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ES2188264T3 - Antagonistas del receptor del neuropeptido y5. - Google Patents

Antagonistas del receptor del neuropeptido y5.

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Publication number
ES2188264T3
ES2188264T3 ES99955470T ES99955470T ES2188264T3 ES 2188264 T3 ES2188264 T3 ES 2188264T3 ES 99955470 T ES99955470 T ES 99955470T ES 99955470 T ES99955470 T ES 99955470T ES 2188264 T3 ES2188264 T3 ES 2188264T3
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Spain
Prior art keywords
alkyl
cycloalkyl
group
independently selected
aryl
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Expired - Lifetime
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ES99955470T
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Inventor
Sundeep Dugar
Bernard R Neustadt
Andrew W Stamford
Yusheng Wu
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Merck Sharp and Dohme LLC
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Schering Corp
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    • 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
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    • A61P3/04—Anorexiants; Antiobesity agents
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/24—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/25—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
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    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/30—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
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    • C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
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    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/38—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by doubly-bound oxygen atoms
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    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
    • C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C311/05—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
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    • 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
    • C07C323/39—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 at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
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    • C07C323/39—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 at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
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    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/56—Nitrogen atoms
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    • C07D211/96—Sulfur atom
    • C—CHEMISTRY; METALLURGY
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    • 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
    • C07D215/04—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • C07D215/08—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms with acylated ring nitrogen atom
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    • C07D295/16—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 acylated on ring nitrogen atoms
    • C07D295/20—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 acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
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    • C07C2601/14—The ring being saturated

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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  • Pyridine Compounds (AREA)

