PE20110367A1 - DERIVADOS DE 4-CIANO-4-FENIL-PIRROLIDIN-2-CARBOXAMIDAS SUSTITUIDAS COMO INHIBIDORES DE LA INTERACCION p53-MDM2 - Google Patents

DERIVADOS DE 4-CIANO-4-FENIL-PIRROLIDIN-2-CARBOXAMIDAS SUSTITUIDAS COMO INHIBIDORES DE LA INTERACCION p53-MDM2

Info

Publication number
PE20110367A1
PE20110367A1 PE2011000600A PE2011000600A PE20110367A1 PE 20110367 A1 PE20110367 A1 PE 20110367A1 PE 2011000600 A PE2011000600 A PE 2011000600A PE 2011000600 A PE2011000600 A PE 2011000600A PE 20110367 A1 PE20110367 A1 PE 20110367A1
Authority
PE
Peru
Prior art keywords
phenyl
chloro
alkyl
pyrrolidin
interaction
Prior art date
Application number
PE2011000600A
Other languages
English (en)
Inventor
Quinjie Ding
Nan Jiang
Jin-Jun Liu
Tina Morgan Ross
Jing Zhang
Zhuming Zhang
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of PE20110367A1 publication Critical patent/PE20110367A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

REFERIDA A UN DERIVADO DE CARBOXAMIDA DE FORMULA (I), DONDE X ES H, F, Cl, CIANO, NITRO, ENTRE OTROS; Y ES H, F, OH, NITRO, ENTRE OTROS; R1 Y R2 SON ALQUILO C1-C6, CICLOALQUILO C3-C10, ALQUENILO C2-C6, ENTRE OTROS; R3 H O ALQUILO C1-C6; R4 Y R5 SON ALQUILO C1-C6, ALQUENILO C2-C6, ARILO C6-C10, ENTRE OTROS; R6 Y R7 SON (CH2)n-R', (CH2)n-NR'R'', (CH2)n-NR'COR'', ENTRE OTROS; R' Y R'' SON H, ALQUILO C1-C6, CICLOALQUILO C3-C10, ENTRE OTROS; n ES UN ENTERO DE 0 A 6. SON COMPUESTOS PREFERIDOS: (2-MORFOLIN-4-ILETIL)-AMIDA DEL ACIDO rac-(2R,3R,4R,5S)-3-(3-CLOROFENIL)-4-(4-CLORO-FENIL)-4-CIANO-5-(2,2-DIMETIL-PROPIL)-PIRROLIDINA-2-CARBOXILICO, rac-(2S,3R.4R,5R)-4-(3-CLORO-FENIL)-3-(4-CLORO-FENIL)-2-(2,2-DIMETIL-PROPIL)-5-[4-(2-MORFOLIN-4-IL-2-OXO-ETIL)-PIPERAZINA-1-CARBONIL]-PIRROLIDINA-3-CARBONITRILO, rac-(2S,3R.4R,5R)-4-(3-CLORO-FENIL)-3-(4-CLORO-FENIL)-2-(2,2-DIMETIL-PROPIL)-5-[4-(2-OXO-2-PIRROLIDIN-1-IL-ETIL)-PIPERAZINA-1-CARBONIL]-PIRROLIDINA-3-CARBONITRILO, ENTRE OTROS. TAMBIEN ESTA REFERIDA A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS INHIBEN LA INTERACCION ENTRE LAS PROTEINAS p53 Y MDM2 Y SON UTILES EN EL TRATAMIENTO DEL CANCER
PE2011000600A 2008-09-18 2009-09-08 DERIVADOS DE 4-CIANO-4-FENIL-PIRROLIDIN-2-CARBOXAMIDAS SUSTITUIDAS COMO INHIBIDORES DE LA INTERACCION p53-MDM2 PE20110367A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US9788408P 2008-09-18 2008-09-18
US22563309P 2009-07-15 2009-07-15

Publications (1)

Publication Number Publication Date
PE20110367A1 true PE20110367A1 (es) 2011-06-13

Family

ID=41402151

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2011000600A PE20110367A1 (es) 2008-09-18 2009-09-08 DERIVADOS DE 4-CIANO-4-FENIL-PIRROLIDIN-2-CARBOXAMIDAS SUSTITUIDAS COMO INHIBIDORES DE LA INTERACCION p53-MDM2

Country Status (29)

Country Link
US (1) US20100075948A1 (es)
EP (1) EP2340021B1 (es)
JP (1) JP5658157B2 (es)
KR (1) KR101380013B1 (es)
CN (1) CN102159207B (es)
AR (1) AR073598A1 (es)
AU (1) AU2009294673B2 (es)
BR (1) BRPI0919325A2 (es)
CA (1) CA2734363C (es)
CL (1) CL2011000589A1 (es)
CO (1) CO6361910A2 (es)
CR (1) CR20110099A (es)
DK (1) DK2340021T3 (es)
EC (1) ECSP11010898A (es)
ES (1) ES2398342T3 (es)
HR (1) HRP20130047T1 (es)
IL (1) IL211167A0 (es)
MA (1) MA32711B1 (es)
MX (1) MX2011002976A (es)
MY (1) MY160424A (es)
NZ (1) NZ591024A (es)
PE (1) PE20110367A1 (es)
PL (1) PL2340021T3 (es)
PT (1) PT2340021E (es)
RS (1) RS52660B (es)
RU (1) RU2506257C2 (es)
TW (1) TWI367207B (es)
WO (1) WO2010031713A1 (es)
ZA (1) ZA201101740B (es)

