Pseudoazulenyl nitrones
View Patent ↗Disclosed herein are pseudoazulenyl nitrone compounds and methods of using these compounds to trap free radicals and to treat, prevent, or ameliorate various diseases associated with free radicals.
1. A compound having a general structural formula (I) or formula (II):
wherein R 1 , R 5 , and R 7 are the same or different and are independently selected from the group consisting of hydrogen, C 1-4 alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, tris(3-hydroxypropyl)methyl, (3-carboxy-1,1-dimethyl)propyl, and 3-sulfonatophenyl; R 2 , R 6 , and R 9 are the same or different and are selected from the group consisting of hydrogen, C═C(H)N + (R 1 )O − , C 1-22 alkyl, C 1-10 alkyleneOC(O)C 1-10 alkyl, and CHO; R 3 is selected from the group consisting of hydrogen, C 1-22 alkyl, SR 12 , and SO 3 − ; X is selected from the group consisting of O, S, and NR 4 ; X′ is selected from the group consisting of O, S, and NR 8 ; R 4 and R 8 are the same or different and are selected from the group consisting of hydrogen, C 1-22 alkyl, phenyl, substituted phenyl, (C 1-22 alkyleneN(R 12 ) 2 + ) n C 1-22 alkyleneN(R 12 ) 2 , C 1-22 alkyleneOR 11 , C 1-22 alkyleneP(R 1 ) 3 + , C 1-22 alkylene aryl, C 1-22 alkylene substituted aryl, C 1-22 alkylene heteroaryl, and C 1-22 alkylene substituted heteroaryl; R 10 is independently selected from the group consisting of hydrogen, C 1-10 alkyl, C 1-10 alkyleneN(R 12 ) 3 + , and C 1-10 alkylene-C 6 H 4 —C 1-10 alkyleneN(R 12 ) 3 + ; R 11 is selected from the group consisting of hydrogen, C 1-10 alkyl, SO 2 CF 3 , SO 2 CH 3 , SO 2 C 6 H 4 CH 3 , and SO 2 C 4 F 9 ; and R 12 is selected from the group consisting of hydrogen, C 1-22 alkyl, aryl, heteroaryl, substituted aryl, and substituted heteroaryl; n is an integer from 0 to 3; or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein X is NR 4 ; X′ is NR 8 , or X is NR 4 and X′ is NR 8 .
3. The compound of claim 1 , wherein R 2 is C═C(H)N + (R 1 )O − .
4. The compound of claim 1 , wherein X is O or X′ is O, or X and X′ are each O.
5. The compound of claim 1 selected from the group consisting of:
6. The compound of claim 1 selected from the group consisting
wherein Ph is phenyl and tBu is tert-butyl.
7. A method of trapping a reactive free radical comprising contacting a compound of claim 1 with the reactive free radical to form an adduct of the compound and the reactive free radical.
8. A method of screening for free radicals comprising contacting a compound suspected of producing free radicals with a compound of claim 1 to form an adduct of the free radical and the compound of claim 1 , and measuring a ratio of the adduct to the compound of claim 1 , wherein a ratio greater than 0 indicates the presence of free radicals.