WO2008142623A3 - Tumor necrosis factor - alpha inhibitors - Google Patents

Tumor necrosis factor - alpha inhibitors Download PDF

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Publication number
WO2008142623A3
WO2008142623A3 PCT/IB2008/051932 IB2008051932W WO2008142623A3 WO 2008142623 A3 WO2008142623 A3 WO 2008142623A3 IB 2008051932 W IB2008051932 W IB 2008051932W WO 2008142623 A3 WO2008142623 A3 WO 2008142623A3
Authority
WO
WIPO (PCT)
Prior art keywords
tnf
necrosis factor
tumor necrosis
pharmaceutically acceptable
present
Prior art date
Application number
PCT/IB2008/051932
Other languages
French (fr)
Other versions
WO2008142623A2 (en
Inventor
Sarala Balachandran
Ram Vishwakarma
Venkatrao Kaki
Vitthal Yadav
Siddheshwar Chauthe
Somesh Sharma
Sapna Parikh
Firuza Kharas
Original Assignee
Piramal Life Sciences Limited
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Piramal Life Sciences Limited filed Critical Piramal Life Sciences Limited
Publication of WO2008142623A2 publication Critical patent/WO2008142623A2/en
Publication of WO2008142623A3 publication Critical patent/WO2008142623A3/en

Links

Classifications

    • 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • C07D213/66—One oxygen atom attached in position 3 or 5 having in position 3 an oxygen atom and in each of the positions 4 and 5 a carbon atom bound to an oxygen, sulphur, or nitrogen atom, e.g. pyridoxal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

Abstract

The present invention relates to small molecules that inhibit Tumor Necrosis Factor- alpha (TNF-α), for example, by interaction with TNF-α protein or its receptor, thereby lowering the overall TNF-α activity, and that are represented by formula (1) or a stereoisomer thereof, tautomer thereof, or mixture thereof in any ratio; a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable polymorph thereof; wherein: A1, A2, X1, X2, n, R1, R2, R3 and R4 are as defined in the specification. The present invention also relates to processes for the preparation of these small molecules and to pharmaceutical compositions containing them. The present invention further relates to a method of treatment of disorders characterized by increased TNF- α activity, such as inflammation.
PCT/IB2008/051932 2007-05-17 2008-05-16 Tumor necrosis factor - alpha inhibitors WO2008142623A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US93054807P 2007-05-17 2007-05-17
US60/930,548 2007-05-17

Publications (2)

Publication Number Publication Date
WO2008142623A2 WO2008142623A2 (en) 2008-11-27
WO2008142623A3 true WO2008142623A3 (en) 2009-12-30

Family

ID=40032246

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2008/051932 WO2008142623A2 (en) 2007-05-17 2008-05-16 Tumor necrosis factor - alpha inhibitors

Country Status (1)

Country Link
WO (1) WO2008142623A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2741760A2 (en) 2011-08-12 2014-06-18 B.S.R.C. "Alexander Fleming" Tnf superfamily trimerization inhibitors
JP6275703B2 (en) 2012-06-08 2018-02-07 ユニバーシティ オブ ピッツバーグ オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション FBXO3 inhibitor
US9849098B2 (en) 2013-12-09 2017-12-26 University of Pittsburgh—of the Commonwealth System of Higher Education Compositions and methods for treating respiratory injury or disease
RU2713886C2 (en) * 2014-12-10 2020-02-10 Юниверсити Оф Питтсбург - Оф Зе Коммонвэлс Систем Оф Хайе Эдьюкейшн Compositions and methods of treating diseases and conditions

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999059959A1 (en) * 1998-05-15 1999-11-25 Astrazeneca Ab Benzamide derivatives for the treatment of diseases mediated by cytokines
US20030013708A1 (en) * 2001-01-16 2003-01-16 Edward Pierson Therapeutic heterocyclic compounds
WO2007004958A1 (en) * 2005-07-04 2007-01-11 Astrazeneca Ab Pyridopyrimidine derivatives as pde4 inhibitors for the treatment of inflammatory and' immune diseases

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999059959A1 (en) * 1998-05-15 1999-11-25 Astrazeneca Ab Benzamide derivatives for the treatment of diseases mediated by cytokines
US20030013708A1 (en) * 2001-01-16 2003-01-16 Edward Pierson Therapeutic heterocyclic compounds
WO2007004958A1 (en) * 2005-07-04 2007-01-11 Astrazeneca Ab Pyridopyrimidine derivatives as pde4 inhibitors for the treatment of inflammatory and' immune diseases

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
DATABASE PUBCHEM 4 March 2009 (2009-03-04), retrieved from http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pcsubstanceBDbFrom=pcsubstance&Cmd=Link& LinkName=pcsubstance_pcsubstance&LinkReadableName=Similar20Substances8ldsFromRes ult=56442818&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pcsubstance.Pcsubstan Results Panel.Pcsubstan_RVDocSum Database accession no. 25118614. *
DATABASE PUBCHEM. [online] 4 March 2009 (2009-03-04), retrieved from http://www.ncbi.nim.nih.gov/sites/entrez?Db=pcsubstance&DbFrom=pcsubstance&Cmd=Link &LinkName=pcsubstance_pcsubstance&LinkReadableName=Result=56442816[SID &ordinalpos=1&itool=EntrezSystem2.PEntrez.Pcsubstance.Pcsubstance_ResuItsPaneLPcsubs tance_RVDocSum Database accession no. 25118610. *
DATABASE PUBCHEM. 4 March 2009 (2009-03-04), retrieved from http://www.nGbi.nlm.nih.gov/sites/entrez?Db=pcsubstance&DbFrom=pcsubstance&Cmd=Link &LinkName=pcsubstance_csubstance&LinkReadableName=Result=44924038[SID]&ordinalp os=1&itool=EntrezSystem2.PEntrez.Pcsubstance.Pcsubstance ResuItsPanel.Pcsubstan_R VDocSum Database accession no. 9825905. *
HE ET AL.: "Small molecule inhibitors of TNF-alpha.", SCIENCE, vol. 310, November 2005 (2005-11-01), pages 1022 - 1025 *

Also Published As

Publication number Publication date
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