FI97472B - Förfarande för framställning av terapeutiskt användbara rapamycinderivat som anti-inflammatoriska och antifungalamedel - Google Patents
Förfarande för framställning av terapeutiskt användbara rapamycinderivat som anti-inflammatoriska och antifungalamedel Download PDFInfo
- Publication number
- FI97472B FI97472B FI921893A FI921893A FI97472B FI 97472 B FI97472 B FI 97472B FI 921893 A FI921893 A FI 921893A FI 921893 A FI921893 A FI 921893A FI 97472 B FI97472 B FI 97472B
- Authority
- FI
- Finland
- Prior art keywords
- rapamycin
- preparation
- pharmaceutically acceptable
- reduced
- inflammatory
- Prior art date
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- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical class C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims description 18
- 238000002360 preparation method Methods 0.000 title claims description 13
- 230000008569 process Effects 0.000 title claims description 10
- 229940121375 antifungal agent Drugs 0.000 title description 4
- 239000003429 antifungal agent Substances 0.000 title description 4
- 239000002260 anti-inflammatory agent Substances 0.000 title description 3
- 230000003110 anti-inflammatory effect Effects 0.000 title description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 title description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims abstract description 40
- 229960002930 sirolimus Drugs 0.000 claims abstract description 40
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims abstract description 11
- -1 sodium triacetoxyborohydride Chemical compound 0.000 claims abstract description 7
- 239000012321 sodium triacetoxyborohydride Substances 0.000 claims abstract description 7
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
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- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 3
- 241000222122 Candida albicans Species 0.000 description 3
- 229930105110 Cyclosporin A Natural products 0.000 description 3
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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- 241000699670 Mus sp. Species 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
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- 239000002552 dosage form Substances 0.000 description 2
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- 239000003937 drug carrier Substances 0.000 description 2
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- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
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- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
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- BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 1
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- UKJFVOWPUXSBOM-UHFFFAOYSA-N hexane;oxolane Chemical compound C1CCOC1.CCCCCC UKJFVOWPUXSBOM-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/18—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/01—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing oxygen
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Transplantation (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Claims (7)
1. Förfarande för framställning av terapeutiskt användbara rapamycinderivat med formeln I ,-CC HoSl·0 0 (I> OMe ry väri X, Y och Z vardera är -CO- eller -CHOH- och ätminsto-ne den ena av grupperna X och Z mäste vara -CHOH-, och när Y Sr -CHOH-, dä är X -CHOH-, eller farmaceutiskt godtagba- 20 ra salter därav, kännetecknat därav, att ra-pamycin reduceras med hjälp av ett lämpligt reduceringsme-del.
2. Förfarande enligt patentkrav 1 för framställning av 15-deoxo-15-hydroxirapamycin eller ett farmaceutiskt 25 godtagbart sait därav, kännetecknat därav, att rapamycin reduceras med hjälp av diisobutylaluminiumhyd-rid.
3. Förfarande enligt patentkrav 1 för framställning av 15,27-dideoxo-15,27-dihydroxirapamycin eller ett farma- 30 ceutiskt godtagbart sait därav, kännetecknat därav, att rapamycin reduceras med hjälp av diisobutylalu-miniumhydrid.
4. Förfarande enligt patentkrav 1 för framställning av 33-deoxo-33-hydroxirapamycin eller ett farmaceutiskt 35 godtagbart sait därav, kännetecknat därav, att II 17 97472 rapamycin reduceras med hjälp av natriumtriacetoxiborhyd- rid.
5. Förfarande enligt patentkrav 1 för framställning av 33-deoxo-33(R)-hydroxirapamycin eller ett farmaceutiskt 5 godtagbart salt därav, kännetecknat därav, att rapamycin reduceras med hjälp av natriumtriacetoxiborhyd-rid.
6. Förfarande enligt patentkrav 1 för framställning av 15,33-dideoxo-15,33-dihydroxirapamycin eller ett farma- 10 ceutiskt godtagbart salt därav, kännetecknat därav, att rapamycin reduceras först med hjälp av diisobu-tylaluminiumhydrid och sedan med hjälp av natriumtriace-toxiborhydrid.
