Compounds and uses thereof for the modulation of hemoglobin

A compound of formula (I):

• or a tautomer thereof, or a pharmaceutically acceptable salt of each thereof, wherein
• L10 is optionally substituted methylene or, preferably, a bond;
• ring A is C6-C10 aryl, a C3-C8 cycloalkyl, a 5-10 membered heteroaryl or a 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, wherein each of the aryl, heteroaryl, cycloalkyl, or heterocycle is optionally substituted with 1-4:
• halo, C1-C6 alkyl, C1-C6 alkoxy, and/or C3-C10 cycloalkyl, wherein the C1-C6 alkyl is optionally substituted with 1-5 halo, C1-C6 alkoxy, and/or C3-C10 cycloalkyl;
• or
• ring A is C6-C10 aryl, or a 5-10 membered heteroaryl, wherein the heteroatom is selected from the group consisting of O, N, S, and oxidized forms of N and S, wherein each of the aryl, or heteroaryl is optionally substituted with 1-4 C1-C6 alkyl and/or C1-C6 alkoxy groups;
• ring B is a 5-10 membered heteroaryl or a 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, wherein each of the heteroaryl and the heterocycle is optionally substituted with 1-4:
• halo, C1-C6 alkyl and/or —CO—C1-C6 alkyl, or
• ring B is:
• wherein ring B′ including the —N—CO— moiety is a 5-6 membered heterocycle containing up to 3 heteroatoms selected from nitrogen, oxygen, and sulfur and oxidized forms of N and S, wherein each of the heteroaryl and the heterocycle is optionally substituted with 1-4 C1-C6 alkyl groups;
• is a single or a double bond;
• each X and Y is independently (CR20R21)e, O, S, SO, SO2, or NR20;
• e is 1 to 4, preferably 1;
• each R20 and R21 independently is hydrogen or C1-C3 alkyl optionally substituted with 1-3 halo, OH, or C1-C6 alkoxy, or CR20R21 is C═O, provided that if one of X and Y is O, S, SO, SO2, then the other is not CO, and X and Y are both not heteroatoms or oxidized forms thereof;
• ring C is C6-C10 aryl or a 5-10 membered heteroaryl 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, each of which is optionally substituted with 1-4:
• halo, oxo, —OR1, C1-C6 alkyl, —COOR1, and/or C1-C6 alkoxy, wherein the C1-C6 alkyl is optionally substituted with 1-5 halo, C1-C6 alkoxy and/or a 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;
• or
• ring C is C6-C10 aryl or a 5-10 membered heteroaryl 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, each of which is optionally substituted with 1-4:
• halo, oxo, —OR1, C1-C6 alkyl, —COOR1, NR5R6,
• R1 is a hydrogen, C1-C6 alkyl or a prodrug moiety;
• wherein the alkyl is optionally substituted with a 5-10 membered heteroaryl 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, which is optionally substituted with with a 5-10 membered heteroaryl 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, wherein the heteroaryl is optionally substituted with C1-C6 alkyl;
• R5 and R6 are each independently hydrogen, optionally substituted C1-C6 alkyl or —COOR3;
• R3 is hydrogen or optionally substituted C1-C6 alkyl;
• V1 and V2 independently are C1-C6 alkoxy;
• or V1 and V2 together with the carbon atom they are attached to form a ring of formula:
• wherein each V3 and V4 are independently O, S, or NH, provided that when one of V3 and V4 is S, the other is NH, and provided that V3 and V4 are both not NH;
• q is 1 or 2;
• each V5 is independently C1-C6 alkyl optionally substituted with 1-3 OH groups, or V5 is CO2R60, where each R60 independently is C1-C6 alkyl or hydrogen;
• t is 0, 1, 2, or 4;
• or CV1V2 is C═V, wherein V is O, NOR80, or NNR81R82;
• R80 is optionally substituted C1-C6 alkyl;
• R81 and R82 independently are selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, COR83, or CO2R84;
• R83 is hydrogen or optionally substituted C1-C6 alkyl;
• and
• R84 is optionally substituted C1-C6 alkyl;
• with the proviso that when ring C is C6-C10 aryl;
• and ring B is optionally substituted 4-10 membered heterocyclyl;
• then ring A excludes optionally substituted 5-10 membered heteroaryl;
• and provided that when ring C is C6-C10 aryl;
• and ring B is optionally substituted 5-10 membered heteroaryl;
• then ring A is not optionally substituted 4-10 membered heterocycle.