EA201270111A1 - Новые производные (6-оксо-1,6-дигидропиримидин-2-ил)амида, их получение и их фармацевтическое применение в качестве ингибиторов фосфорилирования акт(ркв) - Google Patents

Новые производные (6-оксо-1,6-дигидропиримидин-2-ил)амида, их получение и их фармацевтическое применение в качестве ингибиторов фосфорилирования акт(ркв)

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Publication number
EA201270111A1
EA201270111A1 EA201270111A EA201270111A EA201270111A1 EA 201270111 A1 EA201270111 A1 EA 201270111A1 EA 201270111 A EA201270111 A EA 201270111A EA 201270111 A EA201270111 A EA 201270111A EA 201270111 A1 EA201270111 A1 EA 201270111A1
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EA
Eurasian Patent Office
Prior art keywords
phypholyltation
amida
rvc
dihydropyrimidin
oxo
Prior art date
Application number
EA201270111A
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English (en)
Other versions
EA021088B1 (ru
Inventor
Жан-Кристоф Карри
Виктор Серталь
Франк Алле
Карл Андреас Карлссон
Лоран Шио
Фабьенн Томсон
Original Assignee
Санофи
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Publication date
Priority claimed from FR0903239A external-priority patent/FR2947547B1/fr
Priority claimed from FR0957070A external-priority patent/FR2951169B1/fr
Application filed by Санофи filed Critical Санофи
Publication of EA201270111A1 publication Critical patent/EA201270111A1/ru
Publication of EA021088B1 publication Critical patent/EA021088B1/ru

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
    • 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
    • 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
    • C07D403/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D403/10—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 carbon chain containing aromatic 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
    • C07D405/12—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
    • 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
    • C07D413/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Abstract

Настоящее изобретение относится к новым продуктам формулы (I), в которой R1 означает необязательно замещенные арил или гетероарил; R означает Н или же вместе с R1 образует 5- или 6-членный цикл, конденсированный с арильным или гетероарильным остатком, необязательно включающий один или несколько О, S, N, NH или Nalk, являющийся необязательно замещенным; R2, R3 независимо означают Н, галоген или алкил, необязательно замещенный одним или несколькими атомами галогена; R4 означает Н; R5 означает Н или алкил, необязательно замещенный одним или несколькими атомами галогена; причем эти продукты находятся во всех изомерных формах и в виде солей; в качестве лекарственных средств, в частности в качестве ингибиторов фосфорилирования АКТ(РКВ).
EA201270111A 2009-07-02 2010-07-01 Производные (6-оксо-1,6-дигидропиримидин-2-ил)амида, их получение и их фармацевтическое применение в качестве ингибиторов фосфорилирования akt (pkb) EA021088B1 (ru)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
FR0903239A FR2947547B1 (fr) 2009-07-02 2009-07-02 Nouveaux derives de (6-oxo-1,6-dihydro-pyrimidin-2-yl)-amide, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt (pkb)
US24110009P 2009-09-10 2009-09-10
FR0957070A FR2951169B1 (fr) 2009-10-09 2009-10-09 Nouveaux derives de (6-oxo-1,6-dihydro-pyrimidin-2-yl)-amide, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb)
PCT/FR2010/051375 WO2011001114A1 (fr) 2009-07-02 2010-07-01 Nouveaux derives de (6-oxo-1,6-dihydro-pyrimidin-2-yl)-amide, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb)

Publications (2)

Publication Number Publication Date
EA201270111A1 true EA201270111A1 (ru) 2012-07-30
EA021088B1 EA021088B1 (ru) 2015-04-30

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EA201270111A EA021088B1 (ru) 2009-07-02 2010-07-01 Производные (6-оксо-1,6-дигидропиримидин-2-ил)амида, их получение и их фармацевтическое применение в качестве ингибиторов фосфорилирования akt (pkb)

