagonists, however, aldosterone synthase (CYP 11B2) inhibitors may offer a promising alternative. In this study, we used three-dimensional modeling of CYP11B2 to model, the binding modes of the natural substrate 18-hydroxycorticosterone and the recently published CYP11B2 inhibitor R-fadrozole as a rational guide to design 44 structurally simple and achiral 1-benzyl-1H-imidazoles. Their syntheses, in vitro inhibitor potencies, and in silico docking are described. Some promising CYP11B2 inhibitors were identified, with our novel lead, MOERAS 115 (4-((5-phenyl-1H-imidazol-1-yl)methyl) benzonitrile) displaying an IC50 for CYP11B2 of 1.7 nM, and a CYP11B2 (versus CYP11B1) selectivity of 16.5, comparable to R-fadrozole (IC 50 for CYP11B26.0 nM, selectivity 19.8). Molecular docking of the inhibitors in the models enabled us to generate posthoc hypotheses on their binding modes, providing a valuable basis for future studies and further design of CYP11B2 inhibitors.

MULTIHETEROARYL COMPOUNDS AS INHIBITORS OF H-PGDS AND THEIR USE FOR TREATING PROSTAGLANDIN D2 MEDIATED DISEASES

Multiheteroaryl compounds, their preparation, pharmaceutical compositions comprising these compounds, and their pharmaceutical use in the prevention and treatment of prostaglandin D2 mediated diseases and conditions that may be modulated by the inhibition of hematopoietic prostaglandin D synthase (H-PGDS).

Highly selective synthesis of 4(5)-aryl-, 2,4(5)-diaryl-, and 4,5-diaryl-1H-imidazoles via Pd-catalyzed direct C-5 arylation of 1-benzyl-1H-imidazole

Highly selective, practical, and efficient protocols for the preparation of 4(5)-aryl-1H-imidazoles 2, 2,4(5)-diaryl-1H-imidazoles 3, and 4,5-diaryl-1H-imidazoles 1 are described. A key step of these protocols is the regioselective synthesis of 5-aryl-1-benzyl-1H-imidazoles 9 by Pd-catalyzed direct C-5 arylation of commercially available 1-benzyl-1H-imidazole (8) with aryl halides. The three-step synthesis of compounds 3 from 8 also involves the Pd-catalyzed and Cu-mediated direct C-2 arylation of imidazoles 9 with aryl halides under base-free and ligandless conditions. On the other hand, the four-step synthesis of imidazoles 1 from 8 also involves the regioselective bromination of compounds 9 and a Suzuki reaction of the resulting 5-aryl-1-benzyl-4-bromo-1H-imidazoles 11 with arylboronic acids 5 under phase-transfer conditions, followed by N-debenzylation.

2-[(2-Aminobenzyl)sulfinyl]-1-(2-pyridyl)-1,4,5,6- tetrahydrocyclopent[d]imidazoles as a novel class of gastric H+/K+-ATPase inhibitors

Substituted 2-sulfinylimidazoles were synthesized and investigated as potential inhibitors of gastric H+/K+-ATPase. The 4,5-unsubstituted imidazole series 6-11 and the 1,4,5,6-tetrahydrocyclopent[d]imidazole series 12 were found to be potent inhibitors of the acid secretory enzyme H+/K+- ATPase. Structure-activity relationships indicate that the substitution of 2- pyridyl groups at the 1-position of the imidazole moiety combined with (2- aminobenzyl)sulfinyl groups at the 2-position leads to highly active compounds with a favorable chemical stability. Other substitution patterns in the imidazole moiety result in reducing biological activities. 2-[(2- Aminobenzyl)sulfinyl]-1-[2-(3-methylpyridyl)]-1,4,5,6- tetrahydrocyclopent[d]imidazole (12h, T-776) was selected for further development as a potential clinical candidate. Extensive study on the acid degradation of 12h indicates a mechanism of action different from that of omeprazole, the first H+/K+-ATPase inhibitor introduced to the market.