Compounds and uses thereof for the modulation of hemoglobin
Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.
1. A compound selected from the group consisting of
or an N oxide thereof, wherein,
R 14 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, COR 15 or COOR 15 ;
R 15 is optionally substituted C 1 -C 6 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5-10 membered heteroaryl containing up to 5 ring heteroatoms, or optionally substituted 4-10 membered heterocycle containing up to 5 ring heteroatoms, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S;
x is 0, 1, or 2; and
m is 0, 1 or 2.
2. A composition comprising a compound of claim 1 and at least one pharmaceutically acceptable excipient.
3. A method for increasing oxygen affinity of hemoglobin S in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .