阅读说明：本技术 用于治疗结外nk/t细胞淋巴瘤的喹啉衍生物 (Quinoline derivatives for the treatment of extranodal NK/T cell lymphoma ) 是由 陶荣 于 2019-08-05 设计创作，主要内容包括：提供一种用于治疗结外NK/T细胞淋巴瘤的喹啉衍生物。所提供的化合物I或其药学上可接受的盐,可用于治疗门冬酰胺耐药的结外NK/T细胞淋巴瘤患者,尤其对于门冬酰胺耐药的、复发或难治性结外NK/T细胞淋巴瘤患者,疗效评估结果表明其症状得到缓解,其生存期得到延长。(Quinoline derivatives are provided for use in the treatment of extranodal NK/T cell lymphoma. The provided compound I or pharmaceutically acceptable salt thereof can be used for treating asparagine-resistant extranodal NK/T cell lymphoma patients, especially for asparagine-resistant, recurrent or refractory extranodal NK/T cell lymphoma patients, and the curative effect evaluation result shows that the symptoms of the asparagine-resistant, recurrent or refractory extranodal NK/T cell lymphoma patients are relieved and the survival period of the asparagine-resistant, recurrent or refractory extranodal NK/T cell lymphoma patients is prolonged.)

Use of compound I or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment of extra-nodal NK/T cell lymphoma,

the use according to claim 1, wherein the extranodal NK/T cell lymphoma is extranodal NK/T cell lymphoma failed in chemotherapy including but not limited to asparaginase-type antitumor drugs, antifolate antitumor drugs, podophyllum antitumor drugs, steroid hormones, alkylating antitumor drugs, preferably one or more of levo-asparaginase, pemetrexed, methotrexate, etoposide, dexamethasone, ifosfamide, mitoxantrone, gemcitabine, oxaliplatin, cytarabine, capecitabine, docetaxel, bortezomib, apatinib, lenalidomide, prednisone, and/or targeted drug therapy.

Use according to any one of claims 1-2, wherein the extranodal NK/T cell lymphoma is an asparagine-resistant extranodal NK/T cell lymphoma, preferably an asparagine-resistant clinical phase IV extranodal NK/T cell lymphoma.

Use according to any one of claims 1 to 3, characterized in that the pharmaceutically acceptable salt thereof is a salt of compound I with any of the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, heptanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1, 2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-chlorobenzenesulfonic acid, p-toluenesulfonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, dodecylsulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid; preferably in the form of the hydrochloride or maleate salt, more preferably the dihydrochloride salt.

The use according to any one of claims 1 to 4, wherein the medicament is a formulation suitable for any one of oral, parenteral, intraperitoneal, intravenous, intraarterial, transdermal, sublingual, intramuscular, rectal, transbuccal, intranasal, inhalation, vaginal, intraocular, topical, subcutaneous, intralipid, intraarticular, intraperitoneal or intrathecal administration; preferably a formulation suitable for oral administration; more preferably tablet, capsule, powder, granule, dripping pill, paste or powder, and more preferably tablet or capsule.

The use according to any one of claims 1 to 5, wherein the compound I or the pharmaceutically acceptable salt thereof is administered in a daily dose of 2mg to 30 mg, preferably 6 mg to 20mg, more preferably 8mg to 20mg, even more preferably 10mg to 16 mg, yet more preferably 10mg to 14 mg, most preferably 8mg, 10mg, 12mg or 14 mg.

The use according to any one of claims 1 to 6, wherein compound I or a pharmaceutically acceptable salt thereof is administered at intervals between an administration period and a withdrawal period; the ratio of the administration period to the withdrawal period in days is preferably 2: 0.5-5, more preferably 2: 0.5-3, even more preferably 2: 0.5-2, and still more preferably 2: 0.5-1; a further preferred mode of administration at intervals is one of the following: stopping the drug for 2 weeks after 2 weeks of continuous administration, for 1 week after 2 weeks of continuous administration, or for 2 days after 5 days of continuous administration; the intermittent administration mode may be repeated a plurality of times.

The use according to any one of claims 1 to 7, wherein compound I or the pharmaceutically acceptable salt thereof is administered to extranodal NK/T cell lymphoma patients simultaneously or sequentially with other antineoplastic agents including, but not limited to, one or more of antifolate antineoplastic agents, podophyllum antineoplastic agents, steroid hormones, alkylating antineoplastic agents, camptothecin antineoplastic agents, platinum complexes, fluoropyrimidine derivatives, anthraquinone antineoplastic agents, taxanes, EGFR inhibitors, VEGFR inhibitors, mitomycin, trastuzumab.

A pharmaceutical composition for the treatment of extranodal NK/T cell lymphoma comprising Compound I, or a pharmaceutically acceptable salt thereof, in association with at least one pharmaceutically acceptable carrier,

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 the treatment of extranodal NK/T cell lymphoma,