ES2269688T3 - Benzoilsulfonamidas y sulfonilbenzamidinas para su uso como agentes antitumorales. - Google Patents
Benzoilsulfonamidas y sulfonilbenzamidinas para su uso como agentes antitumorales. Download PDFInfo
- Publication number
- ES2269688T3 ES2269688T3 ES02729196T ES02729196T ES2269688T3 ES 2269688 T3 ES2269688 T3 ES 2269688T3 ES 02729196 T ES02729196 T ES 02729196T ES 02729196 T ES02729196 T ES 02729196T ES 2269688 T3 ES2269688 T3 ES 2269688T3
- Authority
- ES
- Spain
- Prior art keywords
- hydrogen
- alkyl
- halo
- alkoxy
- 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.)
- Expired - Lifetime
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- 239000002246 antineoplastic agent Substances 0.000 title description 7
- 239000001257 hydrogen Substances 0.000 claims abstract description 73
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 73
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 125000005843 halogen group Chemical group 0.000 claims abstract description 50
- 239000000460 chlorine Substances 0.000 claims abstract description 44
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 39
- -1 hydroxy, phenyl Chemical group 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 18
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims abstract description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 17
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 13
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 11
- 125000002541 furyl group Chemical group 0.000 claims abstract description 11
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 11
- 125000001425 triazolyl group Chemical group 0.000 claims abstract description 11
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 10
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 125000001246 bromo group Chemical group Br* 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 239000011737 fluorine Chemical group 0.000 claims abstract description 6
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 6
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- 125000000217 alkyl group Chemical group 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 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 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
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- AZJXTFAKHUFRQY-UHFFFAOYSA-N 4-bromo-2-chloro-n-(4-chlorophenyl)sulfonylbenzamide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)NC(=O)C1=CC=C(Br)C=C1Cl AZJXTFAKHUFRQY-UHFFFAOYSA-N 0.000 claims description 4
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 2
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- SNEWXKIDJFOZMO-UHFFFAOYSA-N 4-chloro-n-(4-chlorophenyl)sulfonyl-2-methylbenzamide Chemical compound CC1=CC(Cl)=CC=C1C(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 SNEWXKIDJFOZMO-UHFFFAOYSA-N 0.000 claims 1
- 208000015634 Rectal Neoplasms Diseases 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 2
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- 238000000034 method Methods 0.000 description 22
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
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- 239000011347 resin Substances 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 230000033115 angiogenesis Effects 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 6
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- 229940083542 sodium Drugs 0.000 description 6
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- 241000699666 Mus <mouse, genus> Species 0.000 description 5
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- 239000012298 atmosphere Substances 0.000 description 5
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/51—Y being a hydrogen or a carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/64—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton
- C07C323/67—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton containing sulfur atoms of sulfonamide groups, bound to the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
- C07D213/34—Sulfur atoms to which a second hetero atom is attached
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/18—Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Quinoline Compounds (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29635001P | 2001-06-06 | 2001-06-06 | |
