Design and optimization of benzimidazole-containing transient receptor potential melastatin 8 (TRPM8) antagonists
Mark:
Table 3
Associated context:
In an attempt to reduce the CYP 2C9 inhibition observed in 4, modifications to the benzimidazole core were explored and the 7-position was determined to be permissive for substitution (Table 3). In general, hydrophobic substituents (5, 60-61, 63-66) and polar groups (62 and 67) increased or maintained potency. Acidic functionality was also tolerated, whereas basic moieties resulted in a loss of activity. The most potent compound in this group (67) contained a hydroxypropyl group at the 7-position, although it suffered from poor metabolic stability.
