The present invention relates to pharmaceutical compounds compositions and methods especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder a cancer a tumor an inflammatory disease an autoimmune disease psoriasis dry eye or an immunologically related disease and in some embodiments diseases or disorders related to the dysregulation of kinase such as but not limited to EGFR (including HER) Alk PDGFR BLK BMX/ETK FLT3(D835Y) ITK TEC TXK BTK or JAK and the respective pathways.