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US (2) US8791255B2 (ru)
EP (1) EP2448927B1 (ru)
JP (1) JP5680638B2 (ru)
KR (1) KR20120106714A (ru)
CN (1) CN102548970B (ru)
AR (1) AR077364A1 (ru)
AU (1) AU2010267816B2 (ru)
CA (1) CA2767064C (ru)
CL (1) CL2012000003A1 (ru)
CO (1) CO6480974A2 (ru)
CR (1) CR20110703A (ru)
DK (1) DK2448927T3 (ru)
DO (1) DOP2011000407A (ru)
EA (1) EA021088B1 (ru)
EC (1) ECSP12011570A (ru)
ES (1) ES2464125T3 (ru)
HK (1) HK1169110A1 (ru)
HN (1) HN2011003482A (ru)
HR (1) HRP20140478T1 (ru)
IL (2) IL217295A (ru)
MA (1) MA33501B1 (ru)
ME (1) ME01885B (ru)
MX (1) MX2012000094A (ru)
MY (1) MY153042A (ru)
NI (1) NI201200002A (ru)
NZ (1) NZ597579A (ru)
PE (1) PE20120640A1 (ru)
PL (1) PL2448927T3 (ru)
PT (1) PT2448927E (ru)
RS (1) RS53317B (ru)
SG (2) SG10201402867TA (ru)
SI (1) SI2448927T1 (ru)
SM (1) SMT201400084B (ru)
TW (1) TWI466883B (ru)
UY (1) UY32755A (ru)
WO (1) WO2011001114A1 (ru)
ZA (1) ZA201200026B (ru)

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FR2969614A1 (fr) * 2010-12-28 2012-06-29 Sanofi Aventis Nouveaux derives de pyrimidinones, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb)
ES2612492T3 (es) 2010-12-28 2017-05-17 Sanofi Nuevos derivados de piridiminas, su preparación y su utilización farmacéutica como inhibidores de fosforilación de AKT (PKB)
FR2969609B1 (fr) * 2010-12-28 2013-02-08 Sanofi Aventis Nouveaux derives de 6-oxo-dihydro-pyrimidine, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb)
FR2969610B1 (fr) * 2010-12-28 2013-04-05 Sanofi Aventis Nouveaux derives de (6-oxo-1,6-dihydro-pyrimidin-2-yl)-indolinamide, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt(pkb)
RU2013141559A (ru) * 2011-02-11 2015-03-20 Дана-Фарбер Кэнсер Инститьют, Инк. Способ ингибирования клеток опухоли гамартомы
EP2570127A1 (en) 2011-09-16 2013-03-20 Sanofi Compositions and methods for treating cancer using PI3KB beta inhibitor and MAPK pathway inhibitor, including MEK and RAF inhibitors
JP2016516682A (ja) 2013-03-15 2016-06-09 サノフイ 癌細胞の耐性を克服するための、ｐｉ３ｋベータ阻害剤およびｒａｆ阻害剤を含む抗腫瘍組成物
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Publication number Publication date
EP2448927B1 (fr) 2014-03-12
CN102548970A (zh) 2012-07-04
PL2448927T3 (pl) 2014-09-30
HRP20140478T1 (hr) 2014-07-04
HK1169110A1 (en) 2013-01-18
US20120270867A1 (en) 2012-10-25
IL217295A0 (en) 2012-02-29
US20140303156A1 (en) 2014-10-09
WO2011001114A1 (fr) 2011-01-06
HN2011003482A (es) 2014-11-10
KR20120106714A (ko) 2012-09-26
MY153042A (en) 2014-12-31
US8993565B2 (en) 2015-03-31
IL217295A (en) 2015-10-29
CN102548970B (zh) 2015-11-25
NI201200002A (es) 2012-03-30
ME01885B (me) 2014-12-20
DOP2011000407A (es) 2012-06-15
US8791255B2 (en) 2014-07-29
UY32755A (es) 2011-01-31
JP5680638B2 (ja) 2015-03-04
PE20120640A1 (es) 2012-06-09
ECSP12011570A (es) 2012-02-29
CA2767064A1 (fr) 2011-01-06
AU2010267816B2 (en) 2015-11-12
CL2012000003A1 (es) 2012-08-03
AU2010267816A1 (en) 2012-02-16
SG177469A1 (en) 2012-02-28
SMT201400084B (it) 2014-09-08
RS53317B (en) 2014-10-31
MX2012000094A (es) 2012-05-22
NZ597579A (en) 2013-06-28
JP2012531464A (ja) 2012-12-10
IL217321A0 (en) 2012-02-29
MA33501B1 (fr) 2012-08-01
EA021088B1 (ru) 2015-04-30
EP2448927A1 (fr) 2012-05-09
ES2464125T3 (es) 2014-05-30
TW201103924A (en) 2011-02-01
CO6480974A2 (es) 2012-07-16
ZA201200026B (en) 2013-03-27
SI2448927T1 (sl) 2014-06-30
TWI466883B (zh) 2015-01-01
AR077364A1 (es) 2011-08-24
CA2767064C (fr) 2017-11-07
PT2448927E (pt) 2014-06-12
SG10201402867TA (en) 2014-08-28
DK2448927T3 (da) 2014-06-16
CR20110703A (es) 2012-03-06

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