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AR083475A1 - METABOTROPIC GLUTAMATE RECEIVERS MODULATORS - Google Patents

METABOTROPIC GLUTAMATE RECEIVERS MODULATORS

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Publication number
AR083475A1
AR083475A1 ARP110103856A ARP110103856A AR083475A1 AR 083475 A1 AR083475 A1 AR 083475A1 AR P110103856 A ARP110103856 A AR P110103856A AR P110103856 A ARP110103856 A AR P110103856A AR 083475 A1 AR083475 A1 AR 083475A1
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Argentina
Prior art keywords
alkyl
ring
amino
represents hydrogen
fluorine
Prior art date
Application number
ARP110103856A
Other languages
Spanish (es)
Inventor
Ronalds Zemribo
Markus Henrich
Ulrich Abel
Sibylle Muller
Holger Kubas
Udo Meyer
Mirko Hechenberger
Valerjans Kauss
Original Assignee
Merz Pharma Gmbh & Co Kgaa
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Publication of AR083475A1 publication Critical patent/AR083475A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/20—Oxygen 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
    • C07D401/06—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
    • C07D471/00—Heterocyclic 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
    • C07D471/02—Heterocyclic 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
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated

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  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Proceso para la preparación de dichos compuestos. Los compuestos son moduladores de mGluR5 y por ello son de utilidad para el control y la prevención de trastornos neurológicos agudos y/o crónicos.Reivindicación 1: Un compuesto caracterizado porque se selecciona entre aquellos de la fórmula (1) donde R1 representa arilo, heteroarilo, cicloalquilo C3-12, cicloalquenilo C5-12, o heterociclilo; R2 representa hidrógeno, flúor, o alquilo C1-6; R3 representa hidrógeno, flúor, o alquilo C1-6; o R2 y R3 junto con el átomo de carbono al cual se encuentran unidos forman un anillo de entre 3 y 7 miembros que puede ser saturado o insaturado, donde el anillo opcionalmente puede contener uno o dos heteroátomos seleccionados entre azufre, oxígeno, y nitrógeno y donde el anillo puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, fluorometilo, difluorometilo, trifluorometilo, trifluorometoxi, alquilo C1-6, alcoxi C1-6, amino, hidroxi, ciano, acilo, alquilamino C1-6, di-(alquil C1-6)amino, alquilcarbonilamino C1-6, y oxo; W representa CH2, -CR4R5CH2-, O, S, -CR6R7O-, NR8, o -CR9R10NR11-; Y representa CR12R13, o NR14; R4 representa hidrógeno, flúor, o alquilo C1-6; R5 representa hidrógeno, flúor, o alquilo C1-6; o R4 y R5 junto con el átomo de carbono al cual se encuentran unidos forman un anillo de entre 3 y 7 miembros que puede ser saturado o insaturado, donde el anillo opcionalmente puede contener uno o dos heteroátomos seleccionados entre azufre, oxígeno, y nitrógeno y donde el anillo puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, fluorometilo, difluorometilo, trifluorometilo, trifluorometoxi, alquilo C1-6, alcoxi C1-6, amino, hidroxi, ciano, acilo, alquilamino C1-6, di-(alquil C1-6)amino, alquilcarbonilamino C1-6, y oxo; R6 representa hidrógeno, flúor, o alquilo C1-6; R7 representa hidrógeno, flúor, o alquilo C1-6; o R6 y R7 junto con el átomo de carbono al cual se encuentran unidos forman un anillo de entre 3 y 7 miembros que puede ser saturado o insaturado, donde el anillo opcionalmente puede contener uno o dos heteroátomos seleccionados entre azufre, oxígeno, y nitrógeno y donde el anillo puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, fluorometilo, difluorometilo, trifluorometilo, trifluorometoxi, alquilo C1-6, alcoxi C1-6, amino, hidroxi, ciano, acilo, alquilamino C1-6, di-(alquil C1-6)amino, alquilcarbonilamino C1-6, y oxo; R8 representa hidrógeno, alquilo C1-6, o acilo; R9 representa hidrógeno, flúor, o alquilo C1-6; R10 representa hidrógeno, flúor, o alquilo C1-6; o R9 y R10 junto con el átomo de carbono al cual se encuentran unidos forman un anillo de entre 3 y 7 miembros que puede ser saturado o insaturado, donde el anillo opcionalmente puede contener uno o dos heteroátomos seleccionados entre azufre, oxígeno, y nitrógeno y donde el anillo puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, fluorometilo, difluorometilo, trifluorometilo, trifluorometoxi, alquilo C1-6, alcoxi C1-6, amino, hidroxi, ciano, acilo, alquilamino C1-6, di-(alquil C1-6)amino, alquilcarbonilamino C1-6, y oxo; R11 representa hidrógeno, alquilo C1-6, o acilo; R12 representa hidrógeno, flúor, alquilo