ES2176776T3 - Ligandos del neuropeptido-y. - Google Patents

Ligandos del neuropeptido-y.

Info

Publication number
ES2176776T3
ES2176776T3 ES97939524T ES97939524T ES2176776T3 ES 2176776 T3 ES2176776 T3 ES 2176776T3 ES 97939524 T ES97939524 T ES 97939524T ES 97939524 T ES97939524 T ES 97939524T ES 2176776 T3 ES2176776 T3 ES 2176776T3
Authority
ES
Spain
Prior art keywords
neuropeptide
ligands
neuropeptide ligands
formula
agonists
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Lifetime
Application number
ES97939524T
Other languages
English (en)
Inventor
Vlad Edward Gregor
Yufeng Hong
Anthony Lai Ling
Eileen Valenzuela Tompkins
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Agouron Pharmaceuticals LLC
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Agouron Pharmaceuticals LLC
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Application filed by Agouron Pharmaceuticals LLC filed Critical Agouron Pharmaceuticals LLC
Application granted granted Critical
Publication of ES2176776T3 publication Critical patent/ES2176776T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
    • C07C279/24—Y being a hetero atom
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic 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
    • C07D213/02—Heterocyclic 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
    • C07D213/04—Heterocyclic 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
    • C07D213/24—Heterocyclic 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
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/40—Acylated substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen 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
    • C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen 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 with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Diabetes (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Pulmonology (AREA)
  • Vascular Medicine (AREA)
  • Child & Adolescent Psychology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Emergency Medicine (AREA)
  • Reproductive Health (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Steroid Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyridine Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)

Abstract

Compuesto de fórmula en donde A es O, S, o N-R, en donde R es un alquilo de cadena corta (C1-C8); D es O, S o N-R7; W es N, CH o C-R8; R1 y R3 son independientemente H, radicales alquilo de C1-C14, lineales o ramificados, cíclicos o acíclicos, saturados o insaturados, opcionalmente substituidos por grupos hidroxi, oxialquilo de cadena corta, tioalquilo, oxiarilo o tioarilo, en donde dichos grupos que soportan arilos son substituidos opcionalmente por grupos halógeno, oxialquilo de cadena corta, tioalquilo, alquilo de cadena corta, trifluorometoxi, trifluoroetoxi o trifluorometilo, y opcionalmente dichos grupos alquilo están substituidos por estructuras cíclicas seleccionadas del grupo que consta de anillos que tienen un tamaño de anillo de entre 3 y 10 átomos, o dichos grupos alquilo están substituidos por partes aromáticas o heteroaromáticas, conteniendo opcionalmente dichos grupos arilo o heteroarilo substituyentes en el anillo arílico seleccionado del grupo consistente en grupos alquilode cadena corta, oxialquilo, amino, aminoalquilo de cadena corta, aminoacilo de cadena corta, halógenos, y trifluo rometilo o trifluorometoxi; R2 es en donde W2 es C=O, SO2, C(O)NH; SO; o está ausente; Q es (a) un (-CH2-)z substituido o no substituido, en donde z=1 a 12, y cuando -CH2- está subs tituido, los grupos substituyentes son alquilo de cadena corta, arilo o heteroarilo; y cuando z>1, al menos un grupo -CH2- está reemplazado opcionalmente por un heteroátomo seleccionado del grupo consis tente en O, S o un N substituido o no substituido, en donde la parte substituyente se selecciona del grupo consistente en alquilo de cadena corta, arilo, heteroarilalquilo e hidrógeno; (b) un anillo carbocíclico o heterocíclico saturado de fórmula (-CH2-)x en donde l y m son de 0-5, y en donde x=3-12, preferiblemente de 3-8, y opcionalmente, uno o más grupos -CH2- se substituyen por un radical seleccionado del grupo consistente en alquilo de cadena corta saturado o insaturado, cicloalquilo, arilo y heteroarilo; y opcionalmente al menos uno de los grupos CH2- está reem plazado por un heteroátomo seleccionado del grupo consistente en O, S, Se y N substituido o no substituido, y cuando N está substituido, el grupo substituyente se selecciona del grupo consistente en alquilo de cadena corta, arilo, heteroarilo e hidrógeno; (c) un anillo aromático carbocíclico o heterocíclico de fórmula (-CH=CH-)y en donde l y m son de 0-5, y en donde y opcionalmente al menos uno de los grupos -CH- está substituido por X1, X2 o tanto X1 como X2 en donde X es cualquier substituyente cíclico, por ejemplo grupos alquilos saturados o insaturados, lineales o ramificados, grupos oxialquilos de cadena corta o halógenos, y opcionalmente, al menos uno de los grupos -CH- está reemplazado por N, o alternativamente, uno de los grupos -CH=CH- está reemplazado por un heteroátomo seleccionado del grupo consistente en O, S, Se y N-R11; también opcionalmente, al menos uno de los grupos -CH=CH- es una unión con la cual se puede fusionar otra estructura cíclica, bien saturada o bien insaturada, formando de esta manera sistemas aromáticos o heteroaromáticos condensados seleccionados, por ejemplo, del grupo consistente en clases de naftaleno, indole, benzofurano, quinolina, quinazolina y benzodioxano; X3 es un substituyente en Q el cual puede ser H, alquilo de cadena corta, arilo, oxialquilo de cadena corta, hidroxi, trifluorometilo, y substituyentes cíclicos similares y comunes. R4 se selecciona del grupo consistente en las siguientes fórmulas generales: en donde A1 es O, S, NH o N-alquilo de cadena corta o arilo; R5 a R9, R11 y R12 se seleccionan independientemente del grupo consistente en H, radicales alquilo de C1 a C14, lineales o ramificados, saturados o insaturados, cíclicos o acíclicos, substituidos o no substituidos, o radicales arilos o heteroarilos, y cuando cualquiera de los R5 a R9, R11 o R12 es un radical arilo o heteroarilo substituido, el grupo substituyente se selecciona de los miembros del grupoconsistente en halógeno, oxialquilo de cadena corta, tioalquilo, alquilo de cadena corta, trifluorometoxi y trifluorometilo, y cuando cualquiera de los R5 a R9, R11 o R12 es un radical alquilo substituido, la parte substituyente se selecciona del grupo consistente en sistemas cíclicos no aromáticos que tienen de 3 a 14 átomos de anillo, y sistemas aromáticos y heteroaromáticos y anillos heterocíclicos que tienen de 4- 12 miembros de anillo, y dichos anillos aromáticos y heteroaromáticos opcionalmente están substituidos por radicales seleccionados del grupo consistente en alquilo de cadena corta, oxialquilo, amino, aminoalquilo de cadena corta, amidoacilo de cadena corta, halógenos, perfluoroalquilo, y perfluoroalquilo de cadena corta; o R6 es H, alquilo de C1 a C14, lineal o ramificado, cíclico o acíclico, saturado o insaturado; arilo; heteroarilo; arilalquilo de cadena corta; heteroarilalquilo de cadena corta; arilalquilo de cadena corta condensado; heteroarilalquilo de cadena corta condensado; diarilalquilo de cadena corta; bisheteroarilalquilo de cadena corta; o heteroarilalquilarilo de cadena corta; o derivados parcial o totalmente saturados de los mismos; o R6 puede ser R6 el cual es R6-NH o R6-N-alquilo de cadena corta; R10 es hidrógeno, grupos alquilos de C1-C12, lineales o ramificados, saturados o insaturados, cíclicos o acíclicos, que contienen opcionalmente enlaces dobles o triples; un arilo, opcionalmente substituido con grupos tales como halógeno, alquilo de cadena corta, oxialquilo, aminoalquilo, dialquilaminoalquilo de cadena corta, hidroxi; arilalquilo; oxiarilalquilo; 2-tetrahidrofurfurilo; 3-tetrahidrofurfurilo; hidroxial quilo terminal con cadenas de hidrocarburo de C2-C10 y amidoalquilo tal como el 2-acetamidoetilo; o R9 y R10 pueden formar opcionalmente un anillo de 3 a 10 miembros; y los compuestos comprenden cualquier isómero ópticamente activo de los mismos en forma de isómeros ópticos separados, puros o parcialmente purificados o mezclas racémicas delos mismos; y las sales farmacéuticamente aceptables de los mismos.
ES97939524T 1996-08-23 1997-08-22 Ligandos del neuropeptido-y. Expired - Lifetime ES2176776T3 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US2579196P 1996-08-23 1996-08-23

