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, C1-6alkyl, C3-7cycloalkyl 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 C1-6alkyl or R22 and R23 can be combined to form a 3 to 10-membered ring; R5 is hydrogen; R6 is selected from hydrogen and C1-6alkoxy; R7 is selected from hydrogen and C1-6alkoxy; R8 is selected from hydrogen and halogen; Q is a CR9 or N; R9 is selected from hydrogen, halogen and C1-6alkyl; R11 is hydrogen; R12 is selected from hydrogen and C1-6 alkyl; R13 is selected from hydrogen, C1-6alkyl, C1-6acyl, SO2-C1-6alkyl and C3-7cycloalkyl, wherein each alkyl is unsubstituted or substituted by hydroxyl or halogen; and -NR18R19 is or
, where R10 is selected from hydrogen and C1-6 alkyl; R15 is unsubstituted methyl or represents C2-4alkyl, 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 C1-6alkyl which is unsubstituted or substituted by amino; and R18 is hydrogen or C1-6alkyl or absent to satisfy the valency of the heteroaryl ring.
EFFECT: improved compounds properties.
29 cl, 23 dwg, 24 tbl, 9 ex
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Authors
Dates
2018-02-27—Published
2013-07-11—Filed