title: Design, synthesis and cytotoxicity of novel 3'-N-alkoxycarbonyl docetaxel analogs.
abstract: By-product 9a exhibited potent cytotoxicity against both SK-OV-3 and A549 cell lines. The structure of 9a was characterized using 1D and 2D NMR experiments and confirmed by synthesis to afford a diastereomeric mixture (16a) that was identical to 9a, as well as a pair of diastereomers (R)-16b and (S)-16c. The preliminary SAR study demonstrated that analogs with an (R)-configuration were slightly more potent than analogs with an (S)-configuration. In addition, α,α-gem-dimethyl analogs 16 g-i were the most potent analogs in this series, exhibiting similar potency to docetaxel and greater potency than Taxol against the SK-OV-3 cell line. For the A549 cell line, analogs 16 g-i were more potent (>65-fold) than both docetaxel and Taxol.
authors.affiliation: Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Hao
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Hao
authors.forename: Hong-Fu
authors.initials: HF
authors.lastname: Lu
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: Yu
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D015195:Drug Design; D006801:Humans; D017239:Paclitaxel / Q000737:chemistry / Q000633:toxicity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel
keywords: 3′-N-Alkoxycarbonyl docetaxel analogs; Cytotoxicity; Synthesis