PT98990A - Processo para a preparacao de esteres de acidos carboxilicos de rapamicina - Google Patents
Processo para a preparacao de esteres de acidos carboxilicos de rapamicina Download PDFInfo
- Publication number
- PT98990A PT98990A PT98990A PT9899091A PT98990A PT 98990 A PT98990 A PT 98990A PT 98990 A PT98990 A PT 98990A PT 9899091 A PT9899091 A PT 9899091A PT 98990 A PT98990 A PT 98990A
- Authority
- PT
- Portugal
- Prior art keywords
- carbon atoms
- alkyl
- rapamycin
- pharmaceutically acceptable
- acceptable salt
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 60
- 230000008569 process Effects 0.000 title claims description 37
- 238000002360 preparation method Methods 0.000 title claims description 8
- 150000001733 carboxylic acid esters Chemical class 0.000 title 1
- 125000004432 carbon atom Chemical group C* 0.000 claims description 144
- 229960002930 sirolimus Drugs 0.000 claims description 141
- 150000001875 compounds Chemical class 0.000 claims description 68
- -1 hydroxyphenylmethyl Chemical group 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 52
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound 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 claims description 49
- 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 description 47
- 150000003839 salts Chemical class 0.000 claims description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 34
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 28
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 24
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 19
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000001475 halogen functional group Chemical group 0.000 claims description 18
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 239000007983 Tris buffer Substances 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 239000004472 Lysine Substances 0.000 claims description 6
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 6
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
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- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 230000001506 immunosuppresive effect Effects 0.000 claims description 6
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- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- UGUBQKZSNQWWEV-UHFFFAOYSA-N 4-oxo-4-phenylmethoxybutanoic acid Chemical compound OC(=O)CCC(=O)OCC1=CC=CC=C1 UGUBQKZSNQWWEV-UHFFFAOYSA-N 0.000 claims description 5
- 206010052779 Transplant rejections Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- YRXIMPFOTQVOHG-UHFFFAOYSA-N 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound OC(=O)CN(C)C(=O)OC(C)(C)C YRXIMPFOTQVOHG-UHFFFAOYSA-N 0.000 claims description 4
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- HWBAHOVOSOAFLE-UHFFFAOYSA-N 2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(=O)NCC(O)=O HWBAHOVOSOAFLE-UHFFFAOYSA-N 0.000 claims description 3
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- 150000002431 hydrogen Chemical class 0.000 claims 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 3
- YGSRAYJBEREVRB-UHFFFAOYSA-N 5-[(2-methylpropan-2-yl)oxy]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid Chemical compound CC(C)(C)OC(=O)CCC(C(O)=O)NC(=O)OC(C)(C)C YGSRAYJBEREVRB-UHFFFAOYSA-N 0.000 claims 2
- LDRWTKQWSXGSTM-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxo-4-phenylmethoxybutanoic acid Chemical compound CC(C)(C)OC(=O)NC(CC(O)=O)C(=O)OCC1=CC=CC=C1 LDRWTKQWSXGSTM-UHFFFAOYSA-N 0.000 claims 1
