AR038948A1 - SUBSTITUTED AMIDAS - Google Patents

SUBSTITUTED AMIDAS

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Publication number
AR038948A1
AR038948A1 ARP030100857A ARP030100857A AR038948A1 AR 038948 A1 AR038948 A1 AR 038948A1 AR P030100857 A ARP030100857 A AR P030100857A AR P030100857 A ARP030100857 A AR P030100857A AR 038948 A1 AR038948 A1 AR 038948A1
Authority
AR
Argentina
Prior art keywords
heteroaryl
aryl
independently selected
treatment
substituted
Prior art date
Application number
ARP030100857A
Other languages
Spanish (es)
Original Assignee
Merck & Co Inc
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.)
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Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=32393400&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR038948(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Merck & Co Inc filed Critical Merck & Co Inc
Publication of AR038948A1 publication Critical patent/AR038948A1/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/62Oxygen or sulfur atoms
    • C07D213/63One oxygen atom
    • C07D213/64One oxygen atom attached in position 2 or 6
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • 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
    • A61P25/14Drugs 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
    • A61P25/28Drugs 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
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/06Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/18Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
    • C07C235/20Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/06Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36Radicals substituted by singly-bound nitrogen atoms
    • C07D213/40Acylated substituent nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/89Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic 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
    • C07D239/28Heterocyclic 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
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/34One oxygen atom
    • CCHEMISTRY; METALLURGY
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    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
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    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
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    • 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
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    • C40COMBINATORIAL TECHNOLOGY
    • C40BCOMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
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    • C40B50/00Methods of creating libraries, e.g. combinatorial synthesis
    • C40B50/08Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creation; Particular methods of cleavage from the liquid support
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    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C2601/00Systems containing only non-condensed rings
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    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C2601/12Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14The ring being saturated

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Hospice & Palliative Care (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Diabetes (AREA)
  • Structural Engineering (AREA)
  • Child & Adolescent Psychology (AREA)
  • Addiction (AREA)
  • Psychology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyrane Compounds (AREA)

