- AKT PROTEIN KINASE INHIBITORS
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The present invention provides compounds, including resolved enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof, comprising the Formula: A-L-CR where CR is a cyclical core group, L is a linking group and A is as defined herein. Also provided are methods of using the compounds of this invention as AKT protein kinase inhibitors and for the treatment of hyperproliferative diseases such as cancer.
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Page/Page column 121
(2008/06/13)
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- Synthesis and antirhinovirus activity of 6-(dimethylamino)-2-(trifluoromethyl)-9-(substituted benzyl)-9H-purines
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A series of 6-(dimethylamino)-2-(trifluoromethyl)-9-(substituted benzyl)purines was synthesized and tested for antirhinovirus activity. Most of the compounds were synthesized by alkylation of 6-chloro-2-(trifluoromethyl)-9H-purine with the appropriate benzyl halide followed by displacement of the chloro group with dimethylamine. Alternatively, 6-(dimethylamino)-2-(trifluoromethyl)purine was alkylated with the appropriate benzyl halide. Although several different aryl substituents provided compounds with IC50's = 0.03 μM against rhinovirus serotype 1B, no congener was significantly more active than the parent 2. Twenty-three compounds were tested against 18 other serotypes, but none exhibited a uniform profile of activity.
- Kelley,Linn,Selway
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p. 1757 - 1763
(2007/10/02)
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- SELECTIVITY AND MECHANISM IN THE SIDE-CHAIN HALOGENATION OF METHYLBENZENES PROMOTED PHOTOCHEMICALLY AND BY METAL COMPLEXES IN THE PRESENCE OF HALIDE IONS
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The intramolecular selectivity in a variety of side-chain halogenations of alkyl-aromatics has been determined in AcOH by measuring the isomeric distribution in the reactions of 4-t-butyl- and 4-chloro-1,2-dimethylbenzene (1 and 2, respectively) with: Br2/hν, CAN/Br-, CAN=cerium(IV) ammonium nitrate, cobalt(III) acetate/Br-, S2O8=/Br-, N-bromosuccinimide (in CCl4), Cl2/hν, CAN/Cl-, cobalt(III) acetate/Cl-.In the bromination reactions selectivity is independent of the reaction conditions, thus suggesting that in all brominating systems Br. is the actual reacting species.Very surprisingly, with 1 as the substrate, Cl2/hν is a more selective system than Br2/hν.With 2 the two systems display similar selectivity.It has been suggested that in AcOH the transition state for photochlorination has an electron transfer character which increases as the substrate becomes more electron rich.The idea of a "variable" transition state for the photochlorination in AcOH is supported by data of relative reactivity of substituted toluenes indicating that the effect on the rate increases as the substituent becomes more electron donor.AcOH must have an essential role in this respect since in CCl4 situation returns to be "normal" with chlorination less selective than bromination.Selectivity of CAN/Cl- is very similar to that of Cl2/hν, whereas significant differences are observed with cobalt(III) acetate/Cl-.Probably Cl. and a cobalt(III) chloride complex are the reacting species in CAN/Cl- and cobalt(III) acetate/Cl-, respectively.
- Baciocchi, Enrico,Crescenzi, Manuela
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p. 6525 - 6536
(2007/10/02)
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