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ES97939524T Expired - Lifetime ES2176776T3 (es) 1996-08-23 1997-08-22 Ligandos del neuropeptido-y.

Country Status (11)

Country Link
US (1) US6849733B1 (es)
EP (1) EP0984778B1 (es)
JP (1) JP2001502296A (es)
AT (1) ATE218859T1 (es)
AU (1) AU4159297A (es)
CA (1) CA2268051A1 (es)
DE (1) DE69713402T2 (es)
DK (1) DK0984778T3 (es)
ES (1) ES2176776T3 (es)
PT (1) PT984778E (es)
WO (1) WO1998007420A1 (es)

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JP5523352B2 (ja) 2008-02-28 2014-06-18 バーテックス ファーマシューティカルズ インコーポレイテッド Ｃｆｔｒ修飾因子としてのへテロアリール誘導体
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JP6026284B2 (ja) 2010-03-03 2016-11-16 プロビオドルグ エージー グルタミニルシクラーゼの阻害剤
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Also Published As

Publication number Publication date
EP0984778B1 (en) 2002-06-12
JP2001502296A (ja) 2001-02-20
DK0984778T3 (da) 2002-09-16
US6849733B1 (en) 2005-02-01
AU4159297A (en) 1998-03-06
EP0984778A1 (en) 2000-03-15
DE69713402D1 (de) 2002-07-18
CA2268051A1 (en) 1998-02-26
WO1998007420A1 (en) 1998-02-26
DE69713402T2 (de) 2002-11-07
EP0984778A4 (en) 2000-06-07
ATE218859T1 (de) 2002-06-15
PT984778E (pt) 2002-09-30

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