Arylquinazolines

Patent metadata

Field	Value
Publication number	US-11065253-B2
Application number	US-201916452604-A
Country	US
Kind code	B2
Filing date	Jun 26, 2019
Priority date	May 11, 2013
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

Abstract

The invention relates to novel compounds of the formula (I) which can be used for the inhibition of serine-threonine protein kinases and for the sensitisation of cancer cells to anticancer agents and/or ionising radiation.

First claim

We claim:

1. A method for sensitizing cancer cells to anticancer agents or ionising radiation, comprising administering

or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios, wherein the anticancer agents are selected from mitoxantrone, bleomycin, doxorubicin, epirubicin, idarubicin, zorubicin, daunurobicin and aclarubicin; and wherein the cancer cells express DNA-PK and compound 136 sensitizes the cancer cells through specific inhibition of the repair of DNA double strand breaks due to selective inhibition of DNA-PK.

2. A method for treating cancer, tumours or metastases, comprising administering

or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios, in combination with radiotherapy; wherein the cancer, tumours or metastases express DNA-PK and compound 136 sensitizes the cancer, tumours or metastases through specific inhibition of the repair of DNA double strand breaks due to selective inhibition of DNA-PK.

3. The method of claim 1 , wherein the cancer cells are sensitized to ionising radiation selected from photon irradiation, proton irradiation, heavy-ion irradiation and neutron irradiation.

4. The method of claim 2 , wherein the cancer, tumours or metastases are selected from the group consisting of malignant diseases of bladder, stomach, kidneys, head, neck, esophagus, cervix, thyroid, intestine, liver, brain, prostate, urogenital tract, lymphatic system, larynx, lung, skin, blood, bones and immune system; or the cancer, tumours or metastases are selected from the group consisting of monocytic leukemia, non-small-cell lung carcinoma, small-cell lung carcinoma, pancreatic cancer, glioblastoma, colorectal carcinoma, breast carcinoma, acute myeloid leukemia, chronic myeloid leukemia, acute lymphatic leukemia, chronic lymphatic leukemia, Hodgkin's lymphoma and non-Hodgkin's lymphoma.

5. The method of claim 2 , wherein the radiotherapy comprises ionising radiation.

6. The method of claim 5 , wherein the ionising radiation is selected from photon irradiation, proton irradiation, heavy-ion irradiation and neutron irradiation.

7. The method of claim 1 , wherein the cancer cells are selected from the group consisting of malignant diseases of bladder, stomach, kidneys, head, neck, esophagus, cervix, thyroid, intestine, liver, brain, prostate, urogenital tract, lymphatic system, larynx, lung, skin, blood, bones and immune system; or the cancer cells are selected from the group consisting of monocytic leukemia, non-small-cell lung carcinoma, small-cell lung carcinoma, pancreatic cancer, glioblastoma, colorectal carcinoma, breast carcinoma, acute myeloid leukemia, chronic myeloid leukemia, acute lymphatic leukemia, chronic lymphatic leukemia, Hodgkin's lymphoma and non-Hodgkin's lymphoma.

Assignees

• Merck Patent Gmbh

Inventors

• Fuchss Thomas
• Emde Ulrich
• Buchstaller Hans-Peter
• Mederski Werner

Classifications

• A61K31/517 Primary

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• C07D513/04

  Ortho-condensed systems · CPC title

• C07D498/08

  Bridged systems · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• C07D491/048

  the oxygen-containing ring being five-membered · CPC title