TY - JOUR
T1 - N-substitution Reactions of 2-Aminobenzimidazoles to Access Pharma-cophores
AU - Padilla-Martínez, Itzia I.
AU - Cruz, Alejandro
AU - García-Báez, Efrén V.
AU - Rosales-Hernández, Martha C.
AU - Wejebe, Jessica E.Mendieta
N1 - Publisher Copyright:
© 2023 Bentham Science Publishers.
PY - 2023/3
Y1 - 2023/3
N2 - Benzimidazole (BI) and its derivatives are interesting molecules in medicinal chemistry because several of these compounds have a diversity of biological activities and some of them are even used in clinical applications. In view of the importance of these compounds, synthetic chemists are still interested in finding new procedures for the synthesis of these classes of compounds. Astemizole (antihistaminic), Omeprazole (antiulcerative), and Rabendazole (fungicide) are important examples of compounds used in medicinal chemistry containing BI nuclei. It is interesting to observe that several of these compounds contain 2-aminobenzimidazole (2ABI) as the base nucleus. The structures of 2ABI derivatives are interesting because they have a planar delocalized structure with a cyclic guanidine group, which have three nitrogen atoms with free lone pairs and labile hydrogen atoms. The 10-π electron system of the aromatic BI ring conjugated with the nitrogen lone pair of the hexocyclic amino group, making these heterocycles to have an amphoteric character. Synthetic chemists have used 2ABI as a building block to produce BI derivatives as medicinally important molecules. In view of the importance of the BIs, and because no review was found in the literature about this topic, we reviewed and summarized the procedures related to the recent methodologies used in the N-substitution reactions of 2ABIs by using aliphatic and aromatic halogenides, dihalogenides, acid chlorides, alkylsulfonic chlorides, carboxylic acids, esters, ethyl chloroformates, anhydrides, SMe-isothioureas, alcohols, alkyl cyanates, thiocyanates, carbon disulfide and aldehydes or ketones to form Schiff bases. The use of diazotized 2ABI as intermediate to obtain 2-diazoBIs was included to produce N-substituted 2ABIs of pharmacological interest. Some commentaries about their biological activity were included.
AB - Benzimidazole (BI) and its derivatives are interesting molecules in medicinal chemistry because several of these compounds have a diversity of biological activities and some of them are even used in clinical applications. In view of the importance of these compounds, synthetic chemists are still interested in finding new procedures for the synthesis of these classes of compounds. Astemizole (antihistaminic), Omeprazole (antiulcerative), and Rabendazole (fungicide) are important examples of compounds used in medicinal chemistry containing BI nuclei. It is interesting to observe that several of these compounds contain 2-aminobenzimidazole (2ABI) as the base nucleus. The structures of 2ABI derivatives are interesting because they have a planar delocalized structure with a cyclic guanidine group, which have three nitrogen atoms with free lone pairs and labile hydrogen atoms. The 10-π electron system of the aromatic BI ring conjugated with the nitrogen lone pair of the hexocyclic amino group, making these heterocycles to have an amphoteric character. Synthetic chemists have used 2ABI as a building block to produce BI derivatives as medicinally important molecules. In view of the importance of the BIs, and because no review was found in the literature about this topic, we reviewed and summarized the procedures related to the recent methodologies used in the N-substitution reactions of 2ABIs by using aliphatic and aromatic halogenides, dihalogenides, acid chlorides, alkylsulfonic chlorides, carboxylic acids, esters, ethyl chloroformates, anhydrides, SMe-isothioureas, alcohols, alkyl cyanates, thiocyanates, carbon disulfide and aldehydes or ketones to form Schiff bases. The use of diazotized 2ABI as intermediate to obtain 2-diazoBIs was included to produce N-substituted 2ABIs of pharmacological interest. Some commentaries about their biological activity were included.
KW - 2-Aminobenzimidazoles
KW - 2-aminobenzimidazol Schiff bases
KW - N-acyl-2-aminobenz-imidazoles
KW - N-alkyl-2-aminobenzimidazoles
KW - N-aryl-2-aminobenzimidazoles
KW - astemizole
UR - http://www.scopus.com/inward/record.url?scp=85146218964&partnerID=8YFLogxK
U2 - 10.2174/1570179419666220310124223
DO - 10.2174/1570179419666220310124223
M3 - Artículo de revisión
C2 - 35272598
AN - SCOPUS:85146218964
SN - 1570-1794
VL - 20
SP - 177
EP - 219
JO - Current Organic Synthesis
JF - Current Organic Synthesis
IS - 2
ER -