Benzimidazole analogues

A series of benzimidazole analogues have been designed to alter its DNA binding to different base sequences. 

The influence of the electronic character of substituents in the acetophenone part of the unsaturated ketones was not studied in [241], but results reported in [240], devoted to the reactions of 6-aminouracil and 2-thio-6-aminouracil with benzimidazole analogues of chalcones 303, showed that increasing the electron-withdrawing... 

At about the same time, a group at Oxford reported their synthesis of a benzimidazole analogue of FA (290, R = H) (Scheme 3.53) [48, 156]. Initially, they envisioned that (290) could be obtained from acylation of glutamic acid with (288). The requisite acid chloride (288) was readily obtained in three steps from o-phenylenediamine via (286) and (287). Unfortunately, the extreme insolubility of (288) rendered it inactive towards basic solutions of glutamic acid or glycine. Therefore, an alternative approach was developed in which the chloromethylbenzimidazole (286) was used to alkylate (31) to yield (289), from which (290, R = H) was obtained following careful saponification. Repetition of this latter reaction sequence with 5-chloro-2-chloromethylbenzimidazole, available from 4-chloro-o-phenylenediamine dihydrochloride and chloroacetic acid, afforded (290, R = Cl) [156],... 

Lai, G. Anderson, W. K. A concise synthesis of a benzimidazole analogue of mycophenolic acid using a BF3-Et20 catalyzed amino-Clai-sen rearrangement. Tetrahedron Lett. 1993, 34, 6849-6852. 

Since the same pH dependence was observed with the benzimidazole analogue, this side chain is probably not involved in the binding of the nonfunctional part. In alkaline medium the stability of the complexes of both analogues is the same. Under these conditions the coenzyme may be held by the ionic interaction of the pyrophosphate residue to a specific group in the active center3... 

LaBarbera DV, Skibo EB (2005) Synthesis of imidazo[l,5,4-de]quinoxalin-9-ones, benzimidazole analogues of pyrroloiminoquinone marine natural products. Bioorg Med Chem 13 387-395... 

Catechol bioisosteres are often utilized to overcome pharmacokinetic and toxicological issues linked to this moiety. SuccessfiJ examples of bioisosteric replacement of catechols can be found in catecholamines. Benzimidazole analogues of the adrenergic agonists norepinephrine and isoproterenol (Figure 2.10) were... 

FIGURE 8.4 General structure of norstatines 46 [44], cw-constrained norstatine analogues 47 [40a], benzimidazole analogues 48 [45], and peptidic kinase inhibitors 49 [46]. 

On the other hand, when CMN 131 and the first compound in the second line of the chemical synthesis program, H 77/67, were tested in the conscious dog model, both were clearly active in inhibiting gastric acid secretion. The benzimidazole analogue of H 77/67, H 124/26 (Fig. 3), was syn-... 

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