Reactive oxygen species-based prodrugs
Provided herein are ROS-sensitive prodrug compositions and methods of treating ROS-associated diseases by administering the ROS-sensitive prodrug compositions.
1. A compound of formula:
wherein
—C(O)Z 1 together form a drug moiety;
R 1 is hydrogen;
R 2 is independently hydrogen, halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CN, —SH, —SO 2 Cl, —SO n2 R 10 , —SO y2 NR 7 R 8 , —NHNH 2 , —ONR 7 R 8 , —NHC(O)NHNH 2 , —NHC(O)NR 7 R 8 , —N(O) m2 , —NR 7 R 8 , —C(O)R 9 , —C(O)—OR 9 , —C(O)NR 7 R 8 , —OR 10 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
R 7 , R 8 , R 9 , and R 10 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
Z 1 is a cyclooxygenase (COX) inhibitor drug moiety selected from the group consisting of an ibuprofen drug moiety, a dexibuprofen drug moiety, a naproxen drug moiety, a fenoprofen drug moiety, a ketoprofen drug moiety, a dexketoprofen drug moiety, a flurbiprofen drug moiety, an oxaprozin drug moiety, a loxoprofen drug moiety, an indomethacin drug moiety, a tolmetin drug moiety, a sulindac drug moiety, an etodolac drug moiety, a ketorolac drug moiety, a diclofenac drug moiety, a aceclofenac drug moiety, a mefenamic acid drug moiety, a meclofenamic acid drug moiety, a flufenamic acid drug moiety, a tolfenamic acid drug moiety, an acetylsalicylic acid drug moiety, a diflunisal drug moiety, a salsalate drug moiety, a choline magnesium trisalicylate drug moiety, and a licofelone drug moiety;
an integer from 0 to 2;
an integer from 1 to 2; and
an integer from 1 to 2.
2. The compound of claim 1 , wherein said COX inhibitor drug moiety is an ibuprofen drug moiety, a dexibuprofen drug moiety, a naproxen drug moiety, a fenoprofen drug moiety, a ketoprofen drug moiety, a dexketoprofen drug moiety, a flurbiprofen drug moiety, an oxaprozin drug moiety, or a loxoprofen drug moiety.
3. The compound of claim 1 , wherein the COX inhibitor drug moiety is an indomethacin drug moiety, a tolmetin drug moiety, a sulindac drug moiety, an etodolac drug moiety, a ketorolac drug moiety, a diclofenac drug moiety, a aceclofenac drug moiety, a mefenamic acid drug moiety, a meclofenamic acid drug moiety, a flufenamic acid drug moiety, a tolfenamic acid drug moiety, an acetylsalicylic acid drug moiety, a diflunisal drug moiety, a salsalate drug moiety, a choline magnesium trisalicylate drug moiety, or a licofelone drug moiety.
4. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.