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PE20141405A1 - Nuevos derivados de indolizina, su procedimiento de preparacion y las composiciones farmaceuticas que los contienen - Google Patents

Nuevos derivados de indolizina, su procedimiento de preparacion y las composiciones farmaceuticas que los contienen

Info

Publication number
PE20141405A1
PE20141405A1 PE2014001076A PE2014001076A PE20141405A1 PE 20141405 A1 PE20141405 A1 PE 20141405A1 PE 2014001076 A PE2014001076 A PE 2014001076A PE 2014001076 A PE2014001076 A PE 2014001076A PE 20141405 A1 PE20141405 A1 PE 20141405A1
Authority
PE
Peru
Prior art keywords
indolizine
preparation procedure
alkyl
pharmaceutical compositions
compositions containing
Prior art date
Application number
PE2014001076A
Other languages
English (en)
Inventor
Diguarher Thierry Le
Patrick Casara
Jerome Benoit Starck
Jean-Michel Henlin
James Edward Paul Davidson
James Brooke Murray
Christopher John Graham
I-Jen Chen
Olivier Geneste
John Hickman
Stephane Depil
Tiran Arnaud Le
Miklos Nyerges
Nanteuil Guillaume De
Original Assignee
Servier Lab
Vernalis Randd Ltd
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 Servier Lab, Vernalis Randd Ltd filed Critical Servier Lab
Publication of PE20141405A1 publication Critical patent/PE20141405A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/472Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47Quinolines; Isoquinolines
    • A61K31/475Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53831,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541Non-condensed thiazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
    • A61N5/1001X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic 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
    • C07D207/30Heterocyclic 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 two double bonds between ring members or between ring members and non-ring members
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/80Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
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    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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    • C07D491/02Heterocyclic 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
    • C07D491/04Ortho-condensed systems
    • C07D491/044Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Pathology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Indole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

SE REFIERE A COMPUESTOS DERIVADOS DE INDOLIZINA DE FORMULA (I) DONDE X E Y SON CADA UNO C O N; HET ES UN CICLO AROMATICO O NO DE 5 A 7 MIEMBROS; R1 Y R2 SON CADA UNO H, ALQUILO(C1-C6), ENTRE OTROS; R3 ES ALQUILO(C1-C6), ALQUENILO(C2-C6), CICLOALQUILO, ENTRE OTROS; R4 ES ARILO, HETEROARILO, CICLOALQUILO, ENTRE OTROS; R5 ES H O HALOGENO; Ra, Rb, Rc Y Rd SON CADA UNO HALOGENO, ALQUILO(C1-C6), ALCOXI(C1-C6), HIDROXI, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: N-(4-HIDROXIFENIL)-3-{6-[((3S)-3-(4-MORFOLINILMETIL)-3,4-DIHIDRO-2(1H)-ISOQUINOLINIL)CARBONIL]-1,3-BENZODIOXOL-5-IL}-N-FENIL-5,6,7,8-TETRAHIDRO-1-INDOLIZINA CARBOXAMIDA; 3-{5-CLORO-2-[((3S)-3-(4-MORFOLINILMETIL)-3,4-DIHIDRO-2(1H)-ISOQUINOLINIL)-CARBONIL]FENIL}-N-(4-HIDROXIFENIL)-N-(1-METIL-1H-INDOL-5-IL)-5,6,7,8-TETRAHIDRO-1-INDOLIZINA CARBOXAMIDA; ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO DE PREPARACION Y A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON INHIBIDORES DE LA ACTIVIDAD ANTI-APOPTOTICA DE LAS PROTEINAS Bcl-2 SIENDO UTILES EN EL TRATAMIENTO DE LEUCEMIA, MELANOMA, CANCER DE PULMON DE CELULAS NO PEQUENAS
PE2014001076A 2012-01-24 2013-01-23 Nuevos derivados de indolizina, su procedimiento de preparacion y las composiciones farmaceuticas que los contienen PE20141405A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
FR1200193A FR2986002B1 (fr) 2012-01-24 2012-01-24 Nouveaux derives d'indolizine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent

Publications (1)

Publication Number Publication Date
PE20141405A1 true PE20141405A1 (es) 2014-10-20

