Synthesis of 5,7-disubstituted-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amines as microtubule inhibitors.

ABSTRACT: Compounds 1-4 were previously reported as potent antimitotic and antitumor agents with Pgp modulatory effects. Compounds 5-18 have been synthesized in an attempt to optimize the various activities of 1-4. Compounds 5-10 explored the influence of methoxy substitutions on the 7-benzyl moiety in 1, while 11-18 investigated the influence of incorporation of a sulfur linker at C5 compared to 1-3. Compounds 5-10 demonstrated potent single-digit micromolar tumor cell cytotoxicity, Pgp modulation and microtubule inhibition. Compound 7 of this series was the most potent and showed GI(50) values in the nanomolar range against several human tumor cell lines in the standard NCI preclinical in vitro screen. Antitumor activity and Pgp modulatory effects were found to decrease for the 5-phenylthio compou

SUBMITTER: Gangjee A 

PROVIDER: S-EPMC3582361 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature