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US 2021/0238155 A1Published application
Carbon monoxide prodrugs for the treatment of medical disorders
AssigneeGeorgia State University Research Foundation, Inc.
InventorsBinghe Wang, Xingyue Ji, Ladie Kim De La Cruz, Xiaoxiao Yang
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Abstract
The present invention provides new compounds and compositions thereof that release carbon monoxide for the treatment of medical disorders that are responsive to carbon monoxide, for example, inflammatory, pain, and dermatological disorders.
Claims24
A compound of Formula I, Formula II, or Formula III:
- or a pharmaceutically acceptable salt thereof;
- wherein A is selected from:
- B is selected from:
- B′ is selected from:
- C is selected from:
- RA is selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R1 is independently selected at each occurrence from halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, heteroaryl, thiol, thioalkyl, —(C═O)RS, —O(C═O)RS, cyano, —SO3H, —(P═O)(OH)2, —O(P═O)(OH)2, and nitro;
- R1A is independently selected at each occurrence from halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, heteroaryl, thiol, —(C═O)RS, —O(C═O)RS, cyano, —SO3H, —(P═O)(OH)2, —O(P═O)(OH)2, and nitro;
- R2 and R2′ are independently selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R3 is independently selected at each occurrence from halogen, alkyl, haloalkyl, aryl, heteroaryl, and
- R4 and R4′ are independently alkyl;
- R5 and R5′ are independently selected from hydrogen, halogen, hydroxyl, alkyl, haloalkyl, aryl, and heteroaryl;
- R5″ is selected from hydrogen, alkyl, aryl, and heteroaryl;
- R6 and R6′ are independently selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R7 is independently selected at each occurrence from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R8 and R8′ are independently selected from alkyl and aryl;
- R9 is selected from alkyl, haloalkyl, aryl, and heteroaryl;
- and
- R10 and R10′ are independently selected from alkyl, aryl, and heteroaryl;
- R11 is selected from hydrogen, halogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R12 is selected from hydrogen, halogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R13 and R13′ are independently selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R14 is selected from hydrogen, alkyl, aryl, and heteroaryl;
- RS is selected from hydrogen, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, aryl, and heteroaryl;
- R15 is independently selected at each occurrence from hydrogen, halogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R16 and R16′ are independently selected at each occurrence from alkyl, haloalkyl, aryl, heteroaryl, alkoxy, haloalkoxy, aryloxy, heteroaryloxy, amino, alkylamino, and dialkylamino;
- R17 is selected from halogen, haloalkyl, and nitro;
- and
- Rm, Rn, Ro, and Rp are independently selected from hydrogen, halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, and heteroaryl;
- X1 is —C(R5)(R5′)—, —N(R5″)—, —O—, or —S—;
- m is independently selected from 0, 1, 2, 3, or 4;
- n is independently selected at each occurrence from 0, 1, 2, 3, 4, and 5;
- and
- o is selected from 1, 2, 3, or 4.
31 more elements
A method for the treatment of a medical disorder that can be treated with carbon monoxide comprising administering an effective amount of a compound of Formula IV, Formula V, or Formula VI:
- or a pharmaceutically acceptable salt thereof;
- wherein A1 is selected from:
- B1 is selected from:
- RB is selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- C1 is selected from:
- R1 is independently selected at each occurrence from halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, heteroaryl, thiol, thioalkyl, —(C═O)RS, —O(C═O)RS, cyano, —SO3H, —(P═O)(OH)2, —O(P═O)(OH)2, and nitro;
- R2 and R2′ are independently selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R3 is independently selected at each occurrence from halogen, alkyl, haloalkyl, aryl, heteroaryl, and
- R5 and R5′ are independently selected from hydrogen, halogen, hydroxyl, alkyl, haloalkyl, aryl, and heteroaryl;
- R5″ is selected from hydrogen, alkyl, aryl, and heteroaryl;
- R6 and R6′ are independently selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R7 is independently selected at each occurrence from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R8 and R8′ are independently selected from alkyl and aryl;
- R9 is selected from alkyl, haloalkyl, aryl, and heteroaryl;
- R10 and R10′ are independently selected from alkyl, aryl, and heteroaryl;
- R11 is selected from hydrogen, halogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R13 and R13′ are independently selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R15 is independently selected at each occurrence from hydrogen, halogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R16 and R16′ are independently selected at each occurrence from alkyl, haloalkyl, aryl, heteroaryl, alkoxy, haloalkoxy, aryloxy, heteroaryloxy, amino, alkylamino, and dialkylamino;
- R17 is selected from halogen, haloalkyl, and nitro;
- Rm, Rn, Ro, and Rp are independently selected from hydrogen, halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, and heteroaryl;
- and
- RS is selected from hydrogen, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, aryl, and heteroaryl;
- X1 is —C(R5)(R5′)—, —N(R5″)—, —O—, or —S—;
- m is independently selected from 0, 1, 2, 3, or 4;
- and
- n is independently selected at each occurrence from 0, 1, 2, 3, 4, and 5.
24 more elements
A solid dispersion pharmaceutical composition comprising a compound of Formula (IV), Formula (V), or Formula (VI):
- or a pharmaceutically acceptable salt thereof
- A1 is selected from:
- B1 is selected from:
- C1 is selected from:
- R1 is independently selected at each occurrence from halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, heteroaryl, thiol, thioalkyl, —(C═O)RS, —O(C═O)RS, cyano, —SO3H, —(P═O)(OH)2, —O(P═O)(OH)2, and nitro;
- R2 and R2′ are independently selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R3 is independently selected at each occurrence from halogen, alkyl, haloalkyl, aryl, heteroaryl, and
- R5 and R5′ are independently selected from hydrogen, halogen, hydroxyl, alkyl, haloalkyl, aryl, and heteroaryl;
- R5″ is selected from hydrogen, alkyl, aryl, and heteroaryl;
- R6 and R6′ are independently selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R7 is independently selected at each occurrence from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R8 and R8′ are independently selected from alkyl and aryl;
- R9 is selected from alkyl, haloalkyl, aryl, and heteroaryl;
- R10 and R10′ are independently selected from alkyl, aryl, and heteroaryl;
- R11 is selected from hydrogen, halogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R13 and R13′ are independently selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R15 is independently selected at each occurrence from hydrogen, halogen, alkyl, haloalkyl, aryl, and heteroaryl;
- R16 and R16′ are independently selected at each occurrence from alkyl, haloalkyl, aryl, heteroaryl, alkoxy, haloalkoxy, aryloxy, heteroaryloxy, amino, alkylamino, and dialkylamino;
- R17 is selected from halogen, haloalkyl, and nitro;
- Rm, Rn, Ro, and Rp are independently selected from hydrogen, halogen, hydroxyl, alkyl, haloalkyl, alkoxy, haloalkoxy, aryl, and heteroaryl;
- RB is selected from hydrogen, alkyl, haloalkyl, aryl, and heteroaryl;
- RS is selected from hydrogen, alkyl, haloalkyl, alkoxy, amino, alkylamino, dialkylamino, aryl, and heteroaryl;
- X1 is —C(R5)(R5′)—, —N(R5″)—, —O—, or —S—;
- m is independently selected from 0, 1, 2, 3, or 4;
- and
- n is independently selected at each occurrence from 0, 1, 2, 3, 4, and 5.
23 more elements
Dependencies are inferred from the claim text.