NOVEL COMPOUND, PREPARING METHOD THEREOF, AND USE THEREOF AS INHIBITORS OF HISTONE DEMETHYLASE

• US 20150133564A1
• Filed: 04/02/2014
• Published: 05/14/2015
• Est. Priority Date: 11/13/2013
• Status: Active Grant

• Current Assignee: Industry Academic Cooperation Foundation, Korea Advanced Institute of Science and Technology, SNU R&DB Foundation (Seoul National University)
• Original Assignee: Industry Academic Cooperation Foundation, Korea Advanced Institute of Science and Technology, SNU R&DB Foundation (Seoul National University)
• Inventors: OH, Dong-Chan, KIM, Seong-Hwan, SHIN, Jongheon, KWON, Hak Cheol, KWON, So Hee
• Granted Patent: US 9,650,325 B2
• Time in Patent Office: Days
• US Class Current: 514/681
• CPC Class Codes: A61K 31/122 having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
• CPC Class Codes: C07C 49/747 containing six-membered aromatic rings
• CPC Class Codes: C12N 1/205 Bacterial isolates
• CPC Class Codes: C12P 7/26 Ketones
• CPC Class Codes: C12R 2001/465 Streptomyces
• CPC Class Codes: C12Y 114/11 with 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors (1.14.11)
• CPC Class Codes: C12Y 114/11027 [Histone H3]-lysine-36 demethylase (1.14.11.27)

Abstract

Provided are a novel compound, preparing method thereof, and use thereof as inhibitor of histone demethylase. The compound represented by Chemical Formula 1 has activity which inhibits histone demethylase and thus is capable of specifically and effectively inhibit activity of histone demethylase.

Claims

1. A compound represented by Chemical Formula 1, an isomer thereof, a derivative thereof, or a pharmaceutically acceptable salt thereof:

2. The compound, the isomer, the derivative, or the pharmaceutically acceptable salt of claim 1, wherein R₂, R₄, R₅, R₆, R₇, and R₈ are each independently hydrogen, a hydroxyl group, or a substituted or unsubstituted C₁ to C₂₀ alkly group.

3. The compound, the isomer, the derivative, or the pharmaceutically acceptable salt of claim 1, wherein R₃, R₄, and R₆ are each independently a hydroxyl group.

4. The compound, the isomer, the derivative, or the pharmaceutically acceptable salt of claim 1, wherein R₃ is a C₁ to C₂₀ alkly group substituted with two or more halogen atoms.

5. The compound, the isomer, the derivative, or the pharmaceutically acceptable salt of claim 1, wherein R₃ is a C₁ to C₅ alkly group substituted with two halogen atoms.

6. The compound, the isomer, the derivative, or the pharmaceutically acceptable salt of claim 1, wherein the compound is further represented by Chemical Formula 2:

7. A Streptomyces genus SNC023 strain producing the compound of claim 1, wherein the Streptomyces genus SNC023 strain is deposited under Korean Collection for Type Cultures (KCTC) Accession number KCTC12494BP.

8. The Streptomyces genus SNC023 strain of claim 7, wherein the strain is separated or derived from an epidermis or body of a larva included in a brood ball of Copris tripartitus.

9. A method of producing the compound of claim 1, the method comprising:

culturing a Streptomyces genus SNC023 strain in a culturing medium, wherein the Streptomyces genus SNC023 strain is deposited under KCTC Accession number KCTC12494BP; and

separating the compound of claim 1 from the culturing medium.

10. The method of claim 9, wherein the separating the compound of claim 1 from the culturing medium comprises extracting the culturing medium by using ethyl acetate, water, or a combination thereof.

11. The method of claim 9, wherein the separating the compound of claim 1 from the culturing medium comprises performing concentration, centrifugation, filtration, or chromatography on the culturing medium.

15. A method of inhibiting activity of KDM in a subject, wherein the method comprises contacting the compound of claim 1 with KDM.

16. The method of claim 15, wherein the KDM is KDM4.

17. The method of claim 16, wherein the KDM4 demethylates histone H3 with a tri-methylated lysine in the ninth position.

18. A method of inhibiting activity of KDM, wherein the method comprises incubating in vitro the compound of claim 1 and KDM.

19. The method of claim 18, wherein the KDM is KDM4.

20. The method of claim 19, wherein the KDM4 demethylates histone H3 with a tri-methylated lysine in the ninth position.

12. An inhibitor of histone lysine demethylase (KDM), which is a compound represented by Chemical Formula 1, an isomer thereof, a derivative thereof, or a pharmaceutically acceptable salt thereof:

13. The inhibitor of claim 12, wherein the KDM is KDM4.

14. The inhibitor of claim 13, wherein the KDM4 demethylates triple methyl groups at lysine NO. 9 of histone subunit NO. 3