AR088511A1 - Derivados heterociclicos como moduladores de trpv3 - Google Patents

Derivados heterociclicos como moduladores de trpv3

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Publication number
AR088511A1
AR088511A1 ARP120103976A ARP120103976A AR088511A1 AR 088511 A1 AR088511 A1 AR 088511A1 AR P120103976 A ARP120103976 A AR P120103976A AR P120103976 A ARP120103976 A AR P120103976A AR 088511 A1 AR088511 A1 AR 088511A1
Authority
AR
Argentina
Prior art keywords
cr1ar1b
alkyl
haloalkyl
independently
halogen
Prior art date
Application number
ARP120103976A
Other languages
English (en)
Inventor
Clapham Bruce
B Cox Phil
F Daanen Jerome
Gomtsyan Arthur
E Kort Michael
R Kym Philip
A Voight Eric
G Schmidt Robert
J Dart Michael
Gfesser Gregory
K Bayburt Erol
Original Assignee
Abbvie Inc
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 Abbvie Inc filed Critical Abbvie Inc
Publication of AR088511A1 publication Critical patent/AR088511A1/es

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    • 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
    • C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • 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
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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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
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
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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
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
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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
    • C07D213/60—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
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  • Stabilization Of Oscillater, Synchronisation, Frequency Synthesizers (AREA)

