Oligomer-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 pharmaceutical comprising:
(i) a compound comprising a pyrrolidone residue covalently attached to two water-soluble, non-peptidic oligomers, the compound having the following structure:
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;
X 1 is a first spacer moiety;
X 2 is a second spacer moiety;
POLY 2 is a first water-soluble, non-peptidic oligomer having a molecular weight of below about 1500 Daltons; and
POLY 2 is a second water-soluble, non-peptidic oligomer having a molecular weight of below about 1500 Daltons, and
pharmaceutically acceptable salts thereof; and
(ii) a pharmaceutically acceptable excipient.
2. The composition 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 composition 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 composition 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 composition of claim 4 , wherein the pyrrolidine residue is a residue of levetiracetam.
6. The composition of claim 1 , wherein each of the water-soluble, non-peptidic oligomers is a poly(alkylene oxide).
7. The composition of claim 6 , wherein each of the poly(alkylene oxide)s is a poly(ethylene oxide).
8. The composition of claim 1 , wherein each of the water-soluble, non-peptidic oligomers has from about 1 to about 30 monomers.
9. The composition of claim 1 , wherein each of the water-soluble, non-peptidic oligomers has from about 1 to about 10 monomers.
10. The composition of claim 7 , wherein each of the poly(alkylene oxide)s includes an alkoxy or hydroxy end-capping moiety.
11. The composition of claim 1 , wherein the pyrrolidone residue is covalently attached to the two water-soluble, non-peptidic oligomers via a stable linkage.