US2017182170A1PendingUtilityA1
Nitric Oxide Donors
Est. expirySep 28, 2026(~0.2 yrs left)· nominal 20-yr term from priority
C07F 9/5456A61K 31/095A61K 47/54A61K 31/662C07F 9/5407A61P 35/04A61P 9/10A61P 35/00A61K 47/48023
59
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The invention relates to novel NO donors which are targeted to the mitochondria. The NO donor compounds of the invention allow NO to be selectively provided to the mitochondria.
Claims
exact text as granted — not AI-modifiedWhat we claim is:
1 . A method for inhibiting cytochrome oxidase in the mitochondria of a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof, wherein the compound of formula I has the following structure:
wherein
X − is an anion; and
L is a linker group selected from the group consisting of
(a) (C 1-30 ) alkylene,
(b) (C 1-x ) alkylene-NR—(C 1-y ) alkylene, wherein R is H, alkyl, or aryl,
(c) (C 1-x ) alkylene-NR—C(═O)—(C 1-y ) alkylene, wherein R is H, alkyl, or aryl,
(d) (C 1-x ) alkylene-C(═O)—NR—(C 1-y ) alkylene, wherein R is H, alkyl, or aryl,
(e) alkylene-O—(C 1-y ) alkylene,
(f) (C 1-x ) alkylene-O—C(═O)—(C 1-y ) alkylene,
(g) (C 1-x ) alkylene-S—(C 1-y ) alkylene, or
(h) (C 1-x ) alkylene-aryl-(C 1-y ) alkylene,
wherein x+y=30 and wherein each alkylene is optionally substituted with one or more functional groups independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, carboxyalkyl, cyano, oxy, amino, alkylamino, aminocarbonyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, aralkylaminocarbonyl, alkylcarbonylamino, arylcarbonylamino, aralkylcarbonylamino, alkylcarbonyl, heterocyclocarbonyl, aminosulfonyl, alkylaminosulfonyl, alkylsulfonyl, and heterocyclosulfonyl, or the substituent groups of adjacent carbon atoms in the linker group can be taken together with the carbon atoms to which they are attached to form a carbocycle or a heterocycle.
2 . The method of claim 1 , wherein the compound of formula I is administered as a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula I with one or more pharmaceutically acceptable excipients, carriers or diluents.
3 . The method of claim 1 , wherein the compound of formula I comprises a lipophilic cation linked by a linker group to a thionitrite moiety, wherein the compound has the structure of the general formula I and the lipophilic cation is capable of mitochondrially targeting the thionitrite moiety
4 . The method of claim 1 , wherein the anion is an anion derived from an acid selected from the group comprising hydrochloric, hydrobromic, hydroiodic, sulfuric, sulfurous, nitric, nitrous, phosphoric, phosphorous, alkylsulfonic or arylsulfonic acid.
5 . The method of claim 1 , wherein the compound is of formula (II)
wherein n is from 0 to 27 and R 1 and R 2 are independently selected from the group comprising hydrogen, alkyl and aryl.
6 . The method of claim 5 , wherein R 1 and R 2 are independently selected from the group comprising hydrogen, methyl, ethyl, propyl, butyl, pentyl and hexyl, X − is chloride, bromide, iodide or methanesulfonate and n is from 0 to 10.
7 . The method of claim 5 , wherein R 1 and R 2 are methyl, X − is bromide or methanesulfonate and n is from 0 to 2.
8 . The method of claim 1 , wherein the compound is of formula (III)
wherein n is from 0 to 27 and R 1 , R 2 , R 3 and R 4 are independently selected from the group comprising hydrogen, alkyl and aryl.
9 . The method of claim 8 , wherein R 1 R 2 , R 3 and R 4 are independently selected from the group comprising hydrogen, methyl, ethyl, propyl, butyl, pentyl and hexyl, X − is chloride, bromide, iodide or methanesulfonate and n is from 0 to 10.
10 . The method of claim 8 , wherein R 1 R 2 , and R 3 are methyl, R 4 is hydrogen, X − is bromide or methanesulfonate and n is from 1 to 5.
11 . The method of claim 1 , wherein the compound is of formula (IV)
wherein n is from 0 to 27 and R 1 , R 2 and R 3 are independently selected from the group comprising hydrogen, alkyl and aryl.
12 . The method of claim 11 , wherein R 1 R 2 and R 3 are independently selected from the group comprising hydrogen, methyl, ethyl, propyl, butyl, pentyl and hexyl, X − is chloride, bromide, iodide or methanesulfonate and n is from 0 to 10.
13 . The method of claim 11 , wherein R 1 R 2 , and R 3 are methyl, X − is bromide or methanesulfonate and n is from 1 to 5.
14 . The method of claim 1 , wherein the compound is formula (V)
wherein n is from 0 to 27 and R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group comprising hydrogen, alkyl and aryl.
15 . The method of claim 14 , wherein R 1 , R 2 , R 3 , R 4 and R 5 are independently selected from the group comprising hydrogen, methyl, ethyl, propyl, butyl, pentyl and hexyl, X − is chloride, bromide, iodide or methanesulfonate and n is from 0 to 10.
16 . The method of claim 14 , wherein R 1 , R 2 , R 3 , R 4 and R 5 are methyl, X − is bromide or methanesulfonate and n is from 1 to 5.
17 . The method of claim 1 , wherein the compound is of formula (VI)
wherein n is from 0 to 27 and R 1 , R 2 , R 3 and R 4 are independently selected from the group comprising hydrogen, alkyl and aryl.
18 . The method of claim 17 , wherein R 1 R 2 , R 3 and R 4 are independently selected from the group comprising hydrogen, methyl, ethyl, propyl, butyl, pentyl and hexyl, X − is chloride, bromide, iodide or methanesulfonate and n is from 0 to 10.
19 . The method of claim 17 , wherein R 1 R 2 , R 3 and R 4 are methyl, X − is bromide or methanesulfonate and n is from 1 to 5.
20 . The method of claim 1 , wherein the compound isCited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.