Alkylation of azoles: Synthesis of new heterocyclic‐based AT₁‐non‐peptide angiotensin (II) receptor antagonists

Abstract

Several novel analogues of Losartan 2 were synthesized as potential non-peptide angiotensin (II) receptor antagonists. In these non-peptide analogues, the tetrazole and the substituted imidazole rings of Losartan 2 were replaced, respectively, by a carboxylic acid function or its methyl ester and substituted triazole, imidazole or benzimidazole moieties. The biphenyl bromide precursor 3 (BPE) used to introduce the linker between the acid/ester function and the heterocyclic moiety was synthesized using Suzuki biphenyl coupling and then incorporated into the target molecule by simple nucleophilic substitution. The fixed N-aryl isomeric forms of several azole and benzimidazole tautomers were successfully separated by HPLC using 50% aqueous acetonitrile as eluent. Intermediate reaction products and final target compounds were fully characterized spectroscopically.

Separation and identification of the mixture of 2‐(3,4‐dimethoxyphenyl)‐1‐n‐propyl or (4‐chlorobenzyl)‐5 and (6)‐1H‐benzimidazolecarbonitriles

“…Alkylations of benzimidazoles give frequently similiar yields of both regioisomers; sometimes they give a different ratio . It has been reported that, when 5(6)‐ or 4(7)‐substituted benzimidazoles are alkylated, the product ratios depend on the resonance electronic effects as well as position of the substituent .…”

Applications of quinoxaline‐bridged bis(benzimidazolium) salts as ligand sources for the palladium‐catalyzed Suzuki and Heck cross‐coupling reactions in an aqueous medium

“…[56,57] The 1H-substituted benzimidazole derivatives are traditionally prepared through either reductive amination [58] or through deprotonation followed by nucleophilic substitution with carbon electrophiles. [59,60] For the deprotonation synthetic route, the weak acidity of the NH group can necessitate the use of strong bases and elevated reaction temperatures. Recently, Vannucci et al developed an electro synthetic approach to synthesize a variety of 1H-substituted benzimidazoles.…”

Silver-Catalyzed Cascade Cyclization of Amino-NH-1,2,3-Triazoles with 2-Alkynylbenzaldehydes: An Access to Pentacyclic Fused Triazoles

“…Broad attention has been paid to 1,2,3-triazole-containing heterocycles, which have been widely applied in the fields of medicine [ 1 , 2 , 3 , 4 , 5 ], pesticide [ 6 , 7 , 8 , 9 , 10 ], biochemistry [ 11 , 12 , 13 , 14 ], and material science [ 15 , 16 , 17 , 18 , 19 , 20 ] since the ‘Click’ triazole chemistry was founded at the beginning of this century [ 21 , 22 ]. For instance, some of the well-known drugs bearing triazole moiety are presented in Figure 1 , including A (Cefatrizine) and B (Tazobactum) as β -lactam antibiotic [ 1 , 23 , 24 , 25 , 26 , 27 ], C as anti-cancer reagent [ 23 , 28 ], D as potential nonpeptidic angiotensin (II) receptor antagonists [ 29 , 30 ], E as a toll-like receptor [ 29 , 31 ], F as a mental disorders medicine [ 32 ], and G as a wall teichoic acid active antibiotic [ 11 ].…”