Potent fluorinated corticosteroids

CH-OR CH2 wherein each of A and B is a perhaloalkyl group of 1 to 7 carbon atoms fully substituted on the a-carbon atoms by halogen atoms selected from the group consisting of fluorine and chlorine, at least one of said halogen atoms being fluorine, and R is a member of the group consisting of alkyl of 1 to 18 carbon atoms, haloalkyl of 1 to 18 carbon atoms, cycloalkyl of 5 to 6 carbon atoms, aryl of 6 to 10 carbon atoms and haloaryl of 6 to 10 carbon atoms which comprises interreacting (I) a bis-perhaloalkyl ketone and (II) a vinyl ether of the formula wherein R and perhaloalkyl are defined as above under autogeneous pressure at a temperature in the range of about 20? to C. and thereafter recovering the oxetane from the reaction mixture.

1. A method of applying and firmly bonding a fluorinated hydrocarbon resin coating to the exposed surface of a clean flexible metallic substrate selected from the group consisting of a coil spring in which the helices thereof are in mutual contact and a fine conducting wire of small area cross-section and comprising the steps of: supplying a liquid dispersion bath of a fluorinated hydrocarbon resin selected from the group consisting of hexafluoropropylene-tetrafluoroethylene copolymer and tetrafluoroethylene; slowly immersing said substrate in said dispersion bath under nonagitated conditions for about 2-30 minutes to effect a coating of said dispersion thereon and then slowly removing said substrate from said dispersion bath; then subjecting said removed dispersion coated substrate to a preliminary heating in a non-turbulent atmosphere at a temperature not exceeding about 180F for about 10-120 minutes; then cooling said prelimarily heated dispersion coated substrate to about the ambient temperature of the atmosphere; then subjecting said preliminarily heated and cooled dispersion coated substrate to a further heating to a temperature of about 545 700 F for about 10-180 minutes whereby to drive off any non-resin portions of said dispersion coating and to cause the resin thereof to form as a hot melt in contact with said substrate; and then slowly cooling the thus further heated resin coated substrate to a temperature at least as low as about 150F over a period of about 30-180 minutes, whereby to cause the resin coating thereof to become firmly bonded thereto as an unbroken flexible transparent film.

Chronic lymphocytic leukemia (CLL) is the most common lymphoid neoplasia in Western societies and is currently incurable. Multiple treatment options are practiced, but the available small molecule drugs suffer from dose-limiting toxicity and undesirable side effects. The need for new, less toxic treatments is a pressing concern. Here, we demonstrate that (-)-agelastatin A (1a), a pyrrole-imidazole alkaloid obtained from a marine sponge, exhibits potent in vitro activity against primary cell lines of CLL and disclose the synthesis of several analogues that are equipotent or exceed the potency of the natural product. The novel synthetic analogue, 13-debromo-13-trifluoromethyl agelastatin A (1j), showed higher activity than the natural product when tested against the same cell lines and is the most potent agelastatin derivative reported to date. A detailed in vitro structure-activity relationship of 1a in CLL compared to that of 22 synthetic analogues is described along with preliminary in vivo pharmacokinetic and metabolism studies on the most potent compounds.

The Mellon family were the founders of the original Mellon Institute whence came the "amazing (but totally fallacious) sodium fluoride/dental caries prevention discovery" - the discovery that literally turned 'garbage into gold'. The Mellon family also founded the American Aluminum Company (Alcoa), the largest producer of the waste toxin, sodium fluoride, which, up to this point of 'caries discovery', had relatively little known commercial or industrial value, was an environmental hazard of great public concern, and was very costly in terms of safe disposal.

Perfluoroaromatic compounds can be manufactured via the Fowler process, like fluoroalkanes, but the conditions must be adjusted to prevent full fluorination. They can also be made heating the corresponding perchloroaromatic compound with potassium fluorine at high temperature (typically 500 °C), during which the chlorine atoms are replaced by fluorine atoms. A third route is defluorination of the fluoroalkane; for example, octafluorotoluene can be made from perfluoromethylcyclohexane by heating to 500 °C with a nickel or iron catalyst. [30]

Potent fluorinated corticosteroids

potent fluorinated corticosteroids

The Mellon family were the founders of the original Mellon Institute whence came the "amazing (but totally fallacious) sodium fluoride/dental caries prevention discovery" - the discovery that literally turned 'garbage into gold'. The Mellon family also founded the American Aluminum Company (Alcoa), the largest producer of the waste toxin, sodium fluoride, which, up to this point of 'caries discovery', had relatively little known commercial or industrial value, was an environmental hazard of great public concern, and was very costly in terms of safe disposal.

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