Modulateurs de la proteine kinase c

Details Modulateurs de la proteine kinase c Modulateurs de la proteine kinase c

C - Chemistry, Metallurgy

07

C

167/240, 167/248

C07C 69/013 (2006.01) A61K 31/215 (2006.01) C07C 69/00 (2006.01) C07C 69/65 (2006.01) C07D 209/08 (2006.01) C07D 209/18 (2006.01) C07D 213/74 (2006.01) C07D 401/06 (2006.01) C07D 403/12 (2006.01) C07D 487/06 (2006.01) C07D 521/00 (2006.01) C07F 7/08 (2006.01) C07F 7/18 (2006.01) C07F 9/6561 (2006.01) C07H 13/10 (2006.01)

Patent

CA 1340657

The invention is concerned with phorboid derivatives of the formula: P o - S o - E o wherein P o represents a radical formally derived from a parent compound which (a) binds reversibly or irreversibly to a diacylglycerol-type receptor; and/or (b) activates any form of the enzyme protein kinase C; and (c) contains an hydroxymethyl or 1-hydroxyethyl group bonded to a carbon atom; and wherein S o-E o represents a moiety which is either i) singly or doubly bonded to the carbon atom of the parent compound in place of the hydroxymethyl or 1-hydroxyethyl group; or ii) singly or doubly bonded to a carbon immediately adjacent to the carbon atom to which the hydroxymethyl or 1-hydroxyethyl; and wherein S o is a saturated or unsaturated, straight or branched chain of atoms which separates P o and E o by a linear count of at least two but not more than 6 atoms and contains one to six heteroatoms selected from oxygen, nitrogen and sulfur, a phosphorus atom, or up to 12 halogen atoms; provided that the total number of atoms does not exceed about 35; and wherein E o comprises a saturated or singly or multiply unsaturated group containing up to 8 carbon atoms and optionally containing 1 to 12 halogen atoms, 1 to 4 heteroatoms selected independently from oxygen, nitrogen and sulfur and one phosphorus atom, or wherein S o E o taken together may be a hydrogen, halogen, or ketonic oxygen atom or a hydroxy, amine, or thiol group singly or doubly bonded to the carbon atom of the parent compound P o in place of the hydroxymethyl or 1-hydroxyethyl group. The phorboid derivatives according to the invention block the toxic effects of the hydroxymethyl- containing phorboids and lack the toxic properties of previously available phorboids.

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