Provided are certain cyclic urea compounds that are capable of inhibiting certain serine proteases, and especially the serine proteases matriptase, hepsin and hepatocyte growth factor activator (HGFA) involved in the maturation of hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP), and novel precursors thereof. Compounds of the present disclosure can be used to treat a number of disorders caused by or associated with abnormal matriptase, hepsin and HGFA protease activity by inhibiting the proteolytic cleavage of pro-HGF to mature HGF and pro-MSP to mature MSP caused by these enzymes. Compounds of the present disclosure can be used to treat disorders including precancerous conditions and cancer including metastatic disease, prevention and reversion of cancer resistance, and the inhibition of cancer stem cells. The compounds of this invention are applicable to the treatment of cancers of many tissue types including solid and liquid tumors.
提供了一些能够抑制特定
丝氨酸蛋白酶的环
脲化合物,尤其是涉及
肝细胞生长因子(
HGF)和巨噬细胞刺激蛋白(M
SP)成熟的
丝氨酸蛋白酶matriptase、hepsin和
肝细胞生长因子激活酶(
HGFA),以及其新颖前体。本公开的化合物可用于治疗由或与异常matriptase、hepsin和
HGFA
蛋白酶活性相关的多种疾病,通过抑制这些酶引起的pro-
HGF到成熟
HGF和pro-M
SP到成熟M
SP的蛋白
水解裂解。本公开的化合物可用于治疗包括癌前病变和癌症(包括转移性疾病、预防和逆转癌症耐药性以及抑制癌干细胞)在内的多种疾病。本发明的化合物适用于治疗多种组织类型的癌症,包括实体肿瘤和液体肿瘤。