AR094831A1 - PIRIDONAMORFINAN ANALOGS AND BIOLOGICAL ACTIVITY ON OPIOID RECEPTORS - Google Patents

PIRIDONAMORFINAN ANALOGS AND BIOLOGICAL ACTIVITY ON OPIOID RECEPTORS

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Publication number
AR094831A1
AR094831A1 ARP130104742A ARP130104742A AR094831A1 AR 094831 A1 AR094831 A1 AR 094831A1 AR P130104742 A ARP130104742 A AR P130104742A AR P130104742 A ARP130104742 A AR P130104742A AR 094831 A1 AR094831 A1 AR 094831A1
Authority
AR
Argentina
Prior art keywords
optionally substituted
alkyl
cycloalkyl
cycloalkenyl
heterocycle
Prior art date
Application number
ARP130104742A
Other languages
Spanish (es)
Inventor
Lockman Jeffrey
Tafesse Laykea
A Youngman Mark
Original Assignee
Purdue Pharma Lp
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 Purdue Pharma Lp filed Critical Purdue Pharma Lp
Publication of AR094831A1 publication Critical patent/AR094831A1/en

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Abstract

Reivindicación 1: Un compuesto caracterizado por la fórmula (1), o una sal o solvato farmacéuticamente aceptable de lo mismo, donde: R¹ᵃ es hidrógeno, hidroxi, halógeno, ciano, carboxi, o aminocarbonilo; o alquilo, alquenilo, alquinilo, alcoxi, alqueniloxi or alquiniloxi, cualquiera de los cuales está opcionalmente sustituido con 1, 2, ó 3 sustituyentes, cada uno seleccionado de manera independiente del grupo que consiste de hidroxi, halógeno, haloalquilo, amino, alquilamino, dialquilamino, carboxi, alcoxi, alcoxicarbonilo, arilo, heteroarilo, heterociclo, cicloalquilo, y cicloalquenilo, donde dicho arilo, heteroarilo, heterociclo, cicloalquilo, y cicloalquenilo están opcionalmente sustituidos con 1, 2, ó 3 grupos R⁸ᵃ independientemente seleccionados; o -O-PG, donde PG es un grupo hidroxilo protector; R²ᵃ es (a) hidrógeno o carboxamido; o (b) alquilo, alquenilo, alquinilo, cicloalquilo, cicloalquenilo, heterociclo, arilo, heteroarilo, (cicloalquil)alquilo, (cicloalquenil)alquilo, (heterociclo)alquilo, arilalquilo, heteroarilalquilo, alquilcarbonilo, alcoxicarbonilo, (arilalcoxi)carbonilo, o (heteroarilalcoxi)carbonilo, cualquiera de los cuales está opcionalmente sustituido con 1, 2, ó 3 sustituyentes, cada uno seleccionado de manera independiente del grupo que consiste de hidroxi, alquilo, halógeno, haloalquilo, amino, alquilamino, dialquilamino, carboxi, alcoxi, alcoxicarbonilo, arilo, heteroarilo, heterociclo, cicloalquilo, y cicloalquenilo, donde dicho arilo, heteroarilo, heterociclo, cicloalquilo, y cicloalquenilo están opcionalmente sustituidos con 1, 2, ó 3 grupos R⁸ᵃ seleccionados de manera independiente; R³ᵃ es hidrógeno, hidroxi, o halógeno; o alcoxi, alquilamino, o dialquilamino, cualquiera de los cuales está opcionalmente sustituido con 1, 2, ó 3 sustituyentes, cada uno seleccionado de manera independiente del grupo que consiste de hidroxi, halógeno, haloalquilo, amino, alquilamino, dialquilamino, carboxi, alcoxi, alcoxicarbonilo, arilo, heteroarilo, heterociclo, cicloalquilo, y cicloalquenilo, donde dicho arilo, heteroarilo, heterociclo, cicloalquilo, y cicloalquenilo están opcionalmente sustituidos con 1, 2, ó 3 grupos R⁸ᵃ seleccionados de manera independiente; ⁻ ⁻ ⁻ ⁻ ⁻ es un enlace simple o un doble enlace; R⁴ está ausente, es hidrógeno o alquilo; Y es C(=O) o COR⁴ᵃ; donde