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AR078958A1 - Derivados de oxazolina, su preparacion, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por los receptores taar1 - Google Patents

Derivados de oxazolina, su preparacion, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por los receptores taar1

Info

Publication number
AR078958A1
AR078958A1 ARP100104164A ARP100104164A AR078958A1 AR 078958 A1 AR078958 A1 AR 078958A1 AR P100104164 A ARP100104164 A AR P100104164A AR P100104164 A ARP100104164 A AR P100104164A AR 078958 A1 AR078958 A1 AR 078958A1
Authority
AR
Argentina
Prior art keywords
halogen
lower alkyl
substituted
optionally substituted
disorders
Prior art date
Application number
ARP100104164A
Other languages
English (en)
Inventor
Roger Norcross
Alessandra Polara
Guido Galley
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of AR078958A1 publication Critical patent/AR078958A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D263/00Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
    • C07D263/28Nitrogen atoms not forming part of a nitro radical
    • 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
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42Oxazoles
    • A61K31/4211,3-Oxazoles, e.g. pemoline, trimethadione
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/14Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
    • 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
    • A61P25/06Antimigraine agents
    • 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
    • A61P25/20Hypnotics; Sedatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • 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
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • 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
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/10Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • C07D409/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/10Heterocyclic 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 aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
    • C07D417/02Heterocyclic 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
    • C07D417/12Heterocyclic 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
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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
    • 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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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Child & Adolescent Psychology (AREA)
  • Nutrition Science (AREA)
  • Addiction (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Anesthesiology (AREA)
  • Psychology (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyridine Compounds (AREA)

Abstract

Se ha constatado que los compuestos de la formula 1 tienen afinidad con los receptores asociados con las aminas traza (TAARs), en especial con el TAAR1. Los compuestos pueden utilizarse para el tratamiento de la depresion, los trastornos de ansiedad, el trastorno bipolar, el trastorno de hiperactividad con déficit de atencion (ADHD), los trastornos relacionados con el estrés, los trastornos psicoticos como la esquizofrenia, las enfermedades neurologicas como la enfermedad de Parkinson, los trastornos neurodegenerativos, por ejemplo la enfermedad de Alzheimer, la epilepsia, la migrana, la hipertension, el abuso de sustancias y los trastornos metabolicos como son los trastornos de ingestion de comida, la diabetes, las complicaciones diabéticas, la obesidad, la dislipidemia, los trastornos de consumo y asimilacion de energía, los trastornos y malfuncion de la temperatura corporal, la homeostasis, los trastornos del sueno y del ritmo circadiano y los trastornos cardiovasculares. Reivindicacion 1: Compuestos de la formula (1) en la que Ra es hidrogeno o alquilo inferior; R1 es grupo (2) o puede elegirse entre el grupo formado por (3); R8 es hidrogeno, halogeno o arilo opcionalmente sustituido por halogeno; X es un enlace, -(CH2)n-, -CHRCH2, -CHR(CH2)2-, -O-CHRCH2- o (4); y R es alquilo inferior o alquilo inferior sustituido por halogeno; R2 es a) alquilo inferior; b) hidrogeno; c) NR-arilo, opcionalmente sustituido por uno o más sustituyentes elegidos entre halogeno y alquilo inferior sustituido por halogeno; d) NH-heteroarilo, opcionalmente sustituido por uno o más sustituyentes elegidos entre halogeno y alquilo inferior sustituido por halogeno; e) (CR'R'')m-cicloalquilo opcionalmente sustituido por halogeno, alquilo inferior, alquilo inferior sustituido por halogeno, fenilo sustituido por halogeno o por heteroarilo; f) heterocicloalquilo opcionalmente sustituido por halogeno o alquilo inferior sustituido por halogeno; g) (CR'R'')m-heteroarilo opcionalmente sustituido por halogeno, alcoxi inferior, alquilo inferior sustituido por halogeno, alcoxi inferior sustituido por halogeno, alquilo inferior, cicloalquilo, NHC(O)-alquilo inferior, ciano, S(O)2-alquilo inferior, NR6R7, o por heteroarilo o por heterociclilo que está opcionalmente sustituido por halogeno; h) (CR'R'')m-arilo opcionalmente sustituido por halogeno, alquilo inferior sustituido por halogeno, alcoxi inferior sustituido por halogeno, alquilo inferior, alquinilo, alcoxi inferior, CH2-alcoxi inferior o ciano; i) -O(CH2)o-arilo opcionalmente sustituido por halogeno, alcoxi inferior o alquilo inferior sustituido por halogeno; R' y R'' con independencia entre sí son hidrogeno, alcoxi inferior o alquilo inferior; o junto con el átomo de C pueden formar un grupo cicloalquilo; R3 es arilo o heteroarilo, cuyos anillos aromáticos están opcionalmente sustituidos por uno o más sustituyentes elegidos entre halogeno y alcoxi inferior; R4 es alquilo inferior, arilo o heteroarilo, cuyos anillos aromáticos están opcionalmente sustituidos por uno o más sustituyentes elegidos entre halogeno, ciano y alcoxi inferior; R5 es hidrogeno, alquilo inferior o arilo sustituido por halogeno; o R4 y R5 junto con el átomo de N al que están unidos pueden formar un anillo heterocíclico; R6/R7 con independencia entre sí son hidrogeno, alquilo inferior o (CH2)2-O-alquilo inferior; m es el numero 0, 1 o 2; n es el numero 1, 2 o 3; o es el numero 0 o 1; p es el numero 0, 1 o 2; o una sal de adicion de ácido farmacéuticamente aceptable de los mismos.
ARP100104164A 2009-11-11 2010-11-10 Derivados de oxazolina, su preparacion, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por los receptores taar1 AR078958A1 (es)

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Application Number Priority Date Filing Date Title
EP09175712 2009-11-11

Publications (1)

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AR078958A1 true AR078958A1 (es) 2011-12-14

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ARP100104164A AR078958A1 (es) 2009-11-11 2010-11-10 Derivados de oxazolina, su preparacion, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por los receptores taar1

Country Status (13)

Country Link
US (1) US8354441B2 (es)
EP (1) EP2499121B1 (es)
JP (1) JP5552539B2 (es)
KR (1) KR101461294B1 (es)
CN (1) CN102686572A (es)
AR (1) AR078958A1 (es)
BR (1) BR112012011105A2 (es)
CA (1) CA2780568A1 (es)
ES (1) ES2550976T3 (es)
MX (1) MX2012005363A (es)
RU (1) RU2569887C2 (es)
TW (1) TW201121543A (es)
WO (1) WO2011057973A1 (es)

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RU2012129168A (ru) 2009-12-11 2014-01-20 Сионоги Энд Ко. Лтд. Производные оксазина
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US9029370B2 (en) 2011-06-10 2015-05-12 Hoffmann-La Roche Inc. Substituted benzamide derivatives
EP2912035A4 (en) 2012-10-24 2016-06-15 Shionogi & Co DERIVATIVES OF DIHYDROOXAZINE OR OXAZEPINE HAVING BACE1 INHIBITING ACTIVITY
CN105272975B (zh) * 2014-06-10 2019-03-26 中国科学院上海药物研究所 一类具有1,2,4-恶二唑片段结构的吲哚生物碱及其制备方法和用途
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US20110112080A1 (en) 2011-05-12
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US8354441B2 (en) 2013-01-15
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