| US296350P | 2001-06-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2269688T3 true ES2269688T3 (es) | 2007-04-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02729196T Expired - Lifetime ES2269688T3 (es) | 2001-06-06 | 2002-05-24 | Benzoilsulfonamidas y sulfonilbenzamidinas para su uso como agentes antitumorales. |
Country Status (35)
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60316984T2 (de) * | 2002-11-22 | 2008-07-17 | Eli Lilly And Co., Indianapolis | Benzoylsulfonamide als antitumor-mittel |
| US7767684B2 (en) | 2003-11-13 | 2010-08-03 | Abbott Laboratories | Apoptosis promoters |
| US8614318B2 (en) | 2003-11-13 | 2013-12-24 | Abbvie Inc. | Apoptosis promoters |
| US7973161B2 (en) | 2003-11-13 | 2011-07-05 | Abbott Laboratories | Apoptosis promoters |
| WO2005049593A2 (en) | 2003-11-13 | 2005-06-02 | Abbott Laboratories | N-acylsulfonamide apoptosis promoters |
| JP5284641B2 (ja) * | 2004-05-26 | 2013-09-11 | アボット・ラボラトリーズ | N−スルホニルカルボキシイミドアミドアポトーシス促進剤 |
| JP5134247B2 (ja) * | 2004-09-13 | 2013-01-30 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | スルホンアミド含有化合物の血管新生阻害物質との併用 |
| WO2006030947A1 (ja) * | 2004-09-13 | 2006-03-23 | Eisai R & D Management Co., Ltd. | スルホンアミド含有化合物の血管新生阻害物質との併用 |
| US8772269B2 (en) | 2004-09-13 | 2014-07-08 | Eisai R&D Management Co., Ltd. | Use of sulfonamide-including compounds in combination with angiogenesis inhibitors |
| DE602006021401D1 (de) * | 2005-02-28 | 2011-06-01 | Eisai R&D Man Co Ltd | Neue kombinierte anwendung einer sulfonamid-verbindung zur behandlung von krebs |
| KR20070114774A (ko) * | 2005-02-28 | 2007-12-04 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 술폰아미드 화합물의 혈관 신생 저해 물질과의 신규 병용 |
| WO2006090921A1 (ja) * | 2005-02-28 | 2006-08-31 | Eisai R & D Management Co., Ltd. | スルホンアミド化合物のリンパ球活性化抑制作用 |
| TWI337608B (en) | 2005-05-12 | 2011-02-21 | Abbott Lab | Apoptosis promoters |
| US8624027B2 (en) | 2005-05-12 | 2014-01-07 | Abbvie Inc. | Combination therapy for treating cancer and diagnostic assays for use therein |
| US7208526B2 (en) | 2005-05-20 | 2007-04-24 | Hoffmann-La Roche Inc. | Styrylsulfonamides |
| US7208506B2 (en) | 2005-07-07 | 2007-04-24 | Hoffmann-La Roche Inc. | Heteroarylethenyl derivatives, their manufacture and use as pharmaceutical agents |
| US7625896B2 (en) * | 2005-11-25 | 2009-12-01 | Hoffman-La Roche Inc. | Pyridylsulfonamide derivatives |
| JPWO2007123274A1 (ja) | 2006-04-20 | 2009-09-10 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | スルホンアミド化合物の新規感受性マーカー |
| MX2009002422A (es) | 2006-09-05 | 2009-03-20 | Abbott Lab | Inhibidores bcl para tratar exceso de plaquetas. |
| US7939532B2 (en) * | 2006-10-26 | 2011-05-10 | Hoffmann-La Roche Inc. | Heterocyclyl pyridyl sulfonamide derivatives, their manufacture and use as pharmaceutical agents |
| US7879884B2 (en) | 2007-05-16 | 2011-02-01 | Hoffmann-La Roche Inc. | Aryl pyridyl sulfonamide derivatives, their manufacture and use as pharmaceutical agents |
| US20100160322A1 (en) | 2008-12-04 | 2010-06-24 | Abbott Laboratories | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| US8557983B2 (en) | 2008-12-04 | 2013-10-15 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| US8563735B2 (en) | 2008-12-05 | 2013-10-22 | Abbvie Inc. | Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
| US8586754B2 (en) | 2008-12-05 | 2013-11-19 | Abbvie Inc. | BCL-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
| HUE025527T2 (en) * | 2009-01-19 | 2016-04-28 | Abbvie Inc | Apoptosis inducers for the treatment of cancer, immune and autoimmune diseases |
| JP2012136435A (ja) * | 2009-03-30 | 2012-07-19 | Eisai R & D Management Co Ltd | 腫瘍組織の感受性を検査する方法 |
| KR200457823Y1 (ko) * | 2009-05-08 | 2012-01-05 | 황정용 | 쭈꾸미 포획용 어구 |
| US20220315555A1 (en) | 2009-05-26 | 2022-10-06 | Abbvie Inc. | Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases |
| US9034875B2 (en) | 2009-05-26 | 2015-05-19 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| US8546399B2 (en) | 2009-05-26 | 2013-10-01 | Abbvie Inc. | Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases |
| PH12015500297B1 (en) | 2009-05-26 | 2023-10-20 | Abbvie Ireland Unlimited Co | Adoptosis-inducing agents for the treatment of cancer and immune and automoimmune disease |
| DK2550258T3 (en) * | 2010-03-25 | 2015-12-07 | Abbvie Inc | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| UA113500C2 (xx) | 2010-10-29 | 2017-02-10 | Одержані екструзією розплаву тверді дисперсії, що містять індукуючий апоптоз засіб | |
