CA2384433C - Novel betulinic acid derivatives having antiangiogenic activity, processes for producing such derivatives and their use for treating tumor associated angiogenesis - Google Patents
Novel betulinic acid derivatives having antiangiogenic activity, processes for producing such derivatives and their use for treating tumor associated angiogenesis Download PDFInfo
- Publication number
- CA2384433C CA2384433C CA002384433A CA2384433A CA2384433C CA 2384433 C CA2384433 C CA 2384433C CA 002384433 A CA002384433 A CA 002384433A CA 2384433 A CA2384433 A CA 2384433A CA 2384433 C CA2384433 C CA 2384433C
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- Prior art keywords
- betulinic acid
- derivatives
- acid derivatives
- derivative
- tumor associated
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- QGJZLNKBHJESQX-FZFNOLFKSA-N betulinic acid Chemical class C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C QGJZLNKBHJESQX-FZFNOLFKSA-N 0.000 title claims abstract description 76
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 16
- 230000033115 angiogenesis Effects 0.000 title claims abstract description 15
- 238000000034 method Methods 0.000 title abstract description 32
- 230000001772 anti-angiogenic effect Effects 0.000 title abstract description 10
- 239000000203 mixture Substances 0.000 claims description 24
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- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- INHDSJSGMCZSHA-UHFFFAOYSA-N n,n-bis(5-methyl-2-propan-2-ylcyclohexyl)formamide Chemical compound CC(C)C1CCC(C)CC1N(C=O)C1C(C(C)C)CCC(C)C1 INHDSJSGMCZSHA-UHFFFAOYSA-N 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN1999/000043 WO2001018029A1 (en) | 1999-09-09 | 1999-09-09 | Novel betulinic acid derivatives having antiangiogenic activity, processes for producing such derivatives and their use for treating tumor associated angiogenesis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2384433A1 CA2384433A1 (en) | 2001-03-15 |
| CA2384433C true CA2384433C (en) | 2007-10-23 |
Family
ID=11076668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002384433A Expired - Fee Related CA2384433C (en) | 1999-09-09 | 1999-09-09 | Novel betulinic acid derivatives having antiangiogenic activity, processes for producing such derivatives and their use for treating tumor associated angiogenesis |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP1218402B1 (enExample) |
| JP (1) | JP2003508543A (enExample) |
| KR (1) | KR100618100B1 (enExample) |
| CN (1) | CN1152046C (enExample) |
| AT (1) | ATE267837T1 (enExample) |
| AU (1) | AU780148B2 (enExample) |
| BR (1) | BR9917495A (enExample) |
| CA (1) | CA2384433C (enExample) |
| DE (1) | DE69917684T2 (enExample) |
| ES (1) | ES2224735T3 (enExample) |
| WO (1) | WO2001018029A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI1594885T1 (sl) | 2003-02-11 | 2009-06-30 | Novelix Pharmaceuticals Inc | Zdravilo za inhibiranje rasti tumorjev |
| RU2276980C1 (ru) * | 2005-03-01 | 2006-05-27 | Институт химии и химической технологии СО РАН (ИХХТ СО РАН) | Капилляроукрепляющее средство |
| US20090023698A1 (en) * | 2005-03-29 | 2009-01-22 | Krasutsky Pavel A | Methods of manufacturing bioactive 3-esters of betulinic aldehyde and betulinic acid |
| GB0604535D0 (en) | 2006-03-07 | 2006-04-12 | Sndv Sprl | Betulonic acid derivatives |
| CZ2008528A3 (cs) * | 2008-09-01 | 2009-11-18 | Univerzita Karlova v Praze, Prírodovedecká fakulta | Deriváty triterpenoidu pro lécbu nádorových onemocnení a farmaceutická kompozice je obsahující |
| KR101061911B1 (ko) * | 2009-04-01 | 2011-09-02 | 주식회사 페라온 | 페길레이션된 베튤린 유도체 및 그를 포함하는 화장료 조성물 |
