CN1360593A - 假单胞菌素n－酰基侧链类似物 - Google Patents
假单胞菌素n－酰基侧链类似物 Download PDFInfo
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- CN1360593A CN1360593A CN00810291A CN00810291A CN1360593A CN 1360593 A CN1360593 A CN 1360593A CN 00810291 A CN00810291 A CN 00810291A CN 00810291 A CN00810291 A CN 00810291A CN 1360593 A CN1360593 A CN 1360593A
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- China
- Prior art keywords
- pseudobactin
- hydrogen
- compound
- hydroxyl
- alkyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract description 58
- 108010042415 pseudobactin Proteins 0.000 claims description 81
- ZGDFFAWCXJUFOX-UHFFFAOYSA-N pseudobactin Natural products CC(O)C(NC(=O)C(C)NC(=O)C(NC(=O)C(N)CCCCNC(=O)C1CCNC2N1c3cc(O)c(O)cc3C=C2NC(=O)CCC(=O)N)C(O)C(=O)O)C(=O)NC(C)C(=O)NC4CCCN(O)C4=O ZGDFFAWCXJUFOX-UHFFFAOYSA-N 0.000 claims description 81
- -1 methoxyl group Chemical group 0.000 claims description 65
- UGBOUVVZXRMJNM-FUGGEZGHSA-N (2r,3r)-3-[[(2s)-2-amino-6-[[(1s)-5-[(4-amino-4-oxobutanoyl)amino]-8-hydroxy-9-oxo-1,2,3,4-tetrahydropyrimido[1,2-a]quinoline-1-carbonyl]amino]hexanoyl]amino]-2-hydroxy-4-[[(2s)-1-[[(2r,3r)-3-hydroxy-1-[[(2s)-1-[[(3r)-1-hydroxy-2-oxopiperidin-3-yl]amino]- Chemical compound O=C([C@H](C)NC(=O)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)[C@@H](N)CCCCNC(=O)[C@H]1N2C3=CC(=O)C(O)=CC3=CC(NC(=O)CCC(N)=O)=C2NCC1)[C@@H](O)C(O)=O)[C@H](O)C)N[C@@H]1CCCN(O)C1=O UGBOUVVZXRMJNM-FUGGEZGHSA-N 0.000 claims description 61
- 238000002360 preparation method Methods 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 38
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 21
- 150000002431 hydrogen Chemical group 0.000 claims description 21
- 241001465754 Metazoa Species 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 241000233866 Fungi Species 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- DKRKCXQSIKKJRX-ANCZQRAUSA-N (3r)-3-amino-4-[[(2s)-1-[[(2r,3r)-1-[[(2s)-2-amino-6-[[5-[(4-amino-4-oxobutanoyl)amino]-8,9-dihydroxy-2,3,5,6-tetrahydro-1h-pyrimido[1,2-a]quinoline-1-carbonyl]amino]hexanoyl]-[(2s)-2-[[(3r)-1-hydroxy-2-oxopiperidin-3-yl]amino]propanoyl]amino]-3-hydroxy-1 Chemical compound N([C@@H](C)C(=O)N(C(=O)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](N)C(O)C(O)=O)[C@H](O)C)C(=O)[C@@H](N)CCCCNC(=O)C1N2C3=CC(O)=C(O)C=C3CC(C2=NCC1)NC(=O)CCC(N)=O)[C@@H]1CCCN(O)C1=O DKRKCXQSIKKJRX-ANCZQRAUSA-N 0.000 claims description 10
- 125000002704 decyl group Chemical group [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])* 0.000 claims description 10
- 108010071947 pseudobactin A Proteins 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
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- 229910052736 halogen Inorganic materials 0.000 claims description 7
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- 239000003814 drug Substances 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
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- 230000000843 anti-fungal effect Effects 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
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- 206010061217 Infestation Diseases 0.000 claims description 3
- 208000031888 Mycoses Diseases 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
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- 239000000543 intermediate Substances 0.000 abstract description 8
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- 238000013461 design Methods 0.000 abstract description 3
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- 238000006243 chemical reaction Methods 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 238000003756 stirring Methods 0.000 description 36
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 238000004128 high performance liquid chromatography Methods 0.000 description 19
- 239000000203 mixture Substances 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 239000002243 precursor Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
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- 239000012043 crude product Substances 0.000 description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 230000020176 deacylation Effects 0.000 description 11
- 238000005947 deacylation reaction Methods 0.000 description 11
- 229910052760 oxygen Inorganic materials 0.000 description 11
- 239000001301 oxygen Substances 0.000 description 11
- 239000011347 resin Substances 0.000 description 11
