ABSTRACT - 599643 The disclosure relates to substituted N-Aryl pyridinone fibrotic inhibitors and/or collagen infiltration modulators of formula (I), wherein the variables R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 are independently selected from the group consisting of hydrogen and deuterium； at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11 independently has deuterium enrichment of no less than about 10%； and if R7, R8, R9, R10, and R11 are deuterium, then at least one of R1, R2, R3, R4, R5, and R6 is deuterium. Also disclosed is process of preparation, pharmaceutical compositions thereof, and methods of use of these substituted pyridinone-based fibrosis modulator and/or collagen infiltration modulator, preferably deuterated pirfenidone for treating fibrotic-mediated and the collagen-mediated disorder is selected from the group consisting of idiopathic pulmonary fibrosis, uterine fibroids, multiple sclerosis, renal fibrosis, diabetic kidney disease, endotoxin-induced liver injury after partial hepatectomy or hepatic ischemia, allograft injury after organ transplantation, cystic fibrosis, atrial fibrilation, neutropenia, scleroderma, dermatomyositis, cirrhosis, diffuse parenchymal lung disease, mediastinal fibrosis, tuberculosis, spleen fibrosis caused by sickle-cell anemia, and rheumatoid arthritis.
