AR038619A1 - Derivados de 2-piridinil y 2-pirimidinil-6,7,8,9-tetrahidropirimido(1,2-a)pirimidin-4-ona substituidos por heteroarilo - Google Patents

Derivados de 2-piridinil y 2-pirimidinil-6,7,8,9-tetrahidropirimido(1,2-a)pirimidin-4-ona substituidos por heteroarilo

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Publication number
AR038619A1
AR038619A1 ARP030100657A ARP030100657A AR038619A1 AR 038619 A1 AR038619 A1 AR 038619A1 AR P030100657 A ARP030100657 A AR P030100657A AR P030100657 A ARP030100657 A AR P030100657A AR 038619 A1 AR038619 A1 AR 038619A1
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AR
Argentina
Prior art keywords
group
atom
ring
alkyl group
equal
Prior art date
Application number
ARP030100657A
Other languages
English (en)
Inventor
Mourad Saady
Philippe Yaiche
Alistair Lochead
Alain Nedelec
Original Assignee
Sanofi Aventis
Mitsubishi Pharma Corp
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 EP02290485A external-priority patent/EP1340758A1/en
Priority claimed from EP02290486A external-priority patent/EP1348708A1/en
Application filed by Sanofi Aventis, Mitsubishi Pharma Corp filed Critical Sanofi Aventis
Publication of AR038619A1 publication Critical patent/AR038619A1/es

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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/14Drugs for dermatological disorders for baldness or alopecia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/02Drugs for disorders of the nervous system for peripheral neuropathies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/34Tobacco-abuse
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/06Antiglaucoma agents or miotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • C07D487/04Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
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  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Psychiatry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Addiction (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Pest Control & Pesticides (AREA)
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  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Psychology (AREA)
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  • Agronomy & Crop Science (AREA)
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  • Plant Pathology (AREA)
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Abstract

Un medicamento que comprende dicho derivado ó una sal del mismo como ingrediente activo, que se utiliza para el tratamiento preventivo y/o terapéutico de una enfermedad neurodegenerativa causada por la actividad anormal de la GSK3beta o de la GSK3beta y la cdk5/p25, como ser enfermedad de Alzheimer. Reivindicación 1:Un derivado de pirimidona representado por la fórmula (1) ó una sal del mismo, ó un solvato del mismo ó un hidrato del mismo, caracterizado porque: X representa dos átomos de hidrógeno, un átomo de azufre, un átomo de oxígeno ó un grupo alquilo C1-2 y un átomo de hidrógeno; Y representa un enlace, un grupo etenileno, un grupo etinileno ó un grupo metileno opcionalmente sustituido por uno o dos grupos seleccionados entre un grupo alquilo C1-6, un grupo hidroxi ó un grupo alcoxi C1-4; R1 representa un anillo de 2, 3 ó 4-piridina ó un anillo de 2, 4 ó 5-pirimidina, y el anillo está opcionalmente sustituido por un grupo cicloalquilo C3-6, un grupo alquilo C1-4, un grupo alcoxi C1-4, un grupo bencilo ó un átomo de halógeno; R2 representa anillos bicíclicos heterocíclicos, que tienen entre 1 y 4 heteroátomos seleccionados entre un átomo de oxígeno, un átomo de azufre y un átomo de nitrógeno, y que tienen C5-9, de fórmula (2) donde A, B, C y D representan, cada uno independientemente, un átomo de carbono ó un átomo de nitrógeno, y W representa un anillo cíclico de 5, 6 ó 7 miembros saturado o insaturado, que tiene C3-7 y entre 2 y 0 heteroátomos tales como un átomo de oxígeno, un átomo de azufre ó un átomo de nitrógeno; el grupo R2 está opcionalmente sustituido en un átomo de carbono ó, cuando fuere posible, en un átomo de nitrógeno por uno ó dos átomos ó grupo seleccionados entre un átomo de halógeno, un grupo alquilo C1-6, un grupo hidroxi, un grupo alcoxi C1-4, un anillo de benceno, un anillo de piridina ó un grupo -NR6R7; R3 representa un átomo de hidrógeno, un grupo alquilo C1-6, un grupo hidroxi, un grupo alcoxi C1-4 ó un átomo de halógeno; R4 representa un átomo de hidrógeno, un grupo alquilo C1-6, un grupo alcoxi C1-4 ó un átomo de halógeno; R5 representa un átomo de hidrógeno, un grupo alquilo C1-6, un grupo alquilo perhalogenado C1-2, un grupo alquilo halogenado C1-3 ó un átomo de halógeno; R6 y R7 representan, cada uno independientemente un átomo de hidrógeno, un grupo alquilo C1-6, un grupo bencilo, un anillo de benceno, ó R6 y R7 representan conjuntamente con el átomo de nitrógeno, un anillo de pirrolidina, un anillo de piperidina, un anillo de hexametilenimina, un anillo de morfolina ó un anillo de piperazina, y el anillo está opcionalmente sustituido por 1 ó 2 grupos alquilo C1-6; cuando m es igual a 0, p es igual a 1, 2 ó 3; cuando m es igual a 1, p es igual a 0, 1 ó 2; cuando m es igual a 2, p es igual a 0 ó 1; cuando m es igual a 3, p es igual a 0; y n representa entre 0 y 3; con la condición de que el derivado de fórmula (1) no sea: 9-[2-(1H-indol-3-il)etil]-2-piridin-4-il-6,7,8,9-tetrahidro-4H-pirimido[1,2-a]pirimidin-4-ona; 9-[3-(1H-indol-3-il)propil]-2-piridin-4-il-6,7,8,9-tetrahidro-4H-pirimido[1,2-a]pirimidin-4-ona; 1-[2-(1H-indol-3-il)etil]-7-piridin-4-il-2,3-dihidroimidazo[1,2-a]pirimidin-5(1H)-ona; ó 1-[3-(1H-indol-3-il)propil]-7-piridin-4-il-2,3-dihidroimidazo[1,2-a]pirimidin-5(1H)-ona.
ARP030100657A 2002-02-28 2003-02-28 Derivados de 2-piridinil y 2-pirimidinil-6,7,8,9-tetrahidropirimido(1,2-a)pirimidin-4-ona substituidos por heteroarilo AR038619A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP02290485A EP1340758A1 (en) 2002-02-28 2002-02-28 Heteroaryl substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)one derivatives
EP02290486A EP1348708A1 (en) 2002-02-28 2002-02-28 Heteroaryl substituted 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 7-pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)one derivatives

