Hydantoin based compounds useful as inhibitors of matrix metalloproteinases (MMPs), particularly macrophage elastase (MMP-12) are described. Also described are related compositions and methods of using the compounds to inhibit MMP-12 and treat diseases mediated by MMP-12, such as asthma, chronic obstructive pulmonary disease (COPD), emphysema, acute lung injury, idiopathic pulmonary fibrosis (IPF), sarcoidosis, systemic sclerosis, liver fibrosis, nonalcoholic steatohepatitis (NASH), arthritis, cancer, heart disease, inflammatory bowel disease (IBD), acute kidney injury (AKI), chronic kidney disease (CKD), Alport syndrome, and nephritis.本發明描述適用作基質金屬蛋白酶(MMP)、尤其巨噬細胞彈性蛋白酶(MMP-12)之抑制劑的基於乙內醯脲之化合物。亦描述使用該等化合物以抑制MMP-12且治療由MMP-12介導之疾病的相關組合物及方法,該等疾病係諸如哮喘、慢性阻塞性肺病(COPD)、肺氣腫、急性肺損傷、特發性肺纖維化(IPF)、類肉瘤病、全身性硬化症、肝纖維化、非酒精性脂性肝炎(NASH)、關節炎、癌症、心臟病、發炎性腸病(IBD)、急性腎損傷(AKI)、慢性腎病(CKD)、奧爾波特症候群及腎炎。