CN103304503A - Anti-diabetic compound, as well as preparation method and application thereof - Google Patents
Anti-diabetic compound, as well as preparation method and application thereof Download PDFInfo
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- CN103304503A CN103304503A CN2013102214246A CN201310221424A CN103304503A CN 103304503 A CN103304503 A CN 103304503A CN 2013102214246 A CN2013102214246 A CN 2013102214246A CN 201310221424 A CN201310221424 A CN 201310221424A CN 103304503 A CN103304503 A CN 103304503A
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 230000003178 anti-diabetic effect Effects 0.000 title description 2
- 239000003472 antidiabetic agent Substances 0.000 title description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 8
- 239000002253 acid Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 abstract 2
- 229940126033 PPAR agonist Drugs 0.000 abstract 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- 108010016731 PPAR gamma Proteins 0.000 description 8
- 102000000536 PPAR gamma Human genes 0.000 description 8
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 8
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- 239000008280 blood Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
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- 108010028924 PPAR alpha Proteins 0.000 description 6
- 102000023984 PPAR alpha Human genes 0.000 description 6
- 238000000605 extraction Methods 0.000 description 6
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- 150000003839 salts Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- NKOHRVBBQISBSB-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1CC1C(=O)NC(=O)S1 NKOHRVBBQISBSB-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- 229940122355 Insulin sensitizer Drugs 0.000 description 2
- 210000001789 adipocyte Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003614 peroxisome proliferator Substances 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- JUNAPQMUUHSYOV-UHFFFAOYSA-N 2-(2h-tetrazol-5-yl)acetic acid Chemical class OC(=O)CC=1N=NNN=1 JUNAPQMUUHSYOV-UHFFFAOYSA-N 0.000 description 1
- YRJHXVODUZSSOM-OAYGLCILSA-N CCOc1c(C[n]2nnnc2CC(O)=O)ccc(CNCC(CC(C2)C3)(CC2C2)CC3[C@@H]2O)c1 Chemical compound CCOc1c(C[n]2nnnc2CC(O)=O)ccc(CNCC(CC(C2)C3)(CC2C2)CC3[C@@H]2O)c1 YRJHXVODUZSSOM-OAYGLCILSA-N 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010015181 PPAR delta Proteins 0.000 description 1
- 108010044210 PPAR-beta Proteins 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 description 1
- 206010068676 Pneumoretroperitoneum Diseases 0.000 description 1
- 208000005727 Retropneumoperitoneum Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010612 desalination reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- -1 glitazone compound Chemical class 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 102000006255 nuclear receptors Human genes 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 238000012549 training Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (6)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN201310221424.6A CN103304503B (en) | 2013-06-02 | 2013-06-02 | Anti-diabetic compound, as well as preparation method and application thereof |
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CN201310221424.6A CN103304503B (en) | 2013-06-02 | 2013-06-02 | Anti-diabetic compound, as well as preparation method and application thereof |
Publications (2)
Publication Number | Publication Date |
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CN103304503A true CN103304503A (en) | 2013-09-18 |
CN103304503B CN103304503B (en) | 2015-03-04 |
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CN201310221424.6A Active CN103304503B (en) | 2013-06-02 | 2013-06-02 | Anti-diabetic compound, as well as preparation method and application thereof |
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CN (1) | CN103304503B (en) |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6492355B1 (en) * | 1999-04-09 | 2002-12-10 | Astrazeneca Ab | Adamantane derivatives |
US20050004178A1 (en) * | 2001-11-27 | 2005-01-06 | Arena Pharmaceuticals, Inc. | Human G protein-coupled receptors and modulators thereof for the treatment of metabolic-related disorders |
CN1727334A (en) * | 2005-07-27 | 2006-02-01 | 厦门大学 | Inhibitor of tricycro beta lactamase and preparation method |
CN101005857A (en) * | 2004-07-08 | 2007-07-25 | 诺和诺德公司 | Polypeptide protracting tags |
CN101027064A (en) * | 2004-07-29 | 2007-08-29 | 三共株式会社 | Medicinal composition containing diabetes therapeutic agent |
WO2007129195A2 (en) * | 2006-05-04 | 2007-11-15 | Pfizer Products Inc. | 4-pyrimidine-5-amino-pyrazole compounds |