Publications (1)

Publication Number Publication Date
AR038619A1 true AR038619A1 (es) 2005-01-19

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ID=27767034

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ARP030100657A AR038619A1 (es) 2002-02-28 2003-02-28 Derivados de 2-piridinil y 2-pirimidinil-6,7,8,9-tetrahidropirimido(1,2-a)pirimidin-4-ona substituidos por heteroarilo

Country Status (22)

Country Link
US (2) US7232827B2 (es)
EP (1) EP1480983B1 (es)
JP (1) JP4458851B2 (es)
KR (1) KR101030629B1 (es)
CN (1) CN1315832C (es)
AR (1) AR038619A1 (es)
AT (1) ATE309247T1 (es)
AU (1) AU2003221500B9 (es)
BR (1) BR0308109A (es)
CA (1) CA2474823C (es)
DE (1) DE60302221T2 (es)
DK (1) DK1480983T3 (es)
EA (1) EA007737B1 (es)
ES (1) ES2250883T3 (es)
IL (1) IL163287A (es)
MX (1) MXPA04008364A (es)
NO (1) NO329805B1 (es)
NZ (1) NZ534466A (es)
PL (1) PL372465A1 (es)
SI (1) SI1480983T1 (es)
TW (1) TWI303637B (es)
WO (1) WO2003072579A1 (es)

