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AR119911A1 - RIP1 KINASE HETEROCYCLIC INHIBITORS - Google Patents

RIP1 KINASE HETEROCYCLIC INHIBITORS

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Publication number
AR119911A1
AR119911A1 ARP200102490A ARP200102490A AR119911A1 AR 119911 A1 AR119911 A1 AR 119911A1 AR P200102490 A ARP200102490 A AR P200102490A AR P200102490 A ARP200102490 A AR P200102490A AR 119911 A1 AR119911 A1 AR 119911A1
Authority
AR
Argentina
Prior art keywords
substituted
independently
occurrence
heteroaryl
alkyl
Prior art date
Application number
ARP200102490A
Other languages
Spanish (es)
Inventor
Simon Shaw
Somasekhar Bhamidipati
Vanessa Taylor
Original Assignee
Rigel Pharmaceuticals 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 Rigel Pharmaceuticals Inc filed Critical Rigel Pharmaceuticals Inc
Publication of AR119911A1 publication Critical patent/AR119911A1/en

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Abstract

Compuestos derivados de tetrahidrobenzo[b][1,4]oxazepina como inhibidores de la proteína cinasa 1 que interactúa con el receptor RIP1, composición farmacéutica que comprende a éstos compuestos y el uso de los mismos para el tratamiento de trastornos del envejecimiento. Reivindicación 1: Un compuesto, de acuerdo con la fórmula (1) o una sal farmacéuticamente aceptable, N-óxido, solvato, tautómero o estereoisómero del mismo, en donde: el anillo B es heteroarilo; cada R¹ es independientemente halógeno o grupo - enlazador-R⁶, en donde el enlazador es un enlace o Rᵃ, con la condición de que Rᵃ no sea H o D, y R⁶ es heterociclilo, Rᵇ, -C(Rᶠ)₃ o -C(Rᶠ)=C(Rᶠ)₂; R² es Rᵃ; R³ es Rᵃ; si está presente, cada R⁴ es independientemente Rᵉ; L es un heteroátomo o Rᵃ, con la condición de que Rᵃ no sea H o D; X es CH₂ u O; Z es heteroarilo; m es 1, 2, 3 ó 4; n es 0, 1 ó 2; Rᵃ es independientemente para cada aparición H o D, excepto para las realizaciones en las que L es Rᵃ, alifático C₁₋₁₀, haloalifático C₁₋₁₀, aromático C₅₋₁₀, heterocíclico C₃₋₆ o espiroheterocíclico C₃₋₁₀, Rᵇ es independientemente para cada aparición -OH, -SH, -ORᶜ, -SRᶜ, -NRᵈRᵈ, -Si(Rᵃ)₃, -C(O)OH, -C(O)ORᶜ, -C(O)NRᵈRᵈ, -OC(O)NRᵈRᵈ, -OC(O)alquilo C₁₋₁₀ sustituido con uno o dos NRᵈRᵈ, carboxilo o una combinación de los mismos, y opcionalmente sustituido adicionalmente con un resto aromático, -SH, -O-acilo o -C(O)NH₂; Rᶜ es independientemente para cada aparición alquilo C₁₋₁₀, que puede estar sustituido con 1, 2 ó 3 Rᵉ, alquenilo C₂₋₁₀, que puede estar sustituido con 1, 2 ó 3 Rᵉ, alquinilo C₂₋₁₀, que puede estar sustituido con 1, 2 ó 3 Rᵉ, cicloalquilo C₃₋₆, que puede estar sustituido con 1, 2 ó 3 Rᵉ o aromático C₅₋₁₀, que puede estar sustituido con 1, 2 ó 3 Rᵉ; Rᵈ es independientemente para cada aparición H; alquilo C₁₋₆, que puede estar sustituido con 1, 2 ó 3 Rᵉ o un heterociclilo C₃₋₉; cicloalquilo C₃₋₆, que puede estar sustituido con 1, 2 ó 3 Rᵉ; heterocíclico C₃₋₆, que puede estar sustituido con 1, 2 ó 3 Rᵉ; arilo C₅₋₁₀, que puede estar sustituido con 1, 2 ó 3 Rᵇ; heteroarilo C₅₋₁₀, que puede estar sustituido con 1, 2 ó 3 Rᵉ; o dos grupos Rᵈ junto con el nitrógeno al que están unidos proporcionan un heterocíclico C₃₋₉, que puede estar sustituido con uno o más Rᵉ; o un heteroarilo C₅₋₁₀, que puede estar sustituido con uno o más Rᵉ; Rᵉ es independientemente para cada aparición halógeno, alquilo C₁₋₆, alquenilo C₂₋₁₀, alquinilo C₂₋₁₀, haloalquilo C₁₋₆, cicloalquilo C₃₋₆, heteroarilo C₅₋₁₀ o -ORᵃ; y Rᶠ es independientemente para cada aparición -alquil-fosfato, Rᵃ, Rᵇ o Rᵉ, o dos grupos Rᶠ junto con el átomo de carbono al que están unidos proporcionan un grupo alquenilo C₂₋₆, un cicloalquilo C₃₋₆, que puede estar sustituido con uno o más Rᵉ, o un heterocíclico C₃₋₁₀, que puede estar sustituido con uno o más Rᵉ o acilo.Compounds derived from tetrahydrobenzo[b][1,4]oxazepine as inhibitors of protein kinase 1 that interacts with the RIP1 receptor, pharmaceutical composition comprising these compounds and their use for the treatment of aging disorders. Claim 1: A compound, according to formula (1) or a pharmaceutically acceptable salt, N-oxide, solvate, tautomer or stereoisomer thereof, wherein: ring B is heteroaryl; each R¹ is independently halogen or linker-group-R⁶, where the linker is a bond or Rᵃ, with the proviso that Rᵃ is not H or D, and R⁶ is heterocyclyl, Rᵇ, -C(Rᶠ)₃ or -C (Rᶠ)=C(Rᶠ)₂; R² is Rᵃ; R³ is Rᵃ; if present, each R⁴ is independently Rᵉ; L is a heteroatom or Rᵃ, with the proviso that Rᵃ is not H or D; X is CH₂ or O; Z is heteroaryl; m is 1, 2, 3 or 4; n is 0, 1 or 2; Rᵃ is independently for each H or D occurrence, except for embodiments where L is Rᵃ, C₁₋₁₀ aliphatic, C₁₋₁₀ haloaliphatic, C₅₋₁₀ aromatic, C₃₋₆ heterocyclic, or C₃₋₁₀ spiroheterocyclic, Rᵇ is independently for each occurrence -OH, -SH, -ORᶜ, -SRᶜ, -NRᵈRᵈ, -Si(Rᵃ)₃, -C(O)OH, -C(O)ORᶜ, -C(O)NRᵈRᵈ, -OC(O) NRᵈRᵈ, -OC(O)C₁₋₁₀ alkyl substituted with one or two NRᵈRᵈ, carboxyl or a combination thereof, and optionally further substituted with an aromatic moiety, -SH, -O-acyl or -C(O)NH₂; Rᶜ is independently for each occurrence C₁₋₁₀ alkyl, which may be substituted with 1, 2 or 3 Rᵉ, C₂₋₁₀ alkenyl, which may be substituted with 1, 2 or 3 Rᵉ, C₂₋₁₀ alkynyl, which may be substituted with 1, 2 or 3 Rᵉ, C₃₋₆ cycloalkyl, which may be substituted with 1, 2 or 3 Rᵉ or aromatic C₅₋₁₀, which may be substituted with 1, 2 or 3 Rᵉ; Rᵈ is independently for each occurrence H; C₁₋₆ alkyl, which may be substituted with 1, 2 or 3 Rᵉ or a C₃₋₉ heterocyclyl; C₃₋₆ cycloalkyl, which may be substituted with 1, 2 or 3 Rᵉ; heterocyclic C₃₋₆, which can be substituted with 1, 2 or 3 Rᵉ; C₅₋₁₀ aryl, which may be substituted with 1, 2 or 3 Rᵇ; C₅₋₁₀ heteroaryl, which may be substituted with 1, 2 or 3 Rᵉ; or two Rᵈ groups together with the nitrogen to which they are attached provide a C₃₋₉ heterocyclic, which may be substituted with one or more Rᵉ; or a C₅₋₁₀ heteroaryl, which may be substituted with one or more Rᵉ; Rᵉ is independently for each occurrence halogen, C₁₋₆ alkyl, C₂₋₁₀ alkenyl, C₂₋₁₀ alkynyl, C₁₋₆ haloalkyl, C₃₋₆ cycloalkyl, C₅₋₁₀ heteroaryl, or -ORᵃ; and Rᶠ is independently for each occurrence -alkyl-phosphate, Rᵃ, Rᵇ or Rᵉ, or two Rᶠ groups together with the carbon atom to which they are attached provide a C₂₋₆ alkenyl group, a C₃₋₆ cycloalkyl, which may be substituted with one or more Rᵉ, or a C₃₋₁₀ heterocyclic, which may be substituted with one or more Rᵉ or acyl.