CN101304745A (en) * | 2005-11-10 | 2008-11-12 | 拜耳医药保健股份公司 | Diaryl urea for treating diabetic neuropathy |
CN102186845A (en) * | 2008-10-17 | 2011-09-14 | 阿卡制药有限公司 | S1p receptors modulators and their use thereof |
WO2013052765A1 (en) * | 2011-10-07 | 2013-04-11 | Pisces Therapeutics Llc | Malignant and non-malignant disease treatment with ras antagonists |
-
2013
- 2013-06-02 CN CN201310221424.6A patent/CN103304503B/en active Active
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6492355B1 (en) * | 1999-04-09 | 2002-12-10 | Astrazeneca Ab | Adamantane derivatives |
US20050004178A1 (en) * | 2001-11-27 | 2005-01-06 | Arena Pharmaceuticals, Inc. | Human G protein-coupled receptors and modulators thereof for the treatment of metabolic-related disorders |
CN101005857A (en) * | 2004-07-08 | 2007-07-25 | 诺和诺德公司 | Polypeptide protracting tags |
CN101027064A (en) * | 2004-07-29 | 2007-08-29 | 三共株式会社 | Medicinal composition containing diabetes therapeutic agent |
CN1727334A (en) * | 2005-07-27 | 2006-02-01 | 厦门大学 | Inhibitor of tricycro beta lactamase and preparation method |
CN101304745A (en) * | 2005-11-10 | 2008-11-12 | 拜耳医药保健股份公司 | Diaryl urea for treating diabetic neuropathy |
WO2007129195A2 (en) * | 2006-05-04 | 2007-11-15 | Pfizer Products Inc. | 4-pyrimidine-5-amino-pyrazole compounds |
CN102186845A (en) * | 2008-10-17 | 2011-09-14 | 阿卡制药有限公司 | S1p receptors modulators and their use thereof |
WO2013052765A1 (en) * | 2011-10-07 | 2013-04-11 | Pisces Therapeutics Llc | Malignant and non-malignant disease treatment with ras antagonists |
Non-Patent Citations (1)
Title |
---|
KEES, KENNETH L.等: "Perfluoro-N-[4-(1H-tetraol-5-ylmethyl)phenyl]alanamides. A new class of oral antidiabetic agents", 《JOURNAL OF MEDICINAL CHEMISTRY》, vol. 32, no. 1, 31 December 1989 (1989-12-31), pages 11 - 13 * |
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Publication number | Publication date |
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CN103304503B (en) | 2015-03-04 |
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Legal Events
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SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CB03 | Change of inventor or designer information | ||
CB03 | Change of inventor or designer information |
Inventor after: Jing Biguo Inventor before: Zhang Yuanqiang |
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TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20170727 Address after: 443501 Hubei city of Yichang province Changyang Tujia Autonomous County town town village a group of clinkstone Patentee after: Jing Biguo Address before: 510640 Guangdong City, Tianhe District Province, No. five, road, public education building, unit 371-1, unit 2401 Patentee before: GUANGDONG GAOHANG INTELLECTUAL PROPERTY OPERATION Co.,Ltd. Effective date of registration: 20170727 Address after: 510640 Guangdong City, Tianhe District Province, No. five, road, public education building, unit 371-1, unit 2401 Patentee after: GUANGDONG GAOHANG INTELLECTUAL PROPERTY OPERATION Co.,Ltd. Address before: 528000, Science Park, No. 101 Middle Fenjiang Road, Chancheng District, Guangdong, Foshan, 303 Patentee before: Zhang Yuanqiang |
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Addressee: Zhang Yuanqiang Document name: Notification of Passing Examination on Formalities |
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Effective date of registration: 20180319 Address after: 102600, No. 3, building 2, building 4, Paradise Road, Beijing, Daxing District, 1, unit 317 Patentee after: BEIJING ZHITOUJIA INTELLECTUAL PROPERTY OPERATION CO.,LTD. Address before: 443501 Hubei city of Yichang province Changyang Tujia Autonomous County town town village a group of clinkstone Patentee before: Jing Biguo |
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Effective date of registration: 20181108 Address after: 210008 Hankou Road, Drum Tower District, Nanjing, Jiangsu Province, No. 22 Patentee after: Wei Deying Address before: 102600 3 floor, 2 building, No. 4 Daxing District Garden Road, Beijing, 1 unit 317 Patentee before: BEIJING ZHITOUJIA INTELLECTUAL PROPERTY OPERATION CO.,LTD. |
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Effective date of registration: 20190121 Address after: 102600 Beijing Daxing District Zhongguancun Science and Technology Park Daxing Biomedical Industry Base No. 22 Yongwang Road, 4 1-2 floors Patentee after: Beijing Yunpeng Pengcheng Pharmaceutical Technology Co.,Ltd. Address before: 210008 Hankou Road, Drum Tower District, Nanjing, Jiangsu Province, No. 22 Patentee before: Wei Deying |