ES2337596T3 - Antagonistas del receptor de glucacion, preparacion y usos terapeuticaos. - Google Patents

Antagonistas del receptor de glucacion, preparacion y usos terapeuticaos. Download PDF

Info

Publication number
ES2337596T3
ES2337596T3 ES05757998T ES05757998T ES2337596T3 ES 2337596 T3 ES2337596 T3 ES 2337596T3 ES 05757998 T ES05757998 T ES 05757998T ES 05757998 T ES05757998 T ES 05757998T ES 2337596 T3 ES2337596 T3 ES 2337596T3
Authority
ES
Spain
Prior art keywords
compounds
glucation
antigonists
receiver
preparation
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.)
Active
Application number
ES05757998T
Other languages
English (en)
Inventor
Scott Eugene Conner
Guoxin Zhu
Jianke Li
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.)
Eli Lilly and Co
Original Assignee
Eli Lilly and Co
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 Eli Lilly and Co filed Critical Eli Lilly and Co
Application granted granted Critical
Publication of ES2337596T3 publication Critical patent/ES2337596T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • 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
    • C07D213/89—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 with hetero atoms directly attached to the ring nitrogen atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
    • 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
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C251/48—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/64—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton
    • C07C323/65—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and sulfur atoms, not being part of thio groups, bound to the same carbon skeleton containing sulfur atoms of sulfone or sulfoxide groups bound to the carbon skeleton
    • 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
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • C07D213/60—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 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
    • C07D213/62—Oxygen or sulfur atoms
    • 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
    • C07D213/60—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 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • 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
    • C07D213/60—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 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
    • C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
    • 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
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Abstract

