Opioid agonists and uses thereof
Provided are compounds, including those of Formula I; and pharmaceutically acceptable salts and solvates thereof. The compounds described herein relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology, organic chemistry and polymer chemistry.
1. A compound selected from the formula:
wherein:
R 2 is an substituted alkyl;
(i) R 1 and R 3 are taken together with their intervening atoms to form a fused, substituted thiazole and R 5 is hydrogen, where R 1 and R 3 are positions 4 and 5 of the thiazole, wherein the thiazole is substituted with —X-POLY at position 2 of the thiazole; or
(ii) R 3 and R 5 are taken together with their intervening atoms to form a fused, substituted thiazole and R 1 is hydrogen, where R 1 and R 3 are positions 4 and 5 of the thiazole, wherein the thiazole is substituted with —X-POLY at position 2 of the thiazole;
is a double bond;
G is ═O;
X is a spacer moiety selected from a covalent bond, —C(O)—, —NHC(O)—, —NH—, —CH 2 CHOHCH 2 NH—, and —O—;
POLY is a poly(alkylene oxide) oligomer;
or pharmaceutically acceptable salts thereof.
2. The compound of claim 1 , wherein R 5 is hydrogen.
3. The compound of claim 1 , wherein R 2 is alkyl or cyclopropylmethyl.
4. The compound of claim 1 , wherein R 1 is hydrogen.
5. The compound of claim 1 , wherein the compound of Formula I is selected from the formulae:
and
wherein n is an integer from 1 to 30.
6. The compound of claim 5 , wherein n is an integer from 1 to 10.
7. The compound of claim 1 , wherein R 3 and R 5 are taken together with their intervening atoms to form the substituted thiazole.
8. A compound, selected from
(6S,10R,12R)-2-(2,5,8,11,14-pentaoxahexadecan-16-ylamino)-7-(cyclopropylmethyl)-10,12-dimethyl-7,8,9,10-tetrahydro-6,10-methanothiazolo[4′,5′:4,5]benzo[1,2-d]azocin-5(6H)-one; and
(7S,11R,12R)-2-(2,5,8,11,14-pentaoxahexadecan-16-ylamino)-8-(cyclopropylmethyl)-11,12-dimethyl-8,9,10,11-tetrahydro-7,11-methanothiazolo[5′,4′:3,4]benzo[1,2-d]azocin-6(7H)-one;
or pharmaceutically acceptable salts thereof.
9. A pharmaceutical composition comprising the compound of claim 1 and at least one pharmaceutically acceptable excipient.
10. A composition of matter comprising the compound of claim 1 , wherein the compound is present in a dosage form.
11. The compound of claim 1 , wherein the poly(alkylene oxide) oligomer is a poly(alkylene glycol) oligomer.