R⁴ᵃ es hidrógeno o alquilo; con la condición que I) cuando R⁴ es hidrógeno o alquilo, entonces ⁻ ⁻ ⁻ ⁻ ⁻ es un enlace simple e Y es C(=O); y II) cuando R⁴ está ausente, entonces ⁻ ⁻ ⁻ ⁻ ⁻ es un doble enlace e Y es COR⁴ᵃ; Zᵃ es -C(=O)R⁵ᵃ, donde R⁵ᵃ se selecciona del grupo que consiste de (a) OH; (b) alcoxi opcionalmente sustituido; (c) -NR⁶ᵃR⁷ᵃ; (d) arilo opcionalmente sustituido; (e) heteroarilo opcionalmente sustituido; (f) cicloalquilo opcionalmente sustituido; (g) cicloalquenilo opcionalmente sustituido; (h) heterociclo opcionalmente sustituido; (i) arilalquilo opcionalmente sustituido; (j) heteroarilalquilo opcionalmente sustituido; (k) (cicloalquil)alquilo opcionalmente sustituido; (l) (cicloalquenil)alquilo opcionalmente sustituido; y (m) (heterociclo)alquilo opcionalmente sustituido; donde dos átomos de carbono adyacentes a dichos anillos cicloalquilo opcionalmente sustituido y cicloalquenilo opcionalmente sustituido están opcionalmente fusionados a un anillo de fenilo; y donde R⁶ᵃ es hidrógeno o alquilo; R⁷ᵃ se selecciona del grupo que consiste de hidrógeno, carboxialquilo opcionalmente sustituido, (alcoxicarbonil)alquilo opcionalmente sustituido, (carboxamido)alquilo opcionalmente sustituido, hidroxialquilo, alquilo, cicloalquilo, cicloalquenilo, heterociclo, arilo, heteroarilo, (cicloalquil)alquilo, (cicloalquenil)alquilo, (heterociclo)alquilo, arilalquilo, y heteroarilalquilo, donde dos átomos de carbono adyacentes a dichos anillos cicloalquilo y cicloalquenilo están opcionalmente fusionados a un anillo de fenilo; y donde cicloalquilo, cicloalquenilo, heterociclo, arilo y heteroarilo, y dichas porciones de cicloalquilo, cicloalquenilo, heterociclo, arilo y heteroarilo are opcionalmente sustituido con 1, 2, ó 3 seleccionados de manera independiente grupos R⁸ᵃ; o R⁶ᵃ y R⁷ᵃ juntos con el átomo de nitrógeno al cual se encuentran unidos forman un anillo heterocíclico opcionalmente sustituido; y cada R⁸ᵃ se selecciona de manera independiente del grupo que consiste de hidroxi, halógeno, alquilo, haloalquilo, ciano, nitro, amino, alquilamino, dialquilamino, carboxi, alcoxi, y alcoxicarbonilo.Claim 1: A compound characterized by the formula (1), or a pharmaceutically acceptable salt or solvate thereof, wherein: R¹ᵃ is hydrogen, hydroxy, halogen, cyano, carboxy, or aminocarbonyl; or alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy or alkynyloxy, any of which is optionally substituted with 1, 2, or 3 substituents, each independently selected from the group consisting of hydroxy, halogen, haloalkyl, amino, alkylamino, dialkylamino, carboxy, alkoxy, alkoxycarbonyl, aryl, heteroaryl, heterocycle, cycloalkyl, and cycloalkenyl, wherein said aryl, heteroaryl, heterocycle, cycloalkyl, and cycloalkenyl are optionally substituted with 1, 2, or 3 independently selected R⁸ᵃ groups; or -O-PG, where PG is a protective hydroxyl group; R²ᵃ is (a) hydrogen or carboxamide; or (b) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, (cycloalkyl) alkyl, (cycloalkenyl) alkyl, (heterocycle) alkyl, arylalkyl, heteroarylalkyl, alkylcarbonyl, alkoxycarbonyl, (arylalkoxy) carbonyl, or ( heteroarylalkoxy) carbonyl, any of which is optionally substituted with 1, 2, or 3 substituents, each independently selected from the group consisting of