JP4478561B2 - 薬学的に活性なジスルフィド塩の合成方法 - Google Patents
薬学的に活性なジスルフィド塩の合成方法 Download PDFInfo
- Publication number
- JP4478561B2 JP4478561B2 JP2004501366A JP2004501366A JP4478561B2 JP 4478561 B2 JP4478561 B2 JP 4478561B2 JP 2004501366 A JP2004501366 A JP 2004501366A JP 2004501366 A JP2004501366 A JP 2004501366A JP 4478561 B2 JP4478561 B2 JP 4478561B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- dimesna
- synthesizing
- pharmaceutically active
- mesna
- 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.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims description 33
- 230000002194 synthesizing effect Effects 0.000 title claims description 8
- 150000002019 disulfides Chemical class 0.000 title description 5
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- -1 alkali metal salt Chemical class 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 claims description 3
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
- 229910001882 dioxygen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims 1
- BYUKOOOZTSTOOH-UHFFFAOYSA-N 2-(2-sulfoethyldisulfanyl)ethanesulfonic acid Chemical compound OS(=O)(=O)CCSSCCS(O)(=O)=O BYUKOOOZTSTOOH-UHFFFAOYSA-N 0.000 description 17
- 229950009278 dimesna Drugs 0.000 description 16
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 13
- 229960004635 mesna Drugs 0.000 description 12
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000003223 protective agent Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- KBFJUSPXGQWLBO-UHFFFAOYSA-N sodium;2-(2-sulfoethyldisulfanyl)ethanesulfonic acid Chemical compound [Na].[Na].OS(=O)(=O)CCSSCCS(O)(=O)=O KBFJUSPXGQWLBO-UHFFFAOYSA-N 0.000 description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 description 2
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical class SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029155 Nephropathy toxic Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 238000006701 autoxidation reaction Methods 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- NLXJVFIECSBALS-UHFFFAOYSA-L disodium bromomethyl-dioxido-oxo-lambda5-phosphane Chemical compound BrCP([O-])([O-])=O.[Na+].[Na+] NLXJVFIECSBALS-UHFFFAOYSA-L 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- ICIWUVCWSCSTAQ-UHFFFAOYSA-M iodate Chemical compound [O-]I(=O)=O ICIWUVCWSCSTAQ-UHFFFAOYSA-M 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 159000000000 sodium salts Chemical group 0.000 description 1
- UJIOMPDETDVHAO-UHFFFAOYSA-M sodium;2-acetylsulfanylethanesulfonate Chemical compound [Na+].CC(=O)SCCS([O-])(=O)=O UJIOMPDETDVHAO-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C327/00—Thiocarboxylic acids
- C07C327/20—Esters of monothiocarboxylic acids
- C07C327/22—Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/22—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of hydropolysulfides or polysulfides
- C07C319/24—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of hydropolysulfides or polysulfides by reactions involving the formation of sulfur-to-sulfur bonds
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/135,756 US6504049B1 (en) | 2002-04-30 | 2002-04-30 | Process for synthesizing pharmaceutically active disulfide salts |
| PCT/US2003/013178 WO2003093226A1 (en) | 2002-04-30 | 2003-04-29 | Process for synthesizing pharmaceutically active disulfide salts |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005523935A JP2005523935A (ja) | 2005-08-11 |
| JP2005523935A5 JP2005523935A5 (enExample) | 2006-06-22 |
| JP4478561B2 true JP4478561B2 (ja) | 2010-06-09 |
Family
ID=22469512
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004501366A Expired - Lifetime JP4478561B2 (ja) | 2002-04-30 | 2003-04-29 | 薬学的に活性なジスルフィド塩の合成方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6504049B1 (enExample) |
| EP (1) | EP1499587B1 (enExample) |
