AR044703A1 - CIS-2,4,5 TRIARIL- IMIDAZOLINAS AND ITS ANTIPROLIFERATIVE ACTIVITY - Google Patents

CIS-2,4,5 TRIARIL- IMIDAZOLINAS AND ITS ANTIPROLIFERATIVE ACTIVITY

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AR044703A1
AR044703A1 ARP040102068A ARP040102068A AR044703A1 AR 044703 A1 AR044703 A1 AR 044703A1 AR P040102068 A ARP040102068 A AR P040102068A AR P040102068 A ARP040102068 A AR P040102068A AR 044703 A1 AR044703 A1 AR 044703A1
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Argentina
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lower alkyl
substituted
group
heterocycle
chosen
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ARP040102068A
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Spanish (es)
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Hoffmann La Roche
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    • 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/20—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D233/22—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D233/30—Oxygen or sulfur atoms
    • C07D233/32—One oxygen atom
    • C07D233/36—One oxygen atom with hydrocarbon radicals, substituted by nitrogen atoms, attached to ring nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • 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
    • C07D401/10—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 aromatic rings
    • 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
    • C07D403/06—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
    • 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

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

Abstract

Estos compuestos inhiben la interacción de la proteína MDM2 con un péptido del tipo p53 y tienen actividad antiproliferativa. Reivindicación 1: Por lo menos un compuesto elegido entre los compuestos de la fórmula (1), en la que: X1 y X2 son halógeno; X3 es alcoxi inferior; R se elige entre un resto del grupo de fórmulas (2), en las que: R1 se elige entre el grupo formado por: N-alquilo inferior; heterociclo sin sustituir y heterociclo sustituido con uno o varios sustituyentes elegidos entre el grupo formado por: NH2, NH-C(O)-alquilo inferior, C(O)-alquilo inferior, C(O)-alcoxi inferior, oxo, heterociclo y alquilo inferior sustituido con hidroxi; R2 se elige entre hidrógeno y metilo; R3 se elige entre el grupo formado por: heteroarilo; heterociclo; y CH2-R7; R4 se elige entre el grupo formado por: C(O)-alcoxi inferior; alcoxi inferior; -CH2-N-alquilo inferior; CH2-heterociclo; CH2-heterociclo sustituido con oxo; arilo; NH-C(S)-alquilo inferior; NH-C(S)-N-arilo y NH- C(O)-R8; R5 se elige entre el grupo formado por oxo; heteroarilo; arilo sustituido con un sustituyente elegido entre alcoxi inferior y flúor; C(S)-N-alquilo inferior; C(S)-N-arilo; C(O)-CH2-R12; C(O)-R13; SO2-R14 y alquilo inferior sustituido con un sustituyente elegido entre R15 y C(O)-R16; R6 se elige entre el grupo formado por: alquilo inferior sustituido con N-alquilo inferior; heterociclo inferior sustituido con heterociclo; alquilo inferior sustituido con heterociclo sustituido con uno o dos sustituyentes elegidos entre alquilo inferior, alquilo inferior sustituido con hidroxilalquilo inferior sustituido con alcoxi inferior y oxo; R7 se elige entre el grupo formado por: ciano; hidroxi; alcoxi inferior; heteroarilo; heterociclo; heterociclo sustituido con oxo; N-alquilo inferior; y arilo sustituido con un sustituyente elegido entre el grupo formado por SO2NH2, alcoxi inferior e hidroxi; R8 se elige entre el grupo formado por: N-alquilo inferior; heterociclo; heterociclo sustituido con un sustituyente elegido entre el grupo formado por oxo, C(O)-NH2 y C(O)-NH-alquilo inferior; CH2-R9 y CH2-R10; R9 se elige entre el grupo formado por: NH2; N-alquilo inferior; N-alquilo inferior sustituido con un sustituyente elegido entre hidroxi y alcoxi inferior; C(O)-NH-alcoxi inferior; C(O)-NH-benciloxi; C(O)-heterociclo sustituido con un sustituyente elegido entre trifluormetilo e hidroxi y C(O)-NH-R11; R10 se elige entre un heterociclo y heterociclo sustituido con uno o varios grupos elegidos entre el grupo formado por C(O)-alquilo inferior, C(O)-NH2, C(O)-N-alquilo inferior, alquilo inferior sustituido con hidroxi, hidroxi, alcoxi inferior y oxo; R11 se elige entre alquilo inferior; y alquilo inferior sustituido con un sustituyente elegido entre el grupo formado por alcoxi, heteroarilo sustituido con alquilo inferior, ciano y trifluormetilo; R12 se elige entre el grupo formado por alcoxi inferior; NH2; N-alquilo inferior; N-alquilo inferior sustituido con un sustituyente elegido entre hidroxi y alcoxi inferior; heteroarilo; y heterociclo sustituido con R17; R13 se elige entre el grupo formado por: heteroarilo; heteroarilo sustituido con uno o dos sustituyentes elegidos entre el grupo formado por alquilo inferior, arilo y halógeno; heterociclo; heterociclo sustituido con uno o varios sustituyentes elegidos entre el grupo formado por alquilo inferior, arilo y halógeno; C(O)-alquilo inferior; C(O)-NH2; C(O)-N-alquilo inferior; y oxo; R14 se elige entre el grupo formado por: trifluormetilo; alquilo inferior; arilo sustituido con alquilo inferior; NH2; N-alquilo inferior; N-alquilo inferior sustituido con un sustituyente elegido entre alcoxi inferior y ciano; heteroarilo; heteroarilo sustituido con un sustituyente elegido entre el grupo formado por halógeno, hidroxi, oxo, C(O)-alcoxi inferior, alquilo inferior y alquilo inferior sustituido con hidroxilo; heterociclo y heterociclo sustituido con un sustituyente elegido entre el grupo formado por halógeno, hidroxi, oxo, C(O)-alcoxi inferior, alquilo inferior y alquilo inferior sustituido con hidroxilo; R15 se elige