Abstract

Además, composiciones que comprenden dichos compuestos y métodos para el tratamiento de condiciones y trastornos usando dichos compuestos y composiciones. Reivindicación 1: Un compuesto caracterizado porque es de fórmula (1) o una sal del mismo, donde: las instancias de Rᵃ y Rᵇ son en forma independiente entre sí hidrógeno, alquilo, haloalquilo, halógeno, OH, O(alquilo), o un grupo fenilo que está opcionalmente sustituido con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre el grupo que consiste en alquilo, haloalquilo, y halógeno; u es 0, 1, ó 2; X³ es O; X⁴ es una unión, X⁵ es (CH₂)ₙ, y n es 2; o X³ es O; X⁴ es (CH₂)ₘ, X⁵ es (CH₂)ₙ, m y n son cada uno 1; o X³ es O; X⁴ es (CH₂)ₘ, X⁵ es (CH₂)ₙ, m es 1, y n es 2; o X³ es O; X⁴ es una unión, X⁵ es (CH₂)ₙ, y n es 3; y X¹ es -OH y X² es hidrógeno; G¹ es arilo, heteroarilo, cicloalquilo, heterociclo, o cicloalquenilo; cada uno de los cuales está opcionalmente sustituido con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre el grupo que consiste en alquilo, alquenilo, alquinilo, halógeno, haloalquilo, ORᵍᶜ, N(Rᵍᶜ)₂, N(Rᵍᶜ)C(O)alquilo, heteroarilo, y heterociclo; las unidades heteroarilo y heterociclo en forma independiente entre sí no están sustituidas o están sustituidas con 1, 2, 3, 4, ó 5 sustituyentes seleccionados entre el grupo que consiste en alquilo, O(alquilo), halógeno, y haloalquilo; y donde cada Rᵍᶜ es en forma independiente hidrógeno, alquilo, o haloalquilo; G² es G²ᵈ o -(CR¹ᵍR²ᵍ)ʳ-G²ᵈ donde: r es 1, 2, ó 3; R¹ᵍ y R²ᵍ son iguales o diferentes, y son en forma independiente entre sí hidrógeno, alquilo, halógeno, OR¹ᵍᶜ, N(R¹ᵍᶜ)₂, C(O)alquilo, o haloalquilo; donde cada R¹ᵍᶜ es en forma independiente hidrógeno, alquilo, o haloalquilo; G²ᵈ es arilo, heteroarilo, cicloalquilo, heterociclo, o cicloalquenilo, cada uno de los cuales está opcionalmente sustituido con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre el grupo que consiste en Gᵈ, alquilo, alquenilo, alquinilo, halógeno, haloalquilo, -CN, -ORᶠ, -OC(O)Rᶠ, -OC(O)N(Rᶠ)₂, -S(O)₂Rᵉ, -S(O)₂N(Rᶠ)₂, -C(O)Rᶠ, -C(O)ORᶠ, -C(O)N(Rᶠ)₂, -N(Rᶠ)₂, -N(Rᶠ)C(O)Rᶠ, -N(Rᶠ)S(O)₂Rᵉ, -N(Rᶠ)C(O)O(Rᵉ), -N(Rᶠ)C(O)N(Rᶠ)₂, -(CR¹ᵃR¹ᵇ)q-Gᵈ, -(CR¹ᵃR¹ᵇ)q-ORᶠ, -(CR¹ᵃR¹ᵇ)q-OC(O)Rᶠ, -(CR¹ᵃR¹ᵇ)q-OC(O)N(Rᶠ)₂, -(CR¹ᵃR¹ᵇ)q-S(O)₂Rᵉ, -(CR¹ᵃR¹ᵇ)q-S(O)₂N(Rᶠ)₂, -(CR¹ᵃR¹ᵇ)q-C(O)Rᶠ, -(CR¹ᵃR¹ᵇ)q-C(O)ORᶠ, -(CR¹ᵃR¹ᵇ)q-C(O)N(Rᶠ)₂, -(CR¹ᵃR¹ᵇ)q-N(Rᶠ)₂, -(CR¹ᵃR¹ᵇ)q-N(Rᶠ)C(O)Rᶠ, -(CR¹ᵃR¹ᵇ)q-N(Rᶠ)S(O)₂Rᵉ, -(CR¹ᵃR¹ᵇ)q-N(Rᶠ)C(O)O(Rᵉ), -(CR¹ᵃR¹ᵇ)q-N(Rᶠ)C(O)N(Rᶠ)₂, y -(CR¹ᵃR¹ᵇ)q-CN; R¹ᵃ y R¹ᵇ, son iguales o diferentes, y en cada caso son en forma independiente entre sí hidrógeno, halógeno, alquilo, o haloalquilo; cada instancia de Rᶠ es en forma independiente hidrógeno, alquilo, haloalquilo, Gᵈ, o -(CR¹ᵃR¹ᵇ)q-Gᵈ; cada instancia de Rᵉ es en forma independiente alquilo, haloalquilo, Gᵈ, o -(CR¹ᵃR¹ᵇ)q-Gᵈ; q, en cada caso, es en forma independiente 1, 2, ó 3; cada instancia de Gᵈ es en forma independiente arilo, heteroarilo, cicloalquilo, heterociclo, o cicloalquenilo; y está opcionalmente sustituido en cada caso con 1, 2, 3, 4, ó 5 sustituyentes seleccionados en forma independiente entre el grupo que consiste en alquilo, alquenilo, alquinilo, halógeno, haloalquilo, -CN, -ORʲ, -OC(O)Rʲ, -OC(O)N(Rʲ)₂, -S(O)₂Rᵏ, -S(O)₂N(Rʲ)₂, -C(O)Rʲ, -C(O)ORʲ, -C(O)N(Rʲ)₂, -N(Rʲ)₂, -N(Rʲ)C(O)Rʲ, -N(Rʲ)S(O)₂Rᵏ, N(Rʲ)C(O)O(Rᵏ), -N(Rʲ)C(O)N(Rʲ)₂, -(CR¹ᵃR¹ᵇ)q-ORʲ, -(CR¹ᵃR¹ᵇ)q-OC(O)Rʲ, -(CR¹ᵃR¹ᵇ)q-OC(O)N(Rʲ)₂, -(CR¹ᵃR¹ᵇ)q-S(O)₂Rᵏ, -(CR¹ᵃR¹ᵇ)q-S(O)₂N(Rʲ)₂, -(CR¹ᵃR¹ᵇ)q-C(O)Rʲ, -(CR¹ᵃR¹ᵇ)q-C(O)ORʲ, -(CR¹ᵃR¹ᵇ)q-C(O)N(Rʲ)₂, -(CR¹ᵃR¹ᵇ)q-N(Rʲ)₂, -(CR¹ᵃR¹ᵇ)q-N(Rʲ)S(O)₂Rᵏ, -(CR¹ᵃR¹ᵇ)q-N(Rʲ)C(O)O(Rᵏ), -(CR¹ᵃR¹ᵇ)q-N(Rʲ)C(O)N(Rʲ)₂, y -(CR¹ᵃR¹ᵇ)q-CN; cada instancia de Rʲ es en forma independiente hidrógeno, alquilo, o haloalquilo; y cada instancia de Rᵏ es en forma independiente alquilo o haloalquilo.
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