| JP (1) | JP4478561B2 (enExample) |
| AU (1) | AU2003231169B2 (enExample) |
| CA (1) | CA2483775C (enExample) |
| DK (1) | DK1499587T3 (enExample) |
| ES (1) | ES2523653T3 (enExample) |
| MX (1) | MXPA04010859A (enExample) |
| PT (1) | PT1499587E (enExample) |
| WO (1) | WO2003093226A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2811987A1 (fr) * | 2000-07-18 | 2002-01-25 | Expansia Sa | Procede de preparation du 2,2'-dithiobis(ethanesulfonate) de disodium |
| US8710095B2 (en) | 2002-04-30 | 2014-04-29 | Bionumerik Pharmaceuticals, Inc. | Drugs for prophylaxis or mitigation of taxane-induced neurotoxicity |
| US7317124B2 (en) | 2003-11-13 | 2008-01-08 | Sanofi-Aventis Deutschland Gmbh | Ortho-substituted pentafluorosulfanylbenzenes, process for their preparation and their use as valuable synthetic intermediates |
| JP4936898B2 (ja) * | 2003-12-17 | 2012-05-23 | バイオニューメリック・ファーマスーティカルズ・インコーポレイテッド | ジスルフィド類の合成方法 |
| US7282602B2 (en) * | 2004-09-21 | 2007-10-16 | Bionumerik Pharmaceuticals, Inc. | Medicinal disulfide salts |
| CN101442998B (zh) * | 2006-03-16 | 2012-03-14 | 比奥纽默里克药物公司 | 抗癌活性加强化合物和制剂及其用法 |
| JP5109081B2 (ja) * | 2006-04-26 | 2012-12-26 | 東洋紡株式会社 | アルケンスルホン酸塩を用いたチオカルボアルキルアルカンスルホン酸塩、メルカプトアルカンスルホン酸塩およびジチオビス（アルカンスルホン酸）塩の製造方法 |
| JP5696266B2 (ja) * | 2007-11-20 | 2015-04-08 | ランケナー インスティテュート フォー メディカル リサーチ | ジスルフィド化学療法剤およびその使用方法 |
| EP2249825B1 (en) | 2008-03-14 | 2015-10-07 | Bionumerik Pharmaceuticals, Inc. | Treatment methods and compositions for lung cancer, adenocarcinoma, and other medical conditions |
| AU2008352603B2 (en) | 2008-03-14 | 2012-05-31 | Bionumerik Pharmaceuticals, Inc. | Compositions and methods of use of compounds to increase cancer patient survival time |
| WO2010132771A1 (en) | 2009-05-15 | 2010-11-18 | Lankenau Institute For Medical Research | Methods and kits for measuring toxicity and oxidative stress in live cells |
| CN108914171B (zh) * | 2018-07-19 | 2020-05-19 | 广东工业大学 | 一种加速铜沉积添加剂及其制备方法和应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2396879A (en) * | 1945-04-12 | 1946-03-19 | Eastman Kodak Co | Sulphur-containing esters |
| CS252564B1 (cs) * | 1985-06-17 | 1987-09-17 | Jiri Jary | Způsob výroby 2-merkaptoethansulfonové kyseliny |
| DE69707911T2 (de) * | 1996-10-01 | 2002-04-04 | Bionumerik Pharmaceuticals, Inc. | Verfahren zur herstellung von dithiobis-alkanesulfonaten und phosphonaten |
| FR2811987A1 (fr) | 2000-07-18 | 2002-01-25 | Expansia Sa | Procede de preparation du 2,2'-dithiobis(ethanesulfonate) de disodium |
-
2002
- 2002-04-30 US US10/135,756 patent/US6504049B1/en not_active Expired - Lifetime
-
2003
- 2003-04-29 DK DK03724301.1T patent/DK1499587T3/en active
- 2003-04-29 CA CA2483775A patent/CA2483775C/en not_active Expired - Fee Related
- 2003-04-29 WO PCT/US2003/013178 patent/WO2003093226A1/en not_active Ceased
- 2003-04-29 ES ES03724301.1T patent/ES2523653T3/es not_active Expired - Lifetime
- 2003-04-29 PT PT37243011T patent/PT1499587E/pt unknown
- 2003-04-29 JP JP2004501366A patent/JP4478561B2/ja not_active Expired - Lifetime
- 2003-04-29 EP EP03724301.1A patent/EP1499587B1/en not_active Expired - Lifetime
- 2003-04-29 AU AU2003231169A patent/AU2003231169B2/en not_active Ceased
- 2003-04-29 MX MXPA04010859A patent/MXPA04010859A/es active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| EP1499587A4 (en) | 2006-05-24 |
| JP2005523935A (ja) | 2005-08-11 |
| US6504049B1 (en) | 2003-01-07 |
| AU2003231169B2 (en) | 2008-09-04 |
| CA2483775C (en) | 2011-02-08 |
| MXPA04010859A (es) | 2005-02-14 |
| WO2003093226A1 (en) | 2003-11-13 |
| EP1499587B1 (en) | 2014-11-05 |
| EP1499587A1 (en) | 2005-01-26 |
| AU2003231169A1 (en) | 2003-11-17 |
| ES2523653T3 (es) | 2014-11-28 |
| CA2483775A1 (en) | 2003-11-13 |
| DK1499587T3 (en) | 2015-01-26 |
| PT1499587E (pt) | 2014-11-21 |
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