AU2006204022B2 - Tripeptide and tetrapeptide thioethers - Google Patents
Tripeptide and tetrapeptide thioethers Download PDFInfo
- Publication number
- AU2006204022B2 AU2006204022B2 AU2006204022A AU2006204022A AU2006204022B2 AU 2006204022 B2 AU2006204022 B2 AU 2006204022B2 AU 2006204022 A AU2006204022 A AU 2006204022A AU 2006204022 A AU2006204022 A AU 2006204022A AU 2006204022 B2 AU2006204022 B2 AU 2006204022B2
- Authority
- AU
- Australia
- Prior art keywords
- compound
- glutamyl
- methyl
- cysteinyl
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 150000003568 thioethers Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 162
- -1 L-y-glutamyl Chemical group 0.000 claims description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 34
- 210000001185 bone marrow Anatomy 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 26
- 150000005690 diesters Chemical class 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 239000002246 antineoplastic agent Substances 0.000 claims description 20
- 229940127089 cytotoxic agent Drugs 0.000 claims description 20
- 210000004881 tumor cell Anatomy 0.000 claims description 20
- 230000004069 differentiation Effects 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 230000003389 potentiating effect Effects 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 12
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
- 231100000433 cytotoxic Toxicity 0.000 claims description 10
- 230000001472 cytotoxic effect Effects 0.000 claims description 10
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 claims description 9
- 230000011132 hemopoiesis Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 230000003039 myelosuppressive effect Effects 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000006242 amine protecting group Chemical group 0.000 claims description 6
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 239000004471 Glycine Substances 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 230000004936 stimulating effect Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- ANOBOESHEJYLOW-QSFULLKGSA-N (2S)-2-amino-5-[[(R)-[1-[(2R)-2-amino-3-[(4-phenylphenyl)methylsulfanyl]propanoyl]cyclohexa-2,4-dien-1-yl]-carboxymethyl]amino]-5-oxopentanoic acid Chemical compound N[C@@H](CCC(=O)N[C@H](C1(CC=CC=C1)C([C@@H](N)CSCC1=CC=C(C=C1)C1=CC=CC=C1)=O)C(=O)O)C(=O)O ANOBOESHEJYLOW-QSFULLKGSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000003028 elevating effect Effects 0.000 claims description 4
- 230000000116 mitigating effect Effects 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 230000001988 toxicity Effects 0.000 claims description 4
- 231100000419 toxicity Toxicity 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
- YNBWBEDJANIGKO-QSFULLKGSA-N (2S)-2-amino-5-[[(R)-[1-[(2R)-2-amino-3-[(2-phenylphenyl)methylsulfanyl]propanoyl]cyclohexa-2,4-dien-1-yl]-carboxymethyl]amino]-5-oxopentanoic acid Chemical compound N[C@@H](CCC(=O)N[C@H](C1(CC=CC=C1)C([C@@H](N)CSCC1=C(C=CC=C1)C1=CC=CC=C1)=O)C(=O)O)C(=O)O YNBWBEDJANIGKO-QSFULLKGSA-N 0.000 claims 1
- ACSONAKGOHBGPL-SBOBVTCZSA-N (2S)-2-amino-5-[[(R)-[1-[(2R)-2-amino-3-[(4-benzoylphenyl)methylsulfanyl]propanoyl]cyclohexa-2,4-dien-1-yl]-carboxymethyl]amino]-5-oxopentanoic acid Chemical compound N[C@@H](CCC(=O)N[C@H](C1(CC=CC=C1)C([C@@H](N)CSCC1=CC=C(C=C1)C(C1=CC=CC=C1)=O)=O)C(=O)O)C(=O)O ACSONAKGOHBGPL-SBOBVTCZSA-N 0.000 claims 1
