PE20120640A1 - Nuevos derivados de (6-oxo-1,6-dihidro-pirimidin-2-il)-amida, su preparacion y su utilizacion farmaceutica como inhibidores de fosforilacion de akt (pkb) - Google Patents

Nuevos derivados de (6-oxo-1,6-dihidro-pirimidin-2-il)-amida, su preparacion y su utilizacion farmaceutica como inhibidores de fosforilacion de akt (pkb)

Info

Publication number
PE20120640A1
PE20120640A1 PE2012000004A PE2012000004A PE20120640A1 PE 20120640 A1 PE20120640 A1 PE 20120640A1 PE 2012000004 A PE2012000004 A PE 2012000004A PE 2012000004 A PE2012000004 A PE 2012000004A PE 20120640 A1 PE20120640 A1 PE 20120640A1
Authority
PE
Peru
Prior art keywords
oxo
pkb
inhibitors
amide
halogen
Prior art date
Application number
PE2012000004A
Other languages
English (en)
Inventor
Jean-Christophe Carry
Victor Certal
Frank Halley
Karl Andreas Karlsson
Laurent Schio
Fabienne Thompson
Original Assignee
Sanofi Sa
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
Priority claimed from FR0903239A external-priority patent/FR2947547B1/fr
Priority claimed from FR0957070A external-priority patent/FR2951169B1/fr
Application filed by Sanofi Sa filed Critical Sanofi Sa
Publication of PE20120640A1 publication Critical patent/PE20120640A1/es

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    • 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
    • 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
    • C07D413/12—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

SE REFIERE A COMPUESTOS DERIVADOS DE (6-OXO-1,6-DIHIDRO-PIRIMIDIN-2-IL)-AMIDA DE FORMULA (I) DONDE R1 ES ARILO O HETEROARILO OPCIONALMENTE SUSTITUIDOS CON HALOGENO, CN, FENOXI, ENTRE OTROS; R ES H O FORMA CON R1 UN CICLO DE 5 A 6 MIEMBROS FUSIONADO A UN ARILO O HETEROARILO; R2 Y R3 SON CADA UNO H, HALOGENO O ALQUILO OPCIONALMENTE SUSTITUIDO CON HALOGENO; R4 ES H; R5 ES H O ALQUILO OPCIONALMENTE SUSTITUIDO CON HALOGENO. SON COMPUESTOS PREFERIDOS: 2-[4-(MORFOLIN-4-IL)-6-OXO-1,6-DIHIDROPIRIMIDIN-2-IL]-N-FENILACETAMIDA; N-(4-FLUOROFENIL)-2-[4-(MORFOLIN-4-IL)-6-OXO-1,6-DIHIDROPIRIMIDIN-2-IL]ACETAMIDA; N-(3-CLOROFENIL)-2-[4-(MORFOLIN-4-IL)-6-OXO-1,6-DIHIDROPIRIMIDIN-2-IL]ACETAMIDA; ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO DE PREPARACION Y A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON INHIBIDORES DE LA FOSFORILACION DE AKT (PKB) SIENDO UTILES EN EL TRATAMIENTO DE GLIOBLASTOMA, CANCER DE MAMA, MELANOMA, SARCOMA
PE2012000004A 2009-07-02 2010-07-01 Nuevos derivados de (6-oxo-1,6-dihidro-pirimidin-2-il)-amida, su preparacion y su utilizacion farmaceutica como inhibidores de fosforilacion de akt (pkb) PE20120640A1 (es)

Applications Claiming Priority (3)

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)

Publications (1)

Publication Number Publication Date
PE20120640A1 true PE20120640A1 (es) 2012-06-09

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PE2012000004A PE20120640A1 (es) 2009-07-02 2010-07-01 Nuevos derivados de (6-oxo-1,6-dihidro-pirimidin-2-il)-amida, su preparacion y su utilizacion farmaceutica como inhibidores de fosforilacion de akt (pkb)

Country Status (37)

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

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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)
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)
LT2658844T (lt) 2010-12-28 2017-02-10 Sanofi Nauji pirimidino dariniai, jų gamyba ir jų farmacinis panaudojimas kaip akt (pkb) fosforilinimo slopiklių
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)
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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
CA2904770A1 (en) 2013-03-15 2014-09-18 Sanofi Anti-tumoral composition comprising a pi3kbeta inhibitor and a raf inhibitor, to overcome cancer cells resistance
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Publication number Publication date
CO6480974A2 (es) 2012-07-16
AU2010267816B2 (en) 2015-11-12
NZ597579A (en) 2013-06-28
TWI466883B (zh) 2015-01-01
US20120270867A1 (en) 2012-10-25
MA33501B1 (fr) 2012-08-01
MY153042A (en) 2014-12-31
CL2012000003A1 (es) 2012-08-03
EA021088B1 (ru) 2015-04-30
HN2011003482A (es) 2014-11-10
ECSP12011570A (es) 2012-02-29
TW201103924A (en) 2011-02-01
WO2011001114A1 (fr) 2011-01-06
DK2448927T3 (da) 2014-06-16
SMT201400084B (it) 2014-09-08
US8993565B2 (en) 2015-03-31
CR20110703A (es) 2012-03-06
HK1169110A1 (en) 2013-01-18
US20140303156A1 (en) 2014-10-09
SG10201402867TA (en) 2014-08-28
SI2448927T1 (sl) 2014-06-30
EP2448927B1 (fr) 2014-03-12
PL2448927T3 (pl) 2014-09-30
US8791255B2 (en) 2014-07-29
HRP20140478T1 (hr) 2014-07-04
JP2012531464A (ja) 2012-12-10
KR20120106714A (ko) 2012-09-26
CA2767064A1 (fr) 2011-01-06
JP5680638B2 (ja) 2015-03-04
ZA201200026B (en) 2013-03-27
PT2448927E (pt) 2014-06-12
NI201200002A (es) 2012-03-30
CN102548970B (zh) 2015-11-25
CA2767064C (fr) 2017-11-07
MX2012000094A (es) 2012-05-22
EA201270111A1 (ru) 2012-07-30
SG177469A1 (en) 2012-02-28
CN102548970A (zh) 2012-07-04
EP2448927A1 (fr) 2012-05-09
DOP2011000407A (es) 2012-06-15
AR077364A1 (es) 2011-08-24
IL217295A (en) 2015-10-29
IL217295A0 (en) 2012-02-29
ME01885B (me) 2014-12-20
RS53317B (en) 2014-10-31
AU2010267816A1 (en) 2012-02-16
UY32755A (es) 2011-01-31
ES2464125T3 (es) 2014-05-30
IL217321A0 (en) 2012-02-29

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