阅读说明：本技术 用于治疗结直肠癌的喹啉衍生物 (Quinoline derivatives for the treatment of colorectal cancer ) 是由 江海 刘雯雯 于鼎 陈莉 于 2018-05-24 设计创作，主要内容包括：一种用于治疗结直肠癌的喹啉衍生物,具体涉及1-[[[4-(4-氟-2-甲基-1H-吲哚-5-基)氧基-6-甲氧基喹啉-7-基]氧基]甲基]环丙胺能够有效治疗化疗药物和/或靶向药物治疗失败的结直肠癌,能够稳定或者缓解化疗药物和/或靶向药物治疗失败的结直肠癌患者病情。(A quinoline derivative for treating colorectal cancer, in particular to 1- [ [ [4- (4-fluoro-2-methyl-1H-indol-5-yl) oxy-6-methoxyquinoline-7-yl ] oxy ] methyl ] cyclopropylamine, which can effectively treat colorectal cancer which fails in treatment of a chemotherapeutic drug and/or a targeted drug, and can stabilize or relieve the condition of a colorectal cancer patient who fails in treatment of the chemotherapeutic drug and/or the targeted drug.)

A method of treating colorectal cancer, comprising administering to a patient in need thereof a therapeutically effective amount of Compound I, or a pharmaceutically acceptable salt thereof, wherein the colorectal cancer is a colorectal cancer that has failed treatment with a chemotherapeutic and/or targeted drug,

a method of treating RAS mutated colorectal cancer comprising administering to a patient in need thereof a therapeutically effective amount of compound I or a pharmaceutically acceptable salt thereof; preferably the colorectal cancer is RAS mutated advanced and/or metastatic colorectal cancer; more preferably the colorectal cancer is advanced and/or metastatic colorectal cancer with RAS mutations that failed chemotherapy and/or targeted drug therapy.

The method of claim 1 or 2, wherein the chemotherapeutic agent is selected from the group consisting of camptothecin antineoplastic agents, platinum complexes, and fluoropyrimidine derivatives; the targeted drug is selected from an EGFR inhibitor or a VEGFR inhibitor.

The method of any one of claims 1-3, wherein the colorectal cancer is colorectal adenocarcinoma.

The method of claim 4, wherein the colorectal adenocarcinoma is an ethmoid adenocarcinoma, a medullary carcinoma, a microemulsion head carcinoma, a mucinous adenocarcinoma, a serrate adenocarcinoma, or a signet ring cell carcinoma.

The method of any one of claims 2-5, wherein the RAS mutation is KRAS and NRAS; preferably a mutation at codon 2 of the KRAS gene; preferably, the NRAS gene is mutated at codon 2 and/or 3.

The process of any one of claims 1-6, wherein Compound I, or a pharmaceutically acceptable salt thereof, is the hydrochloride salt, preferably the dihydrochloride salt.

The method of any one of claims 1-7, wherein the daily dose of compound I or a pharmaceutically acceptable salt thereof administered is one of the following daily doses: 2mg to 20 mg, 5 mg to 20 mg, 8 mg to 20 mg, 10mg to 16 mg, 10mg to 14 mg, 10mg, 12mg, 14 mg and 16 mg.

The method of any one of claims 1-8, wherein compound I or a pharmaceutically acceptable salt thereof; the interval administration comprises an administration period and a medicine stopping period, wherein the ratio of the administration period to the medicine stopping period in days is 2: 0.5-5, preferably 2: 0.5-3, more preferably 2: 0.5-2, and even more preferably 2: 0.5-1; the preferred interval administration is one of the following modes: the drug is stopped for 2 weeks after 2 weeks of continuous administration, for 1 week after 2 weeks of continuous administration, and for 2 days after 5 days of continuous administration, and the above intermittent administration may be repeated a plurality of times.

The method according to any one of claims 1 to 9, wherein compound I or a pharmaceutically acceptable salt thereof is administered to a colorectal cancer patient simultaneously or sequentially with other anti-neoplastic agents; the other antitumor drugs are selected from one or more of camptothecin antitumor drugs, platinum complex, fluoropyrimidine derivative, anthraquinone antitumor antibiotics, taxane compounds, EGFR inhibitor, VEGFR inhibitor, mitomycin and trastuzumab.

Use of compound I or a pharmaceutically acceptable salt thereof for the manufacture of a pharmaceutical composition for the treatment of colorectal cancer, wherein the colorectal cancer is a colorectal cancer for which a chemotherapy drug and/or a targeted drug treatment fails,

a pharmaceutical composition for treating colorectal cancer, which comprises compound I or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier, wherein the colorectal cancer is the colorectal cancer which fails to be treated by a chemotherapeutic drug and/or a targeted drug,

a kit comprising (a) at least one unit dose of a pharmaceutical composition of compound I or a pharmaceutically acceptable salt thereof and (b) instructions for treating colorectal cancer; wherein the colorectal cancer is a colorectal cancer that has failed chemotherapy drug and/or targeted drug therapy,