Families Citing this family (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1454910A1 (en) 2003-03-07 2004-09-08 Sanofi-Synthelabo Substituted pyrimidinyl-2-(diaza-bicyclo-alkyl)-pyrimidone derivatives
BRPI0408186A (pt) 2003-03-07 2006-04-04 Sanofi Aventis derivados de 2-(diaza-biciclo-alquil)-pirimidona substituìdos
EP1557417B1 (en) * 2003-12-19 2007-03-07 Sanofi-Aventis Substituted 8'-pyri(mi)dinyl-dihydrospiro-[cycloalkylamine]-pyrimido[1,2-a] pyrimidin-6-one derivatives
WO2005083105A2 (en) * 2004-02-26 2005-09-09 Bayer Healthcare Ag Diagnostics and therapeutics for diseases associated with glycogen synthase kinase 3 beta (gsk3b)
DE102004010194A1 (de) * 2004-03-02 2005-10-13 Aventis Pharma Deutschland Gmbh 4-Benzimidazol-2-yl-pyridazin-3-on-Derivate, ihre Herstellung und Verwendung in Arzneimitteln
DE102004010207A1 (de) 2004-03-02 2005-09-15 Aventis Pharma S.A. Neue 4-Benzimidazol-2-yl-pyridazin-3-on-Derivate
EP2258359A3 (en) 2005-08-26 2011-04-06 Braincells, Inc. Neurogenesis by muscarinic receptor modulation with sabcomelin
EP2275095A3 (en) 2005-08-26 2011-08-17 Braincells, Inc. Neurogenesis by muscarinic receptor modulation
US7985756B2 (en) 2005-10-21 2011-07-26 Braincells Inc. Modulation of neurogenesis by PDE inhibition
EP1942879A1 (en) 2005-10-31 2008-07-16 Braincells, Inc. Gaba receptor mediated modulation of neurogenesis
US20100216734A1 (en) 2006-03-08 2010-08-26 Braincells, Inc. Modulation of neurogenesis by nootropic agents
JP2009536669A (ja) 2006-05-09 2009-10-15 ブレインセルス,インコーポレイティド アンジオテンシン調節による神経新生
US20100184806A1 (en) 2006-09-19 2010-07-22 Braincells, Inc. Modulation of neurogenesis by ppar agents
US20100216805A1 (en) 2009-02-25 2010-08-26 Braincells, Inc. Modulation of neurogenesis using d-cycloserine combinations
FR2947550B1 (fr) * 2009-07-02 2012-05-18 Sanofi Aventis Nouveaux derives de 2,3-dihydro-1h-imidazo{1,2-a}pyrimidin-5-one, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt (pkb)
US8828997B2 (en) * 2009-07-02 2014-09-09 Sanofi 2,3-dihydro-1H-imidazo(1,2-a)pyrimidin-5-one derivatives, preparation thereof, and pharmaceutical use thereof
SG10201403149YA (en) * 2009-07-02 2014-08-28 Sanofi Sa Novel 1,2,3,4-tetrahydro-pyrimido(1,2-a)pyrimidin-6-one derivatives, preparation thereof and pharmaceutical use thereof
FR2947551B1 (fr) * 2009-07-02 2012-05-18 Sanofi Aventis Nouveaux derives de 1,2,3,4-tetrahydro-pyrimido{1,2-a)pyrimidin-6-one, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt (pkb)
CN102715186A (zh) * 2012-06-15 2012-10-10 王学权 一种增效除草组合物
FR2992314B1 (fr) 2012-06-22 2015-10-16 Sanofi Sa Nouveaux derives de 2,3-dihydro-1h-imidazo{1,2-a}pyrimidin-5-one et 1,2,3,4-tetrahydro-pyrimido{1,2-a}pyrimidin-6-one comportant une morpholine substituee, leur preparation et leur utilisation pharmaceutique
KR101886945B1 (ko) * 2014-04-01 2018-08-08 화이자 인코포레이티드 감마-세크레타제 조절제로서의 크로멘 및 1,1a,2,7b-테트라히드로시클로프로파[c]크로멘 피리도피라진디온
US20170165230A1 (en) 2014-04-09 2017-06-15 Christopher Rudd Use of gsk-3 inhibitors or activators which modulate pd-1 or t-bet expression to modulate t cell immunity
ES2968804T3 (es) * 2017-05-24 2024-05-14 Abbisko Therapeutics Co Ltd Derivado de azaarilo, método de preparación del mismo y uso farmacéutico del mismo

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TW520362B (en) * 1996-12-05 2003-02-11 Amgen Inc Substituted pyrimidine compounds and pharmaceutical composition comprising same
AR023052A1 (es) * 1998-09-25 2002-09-04 Mitsuharu Yoshimura Milton Derivados de pirimidona
DK1315731T3 (da) * 2000-09-01 2004-10-11 Sanofi Aventis 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on og 7-pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)on-derivater

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EP1480983B1 (en) 2005-11-09
MXPA04008364A (es) 2005-07-26
NO329805B1 (no) 2010-12-20
NO20043565L (no) 2004-11-25
PL372465A1 (en) 2005-07-25
NZ534466A (en) 2006-04-28
DE60302221D1 (de) 2005-12-15
CN1315832C (zh) 2007-05-16
ES2250883T3 (es) 2006-04-16
TWI303637B (en) 2008-12-01
EA200400936A1 (ru) 2005-02-24
DK1480983T3 (da) 2006-03-27
EA007737B1 (ru) 2006-12-29
SI1480983T1 (sl) 2006-04-30
WO2003072579A1 (en) 2003-09-04
AU2003221500A1 (en) 2003-09-09
US7232827B2 (en) 2007-06-19
US20070225300A1 (en) 2007-09-27
EP1480983A1 (en) 2004-12-01
AU2003221500B9 (en) 2008-11-20
AU2003221500C1 (en) 2008-10-02
KR20040087333A (ko) 2004-10-13
CA2474823C (en) 2011-02-22
CA2474823A1 (en) 2003-09-04
JP2005519086A (ja) 2005-06-30
ATE309247T1 (de) 2005-11-15
CN1649871A (zh) 2005-08-03
DE60302221T2 (de) 2006-08-03
JP4458851B2 (ja) 2010-04-28
US7465737B2 (en) 2008-12-16
TW200402421A (en) 2004-02-16
KR101030629B1 (ko) 2011-04-20
BR0308109A (pt) 2005-01-04
AU2003221500B2 (en) 2008-02-14
US20050222172A1 (en) 2005-10-06
IL163287A (en) 2009-12-24

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