Un compuesto representado estructuralmente por la Fórmula I **(Ver fórmula)** o una de sus sales farmacéuticamente aceptables en la que: Y es -O- ó -S-; Q, D, X, y T representan independientemente carbono (sustituido con hidrógeno o los sustituyentes opcionales como se indica en el presente documento), o nitrógeno (opcionalmente sustituido con oxígeno), con la condición de que no más de dos de Q, D, X, y T sean nitrógeno; R1 es -H, -OH, o -halógeno; R2 es -H o -alquilo(C1-C3) (opcionalmente sustituido con 1 a 3 halógenos); R3 y R4 son independientemente -H, -halógeno, -CN, -OH, -alcoxi(C1-C7), -alquilo(C1-C7) (opcionalmente sustituido con 1 a 3 halógenos), o -alquenilo(C2-C7): R5 se selecciona entre -H, -alquilo(C1-C12) (opcionalmente sustituido con 1 a 3 halógenos), -cicloalquilo(C3-C12),-fenilo, -fenil-fenil-alquilo(C2-C12), -arilo, -aril-alquilo(C2-C12), -heteroarilo, -heteroaril-alquilo(C2-C12), -alquenilo((C2-C12)), -cicloalquenilo(C3-C12), -heterocicloalquilo, -aril-alquenilo(C2-C10), -heteroaril-alquenilo(C2-C10), -alquinilo((C2-C12)), -cicloalquinilo(C3-C12), -aril-alquinilo((C2-C12)), y -heteroaril-alquinilo((C2-C12)), y en el que -alquilo(C1-C12), -cicloalquilo(C3-C12), -fenilo, -fenil-fenil-alquilo(C2-C12), -arilo, -aril-alquilo(C2-C12), -heteroarilo, -heteroaril-alquilo(C2-C12), -heterocicloalquilo, -alquenilo((C2-C12)), -cicloalquenilo(C3-C12), -aril-alquenilo(C2-C10), -heteroaril-alquenilo(C2-C10), -alquinilo((C2-C12)), -cicloalquinilo(C3-C12), -aril-alquinilo((C2-C12)), -heteroaril-alquinilo((C2-C12)), están sustituidos cada uno opcionalmente con uno a tres sustituyentes seleccionados cada uno independientemente entre -hidrógeno, -hidroxi, -ciano, -nitro, -halo, -oxo, -alquilo(C1-C7) (opcionalmente sustituido con 1 a 3 halógenos), -alquil(C1-C7)-C(O) OR12, -alcoxi(C1-C7), -cicloalquilo(C3-C7), -C(O)R12, -C(O)OR12, -OC(O)R12, -OS(O)2R12, -N(R12)2, -NR12C(O)R12, -NR12SO2R12, -SR12, =S(O)R12, -S(O)2R12, y -S(O)2N(R12)2; R6 y R7 se seleccionan independientemente en cada caso entre -H, -halógeno, -hidroxi, -CN, -alcoxi(C1-C7), -alquenilo(C2-C7), -alquilo(C1-C10) (opcionalmente sustituido con 1 a 3 halógenos), -cicloalquilo(C3-C12), terc-butoxiiminometilo, 1,3-dioxan-2-ilo, hidroximetilo, formilo, hidroxiiminometilo, morfilino-4-il-metilo, 4-metilpentiloxi, y pentiloxi; con la condición sin embargo de que cuando D sea nitrógeno, entonces R6 o R7 no estén unidos a D, y con la condición de que cuando T sea nitrógeno, entonces R6 o R7 no estén unidos a T, y con la condición de que cuando Q sea nitrógeno, entonces R6 o R7 no estén unidos a Q y con la condición de que cuando X sea nitrógeno, entonces R6 o R7 no estén unidos a X; pudiendo R6 y R7 formar formar opcionalmente un anillo de seis miembros con los átomos a los cuales están unidos, y el anillo formado de esta manera puede contener opcionalmente hasta dos oxígenos, y adicionalmente, el anillo formado de esta manera puede estar sustituido con hasta cuatro halógenos; R8 y R9 se seleccionan independientemente en cada caso entre -hidrógeno, -hidroxi, -CN, -nitro, -halo, -alquilo(C1-C7) (opcionalmente sustituido con 1 a 3 halógenos), -alcoxi(C1-C7), -cicloalquilo(C3-C7), arilo, -aril-alquilo(C1-C7), -heteroarilo, -heteroaril-alquilo(C1-C7), -ariloxi, -C(O)R12, -COOR12, -OC(O)R12, -OS(O)2R12, -N(R12)2, -NR12C(O)R12, -NR12SO2R12, -SR12, -S(O)R12, -S(O)2R12, -O-alquenilo(C2-C7), y -S(O)2N(R12)2; y en el que -alquilo(C1-C7), -alcoxi(C1-C7), -cicloalquil(C3-C7), -arilo, -aril-alquilo(C1-C7), -heteroarilo, -heteroaril-alquilo(C1-C7), -ariloxi, y -alquenilo(C2-C7) están sustituidos cada uno opcionalmente con uno a tres sustituyentes seleccionados independientemente entre -hidrógeno, -hidroxi, -ciano, -nitro, -halo, -oxo, -alquilo(C1-C7), -alquil(C1-C7)-C(O)OR12, -alcoxilo(C1-C7), -cicloalquilo(C3-C7), -heterocicloalquilo, -C(O)R12, -COOR12, -OC(O)R12, OS(O)2R12, -N(R12)2, -NR12C(O)R12, -NR12SO2R12, -SR12, -S(O)R12, -S(O)2R12, y -S(O)2N(R12)2, R10 se selecciona entre -H, halógeno, -alquilo(C1-C12) (opcionalmente sustituido con 1 a 3 halógenos), -cicloalquilo, -arilo, -aril-alquilo(C1-C7), -heteroarilo, -alquilo(C1-C7), -alquenilo((C2-C12)), -cicloalquenilo(C3-C12), -aril-alquenilo(C2-C10), -heteroaril-alquenilo(C2-C10), -alquinilo((C2-C12)), cicloalquinilo(C3-C12), -aril-alquinilo((C2-C12)), y -heteroaril-alquinilo((C2-C12)); R11 se selecciona independientemente en cada caso entre -H, -halógeno **(Ver fórmula)** en la que la marca en zig-zag muestra el punto de unión a la molécula parental, en la que A, G, y E representan independientemente carbono (sustituido con hidrógeno o los sustituyentes opcionales tal como se indica en el presente documento) o nitrógeno, con la condición de que no más de dos de A, G, y E sean nitrógeno; con la condición sin embargo de que cuando A sea nitrógeno, entonces R8, R9, y R14 no estén unidos a A, y con la condición de que cuando G sea nitrógeno, entonces R8, R9, y R14 no estén unidos a G, y con la condición de que cuando E sea nitrógeno, entonces R8, R9, y R14 no estén unidos a E, **(Ver fórmula)** en la que la marca en zig-zag muestra el punto de unión a la molécula parental, en la que m es un entero de 0, 1, 2, ó 3 y cuando m sea 0, entonces (CH2)m es un enlace y **(Ver fórmula)** en la que la marca en zig-zag muestra el punto de unión a la molécula parental, con la condición de que, sin embargo, cuando D sea nitrógeno, entonces R11 no esté unido a D, y con la condición de que cuando T sea nitrógeno, entonces R11 no esté unido a T, y con la condición de que cuando Q sea nitrógeno, entonces R11 no esté unido a Q, y con la condición de que cuando X sea nitrógeno, entonces R11 no esté unido a X; R12 se selecciona independientemente en cada caso entre -hidrógeno, -alquilo(C1-C7) (opcionalmente sustituido con 1 a 3 halógenos, y -arilo R13 se selecciona independientemente en cada caso entre -hidrógeno, -halógeno, -alquilo(C1-C7) (opcionalmente sustituido con 1 a 3 halógenos), fenilo, y-alquenilo(C2-C7); R14 es independientemente en cada caso -H, halógeno, o -alquilo(C1-C7) (opcionalmente sustituido con 1 a 3 halógenos).
ES05757998T 2004-06-14 2005-06-08 Antagonistas del receptor de glucacion, preparacion y usos terapeuticaos. Active ES2337596T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US57936204P 2004-06-14 2004-06-14
US579362P 2004-06-14