| KR20180059560A (ko) | 2010-10-29 | 2018-06-04 | 애브비 인코포레이티드 | 아폽토시스―유도제를 포함하는 고체 분산체 |
| PH12013501006A1 (en) | 2010-11-23 | 2022-03-30 | Abbvie Ireland Unlimited Co | Methods of treatment using selective bcl-2 inhibitors |
| PT2643322T (pt) | 2010-11-23 | 2017-11-13 | Abbvie Inc | Sais e formas cristalinas de um agente indutor de apoptose |
| CN103159649B (zh) * | 2011-12-19 | 2016-03-09 | 天津市国际生物医药联合研究院 | 磺酰胺类化合物的制备及其应用 |
| CN103159650B (zh) * | 2011-12-19 | 2016-04-20 | 天津市国际生物医药联合研究院 | 芳香杂环磺酰胺类化合物的制备及其应用 |
| US20140275082A1 (en) | 2013-03-14 | 2014-09-18 | Abbvie Inc. | Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases |
| CN105712925B (zh) * | 2014-12-05 | 2019-01-04 | 沈阳中化农药化工研发有限公司 | 一种取代的磺酰胺基(硫代)羰基化合物及其用途 |
| ES3038757T3 (en) | 2015-02-13 | 2025-10-14 | Oxford Drug Design Ltd | Novel n-acyl-arylsulfonamide derivatives as aminoacyl-trna synthetase inhibitors |
| CN105753748B (zh) * | 2016-02-15 | 2018-05-29 | 南京励合化学新材料有限公司 | 一种医药中间体磺酰类化合物的合成方法 |
| GB201617064D0 (en) | 2016-10-07 | 2016-11-23 | Inhibox Limited And Latvian Institute Of Organic Synthesis The | Compounds and their therapeutic use |
| SI3612531T1 (sl) | 2017-04-18 | 2022-11-30 | Shanghai Fochon Pharmaceutical Co., Ltd. | Sredstva, ki sprožajo apoptozo |
| US11479532B2 (en) * | 2017-06-23 | 2022-10-25 | University Of South Florida | 5-aminolevulinate synthase inhibitors and methods of use thereof |
| JP7164784B2 (ja) * | 2017-12-29 | 2022-11-02 | 共信醫藥科技股分有限公司 | ベンゼンスルホンアミド誘導体および脂質ラフトの調節方法 |
| CN114790149B (zh) * | 2021-01-26 | 2024-11-19 | 江苏中旗科技股份有限公司 | 一种以2-氯-4-氟苯胺为原料合成2-氯-4-氟苯甲酸的方法 |
| WO2025031360A1 (zh) * | 2023-08-09 | 2025-02-13 | 上海科技大学 | 磺酰胺类化合物及其用途 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4157257A (en) | 1976-10-01 | 1979-06-05 | Utsunomiya University | Benzenesulfonamide derivatives |
| US4347380A (en) * | 1979-04-20 | 1982-08-31 | Stauffer Chemical Company | N-Acylsulfonamide herbicidal antidotes |
| US4433997A (en) * | 1979-04-20 | 1984-02-28 | Stauffer Chemical Co | N-Acylsulfonamide herbicidal antidotes |
| US4266078A (en) * | 1979-04-20 | 1981-05-05 | Stauffer Chemical Company | N-Acylsulfonamide herbicidal antidotes |
| US4495365A (en) * | 1980-11-21 | 1985-01-22 | Stauffer Chemical Co. | N-Acylsulfonamide herbicidal antidotes |
| US4845128A (en) * | 1984-06-27 | 1989-07-04 | Eli Lilly And Company | N([(4-trifluoromethylphenyl)amino]carbonyl)benzene sulfonamides |
| US5110830A (en) * | 1984-06-27 | 1992-05-05 | Eli Lilly And Company | Benzenesulfonamides treatment of tumors susceptible to |
| JP2679498B2 (ja) * | 1991-12-25 | 1997-11-19 | 王子製紙株式会社 | 感熱記録体 |
| CA2110524A1 (en) | 1992-12-10 | 1994-06-11 | Gerald Burr Grindey | Antitumor compositions and methods of treatment |
| JPH0747772A (ja) * | 1993-08-05 | 1995-02-21 | New Oji Paper Co Ltd | 感熱記録体 |
| AU5772196A (en) | 1995-05-19 | 1996-11-29 | Chiroscience Limited | 3,4-disubstituted-phenylsulphonamides and their therapeutic use |
| DE69628050T2 (de) | 1995-10-25 | 2004-04-01 | Senju Pharmaceutical Co., Ltd. | Angiogenese Hemmer |
| US5929097A (en) | 1996-10-16 | 1999-07-27 | American Cyanamid Company | Preparation and use of ortho-sulfonamido aryl hydroxamic acids as matrix metalloproteinase and tace inhibitors |
| US6380167B1 (en) * | 1999-02-12 | 2002-04-30 | Primecyte, Inc. | Methods for anti-tumor therapy |
| US20020055631A1 (en) | 2000-09-20 | 2002-05-09 | Augeri David J. | N-acylsulfonamide apoptosis promoters |
| AR031130A1 (es) | 2000-09-20 | 2003-09-10 | Abbott Lab | N-acilsulfonamidas promotoras de la apoptosis |
| US6720338B2 (en) | 2000-09-20 | 2004-04-13 | Abbott Laboratories | N-acylsulfonamide apoptosis promoters |
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2002
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- 2002-05-24 EP EP02729196A patent/EP1401806B1/en not_active Expired - Lifetime
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- 2002-05-24 BR BR0210078-9A patent/BR0210078A/pt not_active IP Right Cessation
- 2002-05-24 HR HR20031000A patent/HRP20031000A2/xx not_active Application Discontinuation
- 2002-05-24 MX MXPA03011197A patent/MXPA03011197A/es active IP Right Grant
- 2002-05-24 CA CA002446719A patent/CA2446719A1/en not_active Abandoned
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- 2002-05-24 DE DE60213810T patent/DE60213810T2/de not_active Expired - Fee Related
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