Discovery of 3-aryl-5-aryl-1,2,4-oxadiazoles as a new series of apoptosis inducers. 2. Identification of more aqueous soluble analogs as potential anticancer agents.
As a continuation of our efforts to discover and develop the 3-aryl-5-aryl-1,2,4-oxadiazole series of apoptosis inducers as potential anticancer agents, we explored substitutions at the 2- and 3-positions of the 3-aryl group to improve the aqueous solubility properties and identify development candidates. A small substitution such as methyl or hydroxymethyl at the 2-position was well tolerated. This modification, in combination with a 3-substituted furan ring as the 5-aryl group, resulted in 4g and 4h, which have improved solubility properties. Compound 4g was found to have good in vivo efficacy in animal studies via intravenous administration.
Kemnitzer
William
W
EpiCept Corporation, Inc. 6650 Nancy Ridge Drive, San Diego, CA 92121, USA.
Kuemmerle
Jared
J
Zhang
Han-Zhong
HZ
Kasibhatla
Shailaja
S
Tseng
Ben
B
Drewe
John
J
Cai
Sui Xiong
SX
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007262:Infusions, Intravenous; D051379:Mice; D008956:Models, Chemical; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D010069:Oxadiazoles; D014867:Water