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AR037851A1 - Antagonistas de neuroquinina, composiciones farmaceuticas y el uso de dichos compuestos para la preparacion de medicamentos - Google Patents

Antagonistas de neuroquinina, composiciones farmaceuticas y el uso de dichos compuestos para la preparacion de medicamentos

Info

Publication number
AR037851A1
AR037851A1 ARP020104877A ARP020104877A AR037851A1 AR 037851 A1 AR037851 A1 AR 037851A1 AR P020104877 A ARP020104877 A AR P020104877A AR P020104877 A ARP020104877 A AR P020104877A AR 037851 A1 AR037851 A1 AR 037851A1
Authority
AR
Argentina
Prior art keywords
alkyl
group
cycloalkyl
independently selected
attached
Prior art date
Application number
ARP020104877A
Other languages
English (en)
Original Assignee
Schering Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=23337634&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR037851(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Schering Corp filed Critical Schering Corp
Publication of AR037851A1 publication Critical patent/AR037851A1/es

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Classifications

    • 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
    • C07D498/10—Spiro-condensed systems
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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Abstract

Un antagonista de neuroquinina de la fórmula (1) o una sal aceptable para uso farmacéutico del mismo, en donde Ar1 y Ar2 se seleccionan cada uno independientemente del grupo que consiste en R17-heteroarilo y un resto de fórmula (2); X1 es -O-, -S-, -SO-, -SO2-, -NR34-, -N(COR12)- o -N(SO2R15)-; cuando X1 es -SO-, -SO2-, -N(COR12)- o -N(SO2R15)-, entonces: R1 y R2 se seleccionan cada uno independientemente del grupo que consiste en H, alquilo C1-6, hidroxi(alquilo C1-3), cicloalquilo C1-8, -CH3F, -CHF2 y -CF3; o R1 y R2, junto con el átomo de carbono al que ambos están unidos, forman un anillo de alquileno C3-6; o cuando X1 es -O-, -S- o -NR34 entonces: R1 y R2 se seleccionan cada uno independientemente del grupo que consiste en H, alquilo C1-6, hidroxi(alquilo C1-3), cicloalquilo C3-8, -CH2F, -CH2F2 y -CF3; o R1 y R2, junto con el átomo de carbono al que ambos están unidos, forman un anillo de alquileno C3-6; o R1 y R2 junto con el átomo de carbono al que ambos están unidos forman un grupo C=O; R3 se seleccionan del grupo que consiste en H, alquilo C1-6, hidroxi(alquilo C1-3), cicloalquilo C3-8, -CH2F, -CHF2 y -CF3; cada R6 se seleccionan independientemente del grupo que consiste en H, alquilo C1-6, y -OH; cada R7 se selecciona independientemente del grupo que consiste en H y alquilo C1-6; n2 es 1 a 4; R4 y R5 se seleccionan independientemente del grupo que consiste en -(CR28R29)n1-G, donde, n1 es 0 a 5; y G es -H, -CF3, -CHF2, -CH2F, -OH, -O-(alquilo C1-6), -OCH2F, -OCHF2, -OCF3, -OCH2CF3, -O-(cicloalquilo C3-6), -O-alquilo C1-6-cicloalquilo C3-8, -NR13R14, -SO2NR13R14, -NR12SO2R13, -NR12C(O)R14, -NR12C(O)OR13, -NR12(C(O)NR13R14), -C(O)NR13R14, -C(O)OR13, -cicloalquilo C3-8, (R19)r-arilo, (R19)r-heteroarilo, -OC(O)R14, -OC(O)NR13R14, -C(=NOR14)(R13), -C(O)R13, -C(OR12)(R13)(R14), heterocicloalquenilo opcionalmente sustituido con 1 a 4 sustituyentes independientemente seleccionados del grupo que consiste en R30 y R31, o un resto del seleccionado del grupo de fórmula (3); o R4 y R5 juntos son =O, =NOR12; o R4 y R5, junto con el átomo de carbono al que ambos están unidos, forman un anillo de heterocicloalquilo o heterocicloalquenilo de 4 a 8 miembros que contienen de 1 a 3 grupos independientemente seleccionados de X2, siempre que por lo menos un X2 sea -NR35, -O-, -S-, -S(O)- o -SO2-, el anillo puede sustituirse opcionalmente con 1 a 6 sustituyentes independientemente seleccionados del grupo que consiste en R30 y R31; siempre que R4 y R5 no se seleccionen ambos del grupo que