Pyrroloquinoline quinone derivative or medicinal salt thereof, preparation method and application

A technology of pyrroloquinoline quinone and its derivatives, which is applied in the field of biomedicine, can solve problems affecting drugability, etc., and achieve excellent solubility and ideal drug efficacy

Pending Publication Date: 2022-07-29
CHINA PHARM UNIV
0 Cites 0 Cited by

AI-Extracted Technical Summary

Problems solved by technology

However, PQQ-TME is almost insoluble...
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Abstract

The invention discloses a pyrroloquinoline quinone derivative with a structure as shown in a formula (I) or a medicinal salt thereof, a preparation method and application of the pyrroloquinoline quinone derivative. The derivative has excellent solubility and/or permeability, is obviously superior to PQQ and PQQ salt (commercially available disodium salt), shows an ideal drug effect in anti-inflammatory, anti-diabetes and anti-metabolic disease models, and is superior to PQQ and PQQ salt (commercially available disodium salt). The invention also provides a preparation method of the derivative and an intermediate thereof, a pharmaceutical composition and medical application thereof.

Application Domain

Technology Topic

Image

  • Pyrroloquinoline quinone derivative or medicinal salt thereof, preparation method and application
  • Pyrroloquinoline quinone derivative or medicinal salt thereof, preparation method and application
  • Pyrroloquinoline quinone derivative or medicinal salt thereof, preparation method and application

Examples

  • Experimental program(20)

Example Embodiment

[0037] Example 1
[0038] Synthesis of PQQ trimethyl ester: Take a single-neck flask, dissolve PQQ (3.3 g, 10 mmol) in DMF (200 mL), then add potassium carbonate (6.9 g, 50 mmol) in small portions and stir for 1 hour. Dimethyl sulfate (25 g) was dropped into the reaction suspension at room temperature, and the reaction was continued at room temperature for 5 days after the drop was completed. After DMF was evaporated with an oil pump, water (200 mL) was added to the residue and the residue was made acidic with 4N hydrochloric acid. The reaction solution was stirred at room temperature for 6 hours, and suction filtered to obtain an orange solid PQQ trimethyl ester (3.17 g, yield 85%).
[0039] Reduction of PQQ trimethyl ester: Take a single-neck flask, suspend PQQ trimethyl ester (1.86 g, 5 mmol) in acetonitrile (100 mL), add 1M sodium hydrosulfite solution (100 mL), and stir at room temperature overnight. The reaction solution was directly suction filtered, and the filter cake was dried to obtain reduced PQQ trimethyl ester (1.9 g), which was directly used in the next reaction without purification.
[0040] Synthesis of compound 1: The intermediate of the previous step (187 mg, 0.5 mmol) was placed in a two-necked flask, and dichloromethane (2 mL) was added to the reaction flask after nitrogen protection; A solution of acid chloride (157 mg, 2 mmol) in dichloromethane (2 mL) and triethylamine (220 mg) was allowed to warm and react overnight. Water (2 mL) was added to quench the reaction, the organic phase was separated, the aqueous phase was extracted with dichloromethane, the organic phases were combined and evaporated to dryness, and the residue was subjected to column chromatography (PE:EA=10:1-2:1) to obtain compound 1 ( 155 mg, 68%). 1 H NMR (300MHz, Chloroform-d) δ 12.67(s, 1H), 8.93(s, 1H), 7.33(s, 1H), 4.19(s, 3H), 4.07(s, 3H), 4.02(s, 3H), 2.57(s, 3H), 2.51(s, 3H).

Example Embodiment

[0041] Example 2
[0042] Referring to the method of Example 1, the acetyl chloride in Example 1 was replaced with palmitoyl chloride to obtain compound 2 (319 mg, 75%). 1 H NMR (300MHz, Chloroform-d) δ 12.67(s, 1H), 8.94(s, 1H), 7.32(s, 1H), 4.20(s, 3H), 4.06(s, 3H), 4.03(s, 3H), 2.83 (t, J=7.6Hz, 2H), 2.75 (t, J=7.5Hz, 2H), 1.91 (dt, J=14.3, 7.2Hz, 4H), 1.30 (d, J=8.3Hz, 54H), 0.90(t, J=6.3Hz, 6H).

Example Embodiment

[0043] Example 3
[0044]Referring to the method of Example 1, acetyl chloride in Example 1 was replaced with benzoyl chloride to obtain compound 3 (230 mg, 79%). 1 H NMR (300MHz, Chloroform-d) δ 12.74 (s, 1H), 8.96 (s, 1H), 8.47-8.11 (m, 4H), 7.95-6.91 (m, 7H), 4.21 (s, 3H), 4.01(s, 3H), 3.82(s, 3H).
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

no PUM

Description & Claims & Application Information

We can also present the details of the Description, Claims and Application information to help users get a comprehensive understanding of the technical details of the patent, such as background art, summary of invention, brief description of drawings, description of embodiments, and other original content. On the other hand, users can also determine the specific scope of protection of the technology through the list of claims; as well as understand the changes in the life cycle of the technology with the presentation of the patent timeline. Login to view more.
the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Similar technology patents

Black Trisazo Dyes, Their Preparation And Their Use

ActiveUS20170335110A1Excellent solubilityExcellent ozone fastnessInksTrisazo dyesOrganic chemistry
Owner:LANXESS DEUTDCHLAND GMBH

Uncharged pyrenyloxy sulfonamide dyes for conjugation with biomolecules

InactiveUS20170210904A1Excellent solubilityFluorescence/phosphorescencePyrene dyesIonAzide
Owner:GENE TOOLS

Classification and recommendation of technical efficacy words

  • Excellent solubility
  • Good effect

Ultraviolet absorber

ActiveUS20100239508A1Excellent solubilityMaintain relatively longCosmetic preparationsOrganic chemistrySolubilityAbsorptive capacity
Owner:LEAD CHEM

Highly basic ionomers and membranes and anion/hydroxide exchange fuel cells comprising the ionomers and membranes

InactiveUS20110237690A1Excellent solubilityHigh ionic conductivityIon-exchanger regenerationAnion exchangersIonChemistry
Owner:RGT UNIV OF CALIFORNIA

Hyperlipemia therapeutic agent

ActiveUS20050187292A1Good effectBiocideMetabolism disorderEPA - Eicosapentaenoic acidHyperlipidemia
Owner:KOWA CO LTD +1
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products