| CN102603858B (zh) * | 2012-03-02 | 2014-07-02 | 东北林业大学 | 桦木醇的含氮杂环衍生物、制备方法及用途 |
| WO2014105926A1 (en) | 2012-12-31 | 2014-07-03 | Hetero Research Foundation | Novel betulinic acid proline derivatives as hiv inhibitors |
| CN104910239B (zh) * | 2014-03-14 | 2018-12-07 | 中国科学院上海药物研究所 | 五环三萜类化合物及其制备方法、药物组合物和用途 |
| US20170129916A1 (en) | 2014-06-26 | 2017-05-11 | Hetero Research Foundation | Novel betulinic proline imidazole derivatives as hiv inhibitors |
| MA40886B1 (fr) | 2015-02-09 | 2020-03-31 | Hetero Research Foundation | Nouveau triterpénone en c-3 avec des dérivés d'amide inverse en c-28 en tant qu'inhibiteurs du vih |
| WO2016147099A2 (en) | 2015-03-16 | 2016-09-22 | Hetero Research Foundation | C-3 novel triterpenone with c-28 amide derivatives as hiv inhibitors |
| CN109517022B (zh) | 2017-09-18 | 2022-09-13 | 中国科学院上海药物研究所 | 五环三萜类化合物及其制备方法、药物组合物和用途 |
| CN109700760B (zh) * | 2019-03-07 | 2021-04-06 | 南京中医药大学 | 一种白桦脂酸纳米混悬剂及其制备方法 |
| JP2023533557A (ja) * | 2020-07-07 | 2023-08-03 | 上海 インスティテュート オブ マテリア メディカ、チャイニーズ アカデミー オブ サイエンシーズ | 五環性トリテルペノイドｃ－グリコシド、その製造方法及び使用 |
| CN113135974B (zh) * | 2021-03-24 | 2022-05-06 | 广东工业大学 | 白桦脂醇衍生物及其在制备抗肿瘤药物中的应用 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1415601A (en) * | 1973-03-14 | 1975-11-26 | Biorex Laboratories Ltd | Dihydrobetulinic acid derivatives |
| JPS6417431A (en) * | 1987-07-13 | 1989-01-20 | Nec Corp | Manufacture of semiconductor integrated circuit device |
| JP2694048B2 (ja) * | 1991-05-09 | 1997-12-24 | 日立建機株式会社 | 建設機械の油圧駆動装置 |
| FR2683531B1 (fr) * | 1991-11-13 | 1993-12-31 | Rhone Poulenc Rorer Sa | Nouveaux derives du lupane, leur preparation et les compositions pharmaceutiques qui les contiennent. |
| US5869535A (en) * | 1995-03-21 | 1999-02-09 | The Board Of Trustees Of The University Of Illinois | Method and composition for selectively inhibiting melanoma |
| US5962527A (en) * | 1995-03-21 | 1999-10-05 | The Board Of Trustees Of The University Of Illinois | Method and composition for treating cancers |
| US5679828A (en) * | 1995-06-05 | 1997-10-21 | Biotech Research Labs, Inc. | Betulinic acid and dihydrobetulinic acid derivatives and uses therefor |
-
1999
- 1999-09-09 CN CNB998169404A patent/CN1152046C/zh not_active Expired - Fee Related
- 1999-09-09 AU AU20001/00A patent/AU780148B2/en not_active Ceased
- 1999-09-09 AT AT99963658T patent/ATE267837T1/de not_active IP Right Cessation
- 1999-09-09 BR BR9917495-2A patent/BR9917495A/pt not_active IP Right Cessation
- 1999-09-09 KR KR1020027003120A patent/KR100618100B1/ko not_active Expired - Fee Related
- 1999-09-09 EP EP99963658A patent/EP1218402B1/en not_active Expired - Lifetime
- 1999-09-09 JP JP2001522252A patent/JP2003508543A/ja active Pending
- 1999-09-09 DE DE69917684T patent/DE69917684T2/de not_active Expired - Fee Related
- 1999-09-09 ES ES99963658T patent/ES2224735T3/es not_active Expired - Lifetime
- 1999-09-09 CA CA002384433A patent/CA2384433C/en not_active Expired - Fee Related
- 1999-09-09 WO PCT/IN1999/000043 patent/WO2001018029A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| AU780148B2 (en) | 2005-03-03 |
| EP1218402B1 (en) | 2004-05-26 |
| WO2001018029A1 (en) | 2001-03-15 |
| EP1218402A1 (en) | 2002-07-03 |
| CA2384433A1 (en) | 2001-03-15 |
| CN1152046C (zh) | 2004-06-02 |
| DE69917684T2 (de) | 2005-07-21 |
| BR9917495A (pt) | 2002-06-11 |
| KR20020092908A (ko) | 2002-12-12 |
| ES2224735T3 (es) | 2005-03-01 |
| AU2000100A (en) | 2001-04-10 |
| JP2003508543A (ja) | 2003-03-04 |
| CN1373769A (zh) | 2002-10-09 |
| ATE267837T1 (de) | 2004-06-15 |
| DE69917684D1 (de) | 2004-07-01 |
| KR100618100B1 (ko) | 2006-08-29 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |