Abstract
Up to the late 1950s the goal of potency in the development of novel analgesics was that of the classic opiate morphine. However, in 1957 it was made apparent from reports from CIBA on analgesics based on benzimidazole that levels of activity several orders above this standard could be achieved, and the group is of historical importance on this account.(1,2) The compounds of general formula 3 carry a 2-aminoethyl substituent at N-1 and a benzyl substituent at C-2 with further substituents at C-5 and C-4′ in the more potent derivatives. Two synthetic routes were employed (Scheme 11.1)(3): (a) condense
substituted o-phenylenediamines with a substituted benzyl cyanide (or related compound) and alkylate the product with a 2-t-aminoethyl chloride (1–3), and (b) (appropriate to derivatives with R′ substituents) condense 1-amino-2-diethylaminoethane with a 2-nitrochlorobenzene, reduce the nitro group with (NH4)2S (a 5-NO2 substituent is unchanged), and condense the product 2 with an iminoether formed from a benzyl cyanide and EtOH-HCl.
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Casy, A.F., Parfitt, R.T. (1986). Miscellaneous Groups of Analgesics. In: Opioid Analgesics. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0585-7_11
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