- YMOYURYWGUWMFM-UHFFFAOYSA-N 5-[(2-methylpropan-2-yl)oxy]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid Chemical compound CC(C)(C)OC(=O)NC(CCC(O)=O)C(=O)OC(C)(C)C YMOYURYWGUWMFM-UHFFFAOYSA-N 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
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Classifications
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- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58483390A | 1990-09-19 | 1990-09-19 | |
| US58987890A | 1990-09-28 | 1990-09-28 | |
| US07/657,294 US5130307A (en) | 1990-09-28 | 1991-02-19 | Aminoesters of rapamycin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT98990A true PT98990A (pt) | 1992-08-31 |
Family
ID=27416444
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT98990A PT98990A (pt) | 1990-09-19 | 1991-09-17 | Processo para a preparacao de esteres de acidos carboxilicos de rapamicina |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0549727A1 (fr) |
| JP (1) | JPH06501012A (fr) |
| AU (1) | AU653175B2 (fr) |
| FI (1) | FI931203A7 (fr) |
| HU (1) | HUT65763A (fr) |
| IE (1) | IE913302A1 (fr) |
| MX (1) | MX9101139A (fr) |
| PT (1) | PT98990A (fr) |
| WO (1) | WO1992005179A1 (fr) |
Families Citing this family (181)
| Publication number | Priority date | Publication date | Assignee | Title |
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| DE69021833T2 (de) * | 1989-11-09 | 1996-03-21 | Sandoz Ag | Heteroatome enthaltende tricyclische Verbindungen. |
| NO921449L (no) * | 1991-04-17 | 1992-10-19 | American Home Prod | Karbamater av rapamycin |
| US5262533A (en) * | 1991-05-13 | 1993-11-16 | Merck & Co., Inc. | Amino O-aryl macrolides having immunosuppressive activity |
| US5565560A (en) * | 1991-05-13 | 1996-10-15 | Merck & Co., Inc. | O-Aryl,O-alkyl,O-alkenyl and O-alkynylmacrolides having immunosuppressive activity |
| US5247076A (en) * | 1991-09-09 | 1993-09-21 | Merck & Co., Inc. | Imidazolidyl macrolides having immunosuppressive activity |
| US5284877A (en) * | 1992-06-12 | 1994-02-08 | Merck & Co., Inc. | Alkyl and alkenyl macrolides having immunosuppressive activity |
| US5284840A (en) * | 1992-06-12 | 1994-02-08 | Merck & Co., Inc. | Alkylidene macrolides having immunosuppressive activity |
| DK0593227T3 (da) * | 1992-10-13 | 2006-05-01 | Wyeth Corp | Carbamater af rapamycin |
| US5262423A (en) * | 1992-10-29 | 1993-11-16 | American Home Products Corporation | Rapamycin arylcarbonyl and alkoxycarbonyl carbamates as immunosuppressive and antifungal agents |
| US5258389A (en) * | 1992-11-09 | 1993-11-02 | Merck & Co., Inc. | O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives |
| US5260300A (en) | 1992-11-19 | 1993-11-09 | American Home Products Corporation | Rapamycin carbonate esters as immuno-suppressant agents |
| US5310903A (en) * | 1993-03-05 | 1994-05-10 | Merck & Co., Inc. | Imidazolidyl rapamycin derivatives |
| US5310901A (en) * | 1993-03-05 | 1994-05-10 | Merck & Co., Inc. | O-heteroaryl, O-alkylheteroaryl, O-alkenylheteroaryl and O-alkynlheteroarylrapamycin derivatives |
| USRE40596E1 (en) * | 1993-04-08 | 2008-12-02 | Novartis Ag | Rapamycin assay |
| GB9307491D0 (en) * | 1993-04-08 | 1993-06-02 | Sandoz Ltd | Organic compounds |
| EP1181938B1 (fr) | 1993-04-23 | 2007-11-14 | Wyeth | Conjugués de Rapamycine et anticorps |
| US5504091A (en) * | 1993-04-23 | 1996-04-02 | American Home Products Corporation | Biotin esters of rapamycin |
| US7279561B1 (en) | 1993-04-23 | 2007-10-09 | Wyeth | Anti-rapamycin monoclonal antibodies |
| AU6711994A (en) * | 1993-04-23 | 1994-11-21 | American Home Products Corporation | Rapamycin conjugates and antibodies |
