Substituted 2,3-dihydro-1H-benzo[a]pyrano[2,3-c]phenazines as anti-angiogenic and anti-cancer agents

A compound of formula (Ia):

• and pharmaceutically acceptable salts thereof, wherein
• R1 and R2 are each, independently, H, halogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, amino, alkylamino, dialkylamino, aryl, arylalkyl, heteroaryl, heterocyclyl, nitro, cyano, carboxy, or amido;
• R3 and R4 are each, independently, H, halogen, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C1-C6 alkoxy, C1-C6 alkoxycarbonyl, amino, alkylamino, aryl, arylalkyl, heteroaryl, heterocyclyl, nitro, cyano, carboxy, or amido;
• X is selected from the group consisting of —COOR5, —CONHR6, —CONR6R7, —C(O)R8, and —C(═NOH)R9;
• R5 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocyclyl, aryl, aralkyl or heteroaryl, wherein each of said cycloalkyl, heterocyclyl, aryl, aralkyl or heteroaryl groups is optionally substituted with one or more group(s) selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy and halogen;
• R6 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocyclyl, aryl, aralkyl or heteroaryl, wherein each of said cycloalkyl, heterocyclyl, aryl, aralkyl or heteroaryl groups is optionally substituted with one or more group(s) selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halogen and hydroxy(C1-C4 alkyl);
• R7 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocyclyl, aryl, aralkyl or heteroaryl, wherein each of said cycloalkyl, heterocyclyl, aryl, aralkyl or heteroaryl groups is optionally substituted with one or more group(s) selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, hydroxy, halogen and aryl;
• or R7 is C1-C6 alkoxy;
• or R7 is —CHR10R11, wherein R10 is aryl or heteroaryl and R11 is —C(O)NHR12, wherein R12 is C1-C6 alkyl or cycloalkyl;
• or R7 and R6 are taken together to form together with the nitrogen atom they are attached to a 5- or 6-membered cycloalkyl or a 5- or 6-membered heterocyclyl ring, the latter cycloalkyl or heterocyclyl rings being optionally substituted with one or more group(s) selected from the group consisting of C1-C4 alkyl, hydroxy, aryl and aralkyl;
• R8 is C1-C6 alkyl, C2-C6 alkenyl, cycloalkyl, heterocyclyl, aryl, arylalkynyl or heteroaryl, wherein each of said cycloalkyl, heterocyclyl, aryl, arylalkynyl or heteroaryl groups is optionally substituted with one or more group(s) selected from the group consisting of halogen, C1-C6 haloalkyl, C1-C6 alkoxy, aryl-C1-C2 alkoxy optionally substituted by one or more group(s) selected from halogen, and C1-C4 alkylsulfonylamino;
• R9 is C1-C6 alkyl, C2-C6 alkenyl, cycloalkyl, heterocyclyl, aryl, arylalkynyl or heteroaryl, wherein each of the cycloalkyl, heterocyclyl, aryl, arylalkynyl or heteroaryl groups is optionally substituted with one or more group(s) selected from the group consisting of C1-C6 haloalkyl and C1-C6 alkoxy;
• R14 and R15 are independently selected from H, C1-C4 alkyl, C2-C6 alkenyl, hydroxy, halo, alkoxy, amino, alkylamino, nitro, cyano, carboxy, or amido;
• and
• R16 and R17 are independently selected from H, C1-C4 alkyl, C2-C6 alkenyl, or hydroxy.