- IEWPLHCQXLDPKO-PRRCYPGKSA-N (2S)-2-amino-5-[[(R)-[1-[(2R)-2-amino-3-[(4-pyridin-2-ylphenyl)methylsulfanyl]propanoyl]cyclohexa-2,4-dien-1-yl]-carboxymethyl]amino]-5-oxopentanoic acid Chemical compound N[C@@H](CCC(=O)N[C@H](C1(CC=CC=C1)C([C@@H](N)CSCC1=CC=C(C=C1)C1=NC=CC=C1)=O)C(=O)O)C(=O)O IEWPLHCQXLDPKO-PRRCYPGKSA-N 0.000 claims 1
- RBEHFZUVRVJHCS-HNULWMTKSA-N (2S)-2-amino-5-[[(R)-[1-[(2R)-2-amino-3-[[4-(2-cyanophenyl)phenyl]methylsulfanyl]propanoyl]cyclohexa-2,4-dien-1-yl]-carboxymethyl]amino]-5-oxopentanoic acid Chemical compound N[C@@H](CCC(=O)N[C@H](C1(CC=CC=C1)C([C@@H](N)CSCC1=CC=C(C=C1)C1=C(C=CC=C1)C#N)=O)C(=O)O)C(=O)O RBEHFZUVRVJHCS-HNULWMTKSA-N 0.000 claims 1
- FUODYSPTYORQQE-SBOBVTCZSA-N (2S)-2-amino-5-[[(R)-[1-[(2R)-2-amino-3-[[4-(2-methoxyphenyl)phenyl]methylsulfanyl]propanoyl]cyclohexa-2,4-dien-1-yl]-carboxymethyl]amino]-5-oxopentanoic acid Chemical compound N[C@@H](CCC(=O)N[C@H](C1(CC=CC=C1)C([C@@H](N)CSCC1=CC=C(C=C1)C1=C(C=CC=C1)OC)=O)C(=O)O)C(=O)O FUODYSPTYORQQE-SBOBVTCZSA-N 0.000 claims 1
- HBWNLLPPJCOXJR-HNULWMTKSA-N (2S)-2-amino-5-[[(R)-[1-[(2R)-2-amino-3-[[4-(4-cyanophenyl)phenyl]methylsulfanyl]propanoyl]cyclohexa-2,4-dien-1-yl]-carboxymethyl]amino]-5-oxopentanoic acid Chemical compound N[C@@H](CCC(=O)N[C@H](C1(CC=CC=C1)C([C@@H](N)CSCC1=CC=C(C=C1)C1=CC=C(C=C1)C#N)=O)C(=O)O)C(=O)O HBWNLLPPJCOXJR-HNULWMTKSA-N 0.000 claims 1
- WVXDFTOHKASODW-QSFULLKGSA-N (2S)-2-amino-5-[[(R)-[1-[(2R)-2-amino-3-[[4-[3-(trifluoromethyl)phenyl]phenyl]methylsulfanyl]propanoyl]cyclohexa-2,4-dien-1-yl]-carboxymethyl]amino]-5-oxopentanoic acid Chemical compound N[C@@H](CCC(=O)N[C@H](C1(CC=CC=C1)C([C@@H](N)CSCC1=CC=C(C=C1)C1=CC(=CC=C1)C(F)(F)F)=O)C(=O)O)C(=O)O WVXDFTOHKASODW-QSFULLKGSA-N 0.000 claims 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 1
- NZOYIRZDBOGWCE-PESIQCSKSA-N 4-[4-[[(2R)-2-amino-3-[1-[(R)-[[(4S)-4-amino-4-carboxybutanoyl]amino]-carboxymethyl]cyclohexa-2,4-dien-1-yl]-3-oxopropyl]sulfanylmethyl]phenyl]benzoic acid Chemical compound N[C@@H](CCC(=O)N[C@H](C1(CC=CC=C1)C([C@@H](N)CSCC1=CC=C(C=C1)C1=CC=C(C=C1)C(=O)O)=O)C(=O)O)C(=O)O NZOYIRZDBOGWCE-PESIQCSKSA-N 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- 210000004027 cell Anatomy 0.000 description 29
- 238000002360 preparation method Methods 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 18
- 108700017752 gamma-Glu-S-BzCys-PhGly diethyl ester Proteins 0.000 description 18
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 17
- 108090000765 processed proteins & peptides Proteins 0.000 description 17
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 108010070675 Glutathione transferase Proteins 0.000 description 13
- 102000005720 Glutathione transferase Human genes 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 238000003556 assay Methods 0.000 description 13
- 235000018417 cysteine Nutrition 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 12
- GWEJFLVSOGNLSS-WPFOTENUSA-N ethyl (2s)-2-amino-5-[[(2r)-3-benzylsulfanyl-1-[[(1r)-2-ethoxy-2-oxo-1-phenylethyl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoate Chemical compound C([C@H](NC(=O)CC[C@H](N)C(=O)OCC)C(=O)N[C@@H](C(=O)OCC)C=1C=CC=CC=1)SCC1=CC=CC=C1 GWEJFLVSOGNLSS-WPFOTENUSA-N 0.000 description 12
