We report herein the synthesis and biological evaluation of two series of 7-substituted norfloxacin derivatives. Most compounds tested in this study demonstrated better activity against methicillin-resistant Staphylococcus aureus than norfloxacin. Preliminary in vitro evaluation indicated that the 7-[4-(2-hydroxyiminoethyl)piperazin-1-yl] derivatives 3b-e possess distinct cytotoxicity profiles as compared with their alpha-methylene-gamma-butyrolactone counterparts, 4b,e: i.e., excellent activities against the renal cancer subpanel. Among them, 1-ethyl-6-fluoro-7-¿4-[2-(4-chlorophenyl)-2-hydroxyiminoethyl]-1-p ipe razinyl¿-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (3d) demonstrated the most significant activities against renal cancer cell lines, with log GI(50) values of -6.40 against CAK-1, -6.14 against RXF 393, and -7.54 against UO-31, compared with a mean log GI(50) value of -5.03.

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In a search for the inhibitors of platelet aggregation, certain coumarin derivatives were synthesized and evaluated for antiplatelet activity against thrornbin(Thr)-, arachidonic acid(AA)-, collagen(Co1)-, and platelet-activating-factor(PAF)-induced aggregation in washed rabbit platelets. These compounds were synthesized from 4-hydroxycoumarin (1) or naphthalen-1-01 via alkylation and Refurmatsky-type condensation (Schemes 1-3). Among them, 4-[(2,3,4,5-tetrahydro-4-rnethylidene-5-oxo-2-phenylfuran-2-yl)methoxy]-2~-l-benzopyran-2-one (6b) showed potent antiplatelet effects on AA-and PAF-induced aggregation with Z C , , values of 8.21 and 103.67 UM, respectively (see Tables 1 and 2). The antiplatelet potency of 6b against PAF-induced aggregation could be further improved by introducing a proper substituent at the 2-phenyl group of the lactone ring.

3-b]quinoline and 4-Anilinofuro[3,2-c]quinolineDerivatives. -A variety of linear and angular 4-anilinofuroquinoline derivatives are synthesized and evaluated in vitro against a full panel of cancer cell lines. Several linear furoquinolines, e.g. compounds (III) and (IV), exhibit potent cytotoxicities. Angular furoquinolines (XI) selectively inhibit one of the renal cancer cells and two of the melanoma cancer cells. -(CHEN, Y.-L.; CHEN, I.-L.; WANG, T.-C.; HAN, C.-H.; TZENG*, C.-C.; Eur. J. Med. Chem. 40 (2005) 9, 928-934; Fac. Med. Appl. Chem., Kaohsiung Med. Univ., Kaohsiung 807, Taiwan; Eng.) -R. Staver 07-159