Methods and compositions for treating β-thalassemia and sickle cell disease

摘要

The present invention provides compounds (such as compounds of formula I-a) that induce γ globin expression and pharmaceutical compositions thereof. Such compounds may have beneficial therapeutic effects. Compounds and compositions described herein may be used to treat hemoglobinopathies such as β-thalassemia and sickle cell anemia.;

主权项

1. A method of treating β-thalassemia or sickle cell anemia comprising:
administering an effective amount of a pharmaceutical composition to a patient suffering from β-thalassemia, wherein the pharmaceutical composition comprising a compound of formula (I-a): or a pharmaceutically acceptable salt, solvate, or hydrate thereof,wherein:
R1, R2, R3, R4, R6a, and R6b are each independently selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, heterocyclyl, aryl, —ORA, —OC(O)RA, —SRA, —N(RB)2, —N(RA)C(O)RA, —C(O)N(RB)2, —CN, —NO2, —C(O)RA, —C(O)ORA, —S(O)RA, —SO2RA—SO2N(RB)2, and —NHSO7RB; each instance of R5 is independently selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, heterocyclyl, aryl, —ORA, —OC(O)RA, —SRA, —N(RB)7, —N(RA)C(O)RA, —C(O)N(RB)2, —CN, —NO2, —C(O)RA, —C(O)ORA, —S(O)RA, —SO2RA—SO2N(RB)2, and —NHSO2RB; each RA is independently selected from hydrogen, alkyl, alkenyl, alkynyl, heterocyclyl, and aryl; each RB is independently selected from hydrogen, alkyl, alkenyl, alkynyl, heterocyclyl, and aryl, or two RB taken together with the intervening nitrogen form a heterocycle; n is 0, 1, 2, 3, or 4; and a pharmaceutically acceptable excipient.