CN103058922B - 用于抗肿瘤药物的芳香脲的晶型及其制备方法 - Google Patents
用于抗肿瘤药物的芳香脲的晶型及其制备方法 Download PDFInfo
- Publication number
- CN103058922B CN103058922B CN201210326319.4A CN201210326319A CN103058922B CN 103058922 B CN103058922 B CN 103058922B CN 201210326319 A CN201210326319 A CN 201210326319A CN 103058922 B CN103058922 B CN 103058922B
- Authority
- CN
- China
- Prior art keywords
- phenyl
- crystal form
- urea
- formamyl
- trifluoromethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 57
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title claims abstract description 47
- 239000004202 carbamide Substances 0.000 title claims abstract description 47
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 239000002246 antineoplastic agent Substances 0.000 title abstract description 4
- 229940041181 antineoplastic drug Drugs 0.000 title abstract description 4
- 125000003118 aryl group Chemical group 0.000 title abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 88
- 150000001875 compounds Chemical class 0.000 claims abstract description 40
- 239000001301 oxygen Substances 0.000 claims description 43
- 229910052760 oxygen Inorganic materials 0.000 claims description 43
- 239000012453 solvate Substances 0.000 claims description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 claims description 7
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 108091000080 Phosphotransferase Proteins 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 102000020233 phosphotransferase Human genes 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 3
- 230000012010 growth Effects 0.000 claims description 3
- 238000001228 spectrum Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 238000010992 reflux Methods 0.000 claims description 2
- 230000000630 rising effect Effects 0.000 claims description 2
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims 2
- 238000001816 cooling Methods 0.000 claims 1
- 238000002441 X-ray diffraction Methods 0.000 abstract description 8
- 239000000843 powder Substances 0.000 abstract 2
- 206010028980 Neoplasm Diseases 0.000 description 8
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 5
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
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- 201000011510 cancer Diseases 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000001291 vacuum drying Methods 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- 238000010583 slow cooling Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 108010051742 Platelet-Derived Growth Factor beta Receptor Proteins 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 208000033781 Thyroid carcinoma Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
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- 230000007423 decrease Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 229940034785 sutent Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229940055725 xarelto Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
Claims (6)
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210326319.4A CN103058922B (zh) | 2012-09-06 | 2012-09-06 | 用于抗肿瘤药物的芳香脲的晶型及其制备方法 |
PCT/CN2013/082986 WO2014036953A1 (zh) | 2012-09-06 | 2013-09-05 | 用于抗肿瘤药物的芳香脲的晶型及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210326319.4A CN103058922B (zh) | 2012-09-06 | 2012-09-06 | 用于抗肿瘤药物的芳香脲的晶型及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103058922A CN103058922A (zh) | 2013-04-24 |
CN103058922B true CN103058922B (zh) | 2014-07-16 |
Family
ID=48101856
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201210326319.4A Expired - Fee Related CN103058922B (zh) | 2012-09-06 | 2012-09-06 | 用于抗肿瘤药物的芳香脲的晶型及其制备方法 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN103058922B (zh) |
WO (1) | WO2014036953A1 (zh) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103058922B (zh) * | 2012-09-06 | 2014-07-16 | 湖南有色凯铂生物药业有限公司 | 用于抗肿瘤药物的芳香脲的晶型及其制备方法 |
CN104288147A (zh) * | 2013-07-17 | 2015-01-21 | 湖南有色凯铂生物药业有限公司 | 芳香脲类化合物在制备治疗实体瘤药物中的用途 |
ITMI20131856A1 (it) * | 2013-11-08 | 2015-05-09 | Gnosis Spa | Processo per la preparazione di differenti forme cristalline del s-acetil glutatione e loro utilizzi in formulazioni farmaceutiche e nutraceutiche |
CN112159351B (zh) * | 2020-09-21 | 2021-12-07 | 广州南鑫药业有限公司 | 一种多靶点抗肿瘤药物的制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011130728A1 (en) * | 2010-04-17 | 2011-10-20 | Bayer Healthcare Llc | Synthetic metabolites of fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention diseases and conditions |
CN102643229A (zh) * | 2012-01-17 | 2012-08-22 | 湖南有色凯铂生物药业有限公司 | N-((4-氯-3-三氟甲基)苯基)-n’-((2-氟-4-(2-氨基甲酰基)-4-吡啶基氧)苯基)脲及其作为抗癌药物的应用 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130183268A1 (en) * | 2010-07-19 | 2013-07-18 | Bayer Healthcare Llc | Drug combinations with fluoro-substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions |
CN103058922B (zh) * | 2012-09-06 | 2014-07-16 | 湖南有色凯铂生物药业有限公司 | 用于抗肿瘤药物的芳香脲的晶型及其制备方法 |
-
2012
- 2012-09-06 CN CN201210326319.4A patent/CN103058922B/zh not_active Expired - Fee Related
-
2013
- 2013-09-05 WO PCT/CN2013/082986 patent/WO2014036953A1/zh active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011130728A1 (en) * | 2010-04-17 | 2011-10-20 | Bayer Healthcare Llc | Synthetic metabolites of fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention diseases and conditions |
CN102643229A (zh) * | 2012-01-17 | 2012-08-22 | 湖南有色凯铂生物药业有限公司 | N-((4-氯-3-三氟甲基)苯基)-n’-((2-氟-4-(2-氨基甲酰基)-4-吡啶基氧)苯基)脲及其作为抗癌药物的应用 |
Also Published As
Publication number | Publication date |
---|---|
CN103058922A (zh) | 2013-04-24 |
WO2014036953A1 (zh) | 2014-03-13 |
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SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C56 | Change in the name or address of the patentee |
Owner name: HUNAN NANXIN PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: HUNAN CHEMBIO PHARMACY CO., LTD. |
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CP01 | Change in the name or title of a patent holder |
Address after: 410329 national biological industry base of Hunan, Changsha Patentee after: Hunan Nanxin Pharmaceutical Co.,Ltd. Address before: 410329 national biological industry base of Hunan, Changsha Patentee before: HUNAN NONFERROUS METALS GROUP CHEMBIO PHARMACY Co.,Ltd. |
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C41 | Transfer of patent application or patent right or utility model | ||
TR01 | Transfer of patent right |
Effective date of registration: 20160613 Address after: 410329 national biological industry base of Hunan, Changsha Patentee after: Hunan Nanxin Pharmaceutical Co.,Ltd. Patentee after: GUANGZHOU NANXIN PHARMACEUTICAL Co.,Ltd. Address before: 410329 national biological industry base of Hunan, Changsha Patentee before: Hunan Nanxin Pharmaceutical Co.,Ltd. |
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CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: 410000 Huanyuan South Road, Changsha National biological industry base, Hunan Province Co-patentee after: GUANGZHOU NANXIN PHARMACEUTICAL Co.,Ltd. Patentee after: Hunan Nanxin Pharmaceutical Co.,Ltd. Address before: 410329 national biological industry base of Hunan, Changsha Co-patentee before: GUANGZHOU NANXIN PHARMACEUTICAL Co.,Ltd. Patentee before: Hunan Nanxin Pharmaceutical Co.,Ltd. |
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CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140716 |