| 摘要 |
Compounds represented by the formula (I) or pharmaceutically acceptable salts thereof:
R2—Y—Z-Q-A-R1 Formula (I)
wherein R1, R2, Y, Z, Q, and A are as defined. These compounds are inhibitors of tubulin polymerization by binding at colchicines binding site and are useful in the treatment of tumors or mitotic diseases such as cancers, gout, and other conditions associated with abnormal cell proliferation. |
| 主权项 |
1. A compound for inhibition of tubulin polymerization having a structure shown in formula (Ib) or a pharmaceutically acceptable salt thereof, wherein A is Ch2, O, S, or NH; Q is thiazole; Y is CH2—CH2; R1 and R2 are each independently selected from the group consisting of aryl, and heteroaryl, provided that the heteroaryl does not include furan or thiophene, wherein said aryl and heteroaryl are each optionally substituted with one or more substituents selected from Rf and Rg, wherein Rf and Rg are each independently selected from the group consisting of: hydrogen, halogen, (C1-4)alkyl, (C1-4)alkoxyl, O—(C1-4)alkyl, S—(C1-4) alkyl, aryl, heteroaryl, N(Rc)(Rd), CORc, CON(Rc)(Rd), NRc-CO—N(Rc)(Rd), O—CO—N(Rc)(Rd), NRc—S(O)n—N(Rc)(Rd), or Rf and Rg can join together with carbon, nitrogen or sulfur atoms to which they are attached to form a ring selected from the group consisting of a cycloalkyl and a heterocycloalkyl, Rc and Rd are each independently selected from the group consisting of hydrogen, halogen, (C1-6)alkyl, (C1-6)alkoxyl, (C6-19)aryl, heteroaryl, (C3-12)cycloalkyl, or Rc and Rd can join together with carbon, nitrogen or sulfur atoms, to which they are attached, to form a 5-7 membered ring; and n is 0, 1, or 2. |
