AR094929A1 - Derivados de fenilpirazol como inhibidores potentes de rock1 y rock2 - Google Patents

Derivados de fenilpirazol como inhibidores potentes de rock1 y rock2

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AR094929A1
AR094929A1 ARP140100640A ARP140100640A AR094929A1 AR 094929 A1 AR094929 A1 AR 094929A1 AR P140100640 A ARP140100640 A AR P140100640A AR P140100640 A ARP140100640 A AR P140100640A AR 094929 A1 AR094929 A1 AR 094929A1
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Argentina
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substituted
chrd
independently selected
alkyl
nrara
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L Quan Mimi
Hu Zilun
Wang Cailan
W Glunz Peter
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Bristol Myers Squibb Co
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    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
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    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
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    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
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    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
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    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

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Abstract

Estos compuestos son inhibidores de ROCK selectivos. También, composiciones farmacéuticas que comprenden estos compuestos y métodos para tratar trastornos cardiovasculares, trastornos relacionados con el músculo liso, trastornos oncológicos, trastornos neuropatológicos, trastornos autoinmunitarios, trastornos fibróticos y/o trastornos inflamatorios mediante su uso. Reivindicación 1: Un compuesto caracterizado porque tiene la fórmula (1), o un enantiómero, diastereómero, estereoisómero, sal de aquel aceptable desde el punto de vista farmacéutico, en donde R¹ se selecciona independientemente de H, F, Cl, Br, OH, CN, NRᵃRᵃ, -O-alquilo C₁₋₄ sustituido con 0 - 3 Rᵉ y alquilo C₁₋₄ sustituido con 0 - 3 Rᵉ; R² se selecciona independientemente de H, -(CH₂)ʳORᵇ, -(CH₂)ʳS(O)ₚRᶜ, -(CH₂)ʳC(=O)Rᵇ, -(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳCN, -(CH₂)ʳNRᵃC(=O)Rᵇ, -(CH₂)ʳNRᵃC(=O)ORᵇ, -(CH₂)ʳOC(=O)NRᵃRᵃ, -(CH₂)ʳNRᵃC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)ORᵇ, -(CH₂)ʳS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚRᶜ, alquilo C₁₋₄ sustituido con 0 - 3 Rᵉ, (CH₂)ʳ-carbociclilo C₃₋₆ sustituido con 0 - 3 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 0 - 3 Rᵉ; R³ se selecciona independientemente de F, Cl, Br, CN, alquilo C₁₋₄ sustituido con 0 - 3 Rᵉ, -(CH₂)ʳORᵇ, -(CH₂)ʳS(O)ₚRᶜ, -(CH₂)ʳC(=O)Rᵇ, -(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳCN, -(CH₂)ʳNRᵃC(=O)Rᵇ, -(CH₂)ʳNRᵃC(=O)ORᵇ, -(CH₂)ʳOC(=O)NRᵃRᵃ, -(CH₂)ʳNRᵃC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)ORᵇ, -(CH₂)ʳS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚRᶜ, (CH₂)ʳ-carbociclilo C₃₋₆ sustituido con 0 - 3 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 0 - 3 Rᵉ; R⁴ se selecciona independientemente de H, F, Cl, Br, OH, CN, O-alquilo C₁₋₄ sustituido con 0 - 3 Rᵉ y alquilo C₁₋₄ sustituido con 0 - 3 Rᵉ; R⁵ se selecciona independientemente de H y alquilo C₁₋₄ sustituido con 0 - 3 Rᵉ; R⁶ y R⁷ se seleccionan independientemente de H, CN, alquilo C₁₋₆ sustituido con 0 - 4 Rᵉ, alquenilo C₂₋₄ sustituido con 0 - 3 Rᵉ, -(CH₂)ʳORᵇ, -(CH₂)ʳS(O)ₚRᶜ, -(CH₂)ʳC(=O)Rᵇ, -(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)(CH₂)ʳNRᵃRᵃ, -(CH₂)ʳNRᵃC(=O)Rᵇ, -(CH₂)ʳNRᵃC(=O)ORᵇ, -(CH₂)ʳOC(=O)NRᵃRᵃ,-(CH₂)ʳNRᵃC(=O)NRᵃRᵃ, -(CH₂)ʳC(=O)ORᵇ, -(CH₂)ʳS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚNRᵃRᵃ, -(CH₂)ʳNRᵃS(O)ₚRᶜ, -(CH₂)ʳ-carbociclilo C₃₋₆ sustituido con 0 - 3 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 0 - 3 Rᵉ; alternativamente, R⁶ y R⁷, junto con el átomo de carbono al que ambos están unidos, forman un cicloalquilo sustituido con 0 - 5 Rᵉ; alternativamente, dos grupos R⁶ adyacentes forman un cicloalquilo sustituido con 0 - 5 Rᵉ, en donde n es mayor de 1; R⁸ se selecciona de arilo y heteroarilo, cada uno sustituido con 0 - 5 Rᵉ; R⁹ se selecciona independientemente de F, Cl, Br, CN, =O, alquilo C₁₋₄, alquenilo C₂₋₄, alquinilo C₂₋₄, nitro, -(CHRᵈ)ʳS(O)ₚRᶜ, -(CHRᵈ)ʳS(O)ₚNRᵃRᵃ, -(CHRᵈ)ʳNRᵃS(O)ₚRᶜ, -(CHRᵈ)ʳORᵇ, -(CHRᵈ)ʳCN, -(CHRᵈ)ʳNRᵃRᵃ, -(CHRᵈ)ʳNRᵃC(=O)Rᵇ, -(CHRᵈ)ʳNRᵃC(=O)NRᵃRᵃ, -(CHRᵈ)ʳC(=O)ORᵇ, -(CHRᵈ)ʳC(=O)Rᵇ, -(CHRᵈ)OC(=O)Rᵇ, -(CHRᵈ)ʳC(=O)NRᵃRᵃ, -(CHRᵈ)ʳ-cicloalquilo, -(CHRᵈ)ʳ-heterociclilo, -(CHRᵈ)ʳ-arilo y -(CHRᵈ)ʳ-heteroarilo, en donde el alquilo, cicloalquilo, heterociclilo, arilo o heteroarilo se sustituyen con 0 - 4 Rᵉ; alternativamente, dos grupos R⁹ adyacentes se combinan para formar un anillo carbocíclico o heterocíclico que comprende átomos de carbono y 1 - 3 heteroátomos seleccionados de N, O y S(O)ₚ, en donde los anillos carbocíclicos y heterocíclicos se sustituyen con 0 - 4 Rᵉ; Rᵃ, en cada caso, se selecciona independientemente de H, CN, alquilo C₁₋₆ sustituido con 0 - 5 Rᵉ, alquenilo C₂₋₆ sustituido con 0 - 5 Rᵉ, alquinilo C₂₋₆ sustituido con 0 - 5 Rᵉ, -(CH₂)ʳ-carbociclilo C₃₋₁₀ sustituido con 0 - 5 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 0 - 5 Rᵉ; o Rᵃ y Rᵃ, junto con el átomo de nitrógeno al que ambos están unidos, forman un anillo heterocíclico sustituido con 0 - 5 Rᵉ; Rᵇ, en cada caso, se selecciona independientemente de H, alquilo C₁₋₆ sustituido con 0 - 5 Rᵉ, alquenilo C₂₋₆ sustituido con 0 - 5 Rᵉ, alquinilo C₂₋₆ sustituido con 0 - 5 Rᵉ, -(CH₂)ʳ-carbociclilo C₃₋₁₀ sustituido con 0 - 5 Rᵉ y -(CH₂)ʳ-heterociclilo sustituido con 0 - 5 Rᵉ; Rᶜ, en cada caso, se selecciona independientemente de alquilo C₁₋₆ sustituido con 0 - 5 Rᵉ, alquenilo C₂₋₆ sustituido con 0 - 5 Rᵉ, alquinilo C₃₋₆ sustituido con 0 - 5 Rᵉ; carbociclilo C₃₋₆ y heterociclilo; Rᵈ, en cada caso, se selecciona independientemente de H y alquilo C₁₋₄ sustituido con 0 - 5 Rᵉ; Rᵉ, en cada caso, se selecciona independientemente de alquilo C₁₋₆ sustituido con 0 - 5 Rᶠ, alquenilo C₂₋₆, alquinilo C₂₋₆, -(CH₂)ʳ-cicloalquilo C₃₋₆, F, Cₗ, Bʳ, CN, NO₂, =O, CO₂H, -(CH₂)ʳO-alquilo C₁₋₅, -(CH₂)ʳORᶠ, S(O)ₚRᶠ, C(=O)NRᶠRᶠ, S(O)ₚNRᶠRᶠ y -(CH₂)ʳNRᶠRᶠ; Rᶠ, en cada caso, se selecciona independientemente de H, alquilo C₁₋₅, cicloalquilo C₃₋₆ y fenilo, o Rᶠ y Rᶠ, junto con el átomo de nitrógeno al que ambos están unidos, forman un anillo heterocíclico opcionalmente sustituido con alquilo C₁₋₄; n, en cada caso, se selecciona independientemente de 1, 2 y 3; p, en cada caso, se selecciona independientemente de 0, 1 y 2; y r, en cada caso, se selecciona independientemente de 0, 1, 2, 3 y 4.
ARP140100640A 2013-02-28 2014-02-27 Derivados de fenilpirazol como inhibidores potentes de rock1 y rock2 AR094929A1 (es)

