AR037364A1 - Azetidinil diaminas utiles como ligandos del receptor de nociceptina orl-1 - Google Patents

Azetidinil diaminas utiles como ligandos del receptor de nociceptina orl-1

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Publication number
AR037364A1
AR037364A1 ARP020104356A ARP020104356A AR037364A1 AR 037364 A1 AR037364 A1 AR 037364A1 AR P020104356 A ARP020104356 A AR P020104356A AR P020104356 A ARP020104356 A AR P020104356A AR 037364 A1 AR037364 A1 AR 037364A1
Authority
AR
Argentina
Prior art keywords
alkyl
aryl
phenyl
formula
piperidinyl
Prior art date
Application number
ARP020104356A
Other languages
English (en)
Original Assignee
Schering 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
Application filed by Schering Corp filed Critical Schering Corp
Publication of AR037364A1 publication Critical patent/AR037364A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/10—Expectorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/12—Mucolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/14—Antitussive agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • 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
    • C07D233/56—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 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D401/12—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
    • 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
    • C07D403/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D405/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • 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
    • C07D405/14—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 three or more hetero rings
    • 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
    • C07D417/06—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 carbon chain containing only aliphatic carbon atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pulmonology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Addiction (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Se describen agonistas del receptor de nociceptina ORL-1 de fórmula (1); composiciones farmacéuticas, y métodos de uso de los compuestos para el tratamiento de la tos y del dolor. Reivindicación 1: Un compuesto representado por la fórmula (1) o un solvato o sal farmacéuticamente aceptable del mismo, o un diastereómero o enantiómero del mismo, en donde: a) R1 es -(CH2)nCHR4R5, fluorenilo, pirimidinilo o como se indica en fórmula (2); n es 0, 1, 2 ó 3; R2 es H; y R3 es -C(H)(R)-NR7R8; R es H, arilo, R6-arilo, aril(CH2)1-2, R6-aril(CH2)1-2 o heteroarilo; R4 es H, arilo, R6-arilo, heteroarilo, alquilo C1-6, cicloalquilo C3-6 o alquenilo C2-6; R5 es arilo, R6-arilo, heteroarilo, alquilo C1-6, cicloalquilo C3-6, alquenilo C2-6 o fluorenilo, siempre y cuando que cuando R4 y R5 son cada uno fenilo, R no es fenilo o R6-fenilo; o R4 es H y R5 es tetrahidronaftilo o tetrahidronaftilo sustituido con 1 o 2 sustituyentes seleccionados entre el grupo que consiste en halógeno, alcoxi C1-6, hidroxi, alquilo C1-6 y trihalo alquilo (C1-6); R6 es 1 o 2 sustituyentes seleccionados de manera independiente entre el grupo que consiste en halógeno, alcoxi C1-6, hidroxi, fenilo, fenoxi, alquilo C1-6, trihalo alquilo (C1-6), amino, amido, -NO2, naftilo, benzoilo y benciloxi, o 2 átomos de carbono de anillo adyacentes pueden ser sustituidos con metilendioxi; R7 es -(CH2)xR9 tetrahidronaftilo, tetrahidronaftilo sustituido con 1 o 2 grupos R10, o cicloalquilo C5-7; y R8 es H; o R7 y R8 juntos forman un anillo de la fórmula (3) ó (4); x es 0 a 10; R9 es H, alcoxi C1-6, fenilo, fenilo sustituido con 1 o 2 grupos R10, naftilo, piridilo, imidazolilo, furanilo, pirrolidinilo, pirrolidonilo, piperidinilo, N-(alquilo C1-6)-piperidinilo, N-arilo(alquilo C1-6)piperidinilo o difenilmetilo; R10 se selecciona en forma independiente entre el grupo que consiste en halógeno, alcoxi C1-6, alquilo C1-6, -OCF3 y metilendioxi; R11 es aril alquilo C1-6, di-aril alquilo (C1-6) o piperidinilo; y R17 es H, alquilo C1-6 o bencilo; o b) R2 es -NHR7 o como se expresa en fórmula (5) y R3 es H; y R1 y R7 son como se define en (a).
ARP020104356A 2001-11-16 2002-11-13 Azetidinil diaminas utiles como ligandos del receptor de nociceptina orl-1 AR037364A1 (es)

