Enzyme-triggered carbon monoxide releasing molecules

A method for delivering carbon monoxide to a subject in need thereof, the method comprising administering to the subject a compound having a structure according to Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• the moiety —X—Y— is selected from the group consisting of —O—C(O)— and —C(O)—O—;
• Z is selected from the group consisting of —O— and —S—;
• R1 is selected from the group consisting of —C(O)R1a, H, C1-8 alkyl, C3-8 cycloalkyl, and C6-10 aryl;
• R1a is selected from the group consisting of —NR1bR1c, C1-8 alkyl, C3-8 cycloalkyl, C6-10 aryl, 3- to 8-membered heterocyclyl, 5- to 12-membered heteroaryl, —OR1b, and a solubilizing moiety;
• R1b and R1c are independently selected from H, C1-8 alkyl, C3-8 cycloalkyl, and a solubilizing moiety;
• R2 and R3 are taken together to form a fused tricyclic moiety, or
• R2 and R3 are independently C6-10 aryl;
• R4, R5, and R6 are independently selected from the group consisting of H and C1-6 alkyl;
• R1, R2, R3, R4, R5, and R6 are optionally and independently substituted with one or more R7;
• each R7 is independently selected from the group consisting of C1-4 alkyl, halogen, —CN, —ORa, —C(O)Rb, —C(O)ORa, —OC(O)Rb, —N(Ra)2, —NRaC(O)Rb, —C(O)N(Ra)2, —S(O)Rb, —S(O)2Rb, —S(O)2ORa, —S(O)2N(Ra)2, and —NRaS(O)2Rb;
• each Ra is independently selected from the group consisting of H and C1-4 alkyl;
• each Rb is C1-4 alkyl;
• and
• subscript t is 0, 1, 2, or 3.

A method for treating a disease or condition, the method comprising administering to a subject having said disease or condition an effective amount of a compound having a structure according to Formula I:

• or a pharmaceutically acceptable salt thereof,
• wherein the disease or condition is selected from the group consisting of a cardiovascular condition, an ophthalmic condition, a neurological condition, a urological condition, diabetes, inflammation, bacterial infection, hypertension, hypothermia, asthma, gastric injury, irritable bowel syndrome, kidney dysfunction, sepsis, ischemia, respiratory distress syndrome, autoimmune disorders, thrombosis, cancer, wounds, and rejection in organ transplantation;
• and wherein:
• the moiety —X—Y— is selected from the group consisting of —O—C(O)— and —C(O)—O—;
• Z is selected from the group consisting of —O— and —S—;
• R1 is selected from the group consisting of —C(O)R1a, H, C1-8 alkyl, C3-8 cycloalkyl, and C6-10 and;
• R1a is selected from the group consisting of —NR1bR1c, C1-8 alkyl, C3-8 cycloalkyl, C6-10 aryl, 3- to 8-membered heterocyclyl, 5- to 12-membered heteroaryl, —OR1b, and a solubilizing moiety;
• R1b and R1c are independently selected from H, C1-8 alkyl, C3-8 cycloalkyl, and a solubilizing moiety;
• R2 and R3 are taken together to form a fused tricyclic moiety, or
• R2 and R3 are independently C6-10 aryl;
• R4, R5, and R6 are independently selected from the group consisting of H and C1-6 alkyl;
• R1, R2, R3, R4, R5, and R6 are optionally and independently substituted with one or more R7;
• each R7 is independently selected from the group consisting of C1-4 alkyl, halogen, —CN, —ORa, —C(O)Rb, —C(O)ORa, —OC(O)Rb, —N(Ra)2, —NRaC(O)Rb, —C(O)N(Ra)2, —S(O)Rb, —S(O)2Rb, —S(O)2ORa, —S(O)2N(Ra)2, and —NRaS(O)2Rb;
• each Ra is independently selected from the group consisting of H and C1-4 alkyl;
• each Rb is C1-4 alkyl;
• and
• subscript t is 0, 1, 2, or 3.