| JP4105761B2 (ja) * | 1993-11-19 | 2008-06-25 | アボット・ラボラトリーズ | ラパミシン（マクロライド）の半合成類似体免疫調節剤 |
| US5527907A (en) * | 1993-11-19 | 1996-06-18 | Abbott Laboratories | Macrolide immunomodulators |
| SG64372A1 (en) * | 1993-12-17 | 1999-04-27 | Novartis Ag | Rapamycin derivatives |
| US5389639A (en) * | 1993-12-29 | 1995-02-14 | American Home Products Company | Amino alkanoic esters of rapamycin |
| US5362718A (en) * | 1994-04-18 | 1994-11-08 | American Home Products Corporation | Rapamycin hydroxyesters |
| US5693648A (en) * | 1994-09-30 | 1997-12-02 | Merck & Co., Inc. | O-aryl, O-alkyl, O-alkenyl and O-alkynyl-macrolides having immunosuppressive activity |
| IL129547A (en) | 1994-10-26 | 2001-01-11 | Novartis Ag | Pharmaceutical compositions comprising a macrolide and an acid |
| US6187757B1 (en) | 1995-06-07 | 2001-02-13 | Ariad Pharmaceuticals, Inc. | Regulation of biological events using novel compounds |
| AU712193B2 (en) * | 1995-06-09 | 1999-10-28 | Novartis Ag | Rapamycin derivatives |
| US5780462A (en) * | 1995-12-27 | 1998-07-14 | American Home Products Corporation | Water soluble rapamycin esters |
| US6890546B2 (en) | 1998-09-24 | 2005-05-10 | Abbott Laboratories | Medical devices containing rapamycin analogs |
| US6015815A (en) * | 1997-09-26 | 2000-01-18 | Abbott Laboratories | Tetrazole-containing rapamycin analogs with shortened half-lives |
| US20030129215A1 (en) | 1998-09-24 | 2003-07-10 | T-Ram, Inc. | Medical devices containing rapamycin analogs |
| US7399480B2 (en) | 1997-09-26 | 2008-07-15 | Abbott Laboratories | Methods of administering tetrazole-containing rapamycin analogs with other therapeutic substances using medical devices |
| US8257726B2 (en) | 1997-09-26 | 2012-09-04 | Abbott Laboratories | Compositions, systems, kits, and methods of administering rapamycin analogs with paclitaxel using medical devices |
| US8394398B2 (en) | 1997-09-26 | 2013-03-12 | Abbott Laboratories | Methods of administering rapamycin analogs with anti-inflammatories using medical devices |
| US7378105B2 (en) | 1997-09-26 | 2008-05-27 | Abbott Laboratories | Drug delivery systems, kits, and methods for administering zotarolimus and paclitaxel to blood vessel lumens |
| US8057816B2 (en) | 1997-09-26 | 2011-11-15 | Abbott Laboratories | Compositions and methods of administering paclitaxel with other drugs using medical devices |
| US7357942B2 (en) | 1997-09-26 | 2008-04-15 | Abbott Laboratories | Compositions, systems, and kits for administering zotarolimus and paclitaxel to blood vessel lumens |
| US8257725B2 (en) | 1997-09-26 | 2012-09-04 | Abbott Laboratories | Delivery of highly lipophilic agents via medical devices |
| US7960405B2 (en) | 1998-09-24 | 2011-06-14 | Abbott Laboratories | Compounds and methods for treatment and prevention of diseases |
| US8257724B2 (en) | 1998-09-24 | 2012-09-04 | Abbott Laboratories | Delivery of highly lipophilic agents via medical devices |
| US7455853B2 (en) | 1998-09-24 | 2008-11-25 | Abbott Cardiovascular Systems Inc. | Medical devices containing rapamycin analogs |
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| Publication number | Publication date |
|---|---|
| HU9300776D0 (en) | 1993-06-28 |
| EP0549727A1 (fr) | 1993-07-07 |
| MX9101139A (es) | 1992-05-04 |
| AU8659991A (en) | 1992-04-15 |
| FI931203A0 (fi) | 1993-03-18 |
| WO1992005179A1 (fr) | 1992-04-02 |
| AU653175B2 (en) | 1994-09-22 |
| IE913302A1 (en) | 1992-02-25 |
| HUT65763A (en) | 1994-07-28 |
| FI931203A7 (fi) | 1993-03-18 |
| JPH06501012A (ja) | 1994-01-27 |
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