The present invention is directed to novel compounds according to formulae
wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as defined herein. The
invention also discloses methods of preparation, pharmaceutical
compositions, and methods of disease treatment utilizing pharmaceutical
compositions comprising these compounds. The compounds of this invention
are novel therapeutic agents for the treatment of cancer, diabetes,
metabolic diseases and skin disorders in mammalian subjects. These
compounds are also useful modulators of gene expression. They exert their
activity by interfering with certain cellular signal transduction
cascades. The compounds of the invention are thus also useful for
regulating cell differentiation and cell cycle processes that are
controlled or regulated by various hormones or cytokines. The invention
also discloses pharmaceutical compositions and methods of treatment of
disease in mammals.