A new class of pyrimidine derivatives were identified as potent protein tyrosine kinase (PTK) inhibitors for the treatment of idiopathic pulmonary fibrosis (IPF). Most of these small-molecule inhibitors displayed strong enzymatic activity against BTK and JAK3 kinases at concentrations lower than 10 nM. The representative compound N-(3-((5-chloro-2-(4-((1-morpholino)acetylamino)phenylamino)-4-pyrimidinyl)amino)phenyl)acrylamide (6 a) also exhibited high inhibitory potency toward both BTK and JAK kinase families, as well as ErbB4, at a concentration of 10 nM, achieving rates of inhibition higher than 57 %. Additionally, in vivo biological evaluations showed that 6 a can remarkably decrease the severity of IPF disease. All these investigations suggested that the multi-PTK inhibitor 6 a may serve as a promising agent for the treatment of IPF.

中文翻译：

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新型嘧啶类药物作为多靶蛋白酪氨酸激酶抑制剂，用于治疗特发性肺纤维化（IPF）。

一类新的嘧啶衍生物被鉴定为有效的蛋白酪氨酸激酶（PTK）抑制剂，可用于治疗特发性肺纤维化（IPF）。这些小分子抑制剂中的大多数在浓度低于10 nM时显示出对BTK和JAK3激酶的强酶活性。代表性化合物N-（3-（（5-氯-2-（4-（（1-吗啉代）乙酰氨基）苯基氨基）-4-嘧啶基）氨基）苯基）丙烯酰胺（6a）也对两种化合物均显示出高抑制力。浓度为10 nM的BTK和JAK激酶家族以及ErbB4，抑制率高于57％。此外，体内生物学评估表明6 a可以显着降低IPF疾病的严重程度。所有这些研究表明，多PTK抑制剂6a可以用作治疗IPF的有前途的药物。