ES2452718T3 - Profármacos a base de lisina de inhibidores de la aspartil proteasa y procesos para su preparación - Google Patents
Profármacos a base de lisina de inhibidores de la aspartil proteasa y procesos para su preparación Download PDFInfo
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- ES2452718T3 ES2452718T3 ES06817683.3T ES06817683T ES2452718T3 ES 2452718 T3 ES2452718 T3 ES 2452718T3 ES 06817683 T ES06817683 T ES 06817683T ES 2452718 T3 ES2452718 T3 ES 2452718T3
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- 238000000034 method Methods 0.000 title claims description 67
- 230000008569 process Effects 0.000 title claims description 56
- 238000002360 preparation method Methods 0.000 title claims description 19
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- 239000004472 Lysine Substances 0.000 title description 16
- 239000003696 aspartic proteinase inhibitor Substances 0.000 title description 6
- 229940002612 prodrug Drugs 0.000 title description 4
- 239000000651 prodrug Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 266
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 195
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 135
- -1 methylenedioxy group Chemical group 0.000 claims abstract description 102
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 77
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 55
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 48
- 150000003839 salts Chemical class 0.000 claims abstract description 39
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- 229910052740 iodine Inorganic materials 0.000 claims abstract description 31
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 14
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 13
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 12
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 230000002194 synthesizing effect Effects 0.000 claims description 23
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 20
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- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 11
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- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
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- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 15
- 229910019142 PO4 Inorganic materials 0.000 description 15
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- QAHLFXYLXBBCPS-IZEXYCQBSA-N methyl n-[(2s)-1-[[(5s)-5-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-6-hydroxyhexyl]amino]-1-oxo-3,3-diphenylpropan-2-yl]carbamate Chemical compound C=1C=CC=CC=1C([C@H](NC(=O)OC)C(=O)NCCCC[C@@H](CO)N(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)C1=CC=CC=C1 QAHLFXYLXBBCPS-IZEXYCQBSA-N 0.000 description 15
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- 239000012279 sodium borohydride Substances 0.000 description 1
- JJICLMJFIKGAAU-UHFFFAOYSA-M sodium;2-amino-9-(1,3-dihydroxypropan-2-yloxymethyl)purin-6-olate Chemical compound [Na+].NC1=NC([O-])=C2N=CN(COC(CO)CO)C2=N1 JJICLMJFIKGAAU-UHFFFAOYSA-M 0.000 description 1
- RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000000954 titration curve Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- YFNGWGVTFYSJHE-UHFFFAOYSA-K trisodium;phosphonoformate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)C([O-])=O.OP(O)(=O)C([O-])=O.OP(O)(=O)C([O-])=O YFNGWGVTFYSJHE-UHFFFAOYSA-K 0.000 description 1
- 238000007039 two-step reaction Methods 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US74064205P | 2005-11-30 | 2005-11-30 | |
| US740642P | 2005-11-30 | ||
| PCT/CA2006/001963 WO2007062526A1 (en) | 2005-11-30 | 2006-11-30 | Lysine-based prodrugs of aspartyl protease inhibitors and processes for their preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2452718T3 true ES2452718T3 (es) | 2014-04-02 |
Family
ID=38091843