- 229920005989 resin Polymers 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 238000005984 hydrogenation reaction Methods 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 150000001299 aldehydes Chemical class 0.000 description 8
- 230000001857 anti-mycotic effect Effects 0.000 description 8
- 229940095731 candida albicans Drugs 0.000 description 8
- 238000007429 general method Methods 0.000 description 8
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
- 241001225321 Aspergillus fumigatus Species 0.000 description 7
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
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- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 5
- 125000002769 thiazolinyl group Chemical group 0.000 description 5
- SMDGVPQREIZILS-UHFFFAOYSA-N $l^{1}-oxidanylmethylbenzene Chemical compound [O]CC1=CC=CC=C1 SMDGVPQREIZILS-UHFFFAOYSA-N 0.000 description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical class OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- SRRKNRDXURUMPP-UHFFFAOYSA-N sodium disulfide Chemical compound [Na+].[Na+].[S-][S-] SRRKNRDXURUMPP-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
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- DZEFNRWGWQDGTR-UHFFFAOYSA-N tetradec-1-yne Chemical compound CCCCCCCCCCCCC#C DZEFNRWGWQDGTR-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
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
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- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- CYIFVRUOHKNECG-UHFFFAOYSA-N tridecan-2-one Chemical compound CCCCCCCCCCCC(C)=O CYIFVRUOHKNECG-UHFFFAOYSA-N 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
- 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)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Epoxy Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14398999P | 1999-07-15 | 1999-07-15 | |
| US60/143,989 | 1999-07-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1360593A true CN1360593A (zh) | 2002-07-24 |
Family
ID=22506582
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN00810291A Pending CN1360593A (zh) | 1999-07-15 | 2000-06-08 | 假单胞菌素n－酰基侧链类似物 |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP1200460A1 (fr) |
| JP (1) | JP2003505397A (fr) |
| CN (1) | CN1360593A (fr) |
| AU (1) | AU5724900A (fr) |
| BR (1) | BR0012447A (fr) |
| CA (1) | CA2379851A1 (fr) |
| EA (1) | EA200200160A1 (fr) |
| HU (1) | HUP0202347A2 (fr) |
| MX (1) | MXPA02000321A (fr) |
| NO (1) | NO20020193L (fr) |
| WO (1) | WO2001005814A1 (fr) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE102004051025A1 (de) | 2004-10-20 | 2006-04-27 | Bayer Healthcare Ag | Substituierte Nonadepsipeptide |
| DE102004051023A1 (de) * | 2004-10-20 | 2006-05-04 | Bayer Healthcare Ag | Desoxo-Nonadepsipeptide |
| DE102004053410A1 (de) | 2004-11-05 | 2006-05-11 | Bayer Healthcare Ag | Cyclische Nonadepsipeptidamide |
| DE102006018080A1 (de) | 2006-04-13 | 2007-10-18 | Aicuris Gmbh & Co. Kg | Lysobactinamide |
| PL2427416T3 (pl) * | 2009-05-04 | 2016-09-30 | Podstawione związki aromatyczne i ich zastosowania farmaceutyczne |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5576298A (en) * | 1992-11-30 | 1996-11-19 | Research And Development Institute, Inc. At Montana State University | Peptides from pseudomonas syringae possessing broad-spectrum antibiotic activity |
-
2000
- 2000-06-08 MX MXPA02000321A patent/MXPA02000321A/es unknown
- 2000-06-08 HU HU0202347A patent/HUP0202347A2/hu unknown
- 2000-06-08 CN CN00810291A patent/CN1360593A/zh active Pending
- 2000-06-08 JP JP2001511471A patent/JP2003505397A/ja not_active Withdrawn
- 2000-06-08 EA EA200200160A patent/EA200200160A1/ru unknown
- 2000-06-08 BR BR0012447-8A patent/BR0012447A/pt not_active Application Discontinuation
- 2000-06-08 EP EP00942655A patent/EP1200460A1/fr not_active Withdrawn
- 2000-06-08 WO PCT/US2000/015017 patent/WO2001005814A1/fr not_active Application Discontinuation
- 2000-06-08 CA CA002379851A patent/CA2379851A1/fr not_active Abandoned
- 2000-06-08 AU AU57249/00A patent/AU5724900A/en not_active Abandoned
-
2002
- 2002-01-14 NO NO20020193A patent/NO20020193L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0202347A2 (en) | 2002-10-28 |
| EA200200160A1 (ru) | 2002-08-29 |
| CA2379851A1 (fr) | 2001-01-25 |
| MXPA02000321A (es) | 2002-06-21 |
| NO20020193L (no) | 2002-03-14 |
| BR0012447A (pt) | 2002-04-02 |
| NO20020193D0 (no) | 2002-01-14 |
| JP2003505397A (ja) | 2003-02-12 |
| EP1200460A1 (fr) | 2002-05-02 |
| WO2001005814A1 (fr) | 2001-01-25 |
| AU5724900A (en) | 2001-02-05 |
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