entre el grupo formado por alcoxi inferior; ciano; trifluormetilo; N-alquilo inferior; SO2-alquilo inferior; C(O)-alquilo inferior; SO2-NH2; SO2-N-alquilo inferior; heteroarilo y heterociclo; R16 se elige entre el grupo formado por: alcoxi inferior; NH2; N-alquilo inferior; N-alcoxi inferior; N-benciloxi; N-alquilo inferior sustituido con R18; heterociclo y heterociclo sustituido con uno o dos sustituyentes elegidos entre el grupo formado por hidroxi, alcoxi, trifluormetilo, C(O)-alquilo inferior, C(O)-NH2, C(O)-N-alquilo inferior, alquilo inferior sustituido con hidroxi y oxo; R17 se elige entre el grupo formado por: C(O) -alquilo inferior; C(O)-NH2; C(O)-N-alquilo inferior; hidroxi; oxo y alquilo inferior sustituido con hidroxi; y R18 se elige entre el grupo formado por: alcoxi inferior; ciano; trifluormetilo; heterociclo e hidroxilo; o una sal o un éster farmacéuticamente aceptable del mismo.These compounds inhibit the interaction of the MDM2 protein with a peptide of the p53 type and have antiproliferative activity. Claim 1: At least one compound chosen from the compounds of the formula (1), wherein: X1 and X2 are halogen; X3 is lower alkoxy; R is chosen from a remainder of the group of formulas (2), in which: R1 is selected from the group consisting of: N-lower alkyl; unsubstituted heterocycle and substituted heterocycle with one or more substituents selected from the group consisting of: NH2, NH-C (O) -alkyl, C (O) -alkyl, C (O) -alkoxy, oxo, heterocycle and lower alkyl substituted with hydroxy; R2 is chosen from hydrogen and methyl; R3 is chosen from the group consisting of: heteroaryl; heterocycle; and CH2-R7; R4 is chosen from the group consisting of: C (O) -alkoxy lower; lower alkoxy; -CH2-N-lower alkyl; CH2-heterocycle; CH2-oxo substituted heterocycle; aryl; NH-C (S) -alkyl lower; NH-C (S) -N-aryl and NH-C (O) -R8; R5 is chosen from the group consisting of oxo; heteroaryl; aryl substituted with a substituent chosen from lower alkoxy and fluorine; C (S) -N-lower alkyl; C (S) -N-aryl; C (O) -CH2-R12; C (O) -R13; SO2-R14 and lower alkyl substituted with a substituent selected from R15 and C (O) -R16; R6 is selected from the group consisting of: lower alkyl substituted with N-lower alkyl; lower heterocycle substituted with heterocycle; lower alkyl substituted with heterocycle substituted with one or two substituents chosen from lower alkyl, lower alkyl substituted with lower hydroxylalkyl substituted with lower alkoxy and oxo; R7 is chosen from the group consisting of: cyano; hydroxy; lower alkoxy; heteroaryl; heterocycle; oxo substituted heterocycle; N-lower alkyl; and aryl substituted with a substituent selected from the group consisting of SO2NH2, lower alkoxy and hydroxy; R8 is chosen from the group consisting of: N-lower alkyl; heterocycle; heterocycle substituted with a substituent selected from the group consisting of oxo, C (O) -NH2 and C (O) -NH-lower alkyl; CH2-R9 and CH2-R10; R9 is chosen from the group consisting of: NH2; N-lower alkyl; N-lower alkyl substituted with a substituent selected from hydroxy and lower alkoxy; C (O) -NH-lower alkoxy; C (O) -NH-benzyloxy; C (O) -heterocycle substituted with a substituent selected from trifluoromethyl and hydroxy and C (O) -NH-R11; R10 is chosen from a heterocycle and heterocycle substituted with one or more groups selected from the group consisting of C (O) -alkyl, C (O) -NH2, C (O) -N-lower alkyl, lower alkyl substituted with hydroxy , hydroxy, lower alkoxy and oxo; R11 is chosen from lower alkyl; and lower alkyl substituted with a substituent selected from the group consisting of alkoxy, heteroaryl substituted with lower alkyl, cyano and trifluoromethyl; R12 is chosen from the group consisting of lower alkoxy; NH2; N-lower alkyl; N-lower alkyl substituted with a substituent selected from hydroxy and lower alkoxy; heteroaryl; and heterocycle substituted with R17; R13 is chosen from the group consisting of: heteroaryl; heteroaryl substituted with one or two substituents chosen from the group consisting of lower alkyl, aryl and halogen; heterocycle; heterocycle substituted with one or more substituents chosen from the group consisting of lower alkyl, aryl and halogen; C (O) -alkyl lower; C (O) -NH2; C (O) -N-lower alkyl; and oxo; R14 is chosen from the group consisting of: trifluoromethyl; lower alkyl; aryl substituted with lower alkyl; NH2; N-lower alkyl; N-lower alkyl substituted with a substituent selected from lower alkoxy and cyano; heteroaryl; heteroaryl substituted with a substituent selected from the group consisting of halogen, hydroxy, oxo, C (O) -alkoxy lower, lower alkyl and lower alkyl substituted with hydroxyl; heterocycle and heterocycle substituted with a substituent selected from the group consisting of halogen, hydroxy, oxo, C (O) -alkoxy lower, lower alkyl and lower alkyl substituted with hydroxyl; R15 is chosen from the group consisting of lower alkoxy; cyano; trifluoromethyl; N-lower alkyl; SO2-lower alkyl; C (O) -alkyl lower; SO2-NH2; SO2-N-lower alkyl; heteroaryl and heterocycle; R16 is chosen from the group consisting of: lower alkoxy; NH2; N-lower alkyl; N-lower alkoxy; N-benzyloxy; N-lower alkyl substituted with R18; heterocycle and heterocycle substituted with one or two substituents selected from the group consisting of hydroxy, alkoxy, trifluoromethyl, C (O) -alkyl, C (O) -NH2, C (O) -N-lower alkyl, lower alkyl substituted with hydroxy and oxo; R17 is chosen from the group consisting of: C (O) -alkyl lower; C (O) -NH2; C (O) -N-lower alkyl; hydroxy; oxo and lower alkyl substituted with hydroxy; and R18 is chosen from the group consisting of: lower alkoxy; cyano; trifluoromethyl; heterocycle and hydroxyl; or a pharmaceutically acceptable salt or ester thereof.

