CN-116730971-B - Icetex ane diterpenoid derivative as well as preparation method and application thereof

CN116730971BCN 116730971 BCN116730971 BCN 116730971BCN-116730971-B

Abstract

The invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to an Icetex ane diterpenoid derivative, a preparation method and application thereof. The Iceteane abietylene diterpenoid derivative has a structure shown in a formula (I), is novel in structure, and has good effects of treating and/or preventing acute lung injury;

Inventors

DENG XU
ZHOU YINGJUN
LIU WEI
TANG QIN
LIU MOUDE
XIE WEIXI
LIU TINGTING
ZENG GUANGYAO

Assignees

中南大学

Dates

Publication Date: 20260505
Application Date: 20230208

Claims (3)

1. Use of a compound or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment and/or prophylaxis of acute lung injury: The compound is ; Acute lung injury is a collective transitional inflammatory response syndrome of progressive dyspnea and refractory hypoxia caused by alveolar epithelial cell and capillary endothelial injury resulting from various direct or indirect injuries.
2. Use of a pharmaceutical composition for the manufacture of a medicament for the treatment and/or prophylaxis of acute lung injury, wherein the pharmaceutical composition comprises a compound as defined in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier; Among them, acute lung injury is a collective transitional inflammatory reaction syndrome of progressive dyspnea and refractory hypoxia caused by alveolar epithelial cell and capillary endothelial injury resulting from various direct or indirect injuries.
3. The use according to any one of claims 1 or 2, wherein the acute lung injury is LPS-induced acute lung injury.

Description

Icetex ane diterpenoid derivative as well as preparation method and application thereof Technical Field The invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to an Icetex ane diterpenoid derivative, a preparation method and application thereof. Background Acute lung injury (acute lung injury, ALI) is a collective transitional inflammatory response syndrome of progressive dyspnea and refractory hypoxia caused by various direct or indirect injuries to alveolar epithelial cells and capillary endothelium, severe Acute Respiratory Distress Syndrome (ARDS), a common cause of respiratory failure, with higher morbidity and mortality (f1000res., 2019,8,1-9; n.engl.j.med.,2005,353,1685-1693). At present, mechanical ventilation is mainly used clinically, and medicines such as glucocorticoid and anti-inflammatory medicines have limited treatment effects and can cause various adverse reactions such as coagulation dysfunction, gastric ulcer and osteoporosis. Therefore, ALI lacks an effective treatment means, and a safe and effective acute lung injury treatment drug is urgently needed, so that the survival rate of patients is effectively improved. Icetex ane diterpene is a natural product widely distributed in plants of Labiatae, cupressaceae, celastraceae, euphorbiaceae, verbenaceae, taxaceae, etc., especially Salvia plants of Labiatae are most abundant (Nat. Prod. Rep.,2009,26 (9): 1195-1217). Icetex ane type abietylene diterpene has unique 6/7/6 tricyclic skeleton. The research shows that the compounds have pharmacological activities such as anti-tumor, anti-malaria, antibacterial and antiviral activities (Med. Res. Rev.,2021,41,2971-2997), but the pharmacological research on the prevention and treatment effect of the compounds on acute lung injury has not been reported yet. Disclosure of Invention The present invention aims to solve at least one of the technical problems existing in the prior art. Therefore, the invention provides an Icetex type abietane diterpenoid derivative, a preparation method thereof and application thereof in preparing medicines for treating and/or preventing acute lung injury. In a first aspect of the present invention, there is provided a compound of formula (I) or a pharmaceutically acceptable salt, tautomer, racemate, enantiomer, diastereomer thereof: Wherein: r 1 is selected from H, OH, or R 1 forms c=o with the carbon at position 3; r 2 is selected from H or R 2 forms c=o with the carbon in position 1; r 3 is absent or OH; R 4 is selected from H, OH, or R 4 forms c=o with the carbon at position 20; R 5 is selected from H, or R 5 forms c=o with the carbon at position 7; R 6、R7 is each independently selected from OCH 3, OH, or R 6、R7 forms C=O with carbon at position 11, 12, or R 6、R7, respectively X is absent or C; When X is C, and carbon-carbon double bonds are arranged between 1 and 10 carbon atoms, carbon-carbon single bonds are arranged between 5, 6, 7, 10 and 20 carbon atoms, and carbon-carbon double bonds are arranged between 11 and 12 carbon atoms; When X is C and a carbon-carbon double bond is arranged between 1 and 2 carbon positions, one or two carbon-carbon double bonds exist between 5,6,7,10,20 carbon positions, and a carbon-carbon double bond or a carbon-carbon single bond is arranged between 11 and 12 carbon positions; When X does not exist, carbon-carbon single bonds are arranged between 1, 3 and 10 carbon atoms, and carbon-carbon double bonds are arranged between 5,10 carbon atoms, 6,7 carbon atoms and 11,12 carbon atoms. According to some embodiments of the invention, the compound has a structure represented by general formula (II): Wherein, the R 6、R7 are each independently selected from OCH 3, OH, or R 6、R7 together form According to some embodiments of the invention, the compound has a structure represented by general formula (III) or (IV): Wherein, the R 1 is selected from H, OH, or R 1 forms c=o with the carbon at position 3; r 3 is absent or OH; r 4 is selected from H or OH; R 5 is selected from H, or R 5 forms c=o with the carbon at position 7; R 6、R7 is each independently selected from OCH 3, OH, or R 6、R7 forms C=O with the carbon at the 11-position, 12-position, or R 6, R 7 together form And, the single bond is not simultaneously formed between the 10-carbon and the 20-carbon and between the 11-carbon and the 12-carbon. According to some embodiments of the invention, the compound has a structure according to formula (III), Wherein, the R 1 forms c=o with the carbon at position 3; R 3 is absent; r 4 is selected from H or OH; R 5 forms c=o with the carbon at position 7; R 6、R7 are each independently selected from OCH 3, OH, or R 6、R7 together form According to some embodiments of the invention, the compound has a structure represented by general formula (V): Wherein, the R 4 is selected from H or OH; r 5 is H; R 6、R7 are each independently selected from OCH 3, OH, or R 6、R7 together form According to some embodiments of