WO2011041737A3 - Gain-of-function bcl-2 inhibitors - Google Patents
Gain-of-function bcl-2 inhibitors Download PDFInfo
- Publication number
- WO2011041737A3 WO2011041737A3 PCT/US2010/051208 US2010051208W WO2011041737A3 WO 2011041737 A3 WO2011041737 A3 WO 2011041737A3 US 2010051208 W US2010051208 W US 2010051208W WO 2011041737 A3 WO2011041737 A3 WO 2011041737A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- bcl
- inhibitors
- gain
- function
- bci
- Prior art date
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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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/76—Nitrogen atoms to which a second hetero atom is attached
- C07D213/77—Hydrazine radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/20—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings
- C07C205/21—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings having nitro groups and hydroxy groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C205/22—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings having nitro groups and hydroxy groups bound to carbon atoms of the same non-condensed six-membered aromatic ring having one nitro groups bound to the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/72—Hydrazones
- C07C251/86—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to carbon atoms of six-membered aromatic rings
-
- 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
- C07C323/10—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 singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/18—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 singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/20—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 singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C39/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring
- C07C39/12—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings
- C07C39/15—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring polycyclic with no unsaturation outside the aromatic rings with all hydroxy groups on non-condensed rings, e.g. phenylphenol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/257—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings
- C07C43/295—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
- C07C69/16—Acetic acid esters of dihydroxylic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/12—Acetic acid esters
- C07C69/18—Acetic acid esters of trihydroxylic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
- C07C69/22—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety
- C07C69/30—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen having three or more carbon atoms in the acid moiety esterified with trihydroxylic compounds
-
- 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
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/53—Nitrogen atoms
Abstract
Compounds are described that are useful for treating an apoptosis-associated disease, which are specifically cytotoxic to tumor cells that are overexpressing BcI-XL, and are much less cytotoxic in isogenic cells that are not overexpressing BcI-XL. Methods of using such compounds to treat apoptosis-associated disease is also described.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13/437,795 US8865901B2 (en) | 2009-10-02 | 2012-04-02 | Gain-of-function Bcl-2 inhibitors |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US24830409P | 2009-10-02 | 2009-10-02 | |
US61/248,304 | 2009-10-02 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2010/051201 Continuation-In-Part WO2011041731A2 (en) | 2009-10-02 | 2010-10-01 | Method of inhibiting bcl-2-related survival proteins |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/437,795 Continuation-In-Part US8865901B2 (en) | 2009-10-02 | 2012-04-02 | Gain-of-function Bcl-2 inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2011041737A2 WO2011041737A2 (en) | 2011-04-07 |
WO2011041737A3 true WO2011041737A3 (en) | 2011-08-18 |
Family
ID=43446833
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2010/051208 WO2011041737A2 (en) | 2009-10-02 | 2010-10-01 | Gain-of-function bcl-2 inhibitors |
Country Status (1)
Country | Link |
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WO (1) | WO2011041737A2 (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8865901B2 (en) | 2009-10-02 | 2014-10-21 | Fred Hutchinson Cancer Research Center | Gain-of-function Bcl-2 inhibitors |
CZ303748B6 (en) * | 2011-10-11 | 2013-04-17 | Vysoká skola chemicko - technologická v Praze | Phathalazin-1-ylhydrazones and their use in the treatment of tumor diseases |
JP2015501792A (en) * | 2011-11-10 | 2015-01-19 | メモリアル スローン−ケタリング キャンサー センター | Treatment of ovarian cancer with benzylidene benzohydrazide |
CZ306554B6 (en) * | 2014-05-09 | 2017-03-08 | Vysoká škola chemicko - technologická v Praze | Benzoisothiazole-1,1-dioxide-3-hydrazones and their use in anticancer therapy |
CN111909082B (en) * | 2019-05-07 | 2022-09-13 | 湖南大学 | Pyridine hydrazone derivatives, and preparation method and application thereof |
Citations (3)
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WO2002089745A2 (en) * | 2001-05-10 | 2002-11-14 | Cytovia, Inc. | Substituted n'-(arylcarbonyl)-benzhydrazides, n'-(arylcarbonyl)-benzylidene-hydrazides and analogs as activators of caspases and inducers of apoptosis and the use thereof |
WO2006029850A1 (en) * | 2004-09-14 | 2006-03-23 | The Genetics Company, Inc. | Hydrazone derivatives and their use as beta secretase inhibitors |
WO2010083307A2 (en) * | 2009-01-14 | 2010-07-22 | Dow Agrosciences Llc | Synergistic fungicidal compositions including hydrazone derivatives and copper |
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EA200000087A1 (en) | 1997-07-01 | 2000-08-28 | Атеродженикс, Инк. | EFFICIENCY EFFICIENCY IMPROVEMENT OF HYPERPROLIFERATIVE STATE THERAPY WITH THE HELP OF ANTIOXIDANT |
US5848379A (en) | 1997-07-11 | 1998-12-08 | Exxon Production Research Company | Method for characterizing subsurface petrophysical properties using linear shape attributes |
US20050239873A1 (en) | 1999-08-20 | 2005-10-27 | Fred Hutchinson Cancer Research Center | 2 Methoxy antimycin a derivatives and methods of use |
JP2001078776A (en) | 1999-09-14 | 2001-03-27 | Inst Of Physical & Chemical Res | Nade-binding protein |
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WO2008021211A2 (en) | 2006-08-10 | 2008-02-21 | Fred Hutchinson Cancer Research Center | Compositions and methods for modulating apoptosis in cells over-expressing bcl-2 family member proteins |
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2010
- 2010-10-01 WO PCT/US2010/051208 patent/WO2011041737A2/en active Application Filing
Patent Citations (3)
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WO2002089745A2 (en) * | 2001-05-10 | 2002-11-14 | Cytovia, Inc. | Substituted n'-(arylcarbonyl)-benzhydrazides, n'-(arylcarbonyl)-benzylidene-hydrazides and analogs as activators of caspases and inducers of apoptosis and the use thereof |
WO2006029850A1 (en) * | 2004-09-14 | 2006-03-23 | The Genetics Company, Inc. | Hydrazone derivatives and their use as beta secretase inhibitors |
WO2010083307A2 (en) * | 2009-01-14 | 2010-07-22 | Dow Agrosciences Llc | Synergistic fungicidal compositions including hydrazone derivatives and copper |
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