Basicity carbon versus nitrogen

TABLE 1. Carbon versus nitrogen basicity of enamines10... 

Another successful approach to replacing the benzhydryl stereocenter has been to synthesize and evaluate diarylamines with pendant basic amines. A simple transposition of the nitrogen and carbon atoms of the benzhydryl-piperazine leads to diarylaminopiperidine delta opioid agonists, as Carroll and coworkers at the Research Triangle Institute (RTI) demonstrated [30]. Scientists at AstraZeneca [31] and the R.W. Johnson Research Institute [32] have also disclosed delta opioid agonists possessing the carbon-nitrogen transposition. Boyd and coworkers at R.W. Johnson were the first to report on compounds where the aminopiperidine was further constrained as an aminotropane. Compound 47 has a K = 0.4 nM at the delta opioid receptor, with 14000-fold selectivity versus the mu opioid receptor (Fig. 8). 

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