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Cyclin-dependent kinases (Cdk) and their associated pathways represent some of the most attractive targets for the development of anticancer therapeutics. Based on antitumor activity in animal models, a variety of Cdk inhibitors are undergoing clinical evaluation either as a single agent or in combination with other approved drugs. In our anticancer drug discovery program, a novel series of flavones have been synthesized for evaluation against the activity of Cdk4-D1. This enzyme catalyzes the phosphorylation of retinoblastoma protein, thus inhibiting its function. We have identified a series of potent Cdk4-D1 inhibitors with IC 50 below 250 nmol/L. In this report, we have described the properties of one of the best compound,

Sztmmary. The total assignment of the 1sC-shifts of thc complex Vi'irrclr rosca L. alkaloids vincaleucoblastine, leurosidinc and leurosinc and ol a synthctic isomer of the latter is presentcd. The structure of leurosidine is corrected and a tcntative structure lor the acid-catalyzcd product of isomerization of leurosine is proposed.A recent 1%-NMR. spectral analysis of As+idos$erma alkaloids [2] included a discussion of vindoline, which not only is a natural base but also represents one half of the complcx structures of indolc-indoline alkaloids, viz. vincaleucoblastine (VLD), (l), leurosidine (2) [3] and leurosine (3). As a consequcnce the carbon shifts of the vindoline portion (i.e. the indoline portion) of the 'dimeric' alkaloids 1 and 3 wcre assigned fully, while the velbanamine portion (i. e. the indole portion) was dcscribed only in terms 01 the shifts of the indole ring, the methyl group and the non-protonatcd carbons, The W-NMR. analysis of the methylenes and methines oi the indole half .. /

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