A new series of estradiol analogs was synthesized in an attempt to improve on the anticancer activity of 2-methoxyestradiol, a naturally occurring mammalian tubulin polymerization inhibitor. The compounds were evaluated as inhibitors of tubulin polymerization and the binding of [3H]colchicine to tubulin, as well as for in vitro cytotoxicity in human cancer cell cultures. Overall, the most potent of the new compounds were 2-(2',2',2'-trifluoroethoxy)-6-oximinoestradiol, 2-ethoxy-6-oximinoestradiol, and 2-ethoxy-6-methoximinoestradiol. These agents lacked significant affinity for the estrogen receptor. The cytotoxicities of the compounds correlated in general with their abilities to inhibit tubulin polymerization, thus supporting inhibition of tubulin polymerization as the primary mechanism causing inhibition of cell growth.

Die photoinduzierte Cyclisierung der aus den Chloraniliden (I) erhaltenen intermediären Anionen [analog auch unter Bedingungen C)] führt zu den Oxindolen (II) (teilweise mit Nebenprodukten).

Photostimulated reactions of 2,6-, 2,3-, 3,5-, and 2,5-dihalopyridines (la-e) with pinacolone potassium enolate (2) in liquid NH3 lead to facile replacement of both halogens via a modified SRN1 mechanism, which does not involve intermediate formation of monosubstitution products. The potassium salts of phenylacetonitrile (12a) and a-ethylphenylacetonitrile (12b) react with 2,6-dibromopyridine (la) under similar conditions to afford a mixture of mono-and disubstituted products via a related SRN1 process. 4,7-Dichloroquinoline ( 16) undergoes radical-chain displacement of chloride from C4 with enolate 2. 2,6-Dichloropyrazine (18) and 2,3-dichloropyrazine (20) also undergo monosubstitution with 2 and diisopropyl ketone potassium enolate ( 22), but these reactions appear to be mainly addition-elimination (SNAr) processes. Treatment of 3,6-dichloropyridazine ( 27) with 22 results in addition of 22 to C4 of the substrate. Photoassisted reaction of 2,4-dichloropyrimidine (31) with 12a leads to exclusive chloride displacement from C4 via the SRN1 mechanism.In a recent study1 2 of heteroaromatic SRN1 reactions,3 we found that 2,6-dibromopyridine (la) and 2,6-dichloropyridine (lb) reacted with pinacolone potassium enolate (2) under irradiation with near-ultraviolet light in liquid NH3 to afford disubstitution product 3a in excellent yield. la, X = Br (2,6) 3a (2,6) b, X = Cl (2,6) b (2,3) c, X = Cl (2,3) c (3,5) d, X = Cl (3,5) d (2,5) e, X= Br (2,5)

Reaction of halogenated pyridines, quinolines, pyrimidines, and pyrazines with potassiophenylacetonitrile (5) in liquid ammonia under near‐uv irradiation affords secondary nitriles, which then undergo oxidative decyanation under phase‐transfer catalytic conditions to afford aryl hetaryl ketones in excellent yields.

the filter cake was washed with hot dimethylformamide (4 X 10 mL). The filtrate and washings were combined and evaporated to dryness in vacuo. The residue was crystallized from aqueous DMF (water/DMF, 4:6, v/v) to yield 60 mg (69.2%) of 7: mp 250 °C dec; lH NMR (MejSO-dg) 5.