Abstract

Los compuestos son antagonistas y/o agonistas inversos del receptor de Canabinoide-1 (CB1) y son útiles en el tratamiento, prevención y supresión de enfermedades medidas por el receptor CB1. Los compuestos son útiles como drogas de acción central en el tratamiento de psicosis, déficits de memoria, desórdenes de reconocimiento, migrana, neuropatía, desórdenes neuro-inflamatorios incluyendo esclerosis múltiple y síndrome de GuillaEn-BarTe, y secuelas inflamatorias de encefalitis viral, accidentes cerebrales vasculares, y traumatosis de cráneo, anomalías de ansiedad, stress, epilepsia, enfermedad de Parkinson, desórdenes en los movimientos y esquizofrenia. Los compuestos también son útiles para el tratamiento de desordenes por abuso de sustancias, tratamiento de obesidad, o desordenes de obesidad, así como para el tratamiento de asma, estrenimiento pseudo-obstrucción crónica intestinal, y cirrosis de hígado. Reivindicación 1: Un compuesto de fórmula (1) o una sal de este farmacéuticamente aceptable, en el que: R1 es seleccionado de cicloheteroalquilo, arilo, heteroarilo, y -NRaRc; donde arilo y heteroarilo son opcionalmente sustituidos por uno a tres sustituyentes independientemente seleccionados de Rb; R2 es seleccionado de C1-10alquilo, C3-10cicloalquilo-C1-4alquilo, arilo-C1-4alquilo, y heteroarilo-C1-4alquilo, donde cada cicloalquilo, arilo y heteroarilo es opcionalmente sustituido por uno a tres sustituyentes independientemente seleccionados de Rb; cada Ra es independientemente seleccionado de hidrógeno, metilo, y -CF3; cada Rb es independientemente seleccionado de halógeno, ciano, trifluorometilo, trifluorometoxi, C1-3alquiloxi, y C1-3alquilo; Rc es independientemente seleccionado de hidrógeno, C1-6alquilo, arilo, heteroarilo, arilo-metilo, y heteroarilo-metilo, cada Rc puede ser sustituido o no por uno a tres sustituyentes seleccionados de Rh; Rd es independientemente seleccionado de cicloalquilo, arilo y heteroarilo, cada Rd puede ser sustituido o no por uno a tres sustituyentes seleccionados de Rh; cada Rh es independientemente seleccionado de halógeno, C1-3alquilo, -CN, y -CF3; donde, cuando los grupos piridilo no son sustituidos en nitrógeno, pueden encontrarse opcionalmente presentes como N-óxido.The compounds are antagonists and / or inverse agonists of the Canabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases measured by the CB1 receptor. The compounds are useful as centrally acting drugs in the treatment of psychosis, memory deficits, recognition disorders, migraine, neuropathy, neuro-inflammatory disorders including multiple sclerosis and GuillaEn-BarTe syndrome, and inflammatory sequelae of viral encephalitis, brain accidents vascular, and skull traumatosis, anxiety abnormalities, stress, epilepsy, Parkinson's disease, movement disorders and schizophrenia. The compounds are also useful for the treatment of substance abuse disorders, obesity treatment, or obesity disorders, as well as for the treatment of asthma, chronic intestinal pseudo-obstruction constipation, and liver cirrhosis. Claim 1: A compound of formula (1) or a pharmaceutically acceptable salt thereof, wherein: R1 is selected from cycloheteroalkyl, aryl, heteroaryl, and -NRaRc; wherein aryl and heteroaryl are optionally substituted by one to three substituents independently selected from Rb; R2 is selected from C1-10alkyl, C3-10cycloalkyl-C1-4alkyl, aryl-C1-4alkyl, and heteroaryl-C1-4alkyl, where each cycloalkyl, aryl and heteroaryl is optionally substituted by one to three substituents independently selected from Rb; each Ra is independently selected from hydrogen, methyl, and -CF3; each Rb is independently selected from halogen, cyano, trifluoromethyl, trifluoromethoxy, C1-3alkyloxy, and C1-3alkyl; Rc is independently selected from hydrogen, C1-6alkyl, aryl, heteroaryl, aryl-methyl, and heteroaryl-methyl, each Rc may or may not be substituted by one to three substituents selected from Rh; Rd is independently selected from cycloalkyl, aryl and heteroaryl, each Rd may or may not be substituted by one to three substituents selected from Rh; each Rh is independently selected from halogen, C1-3alkyl, -CN, and -CF3; where, when the pyridyl groups are not substituted on nitrogen, they may optionally be present as N-oxide.

ARP030100857A 2002-11-22 2003-03-12 SUBSTITUTED AMIDAS AR038948A1 (en)

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US42841502P 2002-11-22 2002-11-22

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AR038948A1 true AR038948A1 (en) 2005-02-02

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KR (1) KR100748380B1 (en)
CN (1) CN1639112A (en)
AR (1) AR038948A1 (en)
AU (1) AU2003218005A1 (en)
BR (1) BR0308349A (en)
CR (1) CR7432A (en)
DO (1) DOP2003000609A (en)
EA (1) EA007747B1 (en)
EC (1) ECSP045289A (en)
GE (1) GEP20074208B (en)
HR (1) HRP20040823A2 (en)
IL (1) IL163824A0 (en)
IS (1) IS7411A (en)
JO (1) JO2482B1 (en)
MA (1) MA27185A1 (en)
MX (1) MXPA04008748A (en)
MY (1) MY134457A (en)
NO (1) NO20043803L (en)
PE (1) PE20040599A1 (en)
PL (1) PL200328B1 (en)
RS (1) RS79104A (en)
TN (1) TNSN04176A1 (en)
TW (1) TW200408620A (en)
UA (1) UA76590C2 (en)
WO (1) WO2004048317A1 (en)

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