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CN-121991089-A - Rehmannia pigment compound, preparation method thereof and application thereof in medicines

CN121991089ACN 121991089 ACN121991089 ACN 121991089ACN-121991089-A

Abstract

The application provides a rehmannia pigment compound shown in a formula (I), a stereoisomer or a pharmaceutically acceptable salt thereof, and particularly relates to the technical fields of natural pharmaceutical chemistry and pharmaceutical compounds. The application aims to solve the problems of unclear substance basis of rehmannia pigment, lack of a compound with clear structure and excellent anti-inflammatory activity. The application discloses a rehmannia pigment compound containing a structure shown in a formula (I), and also discloses a preparation method of the compound and application of the compound in medicines. The compound provided by the application has a novel chemical structure and remarkable anti-inflammatory activity, can effectively inhibit the release of nitric oxide in a lipopolysaccharide-induced macrophage model, has cytotoxicity far lower than that of a positive control medicine quercetin, and shows great potential as an anti-inflammatory medicine lead compound.

Inventors

  • DING GANG
  • ZHONG LIWEN
  • CHEN LIN

Assignees

  • 中国医学科学院药用植物研究所

Dates

Publication Date
20260508
Application Date
20251231

Claims (10)

  1. 1. A rehmannia glutinosa dye compound of formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof: ; In the formula (I), X is selected from the formula (X1) or the formula (X2), and the double bond configuration of 13-C and 17-C is independently E formula or Z formula; ; formula (I), formula (X1), formula (X2): r1, R7 and R8 are independently oxygen or sulfur; r2, R6 and R5 are independently oxygen, sulfur or imino; R3 and R4 are independently hydroxy, mercapto or amino.
  2. 2. The rehmannia root pigment compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof according to claim 1, which is a compound having a structure represented by formula (i), formula (ii), formula (iii) or formula (iv): ; ; in the formula (i), the 13-C double bond is E formula, the 17-C double bond is E formula, and X is selected from the formula (X2); In the formula (ii), the 13-C double bond is E formula, the 17-C double bond is E formula, and X is selected from the formula (X1); in the formula (iii), the 13-C double bond is Z type, the 17-C double bond is E type, and X is selected from the formula (X1); In the formula (iv), the 13-C double bond is E type, the 17-C double bond is Z type, and X is selected from the formula (X1).
  3. 3. The rehmannia-pigment compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein the compound is a compound having a structure represented by formula (i-a), formula (ii-b), formula (iii-c), or formula (iv-d): ; ; 。
  4. 4. the rehmannia pigment compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof according to claim 1, wherein X is selected from formula (X1).
  5. 5. The rehmannia-pigment compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof according to claim 1, wherein the 13-C double bond is of formula E and the 17-C double bond is of formula E.
  6. 6. The rehmannia pigment compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein X is selected from formula (X1), R1 is oxygen, R2 is oxygen, sulfur or imino, R5 is oxygen, and R6 is oxygen or imino.
  7. 7. The rehmannia-pigment compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein X is selected from formula (X2), R1 is sulfur, R2 is oxygen or imino, R7 is oxygen, and R8 is sulfur.
  8. 8.A process for preparing the rehmannia root pigment compound, stereoisomer thereof, or pharmaceutically acceptable salt thereof according to any one of claims 1 to 7, comprising the steps of: Carrying out normal phase chromatography on the crude rehmannia pigment product to obtain a primary purification component containing a target component; performing reverse phase chromatography on the primary purified component to obtain a further purified sub-component; subjecting the subfractions to size exclusion chromatography to obtain a secondary component; And (3) performing semi-preparative high performance liquid chromatography and/or preparative high performance liquid chromatography separation on the secondary component to obtain the rehmannia pigment compound.
  9. 9. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of claims 1-7, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or excipients.
  10. 10. Use of a compound according to any one of claims 1-7, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 9, in the manufacture of a medicament for the prevention and/or treatment of an inflammatory disease.

Description

Rehmannia pigment compound, preparation method thereof and application thereof in medicines Technical Field The application relates to the technical field of natural medicinal chemistry and medicinal compounds, in particular to a rehmannia pigment compound, a preparation method thereof and application thereof in medicines. Background Rehmannia glutinosa (REHMANNIA GLUTINOSA) is a traditional Chinese medicine, and fresh or processed rhizome thereof is widely used clinically. The fresh rhizome of rehmannia has a unique yellowish orange appearance, suggesting that it contains specific pigmentary ingredients. In the prior art, although the literature mentions that rehmannia contains chemical components such as 'rehmannia glutinosa', and describes that the rehmannia glutinosa has traditional medicinal effects of nourishing yin, clearing heat, cooling blood, stopping bleeding and the like, the precise chemical structure of specific pigment components constituting the color of the rehmannia glutinosa, and whether the components have specific pharmacological activity, especially anti-inflammatory activity, have not been elucidated for a long time. Thus, there is a general lack of systematic research and development in the art of pigment compounds with definite chemical structures and significant biological activity in rehmannia, which limits the deep understanding of the medicinal substance basis of rehmannia and the development of new drugs. Disclosure of Invention The application aims to solve the problems of unclear substance basis, lack of a compound with a definite structure and excellent anti-inflammatory activity in the prior art. The present application provides a rehmannia pigment compound, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. The application provides a rehmannia pigment compound with a brand new general structure for the first time, the structure is not reported in the prior art, belongs to brand new compound types, and provides brand new chemical entity and structure basis for developing novel functional natural products. To achieve the above object, the present application provides a rehmannia pigment compound represented by the formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof. In formula (I), X is selected from formula (X1) or formula (X2), and the double bond configuration of 13-C and 17-C is independently E or Z; In the formula (I), the formula (X1) and the formula (X2), R1, R7 and R8 are independently oxygen or sulfur, R2, R5 and R6 are independently oxygen, sulfur or imino, and R3 and R4 are independently hydroxyl, sulfhydryl or amino. As a preferred embodiment of the present application, the compound is a compound having a structure represented by formula (i), formula (ii), formula (iii) or formula (iv); in the formula (i), the 13-C double bond is E formula, the 17-C double bond is E formula, and X is selected from the formula (X2); In the formula (ii), the 13-C double bond is E formula, the 17-C double bond is E formula, and X is selected from the formula (X1); in the formula (iii), the 13-C double bond is Z type, the 17-C double bond is E type, and X is selected from the formula (X1); In the formula (iv), the 13-C double bond is E type, the 17-C double bond is Z type, and X is selected from the formula (X1). Further, the compound is a compound having a structure represented by formula (i-a), formula (ii-b), formula (iii-c) or formula (iv-d); alternatively, the X is selected from formula (X1). Optionally, the 13-C double bond is of formula E, and the 17-C double bond is of formula E. Alternatively, X is selected from formula (X1), R1 is oxygen, R2 is oxygen, sulfur or imino, R5 is oxygen, and R6 is oxygen or imino. Alternatively, X is selected from formula (X2), R1 is sulfur, R2 is oxygen or imino, R7 is oxygen, and R8 is sulfur. The present application also provides a process for preparing a rehmannia root pigment compound, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof as defined in any one of the preceding claims, comprising the steps of: Carrying out normal phase chromatography on the crude rehmannia pigment product to obtain a primary purification component containing a target component; performing reverse phase chromatography on the primary purified component to obtain a further purified sub-component; subjecting the subfractions to size exclusion chromatography to obtain a secondary component; And (3) performing semi-preparative high performance liquid chromatography and/or preparative high performance liquid chromatography separation on the secondary component to obtain the rehmannia pigment compound. The application also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of any one of the preceding claims, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or excipients. The appli