Compound of quinoline Derivative, composition containing the same and use in the manufacture of medicinal products, Process for Preparation and Method for Detecting and selecting an agent that modulates the activity of MIF

摘要

Quinoline-derived compounds are provided that are MIF inhibitors useful in treating a variety of disorders, including treating pathological conditions associated with MIF activity. This compound has structure (1) or a pharmaceutically acceptable stereoisomer, prodrug, or salt thereof, in which: X is oxygen or sulfur; Y is selected from the group consisting of -NO, -NO2, -C (= O) R5, -C (= O) OR5, -C (= O) NR5R6, -NR5C (= O) R5, -NR5SO2R5 and - S (O) mR5; Z is -CH2- or -C (= O) -;M is 0, 1 or 2; n is O, 1 or 2; but n is 0, Z is - C (= O);;R1 is selected from the group consisting of hydrogen, tar, replacement tar, arilo, replacement arilo, arilalquilo, replacement arilalquilo, different cycle, replacement different cycle, different cycle electrolysis and replacement different cycle electrolysis, X is 2-4, and R 'and R' are independent of hydrogen, asphalt, alternative asphalt, arilalquilo, alternative arilalquilo, heterocycle, alternative heterocycle, heterocycle or isopropyl alternative and dialquilo group. R2 and R3 were independently selected from halogen, R5, R5, SR5 or nr5r6 groups;R4 is selected from the group consisting of - ch2r7, - C (= O) nr5r6, - C (= O) R7, - C (= O) R7, - C (= O) R7 and R8; R5 and R6 are independent of the group consisting of hydrogen, asphalt, alternative asphalt, arilo, alternative arilalquilo, heterocycle, alternative, Or R5 and R6 are combined with a nitrogen atom to form a heterocyclic or heterocyclic alternative; R7 is selected from the group consisting of asphalt, alternative asphalt, arilo alternative, arilalquilo alternative, heterocyclic alternative and heterocyclic alternative,e. 8. Selected from hydrogen, tar, alternative tar, arilo, alternative arilo, arilalquilo, alternative arilalquilo, heterocycle, alternative non cycle, heterocycle level and alternative heterocycle level groups; However, it is understood that R4 is neither hydrogen nor methyl, R2 and R3 are both hydrogen, X is oxygen e, es-c (= O) och2ch3; R4 is not methyl, R1 is methyl, R2 and R3 are both hydrogen, X is oxygen e, es-no2; R4 is not ch2ch2oh, R1 is hydrogen or methyl, R2 is 7-chlorine, R3 is hydrogen, X is oxygen E and es-c (= O) occ2ch3; R4 is not methyl, R1 is methyl,R2 is hydrogen or 7-chlorine, R3 is hydrogen, X is oxygen, es-c (= O) och2ch3. Compounds containing MIF inhibitors, as well as a pharmaceutically acceptable vehicle, are also provided and used in drug manufacture. The report also describes the preparation process of these compounds and the methods for determining and selecting the fuel cycle fund modulators.