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 108010044467 Isoenzymes Proteins 0.000 description 11
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 11
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- 239000002904 solvent Substances 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 10
- 101001010143 Sus scrofa Glutathione S-transferase P Proteins 0.000 description 9
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 101000637839 Homo sapiens Serine/threonine-protein kinase tousled-like 1 Proteins 0.000 description 8
- 101100393862 Mus musculus Gsto1 gene Proteins 0.000 description 8
- 102100032015 Serine/threonine-protein kinase tousled-like 1 Human genes 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
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- 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 description 7
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- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
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- YFVGRULMIQXYNE-UHFFFAOYSA-M lithium;dodecyl sulfate Chemical compound [Li+].CCCCCCCCCCCCOS([O-])(=O)=O YFVGRULMIQXYNE-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- 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
- C07K5/08—Tripeptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0215—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing natural amino acids, forming a peptide bond via their side chain functional group, e.g. epsilon-Lys, gamma-Glu
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- 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
- A61P35/00—Antineoplastic agents
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
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| US64193205P | 2005-01-06 | 2005-01-06 | |
| US60/641,932 | 2005-01-06 | ||
| PCT/US2006/000219 WO2006074249A1 (en) | 2005-01-06 | 2006-01-04 | Tripeptide and tetrapeptide thioethers |
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| AU2006204022A1 AU2006204022A1 (en) | 2006-07-13 |
| AU2006204022B2 true AU2006204022B2 (en) | 2011-01-20 |
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| AU2006203901A Ceased AU2006203901B2 (en) | 2005-01-06 | 2006-01-05 | Tripeptide and tetrapeptide sulfones |
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| EP (2) | EP1833978B1 (enExample) |
| JP (2) | JP4903716B2 (enExample) |
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| CN (2) | CN101090977B (enExample) |
| AR (2) | AR051890A1 (enExample) |
| AT (2) | ATE410520T1 (enExample) |
| AU (2) | AU2006204022B2 (enExample) |
| BR (2) | BRPI0606520A2 (enExample) |
| CA (2) | CA2587284C (enExample) |
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| EA (2) | EA200701398A1 (enExample) |
| ES (2) | ES2314890T3 (enExample) |
| HR (2) | HRP20090128T3 (enExample) |
| IL (2) | IL182836A (enExample) |
| MX (2) | MX2007008255A (enExample) |
| NZ (2) | NZ555362A (enExample) |
| PL (2) | PL1833978T3 (enExample) |
| PT (2) | PT1833978E (enExample) |
| SI (2) | SI1833978T1 (enExample) |
| TW (2) | TWI317738B (enExample) |
| WO (2) | WO2006074249A1 (enExample) |
| ZA (2) | ZA200704487B (enExample) |