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EP (1) EP2961745B1 (es)
JP (1) JP6423371B2 (es)
CN (1) CN105358547B (es)
AR (1) AR094929A1 (es)
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Families Citing this family (28)

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Publication number Priority date Publication date Assignee Title
EP2961746B1 (en) 2013-02-28 2018-01-03 Bristol-Myers Squibb Company Phenylpyrazole derivatives as potent rock1 and rock2 inhibitors
US9902702B2 (en) 2014-07-15 2018-02-27 Bristol-Myers Squibb Company Spirocycloheptanes as inhibitors of rock
WO2016028971A1 (en) 2014-08-21 2016-02-25 Bristol-Myers Squibb Company Tied-back benzamide derivatives as potent rock inhibitors
AR103990A1 (es) * 2015-01-09 2017-06-21 Bristol Myers Squibb Co Ureas cíclicas como inhibidoras de rock
US10112929B2 (en) 2015-03-09 2018-10-30 Bristol-Myers Squibb Company Lactams as inhibitors of rock
AR107354A1 (es) 2016-01-13 2018-04-18 Bristol Myers Squibb Co Salicilamidas espiroheptanos y compuestos relacionados como inhibidores de rock
US10562887B2 (en) * 2016-05-27 2020-02-18 Bristol-Myers Squibb Company Triazolones and tetrazolones as inhibitors of ROCK
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US9126944B2 (en) 2015-09-08
US20160016910A1 (en) 2016-01-21
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US20140243338A1 (en) 2014-08-28
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