C1-6, amino, alquilamino C1-6, di-(alquil C1-6)amino, acilamino, o heterociclilo; R13 representa hidrógeno, flúor, o alquilo C1-6; o R12 y R13 junto con el átomo de carbono al cual se encuentran unidos forman un anillo de entre 3 y 7 miembros que puede ser saturado o insaturado, donde el anillo opcionalmente puede contener uno o dos heteroátomos seleccionados entre azufre, oxígeno, y nitrógeno y donde el anillo puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, fluorometilo, difluorometilo, trifluorometilo, trifluorometoxi, alquilo C1-6, alcoxi C1-6, amino, hidroxi, ciano, acilo, alquilamino C1-6, di-(alquil C1-6)amino, alquilcarbonilamino C1-6, y oxo; y R14 representa hidrógeno, alquilo C1-6, arilo, o heteroarilo; donde el término “arilo” significa fenilo o naftilo, donde el grupo fenilo o naftilo está opcionalmente sustituido con uno o más sustituyentes, que pueden ser iguales o diferentes, seleccionados en forma independiente entre halógeno, fluorometilo, difluorometilo, trifluorometilo, trifluorometoxi, alquilo C1-6, hidroxialquilo C1-6, alquenilo C2-6, alcoxi C1-6, alcoxi C1-6-alquilo C1-6, amino, hidroxi, nitro, ciano, formilo, alquilcarbonilo C1-6, alcoxicarbonilo C1-6, alquilcarboniloxi C1-6, alquilcarboniloxi C1-6-alquilo C1-6, alquilamino C1-6, di-(alquil C1-6)amino, cicloalquilamino C3-12, alquilcarbonilamino C1-6, fenilcarbonilamino, aminocarbonilo, N-alquilaminocarbonilo C1-6, di-N,N-alquilaminocarbonilo C1-6, pirrolidinilo, piperidinilo, morfolinilo, piperazinilo, cicloalquilo C3-12, piridinilo, y alquilendioxi C1-6; el término “heteroarilo” significa un anillo aromático de 5 ó 6 miembros que contiene entre uno y cuatro heteroátomos seleccionados entre oxígeno, azufre y nitrógeno, o un grupo bicíclico que comprende un anillo de 5 ó 6 miembros que contiene entre uno y cuatro heteroátomos seleccionados entre oxígeno, azufre y nitrógeno fusionado con un anillo benceno o un anillo de 5 ó 6 miembros que contiene entre uno y cuatro heteroátomos seleccionados entre oxígeno, azufre y nitrógeno, donde el grupo heteroarilo puede estar opcionalmente sustituido con uno o más sustituyentes, que pueden ser iguales o diferentes, seleccionados en forma independiente entre halógeno, fluorometilo, difluorometilo, trifluorometilo, trifluorometoxi, alquilo C1-6, hidroxialquilo C1-6, alquenilo C2-6, alcoxi C1-6, amino, hidroxi, nitro, ciano, alquilcarbonilo C1-6, alcoxicarbonilo C1-6, alcoxicarboniloxi C1-6, alquilamino C1-6, y di-(alquil C1-6)amino, cicloalquilamino C3-12, alquilcarbonilamino C1-6, aminocarbonilo, N-alquilaminocarbonilo C1-6, di-N,N-alquilaminocarbonilo C1-6, pirrolidinilo, piperidinilo, morfolinilo, cicloalquilo C3-12, alquilendioxi C1-6, arilo, y piridinilo; e isómeros ópticos, prodrogas, sales farmacéuticamente aceptables, hidratos, solvatos y polimorfos del mismo.Process for the preparation of said compounds. The compounds are modulators of mGluR5 and are therefore useful for the control and prevention of acute and / or chronic neurological disorders. Claim 1: A compound characterized in that it is selected from those of the formula (1) where R1 represents aryl, heteroaryl , C3-12 cycloalkyl, C5-12 cycloalkenyl, or heterocyclyl; R2 represents hydrogen, fluorine, or C1-6 alkyl; R3 represents hydrogen, fluorine, or C1-6 alkyl; or R2 and R3 together with the carbon atom to which they are attached form a ring of between 3 and 7 members that can be saturated or unsaturated, where the ring can optionally contain one or two heteroatoms selected from sulfur, oxygen, and nitrogen and where the ring may be optionally substituted with one or more substituents selected from halogen, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, C1-6 alkyl, C1-6 alkoxy, amino, hydroxy, cyano, acyl, C1-6 alkylamino, di- ( C1-6 alkyl) amino, C1-6 alkylcarbonylamino, and oxo; W represents CH2, -CR4R5CH2-, O, S, -CR6R7O-, NR8, or -CR9R10NR11-; Y represents CR12R13, or NR14; R4 represents hydrogen, fluorine, or C1-6 alkyl; R5 represents hydrogen, fluorine, or C1-6 alkyl; or R4 and R5 together with the carbon atom to which they are attached form a ring of between 3 and 7 members that can be saturated or unsaturated, where the ring can optionally contain one or two heteroatoms selected from sulfur, oxygen, and nitrogen and where the ring may be optionally substituted with one or more substituents selected from halogen, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, C1-6 alkyl, C1-6 alkoxy, amino, hydroxy, cyano, acyl, C1-6 alkylamino, di- ( C1-6 alkyl) amino, C1-6 alkylcarbonylamino, and oxo; R6 represents hydrogen, fluorine, or C1-6 alkyl; R7 represents hydrogen, fluorine, or