Methods of using pyruvate kinase activators

A method for increasing lifetime of the red blood cells (RBCs) in need thereof comprising contacting blood with an effective amount of (1) a compound of formula I or a pharmaceutically acceptable salt thereof;

• (2) a composition comprising a compound of formula I or a salt thereof, and a carrier or (3) a pharmaceutically acceptable composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier:
• formula (I):
• wherein:
• A is aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted, and the aryl or heteroaryl is optionally fused to an optionally substituted carbocyclyl or an optionally substituted heterocyclyl;
• X is selected from —NH—S(O)2—, —N(alkyl)-S(O)2—, —S(O)2—N(H)—, and —S(O)2—N(alkyl)-;
• R1a is selected from hydrogen, alkyl, and arylalkyl;
• and R1b is selected from OR3, N(alkyl)R3 and NHR3;
• or
• R1a is alken-1-yl and R1b is absent;
• each R2 is independently selected from halo, haloalkyl, alkyl, alkoxy and hydroxyl;
• R3 is selected from hydrogen, alkyl, optionally substituted aryl, optionally substituted heteroaryl, arylalkyl, C(O)Ra, and C(O)N(H)Ra, wherein Ra is selected from alkyl, alkenyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl;
• and wherein any aryl or heteroaryl portion of Ra is optionally substituted;
• each R4 is independently selected from haloalkyl, alkyl, alkoxy and hydroxyl;
• n is 0, 1, or 2;
• and
• m is 0, 1, or 2.