JP2013508293A5 - - Google Patents
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- Publication number
- JP2013508293A5 JP2013508293A5 JP2012534373A JP2012534373A JP2013508293A5 JP 2013508293 A5 JP2013508293 A5 JP 2013508293A5 JP 2012534373 A JP2012534373 A JP 2012534373A JP 2012534373 A JP2012534373 A JP 2012534373A JP 2013508293 A5 JP2013508293 A5 JP 2013508293A5
- Authority
- JP
- Japan
- Prior art keywords
- prodrug
- administered
- dose
- eniluracil
- dpd inhibitor
- 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.)
- Pending
Links
- 229960002949 fluorouracil Drugs 0.000 claims description 94
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 92
- 239000003112 inhibitor Substances 0.000 claims description 72
- UEJQGOKMPMUMTO-UHFFFAOYSA-N C(C#C)OC1=NC=C(C(=N1)OCC#C)F Chemical compound C(C#C)OC1=NC=C(C(=N1)OCC#C)F UEJQGOKMPMUMTO-UHFFFAOYSA-N 0.000 claims description 68
- JOZGNYDSEBIJDH-UHFFFAOYSA-N eniluracil Chemical compound O=C1NC=C(C#C)C(=O)N1 JOZGNYDSEBIJDH-UHFFFAOYSA-N 0.000 claims description 51
- 229950010213 eniluracil Drugs 0.000 claims description 51
- 239000002246 antineoplastic agent Substances 0.000 claims description 38
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 23
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 19
- 229960004117 capecitabine Drugs 0.000 claims description 19
- 229940002612 prodrug Drugs 0.000 claims description 15
- 239000000651 prodrug Substances 0.000 claims description 15
- 230000008030 elimination Effects 0.000 claims description 12
- 238000003379 elimination reaction Methods 0.000 claims description 12
- 230000001537 neural effect Effects 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 10
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 claims description 8
- -1 5′-deoxy-4 ′ Chemical compound 0.000 claims description 8
- WFWLQNSHRPWKFK-UHFFFAOYSA-N Tegafur Chemical compound O=C1NC(=O)C(F)=CN1C1OCCC1 WFWLQNSHRPWKFK-UHFFFAOYSA-N 0.000 claims description 6
- 239000008203 oral pharmaceutical composition Substances 0.000 claims description 6
- 238000013268 sustained release Methods 0.000 claims description 6
- 239000012730 sustained-release form Substances 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- IDYKCXHJJGMAEV-RRKCRQDMSA-N 4-amino-5-fluoro-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound C1=C(F)C(N)=NC(=O)N1[C@@H]1O[C@H](CO)[C@@H](O)C1 IDYKCXHJJGMAEV-RRKCRQDMSA-N 0.000 claims description 4
- FBOIBTWYSVRYTJ-VBLCRABPSA-N 5-[(3S,4S,5S)-6-fluoro-3,4,5-trihydroxyoxan-2-yl]-1H-pyrimidine-2,4-dione Chemical compound FC1[C@H]([C@H]([C@@H](C(O1)C=1C(NC(NC=1)=O)=O)O)O)O FBOIBTWYSVRYTJ-VBLCRABPSA-N 0.000 claims description 4
- STRZQWQNZQMHQR-UAKXSSHOSA-N 5-fluorocytidine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 STRZQWQNZQMHQR-UAKXSSHOSA-N 0.000 claims description 4
- 206010029350 Neurotoxicity Diseases 0.000 claims description 4
- 206010044221 Toxic encephalopathy Diseases 0.000 claims description 4
- ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 claims description 4
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 4
- 230000007135 neurotoxicity Effects 0.000 claims description 4