ARP040102068A 2003-06-17 2004-06-15 CIS-2,4,5 TRIARIL- IMIDAZOLINAS AND ITS ANTIPROLIFERATIVE ACTIVITY AR044703A1 (en)

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CA (1) CA2528119A1 (en)
CL (1) CL2004001484A1 (en)
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WO2009151069A1 (en) 2008-06-12 2009-12-17 第一三共株式会社 Imidazothiazole derivative having 4,7-diazaspiro[2.5]octane ring structure
MX2011007598A (en) 2009-01-16 2011-08-08 Daiichi Sankyo Co Ltd Imidazothiazole derivative having proline ring structure.
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WO2017201449A1 (en) 2016-05-20 2017-11-23 Genentech, Inc. Protac antibody conjugates and methods of use
EP3883925A4 (en) * 2018-11-20 2021-12-29 Sironax Ltd Cyclic ureas
WO2023056069A1 (en) 2021-09-30 2023-04-06 Angiex, Inc. Degrader-antibody conjugates and methods of using same

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DE10043456A1 (en) * 2000-09-04 2002-03-14 Merck Patent Gmbh Use of ectoin or ectoin derivatives to stabilize p53
WO2003051359A1 (en) * 2001-12-18 2003-06-26 F.Hoffmann-La Roche Ag Cis-2,4,5- triphenyl-imidazolines and their use in the treatment of tumors

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TW200510387A (en) 2005-03-16
RU2006100730A (en) 2006-08-10
CA2528119A1 (en) 2005-01-13
MXPA05013279A (en) 2006-03-09
CN100465163C (en) 2009-03-04
WO2005003097A1 (en) 2005-01-13
BRPI0411841A (en) 2006-08-08
JP2006527712A (en) 2006-12-07
KR20060021902A (en) 2006-03-08
RU2319696C2 (en) 2008-03-20
CL2004001484A1 (en) 2005-05-27

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