Application of diosgenin-3-site derivative

A technology of diosgenin and derivatives, which is applied in the field of diosgenin-3-position derivatives, can solve the problem of drugs for neovascular ophthalmopathy without convenient eye-drop administration, high treatment cost and large molecular weight, which cannot penetrate the fundus of the eyes Issues such as drug efficacy

Active Publication Date: 2015-02-04
SICHUAN JINGHUACHUANG BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] In recent years, "intravitreal injection" technology has become the focus of minimally invasive treatment of neovascular eye diseases, which has the advantage of good curative effect. However, due to the large molecular weight, the protein molecular drugs currently used cannot exert their drug effects through the fundus, and can only pass through the vitreous cavity. Intra-injection administration method, high treatment cost, multiple complications, and high risk
So far, no small-molecule drugs for the treatment of neovascular-related eye diseases have been found, and there is no convenient way of eye drop administration to treat drugs that inhibit neovascular eye diseases

Method used

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  • Application of diosgenin-3-site derivative
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  • Application of diosgenin-3-site derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Preparation of Example 1 Compound 4 (ZG-1 for short)

[0056]

[0057] a. N-tert-butoxycarbonyl-6-aminocaproic acid diosgenin ester

[0058]Diosgenin (12.5g), compound 2 (7.0g) and a catalytic amount of DMAP were dissolved in anhydrous dichloromethane, and an appropriate amount of EDC was added to react for 6 hours at room temperature. The filtrate was successively washed with dilute sodium chloride solution, saturated sodium bicarbonate solution and water, dried over anhydrous sodium sulfate, and separated on a silica gel column (petroleum ether / ethyl acetate 12:1) to obtain the white solid compound 3N-tert-butoxycarbonyl- Diosgenin 6-aminocaproate (15.2g, 80%). 1 H NMR (400MHz, CDCl3) δ5.37(d, J=4.3Hz, 1H), 4.67–4.50(m, 2H), 4.41(dd, J=15.0, 7.4Hz, 1H), 3.67(s, 1H) ,3.53–3.43(m,1H),3.37(t,J=10.9Hz,1H),3.11(d,J=6.3Hz,2H),2.38–2.21(m,4H),2.08–1.91(m,2H ), 1.04(s,3H), 0.97(d,J=6.9Hz,3H),0.79(d,J=3.5Hz,6H).

[0059] b. 6-aminocaproic acid diosgenin ester

[0060] ...

Embodiment 2

[0061] Preparation of Example 2 Compound 9 (ZG-4 for short)

[0062]

[0063] Referring to the method in Example 1, the amino acid raw materials for the reaction were changed to obtain Compound 9. 1 H NMR (400MHz,MeOD)δ5.33(d,J=5.0Hz,1H),4.67–4.49(m,1H),4.30(dd,J=14.6,7.6Hz,1H),3.85(t,J= 6.4Hz, 1H), 3.39–3.30(m, 1H), 2.93–2.76(m, 2H), 2.41–2.20(m, 2H).

Embodiment 3

[0064] The preparation method of embodiment 3 compound 14 (abbreviated as ZG-3)

[0065]

[0066] a. N-tert-butoxycarbonyl-6-aminocaprylic acid diosgenin ester

[0067] Diosgenin dios (4.14g), compound 12 (2.59g), and DMAP (244mg) were dissolved in anhydrous dichloromethane, and DCC (2.48g) was added at room temperature to react overnight, and filtered. The filtrate was successively washed with dilute sodium chloride solution, saturated sodium bicarbonate solution and water, dried over anhydrous sodium sulfate, and separated on a silica gel column (petroleum ether / ethyl acetate 10:1) to obtain the white solid compound 13N-tert-butoxycarbonyl- 8-aminocaprylic acid diosgenin ester. 1 H NMR (400MHz, CDCl 3 )δ5.30(d,J=5.0Hz,1H),4.60–4.46(m,1H),4.34(dd,J=14.9,7.5Hz,1H),3.44–3.36(m,1H),3.30(t ,J=10.9Hz,1H),3.02(t,J=7.0Hz,2H),2.30–2.14(m,4H),1.98–1.86(m,2H),0.72(t,J=3.1Hz,6H) .

[0068] b. 8-aminocaprylic acid diosgenin ester

[0069] Compound 13 (5.25 g) was dissolved in di...

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Abstract

The invention provides an application of a diosgenin-3-site derivative shown as formula I in preparing an inhibitor for treating angiogenesis. In the formula I, R1 represents an amino linear fatty acid group or amino acid residue; R2 represents H or R3(CO)- or an acceptable salts thereof; and R3 represents H, C1-C4 alkyl or phenyl. Research results show that the diosgenin derivative shown as the formula I has a good inhibition activity for angiogenesis, and can effectively inhibit abnormal proliferation of blood vessels of eyes. Besides, the derivative has no obvious stimulation to eyes and provides novel selection for clinical medication. The formula I is shown in the description.

Description

technical field [0001] The invention relates to the use of a diosgenin-3-position derivative. Background technique [0002] Neovascular eye diseases include age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, neovascular glaucoma, and pathological myopia. Neovascularization is the pathological basis and important clinical manifestation of many eye diseases, and it is the end stage of many eye diseases. It can occur in various eye tissues such as cornea, iris, choroid and retina, and is an important blinding eye disease. Iris, retina, and choroidal neovascularization can cause increased intraocular pressure, vitreous hemorrhage, subretinal hemorrhage, and traction retinal detachment, which can cause severe eye pain and endanger the vision of the affected eye. [0003] In recent years, "intravitreal injection" technology has become the focus of minimally invasive treatment of neovascular eye diseases, which has the advan...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/58A61P27/02A61P27/06A61P27/10
CPCA61K9/0019A61K9/0048A61K9/08A61K31/58A61K2300/00
Inventor 黄文
Owner SICHUAN JINGHUACHUANG BIOTECH
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