hydroxy, alkyl, halogen, haloalkyl, amino, alkylamino, dialkylamino, carboxy, alkoxy, alkoxycarbonyl , aryl, heteroaryl, heterocycle, cycloalkyl, and cycloalkenyl, wherein said aryl, heteroaryl, heterocycle, cycloalkyl, and cycloalkenyl are optionally substituted with 1, 2, or 3 independently selected R⁸ᵃ groups; R³ᵃ is hydrogen, hydroxy, or halogen; or alkoxy, alkylamino, or dialkylamino, any of which is optionally substituted with 1, 2, or 3 substituents, each independently selected from the group consisting of hydroxy, halogen, haloalkyl, amino, alkylamino, dialkylamino, carboxy, alkoxy , alkoxycarbonyl, aryl, heteroaryl, heterocycle, cycloalkyl, and cycloalkenyl, wherein said aryl, heteroaryl, heterocycle, cycloalkyl, and cycloalkenyl are optionally substituted with 1, 2, or 3 independently selected R⁸ᵃ groups; ⁻ ⁻ ⁻ ⁻ ⁻ Is a single link or a double link; R⁴ is absent, is hydrogen or alkyl; Y is C (= O) or COR⁴ᵃ; where R⁴ᵃ is hydrogen or alkyl; with the condition that I) when R⁴ is hydrogen or alkyl, then ⁻ ⁻ ⁻ ⁻ ⁻ is a simple bond and Y is C (= O); and II) when R⁴ is absent, then ⁻ ⁻ ⁻ ⁻ ⁻ is a double bond and Y is COR⁴ᵃ; Zᵃ is -C (= O) R⁵ᵃ, where R⁵ᵃ is selected from the group consisting of (a) OH; (b) optionally substituted alkoxy; (c) -NR⁶ᵃR⁷ᵃ; (d) optionally substituted aryl; (e) optionally substituted heteroaryl; (f) optionally substituted cycloalkyl; (g) optionally substituted cycloalkenyl; (h) optionally substituted heterocycle; (i) optionally substituted arylalkyl; (j) optionally substituted heteroarylalkyl; (k) (optionally substituted cycloalkyl) alkyl; (l) (optionally substituted cycloalkenyl) alkyl; and (m) optionally substituted (heterocycle) alkyl; wherein two carbon atoms adjacent to said optionally substituted cycloalkyl and optionally substituted cycloalkenyl rings are optionally fused to a phenyl ring; and where R⁶ᵃ is hydrogen or alkyl; R⁷ᵃ is selected from the group consisting of hydrogen, optionally substituted carboxyalkyl, (optionally substituted alkoxycarbonyl) alkyl, (carboxamido) optionally substituted alkyl, hydroxyalkyl, alkyl, cycloalkyl, cycloalkenyl, heterocycle, aryl, heteroaryl, (cycloalkyl) alkyl, (cycloalkenyl) alkyl, (heterocycle) alkyl, arylalkyl, and heteroarylalkyl, where two carbon atoms adjacent to said cycloalkyl and cycloalkenyl rings are optionally fused to a phenyl ring; and wherein cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl, and said portions of cycloalkyl, cycloalkenyl, heterocycle, aryl and heteroaryl are optionally substituted with 1, 2, or 3 independently selected R⁸ᵃ groups; or R⁶ᵃ and R⁷ᵃ together with the nitrogen atom to which they are attached form an optionally substituted heterocyclic ring; and each R⁸ᵃ is independently selected from the group consisting of hydroxy, halogen, alkyl, haloalkyl, cyano, nitro, amino, alkylamino, dialkylamino, carboxy, alkoxy, and alkoxycarbonyl.

ARP130104742A 2012-12-14 2013-12-13 PIRIDONAMORFINAN ANALOGS AND BIOLOGICAL ACTIVITY ON OPIOID RECEPTORS AR094831A1 (en)

Applications Claiming Priority (1)

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US201261737583P 2012-12-14 2012-12-14

Publications (1)

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AR094831A1 true AR094831A1 (en) 2015-09-02

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