Aminopyrimido pyrazole/pyrrole derivatives and preparation method and application thereof

Abstract

The invention relates to aminopyrimidinopyrazole / pyrrole derivatives as well as a preparation method and application thereof, belonging to the field of medicines. The invention provides compounds derivatives as shown in a formula I which is described in the specification and optical isomers thereof, and further provides pharmaceutically acceptable salts of the compounds or the optical isomers thereof. Biological experiments prove that the compounds can remarkably inhibit proliferation of various cancer cells such as breast cancer, lung cancer, colorectal cancer, gastric cancer, bile duct cancer and urothelium carcinoma, have a broad-spectrum anticancer effect, also show an inhibiting effect on proliferation of fibroblasts and hepatic stellate cells, can inhibit growth of tumors in vivo, have wide application prospects and provide a new choice for the development of anti-tumor and anti-fibrosis medicines.

Description

technical field [0001] The invention relates to aminopyrimidopyrazole / pyrrole derivatives, a preparation method and application thereof, and belongs to the field of medicine. Background technique [0002] Receptor tyrosine kinases (RTKs) are a class of cell surface transmembrane protein receptors with endogenous protein tyrosine kinase activity, usually composed of an extracellular domain that can bind to a specific ligand, a transmembrane region and An intracellular kinase domain that selectively binds and phosphorylates substrates. Combining ligands with the extracellular domains of RTKs causes structural changes to generate enzyme catalytic activity. It plays an important regulatory role in tumor angiogenesis, tumor cell survival, proliferation, differentiation, migration, etc. More than 50 different RTKs family members have been found, including fibroblast growth factor receptors (fibroblast growth factor, FGFRs), epidermal growth factor receptors (epidermal growth fac...

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Problems solved by technology

However, elevated levels of FGF-2 were detected in IPF patients with idiopathic pulmonary fibrosis, FGFR-1 expression was increased in epithelial cells, endothelial cells and smooth muscle cells / fibroblast-like cells, and FGFR-2 in mesenchymal cells Increased expression, and studies have shown that FGF-2 is significantly overexpressed in diabetic nephropathy and stimulates the proliferation of glomerular mesangial cells; promotes the regeneration of renal tubular cells and leads to cell fibrosis

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