NEW COMPOUNDS OF PYRROLOPYRIMIDINE AS INHIBITORS OF PROTEIN KINASES Russian patent published in 2018 - IPC C07D487/04 A61K31/519 A61P35/00 A61P29/00 A61P17/06 A61P37/02 

FIELD: pharmacology.

SUBSTANCE: invention relates to new pyrrolopyrimidine derivatives of the general formula (VIII) having the properties of a cell proliferation inhibitor mediated by the activity of EGFR, BLK, BMX / ETK, BTK, FLT3 (D835Y), ITK, JAK1, JAK2, JAK3, TEC, or TXK kinase, that can be used to treat and/or prevent a proliferative disorder, cancer or tumour associated with the activity of the said kinases. Such diseases can be represented by sarcoma, squamous cell carcinoma, fibrosarcoma, cervical cancer, stomach cancer, skin cancer, leukemia, lymphoma, lung cancer, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, kidney cancer, prostate cancer, breast cancer, liver cancer, head and neck cancer and pancreatic cancer. In the general formula (VIII) X¹ is O or NH; R¹ and R² are hydrogen; n is 0; R⁴ is selected from hydrogen, C_1-6alkyl, C_3-7cycloalkyl and -NR²²R²³; where alkyl or cycloalkyl is unsubstituted or substituted by hydroxyl or amino; and where each R²² and R²³ are independently selected from hydrogen and C_1-6alkyl or R²² and R²³ can be combined to form a 3 to 10-membered ring; R⁵ is hydrogen; R⁶ is selected from hydrogen and C_1-6alkoxy; R⁷ is selected from hydrogen and C_1-6alkoxy; R⁸ is selected from hydrogen and halogen; Q is a CR⁹ or N; R⁹ is selected from hydrogen, halogen and C_1-6alkyl; R¹¹ is hydrogen; R¹² is selected from hydrogen and C_1-6 alkyl; R¹³ is selected from hydrogen, C_1-6alkyl, C_1-6acyl, SO₂-C_1-6alkyl and C_3-7cycloalkyl, wherein each alkyl is unsubstituted or substituted by hydroxyl or halogen; and -NR¹⁸R¹⁹ is or , where R¹⁰ is selected from hydrogen and C_1-6 alkyl; R¹⁵ is unsubstituted methyl or represents C_2-4alkyl, unsubstituted or substituted by halogen; and m is 1 or 2; or R¹⁹ and R⁹ taken together, form a 5- or 6-membered heteroaryl ring optionally substituted by C_1-6alkyl which is unsubstituted or substituted by amino; and R¹⁸ is hydrogen or C_1-6alkyl or absent to satisfy the valency of the heteroaryl ring.

EFFECT: improved compounds properties.

29 cl, 23 dwg, 24 tbl, 9 ex