Unlock instant, AI-driven research and patent intelligence for your innovation.

Method for preparing icatibant

A technology of substitution degree, -CTC, applied in the field of preparation of icatibant, can solve the problems of unsuitability for industrial production, low purity of icatibant, low application value, etc., and achieves considerable economic and practical value and low impurity content. , the effect of less input of raw materials

Active Publication Date: 2014-06-18
HYBIO PHARMA
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Yet the preparation method of existing icatibant still mainly continues to use about 1990, by the solid-phase synthesis method invented by Herchester AG of Germany, the icatibant product purity that this method makes is low, impurity content is high, Low yield, not suitable for industrial production, low application value

Method used

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

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for preparing icatibant

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1: the preparation of Fmoc-Arg (Pbf)-CTC resin

[0031] Add 11.1 g of 2-chlorotrityl chloride resin with a substitution degree of 0.9 mmol / g into the solid-phase reaction column, and add DMF to swell the resin for 30 minutes. Add 3.50mL DIPEA to 12.98g Fmoc-Arg(Pbf)-OH, activate for 5min, then add DMF swollen resin to react for 10min, then add 3.50mLDIPEA, react at room temperature for 45min, add methanol to block for 20min. Take out the reaction solution, wash 3 times with DMF, wash 3 times with DCM, and then shrink with methanol 3 times, the time of 3 times is 3min, 5min, 8min respectively, to obtain Fmoc-Arg(Pbf)-CTC resin, and the detection degree of substitution is 0.5 mmol / g.

Embodiment 2

[0032] Example 2: Coupling of Fmoc-Oic-OH

[0033] Weigh 10mmol of Fmoc-Arg(Pbf)-CTC resin into the solid phase reactor, swell with DMF for 0.5h, then use 20% DBLK to deprotect Fmoc twice, each time is 10min and 5min respectively, connect Fmoc after washing -Oic-OH. Dissolve 11.73g Fmoc-Oic-OH, 4.9g HOBt and 6.1mL DIC in DCM (a small amount of DMF can be added to aid dissolution), activate in an ice-water bath for 7min, then add to a solid-phase reactor, react at room temperature for 1-2h, and the reaction ends The ninhydrin method shall prevail. After the reaction, remove the reaction solution, wash with DMF, and remove the Fmoc protection twice with 20% DBLK for 10 min and 5 min each time, and prepare to couple the next amino acid after washing.

Embodiment 3

[0034] Example 3: Coupling of Fmoc-D-Cit-OH

[0035]Dissolve 11.91g of Fmoc-D-Cit-OH, 5.00g of HOAt and 11.4g of HATU in DCM (a small amount of DMF can be added to aid dissolution), add 3.87g of DIPEA in an ice-water bath and activate it for 7min, then add it to a solid-phase reactor and react at room temperature for 1 ~2h, the end point of the reaction is determined by the ninhydrin method. After the reaction, the reaction solution was removed, washed with DMF, and the Fmoc protection was removed with 20% DBLK, and the next amino acid was ready to be coupled after washing.

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 Login to View More

Abstract

The invention belongs to the technical field of pharmaceutical chemistry, and discloses a method for preparing icatibant. The method for preparing the icatibant comprises the following steps of: 1) preparing an Fmoc-Arg(Pbf)-CTC resin by using Fmoc-Arg(Pbf)-OH and a 2-chlorotrityl chloride resin with the substitution of 0.5-1.0mmol / g; 2) synthesizing an icatibant-CTC resin by using the Fmoc-Arg(Pbf)-CTC resin in a mode of coupling one by one; and 3) cracking the icatibant-CTC resin to obtain icatibant crude peptide, and purifying to obtain the icatibant. Compared with the prior art, the preparation method has the advantages of simple operation, low material input, low cost, high yield of the icatibant, and suitability for large-scale industrial production; and the prepared icatibant has high purity and low impurity content and has considerable economic practical value and wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method of icatibant. Background technique [0002] Hereditary angioedema (HAE), also known as C1 inhibitor deficiency, is a rare autosomal dominant disorder caused by a genetic defect caused by low levels or dysfunction of a protein called C1 inhibitor Yes, the incidence rate is 1 / 10000-1 / 50000. HAE is characterized by unpredictable episodic edema and swelling of the hands, feet, face, larynx, and abdomen, resulting in disfigurement, disability, or death. For example, swelling of the throat can lead to suffocation, and edema of the digestive tract can cause abdominal pain, nausea and vomiting. Patients with intestinal swelling often experience severe pain in the stomach, nausea and vomiting. Patients usually have a family history of the disease. HAE patients may experience rapid edema of the hands, feet, extremities, face, intestines, lary...

Claims

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

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07K7/06C07K1/20C07K1/06C07K1/04
Inventor 陈大来潘俊锋马亚平袁建成
Owner HYBIO PHARMA