Publications (1)

Publication Number Publication Date
ES2337596T3 true ES2337596T3 (es) 2010-04-27

Family

ID=35219490

Family Applications (1)

Application Number Title Priority Date Filing Date
ES05757998T Active ES2337596T3 (es) 2004-06-14 2005-06-08 Antagonistas del receptor de glucacion, preparacion y usos terapeuticaos.

Country Status (29)

Country Link
US (3) US7816557B2 (es)
EP (2) EP1758853B1 (es)
JP (1) JP5000492B2 (es)
KR (1) KR100835496B1 (es)
CN (1) CN1968921B (es)
AT (1) ATE455756T1 (es)
AU (2) AU2005254950B2 (es)
BR (1) BRPI0512058A (es)
CA (1) CA2569459C (es)
CY (1) CY1109787T1 (es)
DE (1) DE602005019043D1 (es)
DK (1) DK1758853T3 (es)
EA (1) EA013003B1 (es)
EC (1) ECSP067082A (es)
ES (1) ES2337596T3 (es)
HK (1) HK1104174A1 (es)
HR (1) HRP20100148T1 (es)
IL (1) IL179599A (es)
MA (1) MA28706B1 (es)
MX (1) MXPA06014426A (es)
NO (1) NO341028B1 (es)
NZ (1) NZ551015A (es)
PL (1) PL1758853T3 (es)
PT (1) PT1758853E (es)
RS (1) RS51202B (es)
SI (1) SI1758853T1 (es)
UA (1) UA86621C2 (es)
WO (1) WO2005123668A1 (es)
ZA (1) ZA200610298B (es)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1758853T3 (da) * 2004-06-14 2010-04-06 Lilly Co Eli Glucagon-receptorantagonister, fremstilling og terapeutiske anvendelser
US7524870B2 (en) 2004-12-03 2009-04-28 Hoffmann-La Roche Inc. Biaryloxymethylarenecarboxylic acids as glycogen synthase activators
PL1856090T3 (pl) * 2005-02-11 2010-02-26 Lilly Co Eli Podstawione pochodne tiofenu jako antagoniści receptora glukagonu, ich wytwarzanie i terapeutyczne zastosowania
US8318760B2 (en) * 2005-03-21 2012-11-27 Merck Sharp & Dohme Corp. Substituted aryl and heteroaryl derivatives, compositions containing such compounds and methods of use
BRPI0618140A2 (pt) * 2005-11-22 2011-08-16 Lilly Co Eli composto ou sal farmaceuticamente aceitável do mesmo, composição farmacêutica, e, uso de um composto ou um sal do mesmo
JP2009537525A (ja) 2006-05-16 2009-10-29 メルク エンド カムパニー インコーポレーテッド グルカゴン受容体アンタゴニスト化合物、このような化合物を含む組成物及び使用方法
JP5322951B2 (ja) 2007-02-09 2013-10-23 リガンド・ファーマシューティカルズ・インコーポレイテッド グルカゴン受容体の新規アンタゴニスト
KR101599089B1 (ko) 2008-08-13 2016-03-02 메타베이시스 테라퓨틱스, 인크. 글루카곤 길항제
US8809579B2 (en) 2009-02-13 2014-08-19 Merck Sharp & Dohme Corp. Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use
US8039495B2 (en) * 2009-11-16 2011-10-18 Hoffman-La Roche Inc. Biphenyl carboxylic acids and bioisosteres as glycogen synthase activators
AU2011346670B2 (en) 2010-12-23 2015-05-07 Pfizer Inc. Glucagon receptor modulators
WO2012107850A1 (en) 2011-02-08 2012-08-16 Pfizer Inc. Glucagon receptor modulator
US8927577B2 (en) 2011-07-22 2015-01-06 Pfizer Inc. Quinolinyl glucagon receptor modulators
WO2013081993A1 (en) 2011-12-02 2013-06-06 Eli Lilly And Company Anti-glucagon antibodies and uses thereof
US20140210770A1 (en) * 2012-10-04 2014-07-31 Corning Incorporated Pressure sensing touch systems and methods
TW201427658A (zh) * 2012-12-10 2014-07-16 Merck Sharp & Dohme 藉由投予升糖素受體拮抗劑及膽固醇吸收抑制劑治療糖尿病之方法
WO2015066252A1 (en) 2013-11-04 2015-05-07 Merck Sharp & Dohme Corp. Glucagon receptor antagonist compounds, compositions thereof, and methods of use
JP2017519000A (ja) 2014-06-12 2017-07-13 リガンド・ファーマシューティカルズ・インコーポレイテッド グルカゴンアンタゴニスト
CN108290839A (zh) 2015-12-01 2018-07-17 巴斯夫欧洲公司 作为杀真菌剂的吡啶化合物
BR112018010316A2 (pt) 2015-12-01 2018-12-04 Basf Se compostos de fórmula, composição, utilização de um composto de fórmula, método para o combate de fungos fitopatogênicos e semente
CR20190580A (es) 2017-05-30 2020-02-10 Basf Se Compuestos de piridina y pirazina
TW202003453A (zh) 2018-02-13 2020-01-16 美商利根德製藥公司 升糖素受體拮抗劑
CN111184706B (zh) * 2020-03-05 2020-11-17 牡丹江医学院 一种防治胆囊炎的活性药物及其用途
KR102606541B1 (ko) * 2021-04-23 2023-11-29 가천대학교 산학협력단 바이페닐설폰아마이드 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 글루카곤 수용체 활성 관련 질환의 예방 또는 치료용 약학적 조성물