7. Förfarande enligt patentkrav 1 för framställning 15 av 15,27,33-trideoxo-15,27,33-trihydroxirapamycin eller ett farmaceutiskt godtagbart sait därav, kännetecknat därav, att rapamycin reduceras först med hjälp av diisobutylaluminiumhydrid och sedan med hjälp av natriumtriacetoxiborhydrid. * «
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE146592A IE921465A1 (en) | 1991-05-07 | 1992-07-01 | Reduction products of rapamycin as immuno-suppressants,¹antiinflammatory of antifungal agents |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/696,692 US5102876A (en) | 1991-05-07 | 1991-05-07 | Reduction products of rapamycin |
| US69669291 | 1991-05-07 | ||
| US74171491 | 1991-08-07 | ||
| US07/741,714 US5138051A (en) | 1991-08-07 | 1991-08-07 | Rapamycin analogs as immunosuppressants and antifungals |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI921893A0 FI921893A0 (sv) | 1992-04-28 |
| FI921893L FI921893L (sv) | 1992-11-08 |
| FI97472B true FI97472B (sv) | 1996-09-13 |
| FI97472C FI97472C (sv) | 1996-12-27 |
Family
ID=27105845
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI921893A FI97472C (sv) | 1991-05-07 | 1992-04-28 | Förfarande för framställning av terapeutiskt användbara rapamycinderivat som anti-inflammatoriska och antifungalamedel |
Country Status (15)
| Country | Link |
|---|---|
| EP (1) | EP0512754B1 (sv) |
| JP (1) | JP3108192B2 (sv) |
| KR (1) | KR100230877B1 (sv) |
| AT (1) | ATE194352T1 (sv) |
| AU (1) | AU647616B2 (sv) |
| DE (1) | DE69231215T2 (sv) |
| DK (1) | DK0512754T3 (sv) |
| ES (1) | ES2147724T3 (sv) |
| FI (1) | FI97472C (sv) |
| GR (1) | GR3034033T3 (sv) |
| HU (1) | HU217868B (sv) |
| MX (1) | MX9202031A (sv) |
| NZ (1) | NZ242616A (sv) |
| PH (1) | PH30228A (sv) |
| PT (1) | PT512754E (sv) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5776943A (en) * | 1991-05-14 | 1998-07-07 | American Home Products Corporation | Rapamycin metabolites |
| US5118677A (en) * | 1991-05-20 | 1992-06-02 | American Home Products Corporation | Amide esters of rapamycin |
| GB9302567D0 (en) * | 1993-02-10 | 1993-03-24 | Smithkline Beecham Plc | Novel compound |
| CH686761A5 (de) | 1993-05-27 | 1996-06-28 | Sandoz Ag | Galenische Formulierungen. |
| JP3480624B2 (ja) | 1995-06-09 | 2003-12-22 | シャープ株式会社 | 強誘電体薄膜被覆基板、その製造方法、及びキャパシタ構造素子 |
| JP3133922B2 (ja) | 1995-06-09 | 2001-02-13 | シャープ株式会社 | 強誘電体薄膜被覆基板、その製造方法、及びキャパシタ構造素子 |
| EP0937082A2 (en) | 1996-07-12 | 1999-08-25 | Ariad Pharmaceuticals, Inc. | Materials and method for treating or preventing pathogenic fungal infection |
| GB9826882D0 (en) | 1998-12-07 | 1999-01-27 | Novartis Ag | Organic compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5023262A (en) | 1990-08-14 | 1991-06-11 | American Home Products Corporation | Hydrogenated rapamycin derivatives |
-
1992
- 1992-04-28 FI FI921893A patent/FI97472C/sv not_active IP Right Cessation
- 1992-04-28 JP JP04109579A patent/JP3108192B2/ja not_active Expired - Fee Related
- 1992-04-30 DK DK92303916T patent/DK0512754T3/da active
- 1992-04-30 DE DE69231215T patent/DE69231215T2/de not_active Expired - Fee Related
- 1992-04-30 AT AT92303916T patent/ATE194352T1/de not_active IP Right Cessation
- 1992-04-30 MX MX9202031A patent/MX9202031A/es unknown
- 1992-04-30 PT PT92303916T patent/PT512754E/pt unknown
- 1992-04-30 EP EP92303916A patent/EP0512754B1/en not_active Expired - Lifetime
- 1992-04-30 HU HU9201468A patent/HU217868B/hu not_active IP Right Cessation
- 1992-04-30 PH PH44299A patent/PH30228A/en unknown
- 1992-04-30 ES ES92303916T patent/ES2147724T3/es not_active Expired - Lifetime
- 1992-05-01 KR KR1019920007431A patent/KR100230877B1/ko not_active Expired - Fee Related
- 1992-05-05 NZ NZ24261692A patent/NZ242616A/en unknown
- 1992-05-05 AU AU16008/92A patent/AU647616B2/en not_active Ceased
-
2000
- 2000-07-27 GR GR20000401723T patent/GR3034033T3/el not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| FI97472C (sv) | 1996-12-27 |
| FI921893A0 (sv) | 1992-04-28 |
| DK0512754T3 (da) | 2000-09-18 |
| AU1600892A (en) | 1992-11-12 |
| GR3034033T3 (en) | 2000-11-30 |
| DE69231215D1 (de) | 2000-08-10 |
| HUT62589A (en) | 1993-05-28 |
| KR100230877B1 (ko) | 1999-11-15 |
| EP0512754A1 (en) | 1992-11-11 |
| AU647616B2 (en) | 1994-03-24 |
| DE69231215T2 (de) | 2000-11-09 |
| FI921893L (sv) | 1992-11-08 |
| PT512754E (pt) | 2000-11-30 |
| MX9202031A (es) | 1992-11-01 |
| JPH05117279A (ja) | 1993-05-14 |
| HU9201468D0 (en) | 1992-07-28 |
| HU217868B (hu) | 2000-04-28 |
| PH30228A (en) | 1997-02-05 |
| EP0512754B1 (en) | 2000-07-05 |
| KR920021553A (ko) | 1992-12-18 |
| NZ242616A (en) | 1994-07-26 |
| ES2147724T3 (es) | 2000-10-01 |
| ATE194352T1 (de) | 2000-07-15 |
| JP3108192B2 (ja) | 2000-11-13 |
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| Date | Code | Title | Description |
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| BB | Publication of examined application | ||
| MA | Patent expired |