CN105777723A - Quinazoline derivative B crystal form, preparation method and application thereof - Google Patents
Quinazoline derivative B crystal form, preparation method and application thereof Download PDFInfo
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- CN105777723A CN105777723A CN201410822783.1A CN201410822783A CN105777723A CN 105777723 A CN105777723 A CN 105777723A CN 201410822783 A CN201410822783 A CN 201410822783A CN 105777723 A CN105777723 A CN 105777723A
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Abstract
The invention discloses a quinazoline derivative B crystal form, a preparation method and application thereof. Specifically, the XRPD atlas of the quinazoline derivative B crystal form has diffraction peaks at the position of 2theta=7.22, 10.58, 13.76, 14.479, 15.081, 16.201, 19.8, 21.241, 23.06, 25.72, 26.389, and 29.82, wherein the error range of the 2theta is 0.2. The quinazoline derivative B crystal form provided by the invention has good high temperature and high humidity illumination stability, and is very suitable for application in drugs treating angiogenesis related diseases.
Description
Technical field
The present invention relates to the medicine for the treatment of and blood vessel generation relevant disease, be specifically related to quinazoline derivant B crystal form and its preparation method and application.
Background technology
Bad or pathologic blood vessel generation can cause that the vascular nutrition pathological tissue of new life destroys normal structure, thus causing the diseases such as tumor, age related macular degeneration or chronic inflammatory disease, such as in tumor, new vessels can make tumor cell enter into blood circulation, thus invading other normal structures.In above-mentioned disease, tumor includes but are not limited to pulmonary carcinoma, colon cancer, breast carcinoma, ovarian cancer, carcinoma of prostate, gastric cancer and leukemia etc.；Chronic inflammation disease includes but are not limited to ulcerative colitis, systemic lupus erythematosus (sle), diabetes, psoriasis etc..
VEGF (VascularEndothelialGrowthFactor, and receptor VEGF), as (KinaseinsertDomain-containingReceptor, KDR) containing kinase insert domain receptor together form a critically important angiogenesis approach.Research shows, by suppressing KDR to may result in the apoptosis of endotheliocyte, thus suppressing the formation that blood vessel occurs.Therefore can there is the preparation of relevant disease in KDR inhibitor as treatment to blood vessel.
Quinazoline derivant, chemical name 6-(6,7-dimethoxyquinazoline-4-base oxygen base)-N, 2-dimethyl benzofuran-3-Methanamide, is a kind of effective KDR inhibitor, is widely used in treating the disease relevant to blood vessel generation.Chinese invention patent CN101575333 (number of patent application: 200810037240.3) discloses a kind of quinazoline derivant and medical usage thereof.It is well known, however, that same medicine, crystal formation is different, and its stability, mobility and compressibility are likely to and have difference, and the application of medicine can be produced certain impact by these physicochemical properties.And above-mentioned patent is not directed to the crystal formation of quinazoline derivant, therefore, the novel crystal forms of research and development quinazoline derivant, the physicochemical property to improve quinazoline derivant has very important significance.
Summary of the invention
How problem to be solved by this invention is by the problem of the physicochemical property of raising quinazoline derivant.
In order to solve above-mentioned technical problem, the technical solution adopted in the present invention is to provide a kind of quinazoline derivant B crystal form, its XRPD collection of illustrative plates in 2 θ=7.22,10.58,13.76,14.479,15.081,16.201,19.8,21.241,23.06,25.72,26.389,29.82 places have diffraction maximum, wherein 2 θ value range of error are 0.2.
In above-mentioned quinazoline derivant B crystal form, its XRPD collection of illustrative plates is as shown in Figure 1.
In above-mentioned quinazoline derivant B crystal form, the molecular structural formula of described quinazoline derivant B crystal form is:
Present invention also offers a kind of method preparing above-mentioned quinazoline derivant B crystal form, comprise the following steps: weigh the N that 500 milligrams of quinazoline derivant powder are dissolved in 30 milliliters, in dinethylformamide, it is slowly added to pure water to there being a small amount of solid to precipitate out stopping, after standing 12 hours, filter, the obtained white powder of vacuum drying is quinazoline derivant B crystal form.
Present invention also offers the application in the medicine of preparation and blood vessel generation relevant disease of the above-mentioned quinazoline derivant B crystal form.
In above-mentioned application, described is tumor, age related macular degeneration or chronic inflammatory disease with blood vessel generation relevant disease.
In above-mentioned application, described tumor is pulmonary carcinoma, colon cancer, breast carcinoma, ovarian cancer, carcinoma of prostate, gastric cancer or leukemia.
In above-mentioned application, described chronic inflammation disease is ulcerative colitis, systemic lupus erythematosus (sle), diabetes or psoriasis.
Quinazoline derivant B crystal form provided by the invention, has good high temperature, high humidity and light durability, is highly suitable for application in the treatment medicine with blood vessel generation relevant disease.
Accompanying drawing explanation
Fig. 1 is the XRPD collection of illustrative plates of quinazoline derivant B crystal form provided by the invention；
Fig. 2 is the XRPD collection of illustrative plates of quinazoline derivant B crystal form high-temperature stability provided by the invention test；
Fig. 3 is the XRPD collection of illustrative plates of quinazoline derivant B crystal form high humidity stability test provided by the invention；
Fig. 4 is the XRPD collection of illustrative plates of quinazoline derivant B crystal form light durability provided by the invention test.
Detailed description of the invention
The invention discloses a kind of quinazoline derivant B crystal form and its preparation method and application, wherein quinazoline derivant B crystal form has good high temperature, high humidity and light durability, is highly suitable for application in the treatment medicine with blood vessel generation relevant disease.Below in conjunction with Figure of description, the present invention is described in detail.
As shown in Figure 1, quinazoline derivant B crystal form provided by the invention, its XRPD collection of illustrative plates in 2 θ=7.22,10.58,13.76,14.479,15.081,16.201,19.8,21.241,23.06,25.72,26.389,29.82 places have diffraction maximum, wherein 2 θ value range of error are 0.2.
The molecular structural formula of above-mentioned quinazoline derivant B crystal form is:
The preparation method of the above-mentioned quinazoline derivant B crystal form that present invention also offers, comprises the following steps:
Weighing 500 milligrams of quinazoline derivant powder to be dissolved in the DMF of 30 milliliters, be slowly added to pure water and stop to there being a small amount of solid to precipitate out, after standing 12 hours, filtration, the obtained white powder of vacuum drying are quinazoline derivant B crystal form.
Wherein, the purity level of DMF is analytical pure rank.
Above-mentioned quinazoline derivant B crystal form provided by the invention, can be used for the medicine of preparation treatment and blood vessel generation relevant disease, wherein: tumor includes but not limited to pulmonary carcinoma, colon cancer, breast carcinoma, ovarian cancer, carcinoma of prostate, gastric cancer and leukemia etc..Chronic inflammation disease includes but not limited to ulcerative colitis, systemic lupus erythematosus (sle), diabetes or psoriasis etc..
Quinazoline derivant B crystal form provided by the invention has good high-temperature stability, high humidity stability and light durability, and specific experiment result is as follows:
(1) high-temperature stability is investigated.
Being placed in 60 DEG C of baking ovens by quinazoline derivant B crystal form sample, taken out by sample and carry out XRPD test after 5 days, test result is as in figure 2 it is shown, show by the comparative result of Fig. 1 and Fig. 2, and quinazoline derivant B crystal form has good high-temperature stability.
(2) high humidity stability.
Being placed under 92.5% damp condition by quinazoline derivant B crystal form sample, taken out by sample and carry out XRPD test after 5 days, test result is as it is shown on figure 3, show by the comparative result of Fig. 1 and Fig. 3, and quinazoline derivant B crystal form has good high humidity stability.
(3) light durability.