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4973731A (en) 1987-04-23 1990-11-27 Riker Laboratories, Inc. Di-t-butylphenyl alkyl and benzyl ether nitriles
GB9420557D0 (en) 1994-10-12 1994-11-30 Zeneca Ltd Aromatic compounds
EP1054871A2 (en) * 1998-04-01 2000-11-29 Du Pont Pharmaceuticals Company Pyrimidines and triazines as integrin antagonists
JP2002544254A (ja) * 1999-05-17 2002-12-24 ノボ ノルディスク アクティーゼルスカブ グルカゴンアンタゴニスト／逆アゴニスト
HUP0301501A2 (hu) * 2000-06-23 2003-08-28 Novo Nordisk A/S Glükagon antaagonista/inverz agonista vegyületek, ezeket tartalmazó gyógyászati készítmények, valamint a vegyületek alkalmazása gyógyászati készítmények előállítására
US6706744B2 (en) 2000-11-17 2004-03-16 Novo Nordisk A/S Glucagon antagonists/inverse agonists
JP2005511683A (ja) * 2001-12-03 2005-04-28 ノボ　ノルディスク　アクティーゼルスカブ 新規なグルカゴンアンタゴニスト
WO2004002480A1 (en) 2002-06-27 2004-01-08 Novo Nordisk A/S Novel glucagon antagonists/inverse agonists
AU2003291959A1 (en) 2002-12-20 2004-07-14 Novo Nordisk A/S Novel glucagon antagonists
US20080254182A1 (en) 2004-04-26 2008-10-16 Laurens Last Packaged Flowable Ice Product, Such as a Milk Shake
EP1758859B1 (en) 2004-05-28 2013-07-17 Eli Lilly And Company Glucagon receptor antagonists, preparation and therapeutic uses
DK1758853T3 (da) 2004-06-14 2010-04-06 Lilly Co Eli Glucagon-receptorantagonister, fremstilling og terapeutiske anvendelser
PL1856090T3 (pl) * 2005-02-11 2010-02-26 Lilly Co Eli Podstawione pochodne tiofenu jako antagoniści receptora glukagonu, ich wytwarzanie i terapeutyczne zastosowania
US8318760B2 (en) 2005-03-21 2012-11-27 Merck Sharp & Dohme Corp. Substituted aryl and heteroaryl derivatives, compositions containing such compounds and methods of use
EP1951661B1 (en) 2005-11-17 2012-08-08 Eli Lilly And Company Glucagon receptor antagonists, preparation and therapeutic uses
JP5198280B2 (ja) 2005-11-17 2013-05-15 イーライ リリー アンド カンパニー グルカゴン受容体アンタゴニスト、並びにその調製及び治療への使用
BRPI0618484A2 (pt) 2005-11-18 2011-08-30 Lilly Co Eli composto ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, métodos para inibir o receptor de glucagon em um mamìfero, para reduzir seletivamente o nìvel glicêmico em um mamìfero e para tratar diabete tipo 2, e, uso de um composto ou um sal do mesmo
BRPI0618140A2 (pt) 2005-11-22 2011-08-16 Lilly Co Eli composto ou sal farmaceuticamente aceitável do mesmo, composição farmacêutica, e, uso de um composto ou um sal do mesmo
DK1957484T3 (da) 2005-11-23 2010-05-10 Lilly Co Eli Glucagon-receptorantagonister, fremstilling og terapeutiske anvendelser

