Oligomer-Antihistamine Conjugates
The invention provides antihistamine drugs that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the antihistamine drug not attached to the water-soluble oligomer.
1 . A compound having the following structure:
wherein:
(a) is either zero or one;
Z is selected from the group consisting of N, CH and C(CH 3 );
either (i) Ar 1 is an aromatic-containing moiety, and Ar 2 is an aromatic-containing moiety, or (ii)
is combined to form an aromatic-containing moiety;
X is a spacer moiety; and
POLY is a water-soluble, non-peptidic oligomer.
2 . A compound having the following structure:
wherein:
(a) is either zero or one;
Z is selected from the group consisting of N, CH and C(CH 3 );
either (i) Ar 1 is an aromatic-containing moiety, and Ar 2 is an aromatic-containing moiety, or (ii)
is combined to form an aromatic-containing moiety;
X is a spacer moiety; and
POLY is a water-soluble, non-peptidic oligomer.
3 . A compound having the following structure:
wherein:
(a) is either zero or one;
Z is selected from the group consisting of N, CH and C(CH 3 );
either (i) Ar 1 is an aromatic-containing moiety, and Ar 2 is an aromatic-containing moiety, or (ii)
is combined to form an aromatic-containing moiety; and
POLY is a water-soluble, non-peptidic oligomer.
4 . The compound of claim 2 , wherein (a) is zero.
5 . The compound of claim 2 , wherein (a) is one.
6 . The compound of claim 2 , wherein Ar 1 is an aromatic-containing moiety, and Ar 2 is an aromatic-containing moiety.
7 . The compound of claim 6 , wherein each of Ar 1 and Ar 2 is independently selected from the group consisting of
8 . The compound of claim 1 , wherein
is combined to form an aromatic-containing moiety.
9 . The compound of claim 8 , wherein the aromatic-containing moiety is
10 . The compound of claim 2 , wherein the water-soluble, non-peptidic oligomer is a poly(alkylene oxide).
11 . The compound of claim 10 , wherein the poly(alkylene oxide) is a poly(ethylene oxide).
12 . The compound of claim 2 , wherein the water-soluble, non-peptidic oligomer has between 1 and 30 monomers.
13 . The compound of claim 12 , wherein the water-soluble, non-peptidic oligomer has between 1 and 10 monomers.
14 . The compound of claim 10 , wherein the poly(alkylene oxide) includes an alkoxy or hydroxy end-capping moiety.
15 . The compound of claim 2 , wherein the spacer moiety provides a stable linkage.
16 . The compound of claim 2 , wherein the spacer moiety provides a degradable linkage.
17 . The compound of claim 2 , wherein spacer moiety is a covalent bond.
18 . The compound of claim 2 , wherein the spacer moiety is —O—.
19 . A composition comprising a compound of claim 2 , and optionally, a pharmaceutically acceptable excipient.
20 . A composition of matter comprising a compound of claim 2 , wherein the compound is present in a dosage form.
21 . A method comprising administering a compound of claim 2 .
22 . A method comprising binding histamine receptors, wherein said binding is achieved by administering a compound of claim 2 .