C1-6 alkyl; or R6 and R7 together with the carbon atom to which they are attached form a ring of between 3 and 7 members that can be saturated or unsaturated, where the ring can optionally contain one or two heteroatoms selected from sulfur, oxygen, and nitrogen and where the ring may be optionally substituted with one or more substituents selected from halogen, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, C1-6 alkyl, C1-6 alkoxy, amino, hydroxy, cyano, acyl, C1-6 alkylamino, di- ( C1-6 alkyl) amino, C1-6 alkylcarbonylamino, and oxo; R 8 represents hydrogen, C 1-6 alkyl, or acyl; R9 represents hydrogen, fluorine, or C1-6 alkyl; R10 represents hydrogen, fluorine, or C1-6 alkyl; or R9 and R10 together with the carbon atom to which they are attached form a ring of between 3 and 7 members that can be saturated or unsaturated, where the ring can optionally contain one or two heteroatoms selected from sulfur, oxygen, and nitrogen and where the ring may be optionally substituted with one or more substituents selected from halogen, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, C1-6 alkyl, C1-6 alkoxy, amino, hydroxy, cyano, acyl, C1-6 alkylamino, di- ( C1-6 alkyl) amino, C1-6 alkylcarbonylamino, and oxo; R 11 represents hydrogen, C 1-6 alkyl, or acyl; R 12 represents hydrogen, fluorine, C 1-6 alkyl, amino, C 1-6 alkylamino, di- (C 1-6 alkyl) amino, acylamino, or heterocyclyl; R13 represents hydrogen, fluorine, or C1-6 alkyl; or R12 and R13 together with the carbon atom to which they are attached form a ring of between 3 and 7 members that can be saturated or unsaturated, where the ring can optionally contain one or two heteroatoms selected from sulfur, oxygen, and nitrogen and where the ring may be optionally substituted with one or more substituents selected from halogen, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, C1-6 alkyl, C1-6 alkoxy, amino, hydroxy, cyano, acyl, C1-6 alkylamino, di- ( C1-6 alkyl) amino, C1-6 alkylcarbonylamino, and oxo; and R14 represents hydrogen, C1-6 alkyl, aryl, or heteroaryl; wherein the term "aryl" means phenyl or naphthyl, where the phenyl or naphthyl group is optionally substituted with one or more substituents, which may be the same or different, independently selected from halogen, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, C1 alkyl -6, C 1-6 hydroxyalkyl, C 2-6 alkenyl, C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 alkyl, amino, hydroxy, nitro, cyano, formyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonyloxy -6, C 1-6 alkylcarbonyloxy-C 1-6 alkyl, C 1-6 alkylamino, di- (C 1-6 alkyl) amino, C 3-12 cycloalkylamino, C 1-6 alkylcarbonylamino, phenylcarbonylamino, aminocarbonyl, N- C 1-6 alkylaminocarbonyl, di -N, N- C 1-6 alkylaminocarbonyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, C 3-12 cycloalkyl, pyridinyl, and C 1-6 alkylenedioxy; the term "heteroaryl" means a 5- or 6-membered aromatic ring containing between one and four heteroatoms selected from oxygen, sulfur and nitrogen, or a bicyclic group comprising a 5- or 6-membered ring containing between one and four selected heteroatoms. between oxygen, sulfur and nitrogen fused with a benzene ring or a 5- or 6-membered ring containing between one and four heteroatoms selected from oxygen, sulfur and nitrogen, where the heteroaryl group may be optionally substituted with one or more substituents, which may be the same or different, independently selected from halogen, fluoromethyl, difluoromethyl, trifluoromethyl, trifluoromethoxy, C1-6 alkyl, hydroxy C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, amino, hydroxy, nitro, cyano, C1 alkylcarbonyl -6, C1-6 alkoxycarbonyl, C1-6 alkoxycarbonyloxy, C1-6 alkylamino, and di- (C1-6 alkyl) amino, C3-12 cycloalkylamino, C1-6 alkylcarbonylamino , aminocarbonyl, N- C 1-6 alkylaminocarbonyl, di-N, N-C 1-6 alkylaminocarbonyl, pyrrolidinyl, piperidinyl, morpholinyl, C 3-12 cycloalkyl, C 1-6 alkylenedioxy, aryl, and pyridinyl; and optical isomers, prodrugs, pharmaceutically acceptable salts, hydrates, solvates and polymorphs thereof.

ARP110103856A 2010-10-18 2011-10-18 METABOTROPIC GLUTAMATE RECEIVERS MODULATORS AR083475A1 (en)

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US20130274294A1 (en) * 2010-12-20 2013-10-17 David Carcache 4-(Hetero)Aryl-Ethynyl-Octahydro-Indole-1-Esters
US8772276B2 (en) * 2011-05-03 2014-07-08 Merck Sharp & Dohme Corp. Alkyne benzotriazole derivatives
EP2650284A1 (en) * 2012-04-10 2013-10-16 Merz Pharma GmbH & Co. KGaA Heterocyclic derivatives as metabotropic glutamate receptor modulators
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