1:1 adducts of sickle hemoglobin
Provide herein are 1:1 adducts of sickle hemoglobin (HbS) and a compound of formula (I), as defined herein, suitable as modulators of HbS, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.
1. A method for increasing oxygen affinity of sickle hemoglobin (HbS) in vivo in a patient in need thereof which method comprises administering to said patient a sufficient amount of 2-(((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)oxy)methyl)-6-hydroxybenzaldehyde or a salt thereof such that said 2-4(2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)oxy)methyl)-6-hydroxybenzaldehyde or a salt thereof binds to HbS to form a 1:1 adduct in vivo and further wherein said adduct increases the oxygen affinity of said HbS.
2. A method for inhibiting sickling of HbS in a patient which method comprises administering to said patient a sufficient amount of a composition comprising 2-(((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)oxy)methyl)-6-hydroxybenzaldehyde or a salt thereof such that said 2-(((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)oxy)methyl)-6-hydroxybenzaldehyde or a salt thereof binds to HbS to form, in vivo, a 1:1 adduct thereby inhibiting sickling of HbS.