Chloroxyquine derivatives with antitumor activity

Abstract

The invention relates to a chloroxoquinoline derivatives with anti-tumor activity and specifically relates to compounds of a formula I as shown in the specification and pharmaceutically acceptable salts, solvates and prodrugs thereof, wherein R1 is selected from hydrogen, -C1-6 alkyl, -C2-6 alkenyl, -C2-6 alkynyl and -C1-6 alkyl-phenyl, and the alkyl, the alkenyl, the alkynyl and the phenyl can be optionally substituted by halogens, nitryl, cyan, hydroxyl, -C1-6 alkoxy and phenyl; R3 is selected from hydrogen, -CONHR31 and -COOR32, the R31 and the R32 are independently selected from -C1-6 alkyl and -C1-6 alkylamino, respectively, and the amino can be optionally substituted by 1 to 2 -C1-6 alkyls; R7 is selected from halogens, -C1-6 alkoxy, morpholinyl and piperazine; the formula I is as shown in the specification.

Description

technical field [0001] The invention relates to a class of chlorooxyquine derivatives with antitumor activity, a preparation method of the chlorooxyquine derivatives, and their application in the preparation of antitumor drugs. Background technique [0002] 7-chloro-4-oxo-quinoline, generally known as chlorooxyquine, molecular formula: C 9 h 6 ClNO, molecular weight: 179.6, melting point: 282-285°C, white or off-white powder, its chemical structure is as follows: [0003] [0004] This compound has tautomerism, and its tautomer is 7-chloro-4-hydroxyl-quinoline, and the relationship between the two changes is as follows: [0005] [0006] It is known that chlorooxyquine is a new national anti-cancer drug independently developed by Tonghua Maoxiang Pharmaceutical Co., Ltd. in Jilin Province, which belongs to the first category of chemical drugs. The drug was included in the national "1035" project and the national "Ninth Five-Year" scientific and technological researc...

AI Technical Summary

Problems solved by technology

In 2009, Langer et al. reported a simpler synthetic route, that is, using m-chloroaniline and isopropylidene malonate as raw materials, 7-chloro-4-hydroxy-quinone can be obtained through condensation and ring-closing two-step reactions phenoline, this route has higher yield for aniline raw materials with symmetrically substituted halogen atoms on the benzene ring, but this method will generate 5-substituted isomers for the monosubstituted aniline of the benzene ring (Synthesis1 (2009) 69-78 )

[0011] However, chlorooxyquine, as a first-class anti-tumor innovative drug in my country, currently has two problems: (1) the solubility of chlorooxyquine raw material in water is very small, so it cannot be administered in the form of injection clinically

(2) At present, the anti-tumor and tumor-inhibitory rate of chlorooxyquine on the tumor-bearing mouse models of S180 sarcoma and Ehrlich carcinoma solid type is only about 30%, and its anti-tumor activity needs to be improved

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