INHIBITORS OF IKK-beta SERINE-THREONINE PROTEIN KINASE

摘要

Disclosed herein is a compound of: · Cyclopentyl (2S,4E)-2-amino-5-{ 3-[4-carbamoyl-5 (carbamoylamino )-2-thienyl]phenyl} pent-4-enoate; · Cyclopentyl 5-{ 3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl] phenyl} -L-norvalinate; · Cyclopentyl (2S,4E)-2-amino-5-{ 3-[4-carbamoyl-5-( carbamoylamino )-2-thienyl]-5-methylphenyl} pent-4-enoate; · Cyclopentyl (2S,4E)-2-amino-5-{ 5-[4-carbamoyl-5-( carbamoylamino )-2-thienyl]-2-methYlphenyl} pent-4-enoate; · Cyclopentyl O-{ 3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]phenyl} -L-homoserinate; · Cyclopentyl N-{ 3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]benzyl} -L-alaninate; · tert-Butyl N-{ 3-[4-carbamoyl-5-( carbamoylamino )-2-thienyl]benzyl} -L-alaninate; · (2S,4E)-2-ami no-5-{ 3-[ 4-carbamoyl-5-(carbamoylamino)-2-thienyl]phenyl} pent -4-enoic acid; · 5-{ 3-[ 4-carbamoyl-5-( carbamoylamino )-2-thienyl]phenyl} -L-norvaline; · (2S,4E)-2-am ino-5-{ 3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]-5-methylphenyl} pent-4-enoic acid; · (2S,4E)-2-amino-5-{ 5-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]-2-methylphenyl} pent-4-enoic acid; · O-{ 3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]phenyl} -L-homoserine; · N-{ 3-[4-carbamoyl-5-(carbamoylamino)-2-thienyl]benzyl} -L-alanine; and pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions comprising said compounds and uses thereof. Said compounds are useful as inhibitors of IKK-â serine-Theronine protein kinase as such are useful in the treatment of proliferative disease states such as hepatocellular cancer or cancer, bowel cancer, ovarian cancer, head and neck and cervical squamous cancers, gastric or lung cancers, anaplastic oligodendrogliomas, glioblastoma multiforme or medulloblastomas; autoimmune and inflammatory diseases such as rheumatoid arthritis, psoriasis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, chronic obstructive pulmonary disease, asthma, multiple sclerosis, diabetes, atopic dermatitis, graft versus host disease, or systemic lupus erythematosus.