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06817683.3T Active ES2452718T3 (es) | 2005-11-30 | 2006-11-30 | Profármacos a base de lisina de inhibidores de la aspartil proteasa y procesos para su preparación |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US8227450B2 (enExample) |
| EP (1) | EP1971615B1 (enExample) |
| JP (1) | JP2009517412A (enExample) |
| CN (1) | CN101405293B (enExample) |
| AU (1) | AU2006319716B2 (enExample) |
| CA (1) | CA2632095A1 (enExample) |
| ES (1) | ES2452718T3 (enExample) |
| WO (1) | WO2007062526A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10149030A1 (de) | 2001-10-05 | 2003-04-10 | Viscum Ag | Stabile galenische gefriergetrocknete Arzneimittelzubereitung von rViscumin |
| US7388008B2 (en) | 2004-08-02 | 2008-06-17 | Ambrilia Biopharma Inc. | Lysine based compounds |
| JP2009517412A (ja) | 2005-11-30 | 2009-04-30 | アンブリリア バイオファーマ インコーポレイテッド | アスパルチルプロテアーゼ阻害物質のリジンベースのプロドラッグ及びその調製方法 |
| AU2007287353A1 (en) * | 2006-07-17 | 2008-02-28 | Ambrilia Biopharma Inc. | Method for improving pharmacokinetics |
| AU2007337830A1 (en) | 2006-09-21 | 2008-07-03 | Ambrilia Biopharma Inc. | Benzenesulfonamide derivatives as HIV protease inhibitors |
| WO2009148600A2 (en) * | 2008-06-06 | 2009-12-10 | Concert Pharmaceuticals, Inc. | Deuterated lysine-based compounds |
| CA2762582A1 (en) | 2009-05-27 | 2010-12-02 | Merck Sharp & Dohme Corp. | Hiv protease inhibitors |
| WO2012055031A1 (en) | 2010-10-28 | 2012-05-03 | Merck Canada Inc. | Hiv protease inhibitors |
| EP2771332B1 (en) | 2011-10-26 | 2016-06-29 | Merck Canada Inc. | Thiophen and thiazol sulfonamid derivatives as HIV protease inhibitors for the treatment of AIDS |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
| US10369129B2 (en) | 2016-05-31 | 2019-08-06 | Taimed Biologics, Inc. | Long acting pharmaceutical composition of protease inhibitor |
| WO2017209732A1 (en) * | 2016-05-31 | 2017-12-07 | Taimed Biologics, Inc. | A long acting pharmaceutical composition of protease inhibitor |
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| US5013861A (en) | 1985-02-28 | 1991-05-07 | E. R. Squibb & Sons, Inc. | Ester substituted aminoalkanoylureido amino and imino acid and ester compounds |
| JPH06501950A (ja) | 1990-10-11 | 1994-03-03 | ベーリンガー インゲルハイム コマンディトゲゼルシャフト | 環状ペプチド、その調製法およびその薬理組成物としての使用 |
| US5614522A (en) | 1990-11-19 | 1997-03-25 | G.D. Searle & Co. | Retroviral protease inhibitors |
| EP0532466A3 (en) | 1991-09-12 | 1993-06-16 | Ciba-Geigy Ag | Derivatives of 5-amino-4-hydroxy-hexanoic acid and their therapeutical use |
| EP0656888B1 (en) | 1992-08-25 | 1998-01-07 | G.D. Searle & Co. | Sulfonylalkanoylamino hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
| US6022994A (en) | 1992-08-25 | 2000-02-08 | G. D. Searle &. Co. | Succinoylamino hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
| US5463104A (en) | 1992-08-25 | 1995-10-31 | G. D. Searle & Co. | Succinoylamino hydroxyethylamino sulfonamides useful as retroviral protease inhibitors |
| JPH06321950A (ja) | 1993-05-14 | 1994-11-22 | Takeda Chem Ind Ltd | 水溶性ランカシジン誘導体 |
| WO1995006998A1 (en) | 1993-08-31 | 1995-03-09 | Stanley Kugell | Telephone billing method |
| WO1995024385A1 (en) | 1994-03-07 | 1995-09-14 | Vertex Pharmaceuticals Incorporated | Sulphonamide derivatives as aspartyl protease inhibitors |
| US5527829A (en) | 1994-05-23 | 1996-06-18 | Agouron Pharmaceuticals, Inc. | HIV protease inhibitors |
| ES2303337T3 (es) | 1995-01-20 | 2008-08-01 | G.D. Searle Llc | Inhibidores de la proteasa retroviral de bis-hidroxietilamino sulfonamida. |
| US5985870A (en) | 1995-03-10 | 1999-11-16 | G.D. Searle & Co. | Sulfonylalkanoylamino hydroxyethylamino sulfonamide retroviral protease inhibitors |
| US5776718A (en) | 1995-03-24 | 1998-07-07 | Arris Pharmaceutical Corporation | Reversible protease inhibitors |
| US6037157A (en) | 1995-06-29 | 2000-03-14 | Abbott Laboratories | Method for improving pharmacokinetics |
| JP2000501111A (ja) | 1996-01-26 | 2000-02-02 | バーテックス ファーマシューティカルズ インコーポレイテッド | アスパルチルプロテアーゼインヒビター |