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US8088815B2 (en) * 2009-12-02 2012-01-03 Hoffman-La Roche Inc. Spiroindolinone pyrrolidines
JO2998B1 (ar) 2010-06-04 2016-09-05 Amgen Inc مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان
US20120010235A1 (en) * 2010-07-12 2012-01-12 Xin-Jie Chu N-substituted pyrrolidines
US20120046306A1 (en) * 2010-08-18 2012-02-23 David Joseph Bartkovitz Substituted Heteroaryl Spiropyrrolidine MDM2 Antagonists
CN101898998B (zh) * 2010-08-25 2012-09-19 武汉武药科技有限公司 一种盐酸替罗非班中间体的制备方法
US20120065210A1 (en) 2010-09-15 2012-03-15 Xin-Jie Chu Substituted hexahydropyrrolo[1,2-c]imidazolones
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EP3131544B1 (en) 2014-04-17 2018-12-12 The Regents of the University of Michigan Mdm2 inhibitors and therapeutic methods using the same
KR102595395B1 (ko) 2015-02-20 2023-10-27 다이이찌 산쿄 가부시키가이샤 암의 병용 치료법
CA2982435C (en) 2015-04-13 2020-05-26 Daiichi Sankyo Company, Limited Treatment method by combined use of mdm2 inhibitor and btk inhibitor
GB201517216D0 (en) 2015-09-29 2015-11-11 Cancer Res Technology Ltd And Astex Therapeutics Ltd Pharmaceutical compounds
GB201517217D0 (en) 2015-09-29 2015-11-11 Astex Therapeutics Ltd And Cancer Res Technology Ltd Pharmaceutical compounds
JPWO2018074387A1 (ja) 2016-10-17 2019-08-08 第一三共株式会社 Ｍｄｍ２阻害剤とｄｎａメチルトランスフェラーゼ阻害剤との併用治療法
KR102122469B1 (ko) 2016-11-01 2020-06-12 주식회사 엘지화학 변성 공액디엔계 중합체 및 이의 제조방법
GB201704965D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
GB201704966D0 (en) 2017-03-28 2017-05-10 Astex Therapeutics Ltd Pharmaceutical compounds
ES3008911T3 (en) 2017-07-11 2025-03-25 Vertex Pharma Carboxamides as modulators of sodium channels
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JOP20220130A1 (ar) 2019-12-06 2023-01-30 Vertex Pharma مجموعات تترا هيدروفيوران بها استبدال في صورة عوامل تعديل لقنوات الصوديوم
TW202313593A (zh) 2021-06-04 2023-04-01 美商維泰克斯製藥公司 作為鈉通道調節劑之ｎ—（羥基烷基（雜）芳基）四氫呋喃甲醯胺

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Also Published As

Publication number Publication date
BRPI0919325A2 (pt) 2021-03-30
ECSP11010898A (es) 2011-04-29
MY160424A (en) 2017-03-15
JP5658157B2 (ja) 2015-01-21
JP2012502940A (ja) 2012-02-02
AR073598A1 (es) 2010-11-17
CO6361910A2 (es) 2012-01-20
MX2011002976A (es) 2011-04-11
IL211167A0 (en) 2011-04-28
RU2011115111A (ru) 2012-10-27
CL2011000589A1 (es) 2011-08-12
PT2340021E (pt) 2013-01-25
TW201012798A (en) 2010-04-01
PL2340021T3 (pl) 2013-04-30
EP2340021B1 (en) 2012-11-07
TWI367207B (en) 2012-07-01
CN102159207A (zh) 2011-08-17
CA2734363C (en) 2016-10-25
HRP20130047T1 (hr) 2013-02-28
EP2340021A1 (en) 2011-07-06
NZ591024A (en) 2013-01-25
CA2734363A1 (en) 2010-03-25
AU2009294673A1 (en) 2010-03-25
AU2009294673B2 (en) 2014-08-14
KR20110040989A (ko) 2011-04-20
ZA201101740B (en) 2013-08-28
KR101380013B1 (ko) 2014-04-10
HK1160399A1 (en) 2012-08-17
US20100075948A1 (en) 2010-03-25
RU2506257C2 (ru) 2014-02-10
CN102159207B (zh) 2015-02-04
WO2010031713A1 (en) 2010-03-25
CR20110099A (es) 2011-04-04
MA32711B1 (fr) 2011-10-02
ES2398342T3 (es) 2013-03-15
RS52660B (en) 2013-06-28
DK2340021T3 (da) 2012-12-10

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