Oligome-containing pyrrolidine compounds
View Patent ↗The invention relates to (among other things) oligomer-containing pyrrolidine compounds. 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 compound comprising a pyrrolidine residue covalently attached via a stable linkage to a water-soluble, non-peptidic oligomer, wherein the compound is encompassed within the formula:
wherein:
each L is independently selected from the group consisting of hydrogen, hydroxyl, a C 1-6 alkyl radical, a C 2-6 alkenyl radical, and a C 2-6 alkynyl radical;
p is a whole number from 1 to 6;
Y is selected from the group consisting of hydrogen, a C 1-6 alkyl radical, a C 2-6 alkenyl radical, and a C 2-6 alkynyl radical;
R 2 is selected from the group consisting of hydrogen, an alkyl radical, an alkenyl radical, an alkynyl radical, a cycloalkyl radical, and an aryl radical;
X is a spacer moiety; and
POLY is a water-soluble, non-peptidic oligomer having a molecular weight of below about 1500 Daltons.
2. The compound of claim 1 , wherein the pyrrolidine residue is a residue of a pyrrolidine moiety encompassed within the formula:
wherein:
each L is independently selected from the group consisting of hydrogen, hydroxyl, a C 1-6 alkyl radical, a C 2-6 alkenyl radical, and a C 2-6 alkynyl radical;
p is a whole number from 1 to 6;
Y is selected from the group consisting of hydrogen, a C 1-6 alkyl radical, a C 2-6 alkenyl radical, and a C 2-6 alkynyl radical; and
either R 1 and R 2 are each independently selected from the group consisting of hydrogen, a C 1-6 alkyl radical, a C 2-6 alkenyl radical, a C 2-6 alkynyl radical, a C 3-6 cycloalkyl radical, and an aryl radical,
or R 1 and R 2 , together with the nitrogen atom to which they are attached, form a heterocyclic radical.
3. The compound of claim 1 , wherein the pyrrolidine residue is a residue of a pyrrolidine moiety selected from the group consisting of levetiracetam, piracetam, brivaracetam, nefiracetam and oxiracetam.
4. The compound of claim 3 , wherein the pyrrolidine residue is a residue of a pyrrolidine moiety selected from the group consisting of levetiracetam, piracetam, brivaracetam and nefiracetam.
5. The compound of claim 4 , wherein the pyrrolidine residue is a residue of levetiracetam.
6. The compound of claim 1 , wherein the water-soluble, non-peptidic oligomer is a poly(alkylene oxide).
7. The compound of claim 6 , wherein the poly(alkylene oxide) is a poly(ethylene oxide).
8. The compound of claim 1 , wherein the water-soluble, non-peptidic oligomer has from about 1 to about 30 monomers.
9. The compound of claim 8 , wherein the water-soluble, non-peptidic oligomer has from about 1 to about 10 monomers.
10. The compound of claim 7 , wherein the poly(alkylene oxide) includes an alkoxy or hydroxy end-capping moiety.
11. The compound of claim 1 , wherein a single water-soluble, non-peptidic oligomer is covalently attached to the pyrrolidine residue.
12. The compound of claim 1 , wherein two water-soluble, non-peptidic oligomers are covalently attached to the pyrrolidine residue.