Appeal No. 95-3117
Application 08/096,207
reduces the interaction between the carbonyl group and
the
esteratic site. Indeed, when the bulk of the phenyl
group
is further increased by the addition of either a chlorine
atom or a methoxy group, the potency of the resulting
compounds (chlorophenylcarbamoyl eseroline (5)
and methoxyphenylcarbamoyl eseroline (4),
respectively) is reduced approx. 5-fold compared to
phenylcarbamoyl eseroline (3) and to less than 5% of (-)-
physostigmine. Compounds with very bulky carbamoyl side
chain additions, such as
N-benzyl-N-methylallophanyl eseroline (12) and
N-dibenzylallophanyl eseroline (13), showed low anti-AChE
potencies (relative potency <1%).
Based on Yu’s analysis of his own work, we fail to see why
persons having ordinary skill in the art reasonably would have
been led to expect (-)-2'-methylphenylcarbamoyl eseroline or
(-)-2'-methylphenylcarbamoyl noreseroline with bulky
methylphenylcarbamoyl groups to be as potent as N-
phenylcarbamoyl eseroline versus electric eel AChE. Yu I
appears to predict the opposite result, i.e., potency inferior
to N-phenylcarbamoyl eseroline versus electric eel AChE. In
light of (1) the Yu I report of a 5-fold reduction of activity
for substituted-phenylcarbamoyl eseroline as compared to N-
phenylcarbamoyl eseroline and an activity of less than 5% of
(-)-physostigmine and (2) the Yu II report showing comparable
potencies of eserolines and noreserolines, we find that
- 9 -
Page: Previous 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Next
Last modified: November 3, 2007