ARP200102490A 2019-09-06 2020-09-07 RIP1 KINASE HETEROCYCLIC INHIBITORS AR119911A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201962897223P 2019-09-06 2019-09-06

Publications (1)

Publication Number Publication Date
AR119911A1 true AR119911A1 (en) 2022-01-19

Family

ID=80633263

Family Applications (4)

Application Number Title Priority Date Filing Date
ARP200102491A AR119912A1 (en) 2019-09-06 2020-09-07 RIP1 INHIBITOR COMPOUNDS
ARP200102494A AR119915A1 (en) 2019-09-06 2020-09-07 RIP1 INHIBITOR COMPOUNDS AND METHODS FOR MANUFACTURING AND USING THE SAME
ARP200102490A AR119911A1 (en) 2019-09-06 2020-09-07 RIP1 KINASE HETEROCYCLIC INHIBITORS
ARP200102492A AR119913A1 (en) 2019-09-06 2020-09-07 RIP1 INHIBITOR COMPOUNDS AND METHODS FOR MANUFACTURING AND USING THE SAME

Family Applications Before (2)

Application Number Title Priority Date Filing Date
ARP200102491A AR119912A1 (en) 2019-09-06 2020-09-07 RIP1 INHIBITOR COMPOUNDS
ARP200102494A AR119915A1 (en) 2019-09-06 2020-09-07 RIP1 INHIBITOR COMPOUNDS AND METHODS FOR MANUFACTURING AND USING THE SAME

Family Applications After (1)

Application Number Title Priority Date Filing Date
ARP200102492A AR119913A1 (en) 2019-09-06 2020-09-07 RIP1 INHIBITOR COMPOUNDS AND METHODS FOR MANUFACTURING AND USING THE SAME

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AR (4) AR119912A1 (en)

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Publication number Publication date
AR119913A1 (en) 2022-01-19
AR119912A1 (en) 2022-01-19
AR119915A1 (en) 2022-01-19

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