Compounds and uses thereof for the modulation of hemoglobin

A compound of formula (II):

• an N oxide thereof, or a pharmaceutically acceptable salt of each thereof,
• wherein R is —C(O)R31, —C(O)OR31, —CONR13R14, a phosphonate, or a phosphoramidate;
• wherein each R31 is independently a C1-C6 alkyl, C3-C8 cycloalkyl, 4-9 membered heterocycle, or 5-10 membered heteroaryl, each of which is substituted with at least one (CR32R33)eNR34R35;
• R32 and R33 are independently H, C1-C8 alkyl, C3-C9 heterocycle, C3-C8 cycloalkyl, C6-C10 aryl, or C3-C9 heteroaryl;
• or R32 and R33, together with the carbon atom to which they are attached, join to form a C3-C8 cycloalkyl, C6-C10 aryl, C3-C9 heterocycle, or C3-C9 heteroaryl ring system;
• or two adjacent R32 moieties or two adjacent R33 moieties, together with the carbon atoms to which they are attached, join to form a C3-C8 cycloalkyl, C6-C10 aryl, C3-C9 heterocycle, or C3-C9 heteroaryl ring system;
• R34 and R35 are independently a C1-C8 alkyl, C3-C9 heterocycle, or C3-C8 cycloalkyl;
• or R34 and R35, together with the nitrogen atom to which they are attached, join to form a C3-C8 cycloalkyl or C3-C9 heterocycle ring system;
• each heterocycle and heteroaryl ring system is optionally substituted with C1-C3 alkyl, —OH, amino or carboxyl groups;
• e is an integer of from 1 to 4;
• R13 and R14 are independently a C1-C6 alkyl, C3-C8 cycloalkyl, 4-9 membered heterocycle, or 5-10 membered heteroaryl, containing at least one basic nitrogen moiety;
• or R13 and R14, together with the nitrogen atom to which they are attached, join to form a 4-9 membered heterocycle substituted with at least one amino, C1-C6 alkylamino, or di-(C1-C6 alkyl)-amino group;
• and
• R1 is C1-C6 alkyl optionally substituted with 3-6 fluoro atoms.