Compounds and uses thereof for the modulation of hemoglobin

A compound of Formula (I):

• In certain aspects of the invention, a compound of Formula (I) is provided:
• or a tautomer thereof, or a pharmaceutically acceptable salt of each thereof, wherein ring A is an optionally substituted 5-10 membered heteroaryl containing up to 3 ring N, O, and/or S atoms, and oxidized forms of N and/or S atoms;
• wherein ring A is a or 13 substituted relative to the Y substituent;
• ring B is an optionally substituted C6-C10 aryl or 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;
• each Y and Z is independently CR10R11, O, S, SO, SO2, or NR12;
• each R10 and R11 independently is hydrogen or C1-C3 alkyl, optionally substituted with halo, OH, or alkoxy, or CR10R11 is C═O;
• R12 is hydrogen or C1-C6 alkyl;
• provided that if one of Y and Z is O, S, SO, SO2, then the other is not CO, and provided that Y and Z are both not heteroatoms or oxidized forms thereof;
• ring C is C6-C10 aryl;
• 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 or 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;
• R5 is hydrogen, C1-C6 alkyl or a prodrug moiety R, wherein the C1-C6 alkyl is optionally substituted with 1-5 halo;
• R6 is a substituent that is halo, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6S(O)—, C1-C6S(O)2—, wherein the C1-C6 alkyl is optionally substituted with 1-5 halo;
• or
• R6 is 4-10 membered cycloalkyl or heterocycle substituted with an R′R′N— moiety wherein each R′ is independently C1-C6 alkyl or hydrogen;
• 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;
• R84 is optionally substituted C1-C6 alkyl;
• k is 0 or 1;
• and
• p is 0, 1, 2, or 3.