Indole compounds

A compound of the following formula:

• 60
• wherein
• L1 is C(O);
• L2 is a bond;
• R1 is aryl or heteroaryl;
• R2 is alkyl, alkenyl, alkynyl, cyclyl, or heterocyclyl;
• each of Ra, Rb, Rc, and Rd, independently, is R, halogen, nitro, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc, and Rd taken together are O(CH2)nO;
• and
• Re is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, or C(O)NRR′;
• in which each of R, R′, and R″, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5

A compound of the following formula:

• 61
• wherein
• L1 is C(O);
• L2 is a bond;
• R1 is aryl or heteroaryl;
• R2 is COR′″;
• each of Ra, Rb, Rc,and Rd, independently, is R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc and Rd taken together are O(CH2)nO;
• and
• Re is R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, or C(O)NRR′;
• in which each of R, R′, and R″ independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• R′″ is H, alkyl, alkenyl, alkynyl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5.

A compound of the following formula:

• 62
• wherein
• L1 is a bond;
• L2 is C(O);
• R1 is H, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)OR, or C(O)NRR′;
• R2 is aryl or heteroaryl;
• each of Ra, Rb, Rc, and Rd, independently, is H, unsubstituted alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, heterocyclyl, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc and Rd taken together are O(CH2)nO;
• and
• Re is H, alkyl, alkenyl, alkynyl, cyclyl, heterocyclyl, heteroaryl, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, or C(O)NRR′;
• in which each of R, R′, and R″ independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5.

A compound of the following formula:

• 63
• wherein
• L1 is O, S, NR, SO2, or CH2;
• L2 is a bond;
• R1 is 5, 6, or 7-member aryl or heteroaryl tri-substituted with alkyloxy;
• and
• each of R2, Ra, Rb, Rc, Rd, and Re, independently, R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc and Rd taken together are O(CH2)nO;
• in which each of R, R′, and R″, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5.

A compound of the following formula:

• 64
• wherein
• L1 is a bond;
• L2 is O, S, NR, SO2, or CH2;
• R2 is 5, 6, or 7-member aryl or heteroaryl tri-substituted with alkyloxy;
• and
• each of R1, Ra, Rb, Rc, Rd, and Re, independently, R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc and Rd taken together are O(CH2)nO;
• in which each of R, R′, and R″, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5.

A compound of the following formula:

• 65
• wherein
• L1 is O, S, NR, SO2, or CH2;
• L2 is a bond;
• R1 is 5, 6, or 7-member aryl or heteroaryl di-substituted with alkyloxy;
• and
• each of R2, Ra, Rb, Rc, Rd, and Re, independently, R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc and Rd taken together are O(CH2)nO;
• in which each of R, R′, and R″, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5.

A compound of the following formula:

• 66
• wherein
• L1 is a bond;
• L2 is O, S, NR, SO2, or CH2;
• R2 is 5, 6, or 7-member aryl or heteroaryl di-substituted with alkyloxy;
• and
• each of R1, Ra, Rb, Rc, Rd, and Re, independently, R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc and Rd taken together are O(CH2)nO;
• in which each of R, R′, and R″, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5.

A method for treating cancer, comprising administering to a subject in need thereof an effective amount of a compound of the following formula:

• 67
• wherein
• each of L1 and L2, independently, is a bond, C(O), O, S, NR, SO2, or CH2;
• in which if one of L1 and L2 is a bond, the other one is C(O), O, S, NR, SO2, or CH2;
• each of R1 and R2, independently, is R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′;
• each of Ra, Rb, Rc, Rd and Re, independently, R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc and Rd taken together are O(CH2)nO;
• and
• in which each of R, R′, and R″, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5.

A method for inhibiting tubulin polymerization, comprising administering to a subject in need thereof an effective amount of a compound of the following formula:

• 68
• wherein
• each of L1 and L2, independently, is a bond, C(O), O, S, NR, SO2, or CH2;
• in which if one of L1 and L2 is a bond, the other one is C(O), O, S, NR, SO2, or CH2;
• each of R1 and R2, independently, is R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′;
• each of Ra, Rb, Rc, Rd and Re, independently, R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc and Rd taken together are O(CH2)nO;
• and
• in which each of R, R′, and R″, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5.

A method for treating an angiogenesis-related disorder, comprising administering to a subject in need thereof an effective amount of a compound of the following formula:

• 69
• wherein
• each of L1 and L2, independently, is a bond, C(O), O, S, NR, SO2, or CH2;
• in which if one of L1 and L2 is a bond, the other one is C(O), O, S, NR, SO2, or CH2;
• each of R1 and R2, independently, is R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′;
• each of Ra, Rb, Rc, Rd and Re, independently, R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO2R, SO3R, SO2NRR′, SR, NRR′, NRSO2NR′R″, NRSO2R′, NRSO3R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or Rb and Rc, Ra and Rb, or Rc and Rd taken together are O(CH2)nO;
• and
• in which each of R, R′, and R″, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl;
• and n is 1, 2, 3, 4, or 5.