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P70 s6 kinase inhibitor and mtor inhibitor combination therapy

A technology of inhibitors and compounds, which can be used in drug combinations, medical preparations containing active ingredients, muscular system diseases, etc., and can solve problems such as growth arrest

Inactive Publication Date: 2011-10-05
ELI LILLY & CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Inhibition of mTOR activity in tumor cells has been shown to lead to G1 growth arrest due to translational disruption of regulated cyclins

Method used

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  • P70 s6 kinase inhibitor and mtor inhibitor combination therapy
  • P70 s6 kinase inhibitor and mtor inhibitor combination therapy

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Experimental program
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Effect test

Embodiment Construction

[0008] Compound 4-[4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl]-1H-pyridine Azolo[3,4-d]pyrimidine

[0009]

[0010] is a p70 S6 kinase inhibitor.

[0011] Compound 4-[4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl]-1H-pyridine Azolo[3,4-d]pyrimidine is a base and as such will react with any of a number of organic and inorganic acids to form pharmaceutically acceptable salts. The term "pharmaceutically acceptable salt" as used herein refers to the compound 4-[4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl- Salts of 1H-imidazol-2-yl]-piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine. Such salts include the pharmaceutically acceptable salts listed in Journal of Pharmaceutical Science, 66, 2-19 (1977), which are known to those skilled in the art. Tosylate (also known as p-toluenesulfonate) and hydrochloride are preferred. Tosylate salts are particularly preferred.

[0012] "mTOR inhibitor" refers to...

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PUM

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Abstract

The present invention provides a combination therapy comprising the compound 4-[4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine, or a pharmaceutically acceptable salt thereof, and an mTOR inhibitor for use in the treatment of glioblastoma multiforme, adenocarcinomas of the colon, non-small-cell lung cancer, small-cell lung cancer, cisplatin-resistant small-cell lung cancer, ovarian cancer, leukemia, pancreatic cancer, prostate cancer, mammary carcinoma, renal cell carcimoma, multiple myeloma, Kaposis Sarcoma, Hodgkins lymphoma, lymphangioleiomyomatosis, Non-Hodgkins lymphoma or sarcoma.

Description

Background of the invention [0001] The phosphatidylinositol-3-kinase (PI3K) / AKT / mammalian target of rapamycin (mTOR) pathway encompasses a large number of signaling points critical in the control of cell growth and survival. mTOR is a serine-threonine protein kinase involved in the control of many cellular functions such as cell proliferation, cell survival, protein synthesis and transcription. Inhibition of mTOR activity in tumor cells has been shown to result in arrest of G1 growth due to disruption of translation of regulated cyclins. P70 S6 kinase is a serine-threonine protein kinase that is a downstream effector of the PI3K / AKT / mTOR signaling pathway. P70 S6 kinase phosphorylates the intracellular ribosomal protein S6 and regulates ribosome biogenesis, cell growth and cell cycle progression in response to mitogenic stimuli. P70 S6 kinase is normally activated in many solid tumors. Inhibitors of p70 S6 kinase for the treatment of such tumors are disclosed in WO 2006 / 046...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/436A61K31/519A61K45/06A61P35/00
CPCA61K45/06A61K31/519A61K31/436A61P1/04A61P1/18A61P11/00A61P13/08A61P13/12A61P15/00A61P19/00A61P21/00A61P25/00A61P35/00A61P35/02A61P43/00A61K2300/00
Inventor S.吉加纳奇G.P.多诺霍
Owner ELI LILLY & CO
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