JP2012504631A5 - - Google Patents
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- JP2012504631A5 JP2012504631A5 JP2011530162A JP2011530162A JP2012504631A5 JP 2012504631 A5 JP2012504631 A5 JP 2012504631A5 JP 2011530162 A JP2011530162 A JP 2011530162A JP 2011530162 A JP2011530162 A JP 2011530162A JP 2012504631 A5 JP2012504631 A5 JP 2012504631A5
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- JP
- Japan
- Prior art keywords
- carbon atoms
- bond
- carbonyl
- group
- hydrogen
- 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.)
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 281
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 137
- 125000000217 alkyl group Chemical group 0.000 claims description 118
- 150000001875 compounds Chemical class 0.000 claims description 116
- 229910052799 carbon Inorganic materials 0.000 claims description 67
- 150000001721 carbon Chemical group 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 54
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 210000004027 cell Anatomy 0.000 claims description 25
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- -1 monofluoromethyl Chemical group 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 210000002540 macrophage Anatomy 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 239000011593 sulfur Substances 0.000 claims description 12
- 239000000651 prodrug Substances 0.000 claims description 11
- 229940002612 prodrug Drugs 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 11
- QAPXLUZMMFIIBI-UHFFFAOYSA-N 1,1,3,3-tetrafluoropropan-2-one Chemical compound FC(F)C(=O)C(F)F QAPXLUZMMFIIBI-UHFFFAOYSA-N 0.000 claims description 10
- HKIPCXRNASWFRU-UHFFFAOYSA-N 1,3-difluoropropan-2-one Chemical compound FCC(=O)CF HKIPCXRNASWFRU-UHFFFAOYSA-N 0.000 claims description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- 101001116987 Homo sapiens Proton-coupled folate transporter Proteins 0.000 claims description 10
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 10
- 102000006815 folate receptor Human genes 0.000 claims description 10
- 108020005243 folate receptor Proteins 0.000 claims description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 10
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 claims description 10
- 102000046517 human SLC46A1 Human genes 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 150000002431 hydrogen Chemical group 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 108090000790 Enzymes Proteins 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 108020003175 receptors Proteins 0.000 claims description 4
- 102000005962 receptors Human genes 0.000 claims description 4
- 230000008685 targeting Effects 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 230000004543 DNA replication Effects 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 2
- 239000003966 growth inhibitor Substances 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 claims description 2
- 230000002934 lysing effect Effects 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 230000037361 pathway Effects 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 9
- 102000056797 Proton-Coupled Folate Transporter Human genes 0.000 claims 2
- 108091007566 SLC46A1 Proteins 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 210000003679 cervix uteri Anatomy 0.000 claims 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 1
- 230000003834 intracellular effect Effects 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 230000035515 penetration Effects 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-L glutamate group Chemical group N[C@@H](CCC(=O)[O-])C(=O)[O-] WHUUTDBJXJRKMK-VKHMYHEASA-L 0.000 description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102000037909 Folate transporters Human genes 0.000 description 2