Also Published As

Publication number Publication date
EA200700027A1 (ru) 2007-06-29
DE602005019043D1 (de) 2010-03-11
AU2005254950A1 (en) 2005-12-29
RS51202B (sr) 2010-12-31
ATE455756T1 (de) 2010-02-15
US20070249688A1 (en) 2007-10-25
EP1758853B1 (en) 2010-01-20
CY1109787T1 (el) 2014-09-10
PL1758853T3 (pl) 2010-06-30
ZA200610298B (en) 2008-02-27
MXPA06014426A (es) 2007-03-01
EP1758853A1 (en) 2007-03-07
HRP20100148T1 (hr) 2010-04-30
NO20070213L (no) 2007-03-12
US7816557B2 (en) 2010-10-19
MA28706B1 (fr) 2007-06-01
IL179599A0 (en) 2007-05-15
KR100835496B1 (ko) 2008-06-09
JP2008502683A (ja) 2008-01-31
BRPI0512058A (pt) 2008-02-06
CA2569459C (en) 2013-01-29
US8609892B2 (en) 2013-12-17
EA013003B1 (ru) 2010-02-26
CN1968921B (zh) 2011-11-23
US20110124648A1 (en) 2011-05-26
AU2010246329A1 (en) 2010-12-09
NO341028B1 (no) 2017-08-07
AU2005254950B2 (en) 2010-08-19
HK1104174A1 (en) 2008-01-04
ECSP067082A (es) 2007-01-26
SI1758853T1 (sl) 2010-05-31
DK1758853T3 (da) 2010-04-06
EP2159221A1 (en) 2010-03-03
UA86621C2 (ru) 2009-05-12
JP5000492B2 (ja) 2012-08-15
KR20070026585A (ko) 2007-03-08
US20100324140A1 (en) 2010-12-23
CN1968921A (zh) 2007-05-23
NZ551015A (en) 2010-07-30
CA2569459A1 (en) 2005-12-29
PT1758853E (pt) 2010-03-02
WO2005123668A1 (en) 2005-12-29
IL179599A (en) 2011-11-30

Similar Documents

Publication Publication Date Title
ES2337596T3 (es) Antagonistas del receptor de glucacion, preparacion y usos terapeuticaos.
CR9304A (es) Antagonistas del receptor de glucagon, preparaciones y usos terapeuticos
DK1957484T3 (da) Glucagon-receptorantagonister, fremstilling og terapeutiske anvendelser
WO2007106181A3 (en) Glucagon receptor antagonists, preparation and therapeutic uses
WO2007120270A3 (en) Glucagon receptor antagonists, preparation and therapeutic uses
DK1951659T3 (da) Glucagonreceptorantagonister, fremstilling og terapeutisk anvendelse heraf
SI1735278T1 (sl) Agenti histamin h receptorja priprava in terapevtska uporaba
WO2005082893A3 (en) Histamine h3 receptor antagonists, preparation and therapeutic uses
ATE523488T1 (de) Histamin-h3-rezeptor-mittel, deren herstellung und therapeutische verwendung