consiste en H, alquilo y cicloalquilo; siempre que también cuando uno de R4 y R5 sea -OH, entonces el otro de R4 y R5 no sea alquilo o (R19)r-arilo; R8, R9 y R10 se seleccionan cada uno independientemente del grupo que consiste en H, alquilo C1-6, cicloalquilo C3-8, -OR12, halógeno, -CN, -NO2, -CF3, -CHF2, -CH2F, -CH2CF3, -OCF3, -OCHF2, -OCH2F, -OCH2CF3, -COOR12, -CONR21R22, -OC(O)NR21R22, -OC(O)R12, -NR21COR12, -NR21CO2R15, -NR21CONR21R22, -NR21SO2R15, -NR21R22, -SO2NR21R22, -S(O)n6R15, (R19)r-arilo y (R19)r- heteroarilo; R12 es H, alquilo C1-6 o cicloalquilo C3-8; R13 y R14 se seleccionan cada uno independientemente del grupo que consiste en H, alquilo C1-6, cicloalquilo C3-8, cicloalquilo C3-8-alquilo C1-6, -CH2CF3, arilo y heteroarilo; o R13 y R14, junto con el átomo de nitrógeno al que ambos están unidos, forman un anillo saturado o insaturado de 4 a 7 miembros, que está opcionalmente sustituido con -OR12, en donde uno de los átomos de carbono del anillo se reemplaza opcionalmente por un heteroátomo seleccionado del grupo que consiste en -O-, -S- y -NR34-; n6 es 0, 1 ó 2; R15 es alquilo C1-6, cicloalquilo C3-8, -CF3 o -CH2CF3; R16 es H, alquilo C1-6, cicloalquilo(C3-8)-alquilo(C1-8), hidroxialquilo C2-6 o -P(O)(OH)2; cada R19 es un sustituyente del anillo arilo o heteroarilo al que está unido, y se selecciona independientemente del grupo que consiste en H, alquilo C1-6, cicloalquilo C3-8, alcoxi C1-6, -OH, halógeno, -CN, -NO2, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, -O-(alquilo C1-6), -O-(cicloalquilo C3-8), -COOR12, -CONR21R22, -OC(O)NR21R22, -OC(O)R12, -NR21R22, -NR21COR12, -NR21CO2R12, -NR21CONR21R22, -NR21SO2R15 y -S(O)n6R15; R21 Y R22 se seleccionan independientemente del grupo que consiste en H, alquilo C1-6, cicloalquilo C3-8 y bencilo; o R21 y R22, junto con el atomo de nitrógeno al que ambos están unidos, forman un anillo saturado o insaturado de 4 a 7 miembros, en donde uno de los átomos de carbono del anillo se reemplaza opcionalmente por un heteroátomo seleccionado del grupo que consiste en -O-, -S- y -NR34-; R23 y R24 se seleccionan cada uno independientemente del grupo que consiste en H y alquilo C1-6; o R23 y R24, junto con el átomo de carbono al que ambos están unidos, forman un grupo C=O o grupo ciclopropilo; R27 es H, -OH o alquilo C1-6; R28 y R29 se seleccionan cada uno independientemente del grupo que consiste en H y alquilo C1-2; R30 y R31 se seleccionan cada uno independientemente del grupo que consiste en H, -OH, alquilo C1-6; cicloalquilo C3-8, cicloalquilo C3-8-alquilo C1-8 y -C(O)NR13R14; o R30 y R31, junto con el átomo de carbono al que ambos están unidos, forman =O, =S, un anillo de ciclopropilo o =NR35; R32 y R33 se seleccionan cada uno independientemente del grupo que consiste en H y alquilo C1-6; R34 es H, alquilo C1-6, cicloalquilo C3-8, cicloalquilo C3-8-alquilo C1-8 o hidroxialquilo C2-6; R35 es H, alquilo C1-6, cicloalquilo C3-8, cicloalquilo C3-8-alquilo C1-8, -P(O)(OH)2, alilo, hidroxialquilo C2-6, alcoxi C1-6-alquilo C1-6, -SO2R15 o -(CH2)2-N(R12)-SO2-R15; R36 es H, alquilo C1-6, cicloalquilo C3-8, cicloalquilo C1-8-alquilo C1-8, -NO2, -CN u OR12; R37 es de 1 a 3 sustituyentes seleccionados independientemente del grupo que consiste en H, alquilo C1-6, -OH, alcoxi C1-6 y halógeno; r es 1 a 3; X2 es -NR35-, -O-, -S-, -S(O)-, -SO2-, -CH2-, -CF2- o -CR12F-; X3 es -NR34-, -N(CONR13R14)-, -N(CO2R13)-, -N(SO2R15)-, -N(COR12)-, -N(SO2NHR13)-, -O-, -S-, -S(O)-, -SO2-, -CH2-, -CF2- o -CR12F-; n3 es 1 a 5, y n5 es 1 a 3, o un diastereómero, enantiómero, estereoisómero, regioestereómero, rotómero, tautómero y prodroga de los mismos; composiciones farmacéuticas y el uso de dichos compuestos para la preparación de medicamentos útil para tratar una cantidad de trastornos, incluyendo emesis, depresión, ansiedad, y tos.
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