Being placed under 4500lux intensity of illumination by quinazoline derivant B crystal form sample, taken out by sample and carry out XRPD test after 5 days, test result as shown in Figure 4, is shown by the comparative result of Fig. 1 and Fig. 4, and quinazoline derivant B crystal form has good light durability.
The present invention is not limited to above-mentioned preferred forms, and anyone should learn the structure change made under the enlightenment of the present invention, and every have same or like technical scheme with the present invention, each falls within protection scope of the present invention.
Claims (8)
1. quinazoline derivant B crystal form, it is characterized in that, its XRPD collection of illustrative plates in 2 θ=7.22,10.58,13.76,14.479,15.081,16.201,19.8,21.241,23.06,25.72,26.389,29.82 places have diffraction maximum, wherein 2 θ value range of error are 0.2.
2. quinazoline derivant B crystal form as claimed in claim 1, it is characterised in that its XRPD collection of illustrative plates is as shown in Figure 1.
3. quinazoline derivant B crystal form as claimed in claim 1, it is characterised in that the molecular structural formula of described quinazoline derivant B crystal form is:
4. the method preparing quinazoline derivant B crystal form as claimed in claim 1, it is characterized in that, comprise the following steps: weigh the N that 500 milligrams of quinazoline derivant powder are dissolved in 30 milliliters, in dinethylformamide, it is slowly added to pure water to there being a small amount of solid to precipitate out stopping, after standing 12 hours, filter, the obtained white powder of vacuum drying is quinazoline derivant B crystal form.
5. the application in the medicine of preparation and blood vessel generation relevant disease of the quinazoline derivant B crystal form as described in claim 1,2 or 3.
6. apply as claimed in claim 5, it is characterised in that described is tumor, age related macular degeneration or chronic inflammatory disease with blood vessel generation relevant disease.
7. apply as claimed in claim 6, it is characterised in that described tumor is pulmonary carcinoma, colon cancer, breast carcinoma, ovarian cancer, carcinoma of prostate, gastric cancer or leukemia.
8. apply as claimed in claim 6, it is characterised in that described chronic inflammation disease is ulcerative colitis, systemic lupus erythematosus (sle), diabetes or psoriasis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410822783.1A CN105777723A (en) | 2014-12-22 | 2014-12-22 | Quinazoline derivative B crystal form, preparation method and application thereof |
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| CN201410822783.1A CN105777723A (en) | 2014-12-22 | 2014-12-22 | Quinazoline derivative B crystal form, preparation method and application thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113038938A (en) * | 2018-11-15 | 2021-06-25 | 和记黄埔医药（上海）有限公司 | Fuquintinib pharmaceutical preparation and application thereof |
| US11236077B2 (en) | 2018-03-30 | 2022-02-01 | Hangzhou Solipharma Co., Ltd. | Fruquintinib eutectic crystal, preparation method therefor, composition, and uses thereof |
| WO2024023796A1 (en) * | 2022-07-29 | 2024-02-01 | Macfarlan Smith Limited | Polymorphs, co-crystals and solvates of fruquintinib, processes for the preparation and use thereof |
-
2014
- 2014-12-22 CN CN201410822783.1A patent/CN105777723A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11236077B2 (en) | 2018-03-30 | 2022-02-01 | Hangzhou Solipharma Co., Ltd. | Fruquintinib eutectic crystal, preparation method therefor, composition, and uses thereof |
| CN113038938A (en) * | 2018-11-15 | 2021-06-25 | 和记黄埔医药（上海）有限公司 | Fuquintinib pharmaceutical preparation and application thereof |
| CN113038938B (en) * | 2018-11-15 | 2023-12-15 | 和记黄埔医药（上海）有限公司 | Pharmaceutical preparation of furquitinib and application thereof |
| WO2024023796A1 (en) * | 2022-07-29 | 2024-02-01 | Macfarlan Smith Limited | Polymorphs, co-crystals and solvates of fruquintinib, processes for the preparation and use thereof |
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Application publication date: 20160720 |