Quinolone based compounds exhibiting prolyl hydroxylase inhibitory activity, and compositions, and uses thereof

A method of treating ischemia in a subject comprising administering to a subject with ischemia a therapeutically effective amount of a compound of the Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• n is 1 to 6;
• R1 is chosen from H, lower alkyl and substituted lower alkyl;
• R2 is chosen from H, lower alkyl and substituted lower alkyl;
• R3 and R4 are independently chosen from H, lower alkyl, substituted lower alkyl, lower haloalkyl, substituted lower haloalkyl, or R3 and R4 can join together to form a 3 to 6 membered ring or a substituted 3 to 6 membered ring;
• R5 is chosen from OH, SH, NH2, lower alkyl, substituted lower alkyl, lower alkoxy, substituted lower alkoxy and sulfanyl;
• R6 is chosen from H, OH, SH, NH2, NHSO2R1 and sulfonyl;
• and
• each of R7, R8, R9 and R10 is independently chosen from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, NR3′R4′, C(O)OH, OR13, SR13, SO2R13, CN, NO2, halo, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heterocycloalkyl, substituted heterocycloalkyl, alkylsilyl, substituted alkylsilyl, alkynylsilyl, substituted alkynylsilyl, alkoxy, substituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, and —X—R12, wherein:
• R3′ and R4′ are independently chosen from H, lower alkyl, substituted lower alkyl, lower haloalkyl, and substituted lower haloalkyl;
• X is chosen from —N(R11)—Y— and —Y—N(R11)—;
• Y is chosen from C(O), SO2, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene, and substituted alkynylene;
• R11 is chosen from H, lower alkyl, and substituted lower alkyl;
• R12 is chosen from H, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl;
• and
• R13 is chosen from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl and NR3′R4′;
• wherein optionally at least one of adjacent pairs R6 and R7, R7 and R8, R8 and R9, R9 and R10, and R10 and R1, join together to form a 4 to 7 membered ring or a substituted 4 to 7 membered ring.

A method of treating anemia in a patient in need of such treatment comprising administering to the patient a therapeutically effective amount of a compound of the Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• n is 1 to 6;
• R1 is chosen from H, lower alkyl and substituted lower alkyl;
• R2 is chosen from H, lower alkyl and substituted lower alkyl;
• R3 and R4 are independently chosen from H, lower alkyl, substituted lower alkyl, lower haloalkyl, substituted lower haloalkyl, or R3 and R4 can join together to form a 3 to 6 membered ring or a substituted 3 to 6 membered ring;
• R5 is chosen from OH, SH, NH2, lower alkyl, substituted lower alkyl, lower alkoxy, substituted lower alkoxy and sulfanyl;
• R6 is chosen from H, OH, SH, NH2, NHSO2R1 and sulfonyl;
• and
• each of R7, R8, R9 and R10 is independently chosen from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, NR3′R4′, C(O)OH, OR13, SR13, SO2R13, CN, NO2, halo, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, heterocycloalkyl, substituted heterocycloalkyl, alkylsilyl, substituted alkylsilyl, alkynylsilyl, substituted alkynylsilyl, alkoxy, substituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, and —X—R12, wherein:
• R3′ and R4′ are independently chosen from H, lower alkyl, substituted lower alkyl, lower haloalkyl, and substituted lower haloalkyl;
• X is chosen from —N(R11)—Y— and —Y—N(R11)—;
• Y is chosen from C(O), SO2, alkylene, substituted alkylene, alkenylene, substituted alkenylene, alkynylene, and substituted alkynylene;
• R11 is chosen from H, lower alkyl, and substituted lower alkyl;
• R12 is chosen from H, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl and substituted heteroaryl;
• and
• R13 is chosen from H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl and NR3′R4′;
• wherein optionally at least one of adjacent pairs R6 and R7, R7 and R8, R8 and R9, R9 and R10, and R10 and R1, join together to form a 4 to 7 membered ring or a substituted 4 to 7 membered ring.