N-optionally substituted aryl-2-oligomer-3-alkoxypropionamides
View Patent ↗The invention relates to (among other things) N-optionally substituted aryl-2-oligomer-3-alkoxypropionamides and compositions comprising the same. A compound of the invention, when administered by any of a number of administration routes, exhibits one or more advantages over corresponding compounds lacking the oligomer.
1. A method of making a conjugate, the method comprising reacting, under conjugation conditions, a 3-alkoxypropionamide moiety with an activated poly(alkylene oxide) oligomer having a terminal reactive group suitable for reaction with a functional group comprised within the 3-alkoxypropionamide moiety.
2. The method of claim 1 , wherein the 3-akoxypropionamide moiety is
and the activated poly(alkylene oxide) oligomer is
wherein
Q is N-succinimide, N-sulfosuccinimide, N-phthalimide, N-glutarimide, N-tetrahydrophthalimide, N-norbornene-2,3-dicarboximide, benzotriazole, 7-azabenzotriazole, or imidazole; and
R 2 is hydrogen or a C 1 -C 20 alkyl;
comprising reacting the 3-alkoxyproprionamide moiety with the activated poly(alkylene oxide) to thereby form a reaction mixture comprising
wherein:
Ar is aryl, optionally substituted with halo;
R 1 is lower alkyl; and
n is 1to about 30.
3. The method of claim 2 , wherein said reacting is carried out in the presence of a coupling reagent.
4. The method of claim 2 , further comprising after said reacting step, purifying the reaction mixture to isolate
5. The method of claim 2 ,
wherein:
Ar is
and
R 1 is —CH 3 .
6. The method of claim 2 , wherein Ar is benzyl, phenyl, napthyl, biphenyl, or phenanthrenyl.
7. The method of claim 2 , wherein n is 2 to about 30.
8. The method of claim 2 , wherein n is 2 to about 10.
9. The method of claim 2 , wherein n is 1 to about 9.