Substituted aldehyde compounds and methods for their use in increasing tissue oxygenation

A compound of Formula (I):

• or a tautomer or pharmaceutically acceptable salt thereof, wherein:
• Q is cycloalkyl or cycloalkenyl optionally substituted with one to three Ra;
• Y is O, S(O)q or CR1aR1b, where
• R1a is H or halo, and
• R1b is selected from the group consisting of H, halo, and OH;
• X is selected from the group consisting of O, S(O)q, CH(CH2)nR8, and C(R9)2, where
• q is 0, 1 or 2,
• n is 0 or 1,
• R8 is OH, and
• R9 is independently H or halo;
• or Y—X taken together is —NHC(O)— or —C(O)NH—;
• T1, T2, T3, and T4 are independently C or N provided that at least one of T1, T2, T3, and T4 is C;
• R2, R3, R4, and R5 are independently absent or selected from the group consisting of hydrogen, halo, Rb, ORd, —O(CH2)zORd, —O(CH2)zNRdRd, OC(O)Re, SRd, CN, NO2, CO2Rd, CONRdRd, C(O)Rd, OC(O)NRdRd, NRdRd, NRdC(O)Re, NRdC(O)2Re, NRdC(O)NRdRd, S(O)Re, S(O)2Re, NRdS(O)2Re, S(O)2NRdRd, and N3, where z is 0, 1, 2, 3, 4, 5, or 6;
• or
• R5 is —(CH2)pR5a, where p is 0 or 1 and R5a is OH;
• R6 and R7 together form oxo or an aldehyde protecting group, or
• R6 together with R1b, R8, or R5 forms a cyclic ether, where
• one of R1b, R8, or R5a is O, R6 is a bond, and
• R7 is selected from the group consisting of OH, C1-8alkoxy, and haloC1-8alkoxy;
• each Ra is independently selected from the group consisting of of halo, CN, Rb, ORd, O(CH2)uORd, O(CH2)uNRdRd, O(CH2)uNRdC(O)Re, O(CH2)uNRdC(O)2Re, O(CH2)uNRdS(O)2Re, NH2, —(CH2)kOC(O)Re, —(CH2)kSRd, NO2, —(CH2)kCO2(C1-8alkyl)OH, —(CH2)kCO2(C1-8alkyl)(heteroaryl)C(O)(C1-8alkyl), —(CH2)kCO2Rd, —(CH2)kCONRdRd, —(CH2)kNRdC(O)Re, —(CH2)kNRdC(O)2Re, —(CH2)k C(O)Rd, —(CH2)kOC(O)NRdRd, —NRd(CH2)uORd, —NRd(CH2)uNRdRd, —NRd(CH2)uNRdC(O)Re, —NRd(CH2)uNRdC(O)2Re, —NRd(CH2)uNRdS(O)2Re, —(CH2)kNRdC(O)Re, —(CH2)kNRdC(O)2Rd, —(CH2)kNRdC(O)NRdRd, —(CH2)kS(O)Re, —(CH2)kS(O)2Re, —(CH2)kNRdS(O)2Re, —(CH2)kS(O)2NRdRd, N3, —(CH2)karyl optionally substituted with one to three Rc, —NRd(CH2)karyl optionally substituted with one to three Rc, —(CH2)kheteroaryl optionally substituted with one to three Rc, —NRd(CH2)kheteroaryl optionally substituted with one to three Rc, —(CH2)kheterocycloalkyl optionally substituted with one to three Rc,
• and —NRd(CH2)kheterocycloalkyl optionally substituted with one to three Rc where k is 0, 1, 2, 3, 4, 5, or 6 and u is 1, 2, 3, 4, 5, or 6;
• each Rb is independently selected from the group consisting of C1-8alkyl, C2-8alkenyl, and C2-8 alkynyl, each optionally independently substituted with one to three halo, ORd, or NRdRd;
• each Rc is independently selected from the group consisting of halo, C1-8alkyl, haloC1-8alkyl, C2-8alkenyl, haloC2-8alkenyl, C2-8alkynyl, haloC2-8alkynyl, (CH2)mORf, OC(O)Rg, SRf, CN, NO2, CO2Rf, CONRfRf, C(O)Rf, OC(O)NRfRf, (CH2)mNRfRf, NRfC(O)Rg, NRfC(O)2Rg, NRfC(O)NRfRf, S(O)Rg, S(O)2Rg, NRfS(O)2Rg, S(O)2NRfRf, N3, heteroaryl optionally substituted with one to three Rh, cycloalkyl optionally substituted with one to three Rh, and heterocycloalkyl optionally substituted with one to three Rh where m is selected from the group consisting of 0, 1, 2, 3, 4, 5, and 6;
• each Rh is independently selected from the group consisting of halo, C1-8alkyl, haloC1-8alkyl, ORj, OC(O)R, SRj, NO2, CO2Rj, CONRjRj, C(O)Rj, OC(O)NRjRj, NRjRj, NRjC(O)Rt, NRjC(O)2Rt, NRjC(O)NRjRj, S(O)Rt, S(O)2Rt, NRjS(O)2Rt, and S(O)2NRjRj;
• each Rd is independently selected from the group consisting of hydrogen, C1-8 alkyl, haloC1-8alkyl, C2-8 alkenyl, haloC2-8alkenyl, C2-8 alkynyl, haloC2-8alkynyl, —(CH2)kheterocycloalkyl, and —(CH2)uO—(CH2)uH where k is 0, 1, 2, 3, 4, 5, or 6 and each u is independently 1, 2, 3, 4, 5, or 6;
• Rf and Rj are each independently selected from the group consisting of hydrogen, C1-8 alkyl, haloC1-8alkyl, C2-8 alkenyl, haloC2-8alkenyl, C2-8 alkynyl, and haloC2-8alkynyl;
• and
• Re, Rg, and Rt are each independently selected from the group consisting of C1-8alkyl, haloC1-8alkyl, C2-8 alkenyl, haloC2-8alkenyl, C2-8 alkynyl, and haloC2-8alkynyl;
• provided that X and Y are not both O;
• provided that when X is O, R1b is not OH;
• and
• provided that when Y is O, and n is 0, R8 is not OH.