- 231100000228 neurotoxicity Toxicity 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims 2
- 238000000034 method Methods 0.000 description 32
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Natural products O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 229940035893 uracil Drugs 0.000 description 3
- UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- HAUXRJCZDHHADG-UHFFFAOYSA-N 2,4-dioxo-1h-pyrimidine-5-carbonitrile Chemical compound O=C1NC=C(C#N)C(=O)N1 HAUXRJCZDHHADG-UHFFFAOYSA-N 0.000 description 1
- CYMBDTMRFAUHRM-UHFFFAOYSA-N 5-(1-chloroethenyl)-1h-pyrimidine-2,4-dione Chemical compound ClC(=C)C1=CNC(=O)NC1=O CYMBDTMRFAUHRM-UHFFFAOYSA-N 0.000 description 1
- BLXGZIDBSXVMLU-UHFFFAOYSA-N 5-(2-bromoethenyl)-1h-pyrimidine-2,4-dione Chemical compound BrC=CC1=CNC(=O)NC1=O BLXGZIDBSXVMLU-UHFFFAOYSA-N 0.000 description 1
- LKTQRCSUYNIRSM-UHFFFAOYSA-N 5-(2-bromoethynyl)-1h-pyrimidine-2,4-dione Chemical compound BrC#CC1=CNC(=O)NC1=O LKTQRCSUYNIRSM-UHFFFAOYSA-N 0.000 description 1
- BLXGZIDBSXVMLU-OWOJBTEDSA-N 5-[(e)-2-bromoethenyl]-1h-pyrimidine-2,4-dione Chemical compound Br\C=C\C1=CNC(=O)NC1=O BLXGZIDBSXVMLU-OWOJBTEDSA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- ZRYZBEQILKESAW-UHFFFAOYSA-N 5-ethenyl-1h-pyrimidine-2,4-dione Chemical compound C=CC1=CNC(=O)NC1=O ZRYZBEQILKESAW-UHFFFAOYSA-N 0.000 description 1
- TUFMBCUUDJKPJB-UHFFFAOYSA-N 5-hex-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CCCCC#CC1=CNC(=O)NC1=O TUFMBCUUDJKPJB-UHFFFAOYSA-N 0.000 description 1
- KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US25144909P | 2009-10-14 | 2009-10-14 | |
| US61/251,449 | 2009-10-14 | ||
| PCT/US2010/052734 WO2011047195A1 (en) | 2009-10-14 | 2010-10-14 | Treating neurotoxicity associated with combinations of 5 - fu or its prodrugs and dpd inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015190757A Division JP2016014051A (ja) | 2009-10-14 | 2015-09-29 | ５−ｆｕ又はそのプロドラッグと、ｄｐｄ阻害剤との組合せに付随した神経毒性の処置 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2013508293A JP2013508293A (ja) | 2013-03-07 |
| JP2013508293A5 true JP2013508293A5 (enExample) | 2014-05-15 |
Family
ID=43466528
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2012534373A Pending JP2013508293A (ja) | 2009-10-14 | 2010-10-14 | ５−ｆｕ又はそのプロドラッグと、ｄｐｄ阻害剤との組合せに付随した神経毒性の処置 |
| JP2015190757A Pending JP2016014051A (ja) | 2009-10-14 | 2015-09-29 | ５−ｆｕ又はそのプロドラッグと、ｄｐｄ阻害剤との組合せに付随した神経毒性の処置 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015190757A Pending JP2016014051A (ja) | 2009-10-14 | 2015-09-29 | ５−ｆｕ又はそのプロドラッグと、ｄｐｄ阻害剤との組合せに付随した神経毒性の処置 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US8658618B2 (enExample) |
| EP (1) | EP2488182B1 (enExample) |
| JP (2) | JP2013508293A (enExample) |
| KR (1) | KR20120127709A (enExample) |
| CN (1) | CN102811721A (enExample) |
| AU (1) | AU2010306698B2 (enExample) |
| BR (1) | BR112012008951A2 (enExample) |
| CA (1) | CA2777546C (enExample) |
| CO (1) | CO6541596A2 (enExample) |
| EA (1) | EA201270551A1 (enExample) |
| ES (1) | ES2644237T3 (enExample) |
| IL (1) | IL219179A0 (enExample) |