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| US8198247B2 (en) | 2004-12-21 | 2012-06-12 | Telik, Inc. | Process for and intermediates in the preparation of canfosfamide and its salts |
| ATE410520T1 (de) * | 2005-01-06 | 2008-10-15 | Telik Inc | Tripeptid- und tetrapeptid-thioether |
| US20070154963A1 (en) * | 2005-12-30 | 2007-07-05 | Danying Cai | Method to determine whether a compound is a cellular GSTpi inhibitor |
| US20090221703A1 (en) | 2006-07-09 | 2009-09-03 | Chongxi Yu | High penetration composition and uses thereof |
| US20090238763A1 (en) | 2006-07-09 | 2009-09-24 | Chongxi Yu | High penetration compositions and uses thereof |
| AU2016213759B2 (en) * | 2006-11-08 | 2018-03-29 | Chongxi Yu | Transdermal delivery systems of peptides and related compounds |
| EP2091914A4 (en) | 2006-11-08 | 2010-12-29 | Chongxi Yu | TRANSDERMAL ADMINISTRATION SYSTEMS FOR PEPTIDES AND RELATED CONNECTIONS |
| CA2691446C (en) | 2007-06-04 | 2021-07-06 | Techfields Inc | Pro-drugs of nsaias with very high skin and membranes penetration rates and their new medicinal uses |
| KR20200022525A (ko) | 2008-12-04 | 2020-03-03 | 충시 위 | 고투과력을 가진 조성물 및 이의 적용 |
| DE102008060888A1 (de) | 2008-12-09 | 2010-06-10 | Evonik Stockhausen Gmbh | Verfahren zur Herstellung von Acrolein umfassend die Aufarbeitung einer Rohglycerin-Phase |
| BRPI1011439B8 (pt) | 2009-05-08 | 2021-05-25 | Yu Chongxi | composição de alta penetração, composição farmacêutica, sistemas de aplicação terapêutico transdérmico e uso da referida composição |
| CA2797458A1 (en) * | 2010-06-07 | 2011-12-15 | Telik, Inc. | Tablet formulation of ezatiostat |
| US8841476B2 (en) | 2010-06-07 | 2014-09-23 | Telik, Inc. | Preparation of crystalline ezatiostat hydrochloride ansolvate form D |
| US20130035389A1 (en) * | 2011-08-05 | 2013-02-07 | Telik, Inc. | Methods for treating myelodysplastic syndrome with ezatiostat |
| JP5970439B2 (ja) * | 2013-09-20 | 2016-08-17 | チョンシー ユー | ペプチド及び関連化合物の経皮送達システム |
| CN106146616A (zh) * | 2015-04-03 | 2016-11-23 | 浙江海正药业股份有限公司 | 环肽类化合物及其制备和用途 |
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| US5599903A (en) * | 1992-04-03 | 1997-02-04 | Terrapin Technologies, Inc. | Glutathione analogs and paralog panels comprising glutathione mimics |
| US5556942A (en) * | 1991-04-29 | 1996-09-17 | Terrapin Technologies, Inc. | Glutathione S-transferase-activated compounds |
| US5786336A (en) * | 1991-04-29 | 1998-07-28 | Terrapin Technologies, Inc. | Target-selective protocols based on mimics |
| US5767086A (en) * | 1992-04-03 | 1998-06-16 | Terrapin Technologies, Inc. | Bone marrow stimulation by certain glutathione analogs |
| US5955432A (en) * | 1992-04-03 | 1999-09-21 | Terrapin Technologies, Inc. | Metabolic effects of certain glutathione analogs |
| CA2105492C (en) * | 1993-09-03 | 2000-02-01 | Lawrence M. Kauvar | Glutathione analogs and paralog panels comprising glutathione mimics |
| US5908919A (en) * | 1993-10-01 | 1999-06-01 | Terrapin Technologies | Urethane mediated, GST specific molecular release systems |
| WO1996040205A1 (en) | 1995-06-07 | 1996-12-19 | Terrapin Technologies, Inc. | Metabolic effects of certain glutathione analogs |
| AU4124697A (en) * | 1996-09-02 | 1998-03-26 | Manchester Metropolitan University, The | S-blocked glutathiones |
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