COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN

1 . A compound of Formula (I)

or a tautomer thereof, or pharmaceutically acceptable salt of each of thereof or a pharmaceutically acceptable salt thereof, wherein

R 3 is C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 6 alkoxy, C 3 -C 8 cycloalkoxy, or —NR 1 R 2 ;

each R 1 and R 2 independently is hydrogen, C 1 -C 6 alkyl, C 3 -C 8 cycloalkyl, C 6 -C 10 aryl, 4-10 membered heterocycle or 5-10 membered heteroaryl, each 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 alkyl, cycloalkyl, heterocycle, aryl or heteroaryl is optionally substituted, or R 1 and R 2 together with the nitrogen atom they are attached to form an optionally substituted 4-7 membered heterocycle; or

R 3 is C 6 -C 10 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 C 1 -C 6 alkyl;

L 1 is a bond or is NR 70 , O, S, or (CR 71 R 72 )d; wherein each R 70 , R 71 , and R 72 independently are hydrogen or C 1 -C 6 alkyl;

d is 1, 2, or 3;

L 2 is C═O or SO 2 ;

ring B is a optionally substituted C 6 -C 10 aryl, optionally substituted 5-10 membered heteroaryl having 1-3 nitrogen atoms or oxidized forms of N, 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; or

ring B is a 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;

each Y and Z is independently CR 10 R 11 , O, S, SO, SO 2 , or NR 10 ; each R 10 and R 11 independently is hydrogen or C 1 -C 3 alkyl optionally substituted with 1-3 halo, OH, or C 1 -C 6 alkoxy, or CR 10 R 11 is C═O, provided that if one of Y and Z is O, S, SO, SO 2 , then the other is not CO, and Y and Z are both not heteroatoms or oxidized forms thereof;

wherein Y is α or β substituted relative to the -L 1 L 2 R 3 ;

wherein Z and —CV 1 V 2 H are joined to adjacent atoms on ring C;

ring C is a optionally substituted C 6 -C 10 aryl or optionally substituted 5-10 membered heteroaryl containing 1-3 nitrogen atoms, or an oxidized form of N; or

ring C is C 6 -C 10 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 —OR 19 , C 1 -C 6 alkyl, and/or C 1 -C 6 alkoxy, wherein the C 1 -C 6 alkyl is optionally substituted with 1-5 halo, C 1 -C 6 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; and

R 19 is hydrogen or a prodrug moiety R;

V 1 and V 2 independently are C 1 -C 6 alkoxy, or V 1 and V 2 together with the carbon atom they are attached to form a ring of formula:

wherein each V 3 and V 4 are independently O, S, or NH, provided that when one of V 3 and V 4 is S, the other is NH, and provided that V 3 and V 4 are both not NH; q is 1 or 2; each V 5 is independently C 1 -C 6 alkyl or CO 2 R 60 , where each R 60 independently is C 1 -C 6 alkyl or hydrogen; t is 0, 1, 2, or 4; or CV 1 V 2 is C═V, wherein V is O, NOR 80 , or NNR 81 R 82 ;

R 80 is optionally substituted C 1 -C 6 alkyl;

R 81 and R 82 independently are selected from the group consisting of hydrogen; optionally substituted C 1 -C 6 alkyl, COR 83 and CO 2 R 84 ;

R 83 is hydrogen or optionally substituted C 1 -C 6 alkyl; and

R 84 is optionally substituted C 1 -C 6 alkyl.

2 - 19 . (canceled)