| MX (1) | MX2012004383A (enExample) |
| WO (1) | WO2011047195A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014089004A1 (en) * | 2012-12-04 | 2014-06-12 | Adherex Technologies, Inc. | Methods for treating 5-fluorouracil prodrug non-responsive cancer patients |
| CN106692173A (zh) * | 2015-11-18 | 2017-05-24 | 北京诺普德医药科技有限公司 | 一种抗肿瘤复方组合物及其应用 |
| EP4629999A1 (en) * | 2022-12-06 | 2025-10-15 | Elion Oncology, Inc. | Combined use of eniluracil and capecitabine for treating cancer |
| US20250017931A1 (en) * | 2023-07-13 | 2025-01-16 | Processa Pharmaceuticals, Inc., | Methods of personalizing cancer treatment |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5687599A (en) | 1979-12-19 | 1981-07-16 | Yamasa Shoyu Co Ltd | E 55 22halogenovinyl arabinofuranosyluracil and its preparation |
| GB8629892D0 (en) | 1986-12-15 | 1987-01-28 | Wellcome Found | Antiviral compounds |
| US5157114A (en) | 1988-08-19 | 1992-10-20 | Burroughs Wellcome Co. | 2',3'-dideoxy-3'-fluoro-5-ethyngluridine |
| ATE161722T1 (de) | 1990-07-19 | 1998-01-15 | Wellcome Found | Enzyminaktivatoren |
| GB9020930D0 (en) * | 1990-09-26 | 1990-11-07 | Wellcome Found | Pharmaceutical combinations |
| US5476855A (en) | 1993-11-02 | 1995-12-19 | Mahmoud H. el Kouni | Enzyme inhibitors, their synthesis and methods for use |
| NZ330360A (en) | 1997-06-02 | 1999-03-29 | Hoffmann La Roche | 5'-deoxy-cytidine derivatives, their manufacture and use as antitumoral agents |
| US6716452B1 (en) | 2000-08-22 | 2004-04-06 | New River Pharmaceuticals Inc. | Active agent delivery systems and methods for protecting and administering active agents |
| US20040028687A1 (en) | 2002-01-15 | 2004-02-12 | Waelti Ernst Rudolf | Methods and compositions for the targeted delivery of therapeutic substances to specific cells and tissues |
| AU2005311730B2 (en) * | 2004-12-03 | 2011-11-17 | Adherex Technologies, Inc. | Methods for administering DPD inhibitors in combination with 5-FU and 5-FU prodrugs |
-
2010
- 2010-10-14 EA EA201270551A patent/EA201270551A1/ru unknown
- 2010-10-14 KR KR1020127012289A patent/KR20120127709A/ko not_active Withdrawn
- 2010-10-14 MX MX2012004383A patent/MX2012004383A/es not_active Application Discontinuation
- 2010-10-14 BR BR112012008951A patent/BR112012008951A2/pt not_active IP Right Cessation
- 2010-10-14 ES ES10768670.1T patent/ES2644237T3/es active Active
- 2010-10-14 EP EP10768670.1A patent/EP2488182B1/en active Active
- 2010-10-14 AU AU2010306698A patent/AU2010306698B2/en active Active
- 2010-10-14 WO PCT/US2010/052734 patent/WO2011047195A1/en not_active Ceased
- 2010-10-14 CN CN2010800562916A patent/CN102811721A/zh active Pending
- 2010-10-14 US US12/904,974 patent/US8658618B2/en active Active
- 2010-10-14 CA CA2777546A patent/CA2777546C/en active Active
- 2010-10-14 JP JP2012534373A patent/JP2013508293A/ja active Pending
-
2012
- 2012-04-15 IL IL219179A patent/IL219179A0/en unknown
- 2012-05-14 CO CO12078833A patent/CO6541596A2/es not_active Application Discontinuation
-
2015
- 2015-09-29 JP JP2015190757A patent/JP2016014051A/ja active Pending
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