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PE2014001076A PE20141405A1 (es) 2012-01-24 2013-01-23 Nuevos derivados de indolizina, su procedimiento de preparacion y las composiciones farmaceuticas que los contienen

Country Status (50)

Country Link
US (3) US9120791B2 (es)
EP (1) EP2807159B1 (es)
JP (1) JP5978317B2 (es)
KR (1) KR101946911B1 (es)
CN (1) CN104144930B (es)
AP (1) AP4028A (es)
AR (1) AR089774A1 (es)
AU (1) AU2013213474B2 (es)
BR (1) BR112014018165B1 (es)
CA (1) CA2861160C (es)
CL (1) CL2014001829A1 (es)
CR (1) CR20140311A (es)
CU (1) CU20140089A7 (es)
CY (1) CY1118547T1 (es)
DK (1) DK2807159T3 (es)
DO (1) DOP2014000156A (es)
EA (1) EA026641B1 (es)
EC (1) ECSP14008606A (es)
ES (1) ES2616679T3 (es)
FR (1) FR2986002B1 (es)
GE (1) GEP201606540B (es)
GT (1) GT201400142A (es)
HK (1) HK1203507A1 (es)
HR (1) HRP20170153T1 (es)
HU (1) HUE031895T2 (es)
IL (1) IL233663B (es)
JO (1) JO3195B1 (es)
LT (1) LT2807159T (es)
MA (1) MA35903B1 (es)
MD (1) MD4490C1 (es)
ME (1) ME02601B (es)
MX (1) MX351206B (es)
MY (1) MY172811A (es)
NI (1) NI201400081A (es)
NZ (1) NZ626942A (es)
PE (1) PE20141405A1 (es)
PH (1) PH12014501488B1 (es)
PL (1) PL2807159T3 (es)
PT (1) PT2807159T (es)
RS (1) RS55739B1 (es)
RU (1) RU2646223C2 (es)
SA (1) SA113340219B1 (es)
SG (1) SG11201403748RA (es)
SI (1) SI2807159T1 (es)
TN (1) TN2014000283A1 (es)
TW (1) TWI476198B (es)
UA (1) UA112215C2 (es)
UY (1) UY34578A (es)
WO (1) WO2013110890A1 (es)
ZA (1) ZA201405101B (es)

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FR2986002B1 (fr) 2012-01-24 2014-02-21 Servier Lab Nouveaux derives d'indolizine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR3008979B1 (fr) * 2013-07-23 2015-07-24 Servier Lab Nouveaux derives phosphates, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR3008977A1 (fr) * 2013-07-23 2015-01-30 Servier Lab Nouveaux derives d'isoindoline ou d'isoquinoline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR3008976A1 (fr) 2013-07-23 2015-01-30 Servier Lab "nouveaux derives d'indolizine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent"
FR3008978A1 (fr) * 2013-07-23 2015-01-30 Servier Lab "nouveaux derives d'indole et de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent"
FR3008975A1 (fr) * 2013-07-23 2015-01-30 Servier Lab Nouveaux derives de pyrrole, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR3015483B1 (fr) * 2013-12-23 2016-01-01 Servier Lab Nouveaux derives de thienopyrimidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
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FR3037958B1 (fr) * 2015-06-23 2019-01-25 Les Laboratoires Servier Nouveaux derives d'hydroxy-acide, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR3037959B1 (fr) * 2015-06-23 2017-08-04 Servier Lab Nouveaux derives bicycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR3037956B1 (fr) * 2015-06-23 2017-08-04 Servier Lab Nouveaux derives d'acide amine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
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WO2019020070A1 (zh) 2017-07-27 2019-01-31 江苏恒瑞医药股份有限公司 哌嗪并杂芳基类衍生物、其制备方法及其在医药上的应用
FR3072679B1 (fr) * 2017-10-25 2020-10-30 Servier Lab Nouveaux derives macrocycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO2019134970A1 (en) 2018-01-05 2019-07-11 Les Laboratoires Servier Novel salts of a bcl-2 inhibitor,related crystalline forms,method for preparing the same and pharmaceutical compositions containing the same
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US20220211718A1 (en) 2019-05-14 2022-07-07 Les Laboratoires Servier Bcl-2 inhibitors for use in the treatment of a bcl-2 mediated cancer carrying the gly101val mutation
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