Abstract

Un compuesto que tiene la fórmula estructural **(Fórmula)** o una de sus sales farmacéuticamente aceptable, en la que a y b son independientemente 0, 1 ó 2, con la condición de que la suma de a y b sea de 0 a 3; Q es **(Fórmula)** o **(Fórmula)** X es -O-, -S-, -SO-, -SO2-, -CH(OR8)-, -C(O)-, -C(R23)2-, -(CR25)=C(R25)-, **(Fórmula)**, R1 es R15-arilo, R24-heteroarilo, -NHR12, -N(R12)2, -alquilo(C1-C9)-OC(O)R8, ariloxi-alquilo(C1-C9), **(Fórmula)** en el que m es 1-4, o **(Fórmula)**en el que d y e son independientemente 0, 1 ó 2; R2, R3, R4 y R5 se seleccionan independientemente del grupo que consta de H, alquilo C1-C5 lineal o ramificado, cicloalquilo (C3-C12), R14-(cicloalquilo C3-C12), halógeno, -OR8, -N(R8)2, -CO2R8 y CF3; R6 y R7 se seleccionan independientemente del grupo que consta de H, alquilo (C1-C9), alquenilo (C1C9), hidroxi-alquilo(C1-C9), amino-alquilo(C1-C9), alcoxi(C1-C9)-alquilo(C1-C9), cicloalquilo (C3-C12) y cicloalquil(C3-C12)-alquilo (C1-C6), o R6 y R7 junto con el carbono al que están unidos forman, un anillo carbocíclico de 3, 4, 5, 6 ó 7 miembros, o un anillo heterocíclico de 4, 5, 6 ó 7 miembros, donde 1, 2 ó 3 miembros del anillo se seleccionan independientemente del grupo que consta de O, S y N; R8 se selecciona independientemente del grupo que consta de H, alquilo (C1-C6), cicloalquilo (C3-C12), R15-arilo y R24-heteroarilo; R9 es alquilo (C1-C6), cicloalquilo (C3-C12), R15-arilo o R24-heteroarilo; R11 se selecciona independientemente del grupo que consta de H, alquilo (C1-C6), y cicloalquilo (C3C12); R12 se selecciona independientemente del grupo que consta de alquilo (C1-C9) lineal o ramificado, hidroxi-alquilo(C2-C9), alcoxi(C1-C9)-alquilo(C2-C9), N(R11)(R19)-alquilo(C2-C9), HS-alquilo(C2-C9), alquiltio(C1-C9)-alquilo(C2-C9), cicloalquilo (C3-C12), R14-cicloalquilo(C3-C12), R15-arilo, R24-heteroarilo, R15-aril-alquilo(C1-C6), R24-heteroaril-alquilo(C1-C6), **(Fórmula)** en el que j y k son independientemente 0, 1 ó 2, **(Fórmula)** en el que q es1 ó 2, y s es 0, 1 ó 2; o dos grupos R12 junto con el nitrógeno al que están unidos forman un anillo de fórmula: **(Fórmula)** en el que p es 0, 1 ó 2; R10 es -NR18-, -O- o -S-; R13 es de 1 a 3 sustituyentes independientemente seleccionados del grupo que consta de hidrógeno, alquilo (C1-C6), halógeno, alcoxi (C1-C6) y CF3; R14 es de 1 a 3 sustituyentes independientemente seleccionados del grupo que consta de alquilo (C1-C6), bencilo, R13-arilo y R13-heteroarilo; R15 es de 1 a 3 sustituyentes independientemente seleccionados del grupo que consta de hidrógeno, alquilo (C1-C6), halógeno, polihalógeno-alquilo(C1-C6), R17O-N(R17)2, -S(R17), R17O-alquilo(C1-C6), (R17)2N-alquilo(C1-C6), formilo, -C(O)R17, -COOR17, -CON(R17)2, -OC(O)N(R17)2, -N(R17)C(O)30 N(R17)2, -NR17C(O)R17, -NR17C(O)OR14, R17S(O)-, R17SO2-, -R17SO2NR17- y tri-alquil(C1-C6)-sililo. R16 es 1-3 sustituyentes independientemente seleccionados del grupo que consiste en H, alquilo (C1-C6), cicloalquilo (C3-C12), espirocicloalquilo (C3-C12), espiro-alquilendioxi (C3-C4), R15-arilo, R24heteroarilo, bencilo, N-piperidinilo, -COR8, -C(O)NR8R9, -NR8R9 y -NR8C(O)R9, o cuando dos grupos 35 R16 están unidos a átomos de carbono adyacentes del anillo, junto con dichos átomos de carbono, pueden formar un anillo de cicloalquilo (C5-C7); R17 se selecciona independientemente del grupo que consta de H, alquilo (C1-C6), cicloalquilo (C3C12), cicloalquil(C3-C12)-alquilo(C1-C6), R13-arilo y R13-heteroarilo; R18 se selecciona independientemente del grupo que consta de H, alquilo (C1-C6), cicloalquilo (C3C12), cicloalquil(C3-C12)-alquilo(C1-C6), R15-arilo, R24 -heteroarilo, -CO2R9, C(O)N(R8)2, -COR8 y -SO2R9; R19 es H, cicloalquil(C3-C12)-alquilo(C1-C6), R15-arilo, R24-heteroarilo, -CO2R9, C(O)N(R8)2, -COR8 y -SO2R9; R20 es alquilo (C1-C6), cicloalquilo (C3-C12), cicloalquil(C3-C12)-alquilo(C1-C6), hidroxi-alquilo(C1C6), oxoalquilo(C1-C6), o polihalógeno-alquilo(C1-C6); R21 y R22 se seleccionan independientemente del grupo que consta de H, alquilo (C1-C6), cicloalquil(C3-C12)-alquilo(C1-C6), hidroxi-alquilo(C1-C6), R15-arilo, R24-heteroarilo, R15-aril-alquilo(C1-C6) o R24-heteroaril-alquilo(C1-C6); R23 se selecciona independientemente del grupo que consta de H, halógeno, alquilo (C1-C6), cicloalquilo (C3-C12), R15-arilo y R24-heteroarilo; R24 es de 1 a 2 sustituyentes independientemente seleccionados del grupo que consta de hidrógeno, alquilo (C1-C6), halógeno, polihalógeno-alquilo(C1-C6), R17O-, -N(R17)2, -S-(R17), R17O-alquilo(C1-C6), -(R17)2N- alquilo(C1-C6), formilo, -C(O)R17, COOR17, -CON(R17)2, OC(O)N(R17)2, -N(R17)C(O)N(R17)2, NR17C(O)R17, -N(R17)C(O)OR14, R17-S(O), R17SO2, R17SO2NR17- y tri-alquil(C1-C6)sililo; y R25 se selecciona independientemente del grupo que consta de hidrógeno, halógeno, alquilo (C1-C6), y polihalógeno-alquilo(C1-C6).
ES99955470T 1998-06-08 1999-06-07 Antagonistas del receptor del neuropeptido y5. Expired - Lifetime ES2188264T3 (es)

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JP (1) JP2002517483A (es)
KR (1) KR20010052587A (es)
CN (1) CN1311773A (es)
AR (1) AR019626A1 (es)
AT (1) ATE232200T1 (es)
AU (1) AU4317899A (es)
CA (1) CA2334298C (es)
CO (1) CO5031253A1 (es)
DE (1) DE69905248T2 (es)
ES (1) ES2188264T3 (es)
HU (1) HUP0103796A3 (es)
IL (1) IL139913A0 (es)
MY (1) MY133223A (es)
PE (1) PE20000564A1 (es)
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ZA (1) ZA200006992B (es)

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US6897234B2 (en) 1999-12-17 2005-05-24 Bristol-Myers Squibb Pharma Company N-ureidoalkyl-piperidines as modulators of chemokine receptor activity
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GB0010757D0 (en) * 2000-05-05 2000-06-28 Astrazeneca Ab Chemical compounds
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