| AU720615B2 (en) | 1997-01-17 | 2000-06-08 | Pharmacia & Upjohn Company | Bis-sulfonomides hydroxamic acids as MMP inhibitors |
| PT877019E (pt) | 1997-05-09 | 2002-05-31 | Hoechst Ag | Acidos diaminocarboxilicos substituidos |
| US6436989B1 (en) | 1997-12-24 | 2002-08-20 | Vertex Pharmaceuticals, Incorporated | Prodrugs of aspartyl protease inhibitors |
| EE200000386A (et) * | 1997-12-24 | 2001-12-17 | Vertex Pharmaceuticals Incorporated | Aspartüülproteaasi inhibiitorite eelravimid |
| US5986102A (en) | 1998-04-29 | 1999-11-16 | Pharmacopeia, Inc. | Hydroxypropylamide peptidomimetics as inhibitors of aspartyl proteases |
| ATE311391T1 (de) | 1999-02-12 | 2005-12-15 | Vertex Pharma | Aspartyl-protease-inhibitoren |
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| US6656968B1 (en) * | 1999-06-16 | 2003-12-02 | Temple University - Of The Commonwealth System Of Higher Education | (Z)-styryl acetoxyphenyl sulfides as cyclooxygenase inhibitors |
| US6455587B1 (en) * | 2000-03-15 | 2002-09-24 | Pharmacor Inc. | Amino acid derivatives as HIV aspartyl protease inhibitors |
| US6506786B2 (en) | 2001-02-13 | 2003-01-14 | Pharmacor Inc. | HIV protease inhibitors based on amino acid derivatives |
| EP1480941B1 (en) | 2002-03-04 | 2011-01-26 | Ambrilia Biopharma Inc. | Urea derivatives as hiv aspartyl protease inhibitors |
| CA2374362C (en) | 2002-03-04 | 2008-01-22 | Brent Richard Stranix | Urea derivatives as hiv aspartyl protease inhibitors |
| PL376900A1 (pl) | 2002-12-16 | 2006-01-09 | Boehringer Ingelheim International Gmbh | Zastosowanie kombinacji zawierającej nienukleozydowy inhibitor odwrotnej transkryptazy (NNRTI) i inhibitor cytochromu P450, taki jak inhibitor proteazy |
| US6632816B1 (en) * | 2002-12-23 | 2003-10-14 | Pharmacor Inc. | Aromatic derivatives as HIV aspartyl protease inhibitors |
| AU2004312284B2 (en) | 2004-01-08 | 2010-08-05 | Medivir Ab | Non-nucleotide reverse transcriptase inhibitors |
| US7388008B2 (en) | 2004-08-02 | 2008-06-17 | Ambrilia Biopharma Inc. | Lysine based compounds |
| ATE417823T1 (de) | 2004-08-02 | 2009-01-15 | Ambrilia Biopharma Inc | Verbindungen auf lysinbasis |
| EP1877091B1 (en) | 2005-04-27 | 2015-03-25 | TaiMed Biologics, Inc. | Method for improving pharmacokinetics of protease inhibitors and protease inhibitor precursors |
| JP2009517412A (ja) | 2005-11-30 | 2009-04-30 | アンブリリア バイオファーマ インコーポレイテッド | アスパルチルプロテアーゼ阻害物質のリジンベースのプロドラッグ及びその調製方法 |
| AU2007287353A1 (en) | 2006-07-17 | 2008-02-28 | Ambrilia Biopharma Inc. | Method for improving pharmacokinetics |
| AU2007337830A1 (en) | 2006-09-21 | 2008-07-03 | Ambrilia Biopharma Inc. | Benzenesulfonamide derivatives as HIV protease inhibitors |
-
2006
- 2006-11-30 JP JP2008542573A patent/JP2009517412A/ja active Pending
- 2006-11-30 WO PCT/CA2006/001963 patent/WO2007062526A1/en not_active Ceased
- 2006-11-30 CA CA002632095A patent/CA2632095A1/en not_active Abandoned
- 2006-11-30 EP EP06817683.3A patent/EP1971615B1/en active Active
- 2006-11-30 AU AU2006319716A patent/AU2006319716B2/en not_active Ceased
- 2006-11-30 ES ES06817683.3T patent/ES2452718T3/es active Active
- 2006-11-30 CN CN200680051907.4A patent/CN101405293B/zh not_active Expired - Fee Related
- 2006-11-30 US US12/086,184 patent/US8227450B2/en not_active Expired - Fee Related
-
2008
- 2008-06-19 US US12/214,995 patent/US8580995B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2009517412A (ja) | 2009-04-30 |
| US20100130765A1 (en) | 2010-05-27 |
| CN101405293A (zh) | 2009-04-08 |
| US20090253926A1 (en) | 2009-10-08 |
| AU2006319716A1 (en) | 2007-06-07 |
| EP1971615B1 (en) | 2014-01-01 |
| EP1971615A4 (en) | 2011-06-22 |
| HK1124861A1 (en) | 2009-07-24 |
| US8227450B2 (en) | 2012-07-24 |
| AU2006319716B2 (en) | 2012-02-02 |
| WO2007062526A1 (en) | 2007-06-07 |
| EP1971615A1 (en) | 2008-09-24 |
| US8580995B2 (en) | 2013-11-12 |
| CN101405293B (zh) | 2013-03-13 |
| WO2007062526A8 (en) | 2007-08-30 |
| CA2632095A1 (en) | 2007-06-07 |
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