Applications Claiming Priority (1)

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US33228401P 2001-11-16 2001-11-16

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AR037364A1 true AR037364A1 (es) 2004-11-03

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ID=23297560

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ARP020104356A AR037364A1 (es) 2001-11-16 2002-11-13 Azetidinil diaminas utiles como ligandos del receptor de nociceptina orl-1

Country Status (14)

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US (2) US20030195185A1 (es)
EP (1) EP1444200B1 (es)
JP (1) JP2005509674A (es)
CN (1) CN1585747A (es)
AR (1) AR037364A1 (es)
AT (1) ATE325092T1 (es)
AU (1) AU2002340476A1 (es)
CA (1) CA2466728C (es)
DE (1) DE60211198T2 (es)
ES (1) ES2259106T3 (es)
HK (1) HK1063317A1 (es)
MX (1) MXPA04004676A (es)
TW (1) TW200300757A (es)
WO (1) WO2003043980A1 (es)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2008179541A (ja) * 2005-05-02 2008-08-07 Mochida Pharmaceut Co Ltd 神経因性疼痛治療薬
PE20071159A1 (es) * 2005-10-31 2007-11-30 Schering Corp Derivados de tropano 3-monosustituido como ligandos de receptores de nociceptina
ES2452822T3 (es) 2006-06-28 2014-04-02 Amgen Inc. Inhibidores del transportador 1 de glicina
CA2686517A1 (en) 2007-05-10 2008-11-20 Pfizer Limited Azetidine derivatives and their use as prostaglandin e2 antagonists
CA2759614C (en) * 2009-04-22 2017-09-19 Janssen Pharmaceutica Nv Azetidinyl diamides as monoacylglycerol lipase inhibitors
AU2012324015A1 (en) 2011-12-01 2013-06-20 Purdue Pharma L.P. Azetidine-substituted quinoxaline-type piperidine compounds and uses thererof
CN105949103A (zh) * 2016-07-11 2016-09-21 上海应用技术学院 一种1-二苯甲基-3-甲基氮杂环丁烷盐酸盐的合成工艺

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4196124A (en) * 1974-10-30 1980-04-01 Schering Corporation 1-Benzhydryl-2-benzimidoyl-azetidine
US4052383A (en) * 1974-10-30 1977-10-04 Schering Corporation N-diphenylalkyl-2-benzyl azacyclic compounds
DE19519245C2 (de) * 1995-04-14 2003-04-30 Boehringer Ingelheim Kg Neue Arylglycinamidderivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zusammensetzungen
TW449590B (en) * 1995-04-14 2001-08-11 Boehringer Ingelheim Kg New arylglycinamide derivatives, processes for the manufacture thereof and pharmaceutical compositions containing these compounds
ID29137A (id) * 1998-07-27 2001-08-02 Schering Corp Ligan-ligan afinitas tinggi untuk reseptor nosiseptin orl-1
US6262066B1 (en) * 1998-07-27 2001-07-17 Schering Corporation High affinity ligands for nociceptin receptor ORL-1

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TW200300757A (en) 2003-06-16
CN1585747A (zh) 2005-02-23
DE60211198T2 (de) 2007-02-08
EP1444200A1 (en) 2004-08-11
JP2005509674A (ja) 2005-04-14
MXPA04004676A (es) 2004-08-12
US20040157822A1 (en) 2004-08-12
AU2002340476A1 (en) 2003-06-10
EP1444200B1 (en) 2006-05-03
CA2466728C (en) 2008-09-02
US6903123B2 (en) 2005-06-07
CA2466728A1 (en) 2003-05-30
HK1063317A1 (en) 2004-12-24
DE60211198D1 (de) 2006-06-08
WO2003043980A1 (en) 2003-05-30
ES2259106T3 (es) 2006-09-16
US20030195185A1 (en) 2003-10-16
ATE325092T1 (de) 2006-06-15

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