- 108091006783 Folate transporters Proteins 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 102000002114 Reduced Folate Carrier Human genes 0.000 description 1
- 108050009454 Reduced Folate Carrier Proteins 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/242,988 | 2008-10-01 | ||
| US12/242,988 US8252804B2 (en) | 2008-10-01 | 2008-10-01 | Selective proton coupled folate transporter and folate receptor, and GARFTase inhibitor compounds and methods of using the same |
| PCT/US2009/058968 WO2010039792A1 (en) | 2008-10-01 | 2009-09-30 | Selective proton coupled folate transporter and folate receptor, and garftase inhibitor compounds and methods of using the same |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014182217A Division JP2014224159A (ja) | 2008-10-01 | 2014-09-08 | 選択的プロトン共役葉酸トランスポーターおよび葉酸受容体、ならびにｇａｒｆｔアーゼインヒビター化合物、ならびにそれらの使用方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2012504631A JP2012504631A (ja) | 2012-02-23 |
| JP2012504631A5 true JP2012504631A5 (enExample) | 2012-11-15 |
Family
ID=42058108
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011530162A Withdrawn JP2012504631A (ja) | 2008-10-01 | 2009-09-30 | 選択的プロトン共役葉酸トランスポーターおよび葉酸受容体、ならびにｇａｒｆｔアーゼインヒビター化合物、ならびにそれらの使用方法 |
| JP2014182217A Pending JP2014224159A (ja) | 2008-10-01 | 2014-09-08 | 選択的プロトン共役葉酸トランスポーターおよび葉酸受容体、ならびにｇａｒｆｔアーゼインヒビター化合物、ならびにそれらの使用方法 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014182217A Pending JP2014224159A (ja) | 2008-10-01 | 2014-09-08 | 選択的プロトン共役葉酸トランスポーターおよび葉酸受容体、ならびにｇａｒｆｔアーゼインヒビター化合物、ならびにそれらの使用方法 |
Country Status (5)
| Country | Link |
|---|---|
| US (5) | US8252804B2 (enExample) |
| EP (2) | EP2348843B1 (enExample) |
| JP (2) | JP2012504631A (enExample) |
| CA (2) | CA2993404C (enExample) |
| WO (1) | WO2010039792A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8252804B2 (en) | 2008-10-01 | 2012-08-28 | Duquesne University Of The Holy Spirit | Selective proton coupled folate transporter and folate receptor, and GARFTase inhibitor compounds and methods of using the same |
| US20110082158A1 (en) * | 2008-10-01 | 2011-04-07 | Aleem Gangjee | Selective proton coupled folate transporter and folate receptor, and garftase and/or other folate metabolizing enzymes inhibitor compounds and methods of using the same |
| CA2964140A1 (en) * | 2014-12-02 | 2016-06-09 | Eli Lilly And Company | 1 -oxo-1,2-dihydroisoquinolin-7-yl-(5-substituted-thiophen-2-yl)-sulfonamide compounds, formulations containing those compounds, and their use as aicarft inhibitors in the treatment of cancers |
| US9481678B2 (en) * | 2015-02-09 | 2016-11-01 | Duquesne University Of The Holy Ghost | Substituted pyrrolo[2,3-D]dipyrimidines for selectively targeting tumor cells with FR-alpha and FR-beta type receptors |
| CN105111197B (zh) * | 2015-08-26 | 2021-05-04 | 上海鼎雅药物化学科技有限公司 | 雷替曲塞的合成方法 |
| WO2023086821A1 (en) * | 2021-11-11 | 2023-05-19 | Duquesne University Of The Holy Spirit | Targeted therapy of pyrrolo[2,3-d]pyrimidine antifolates in a syngeneic mouse model of high grade serous ovarian cancer |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4496639A (en) | 1983-07-05 | 1985-01-29 | Ceramatec, Inc. | Hydrogen selenide treatment of electrolytes |
| WO1991000092A1 (en) * | 1989-06-13 | 1991-01-10 | Smithkline Beecham Corporation | Inhibition of interleukin-1 and tumor necrosis factor production by monocytes and/or macrophages |
| JPH03173890A (ja) * | 1989-09-21 | 1991-07-29 | Takeda Chem Ind Ltd | ピロロ［２，３―ｄ］ピリミジン誘導体，その製造法，用途及び中間体 |
| US4996206A (en) * | 1989-12-11 | 1991-02-26 | The Trustees Of Princeton University | N-(pyrrolo[2,3-d]pyrimidin-3-ylacyl)-glutamic acid derivatives |
| US5248775A (en) * | 1989-12-11 | 1993-09-28 | The Trustees Of Princeton University | Pyrrolo(2,3-d)pyrimidines |
| JPH04117381A (ja) | 1989-12-20 | 1992-04-17 | Takeda Chem Ind Ltd | 縮合複素環化合物，その製造法，用途及び中間体 |
