阅读说明：本技术 用于治疗房性心律失常的task-1抑制剂 (TASK-1 inhibitors for the treatment of atrial arrhythmias ) 是由 康斯坦丝·施密特 沃尔特·埃米尔·黑费利 雨果·卡图斯 尼尔斯·德凯尔 菲力克斯·维德曼 于 2019-08-14 设计创作，主要内容包括：本发明涉及具有式(I)所示结构的化合物或其药学上可接受的盐或前药,其用于治疗和/或预防对象的房性心律失常,其中R～1是乙基、-H或甲基,并且R～2是具有式(II)所示结构的侧链,其中X～1为C＝O、CH-2、C＝S、C-OH、C-NH-2或C-NO-2,X～2至X～4独立地选自CH-2、C＝O、C＝S、C-OH和C-NH-2或R～2为-NH-2。本发明还涉及与所述化合物有关的药物组合物和试剂盒。(The present invention relates to compounds having the structure shown in formula (I) or pharmaceutically acceptable salts or prodrugs thereof, which are used for treating and/or preventing atrial arrhythmia of a subject, wherein R 1 Is ethyl, -H or methyl, and R 2 Is a side chain having a structure represented by the formula (II) wherein X 1 Is C-O, CH 2 、C＝S、C‑OH、C‑NH 2 Or C-NO 2 ，X 2 To X 4 Independently selected from CH 2 C-O, C-S, C-OH and C-NH 2 Or R 2 is-NH 2 . The invention also relates to a method for producing the samePharmaceutical compositions and kits related to the compounds.)

1. a compound having a structure represented by formula (I) or a pharmaceutically acceptable salt or prodrug thereof for use in treating and/or preventing atrial arrhythmia in a subject,

wherein

R¹Is ethyl, -H or methyl, and

R²is a side chain with a structure shown in a formula (II),

wherein

X¹Is C-O, CH₂、C＝S、C-OH、C-NH₂Or C-NO₂，

X²To X⁴Independently selected from CH₂C-O, C-S, C-OH and C-NH₂，

Or R²is-NH₂。

2. A compound for use according to claim 1, wherein R¹Is ethyl and X²To X⁴Is CH₂。

3. A compound for use according to claim 1 or 2, wherein X¹Is C ═ O or CH₂C ═ O is preferred.

4. A compound for use according to any one of claims 1 to 3, wherein the compound has the structure of formula (III), (IV), (V) or (VI)

5. The compound for use according to any one of claims 1 to 4, wherein the atrial arrhythmia is atrial fibrillation, atrial flutter, premature atrial contraction, supraventricular tachycardia, sick sinus syndrome and Wolpa-Huai syndrome, preferably atrial fibrillation.

6. The compound for use according to any one of claims 1 to 5, wherein the atrial arrhythmia is new atrial fibrillation, paroxysmal atrial fibrillation, persistent atrial fibrillation, or permanent atrial fibrillation.

7. Compound for use according to any one of claims 1 to 6, wherein the use comprises avoiding side effects caused by central nerve stimulation, in particular seizures, paresthesia, restlessness, obnubilation, nausea, vomiting and/or hallucinations.

8. The compound for use according to any one of claims 1 to 7, wherein the use comprises intravenous administration and/or oral administration.

9. The compound for use according to any one of claims 1 to 8, wherein use comprises intravenously administering the compound at a dose of 0.1 to 10mg/kg body weight, preferably 0.25 to 2mg/kg body weight, more preferably 1.5 to 1.8mg/kg body weight.

10. The compound for use according to any one of claims 1 to 9, wherein use comprises intravenous administration of the compound at a dose of 0.004 g/day to 3 g/day, preferably 0.01 g/day to 0.3 g/day, more preferably 0.05 g/day to 0.27 g/day.

11. The compound for use according to any one of claims 1 to 10, wherein use comprises oral administration of the compound at a dose of 0.2mg/kg body weight to 20mg/kg body weight, preferably 0.5mg/kg body weight to 4mg/kg body weight, more preferably 3mg/kg body weight to 3.6mg/kg body weight.

12. The compound for use according to any one of claims 1 to 11, wherein use comprises oral administration of the compound at a dose of 0.008 g/day to 6 g/day, preferably 0.02 g/day to 0.6 g/day, more preferably 0.1 g/day to 0.54 g/day.

13. A compound for use according to any one of claims 1 to 12, wherein the subject is a mammal, preferably a human.

14. A pharmaceutical composition comprising at least one compound as defined in any one of claims 1 to 4 for use in the treatment and/or prevention of an atrial arrhythmia in a subject.

15. A kit comprising at least one compound as defined in any one of claims 1 to 4 and a cardioversion device and/or other cardioversion drugs.