| EP0438261A3 (en) | 1990-01-16 | 1992-02-26 | Takeda Chemical Industries, Ltd. | Condensed heterocyclic glutamic acid derivatives, their production and use |
| JPH0578362A (ja) | 1990-01-16 | 1993-03-30 | Takeda Chem Ind Ltd | 縮合複素環化合物，その製造法，用途及び中間体 |
| US5939420A (en) * | 1991-04-08 | 1999-08-17 | Duquesne University Of The Holy Ghost | Pyrrolo 2,3d!derivatives |
| JP3144903B2 (ja) | 1991-08-21 | 2001-03-12 | エーザイ株式会社 | 縮合ピリミジン誘導体 |
| ATE173251T1 (de) * | 1991-08-21 | 1998-11-15 | Eisai Co Ltd | Kondensierte pyrimidinderivate als antitumorverbindungen |
| JPH06172358A (ja) * | 1991-12-27 | 1994-06-21 | Takeda Chem Ind Ltd | 縮合ピリミジン誘導体、その製造法および用途 |
| EP0549291A1 (en) | 1991-12-27 | 1993-06-30 | Takeda Chemical Industries, Ltd. | Thymidylate synthase inhibitors |
| US5608082A (en) | 1994-07-28 | 1997-03-04 | Agouron Pharmaceuticals, Inc. | Compounds useful as antiproliferative agents and GARFT inhibitors |
| IL119142A (en) | 1996-08-28 | 2002-03-10 | Yissum Res Dev Co | Slow release agrochemical composition |
| EP0923287A4 (en) * | 1996-08-30 | 2001-08-01 | Lilly Co Eli | NON-CLASSIC PYRROLO (2,3-D) PYRIMIDINE ANTIFOLATE |
| WO2000013688A1 (en) * | 1998-09-04 | 2000-03-16 | Agouron Pharmaceuticals, Inc. | Compounds useful as aicarft inhibitors |
| EP1424336A4 (en) * | 2001-09-03 | 2004-11-10 | Takeda Chemical Industries Ltd | 1,3-BENZOTHIAZINE DERIVATIVES AND THEIR USE |
| AU2003258061A1 (en) * | 2002-08-02 | 2004-02-23 | Salmedix, Inc. | Therapeutic inhibitionof protein kinases in cancer cells |
| US20050165029A1 (en) * | 2004-01-13 | 2005-07-28 | Ambit Biosciences Corporation | Pyrrolopyrimidine derivatives and analogs and their use in the treatment and prevention of diseases |
| US8030319B2 (en) * | 2005-02-10 | 2011-10-04 | Duquesne University Of The Holy Ghost | Methods for treating cancer and other pathological proliferating disorders by inhibiting mitosis using pyrrolo[2 3-d]pyrimidines |
| US7981902B2 (en) * | 2006-06-28 | 2011-07-19 | Duquesne University Of The Holy Ghost | Substituted pyrrolo[2,3-d]pyrimidines for selectively targeting tumor cells with FR type receptors |
| US8258143B2 (en) * | 2006-06-28 | 2012-09-04 | Duquesne University Of The Holy Ghost | Methods of using substituted pyrrolo[2,3-d]pyrimidines for targeting tumor cells and treating cancer |
| US20090326224A1 (en) | 2006-09-01 | 2009-12-31 | Duquesne University Of The Holy Spirit | Thieno pyrimidine compounds |
| CN101195625A (zh) * | 2007-12-06 | 2008-06-11 | 上海交通大学 | 用于抗肿瘤药物抗叶酸剂及其盐和中间体 |
| US8252804B2 (en) | 2008-10-01 | 2012-08-28 | Duquesne University Of The Holy Spirit | Selective proton coupled folate transporter and folate receptor, and GARFTase inhibitor compounds and methods of using the same |
-
2008
- 2008-10-01 US US12/242,988 patent/US8252804B2/en not_active Expired - Fee Related
-
2009
- 2009-09-30 JP JP2011530162A patent/JP2012504631A/ja not_active Withdrawn
- 2009-09-30 WO PCT/US2009/058968 patent/WO2010039792A1/en not_active Ceased
- 2009-09-30 EP EP09818418.7A patent/EP2348843B1/en not_active Not-in-force
- 2009-09-30 EP EP15187759.4A patent/EP2995199B1/en not_active Not-in-force
- 2009-09-30 CA CA2993404A patent/CA2993404C/en not_active Expired - Fee Related
- 2009-09-30 CA CA2739250A patent/CA2739250C/en not_active Expired - Fee Related
-
2012
- 2012-07-26 US US13/558,873 patent/US9511069B2/en not_active Expired - Fee Related
-
2014
- 2014-09-08 JP JP2014182217A patent/JP2014224159A/ja active Pending
-
2016
- 2016-11-03 US US15/342,359 patent/US10000498B2/en active Active
-
2018
- 2018-06-06 US US16/000,954 patent/US10611767B2/en not_active Expired - Fee Related
-
2020
- 2020-02-26 US US16/801,943 patent/US11053252B2/en not_active Expired - Fee Related
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