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AR096148A1 - COMBINED THERAPY FOR TREATMENT OF CANCER - Google Patents

COMBINED THERAPY FOR TREATMENT OF CANCER

Info

Publication number
AR096148A1
AR096148A1 ARP140101779A ARP140101779A AR096148A1 AR 096148 A1 AR096148 A1 AR 096148A1 AR P140101779 A ARP140101779 A AR P140101779A AR P140101779 A ARP140101779 A AR P140101779A AR 096148 A1 AR096148 A1 AR 096148A1
Authority
AR
Argentina
Prior art keywords
heteroaryl
aryl
alkyl
optionally substituted
occurrence
Prior art date
Application number
ARP140101779A
Other languages
Spanish (es)
Inventor
R Agarwal Veena
Bhatia Dimple
Sonawane Vinay
Rathos Maggie
Original Assignee
Piramal Entpr Ltd
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 Piramal Entpr Ltd filed Critical Piramal Entpr Ltd
Publication of AR096148A1 publication Critical patent/AR096148A1/en

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    • 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
    • A61K31/33—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
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/243—Platinum; Compounds thereof
    • 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
    • A61K31/13—Amines
    • A61K31/131—Amines acyclic
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    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
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    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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    • 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
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Abstract

Reivindicación 1: Una combinación farmacéutica que comprende un inhibidor de Pl3K/mTOR seleccionado de los compuestos de la fórmula (1); en donde, R¹ es arilo C₆₋₁₄ o heteroarilo, en donde cada uno de arilo C₆₋₁₄ o heteroarilo está sustituido en forma opcional con uno o más de Rᵃ; R² es -CN; R³ es hidrógeno o alquilo C₁₋₈, en donde alquilo C₁₋₈ está sustituido en forma opcional con -CN; R⁴ es arilo C₆₋₁₄ o heteroarilo, en donde cada uno de arilo C₆₋₁₄ o heteroarilo está sustituido en forma opcional con uno o más de Rᵃ; Rᵃ en cada ocurrencia es halógeno, -CN, -ORˣ, -SRˣ, -NRˣRʸ, alquilo C₁₋₈, arilo C₆₋₁₄ heterociclilo o alquilheterociclilo, en donde alquilo C₁₋₈ y heterociclilo está sustituido en forma opcional con uno o más de Rᵇ; Rˣ y Rʸ en cada ocurrencia son en forma independiente hidrógeno, alquilo C₁₋₈, arilo C₆₋₁₄ o heteroarilo, en donde cada uno de alquilo C₁₋₈, arilo C₆₋₁₄ o heteroarilo están sustituidos en forma opcional con Rᵇ; y Rᵇ en cada ocurrencia es halógeno, -CN o -NH₂; o sus sales o solvatos aceptables desde el punto de vista farmacéutico; y uno o más agentes anti-proliferativos. Reivindicación 37: Una composición farmacéutica que comprende una cantidad terapéuticamente efectiva de un inhibidor de Pl3K/mTOR seleccionado de los compuestos de la fórmula (1); y una cantidad terapéuticamente efectiva de uno o más agentes anti-proliferativos; en asociación con uno o más aceptable desde el punto de vista farmacéutico vehiculo, diluyente o excipiente.Claim 1: A pharmaceutical combination comprising a Pl3K / mTOR inhibitor selected from the compounds of the formula (1); wherein, R¹ is C₆₋₁₄ aryl or heteroaryl, wherein each of C₆₋₁₄ aryl or heteroaryl is optionally substituted with one or more of Rᵃ; R² is -CN; R³ is hydrogen or C₁₋₈ alkyl, wherein C₁₋₈ alkyl is optionally substituted with -CN; R⁴ is C₆₋₁₄ aryl or heteroaryl, wherein each of C₆₋₁₄ aryl or heteroaryl is optionally substituted with one or more of Rᵃ; Rᵃ in each occurrence is halogen, -CN, -ORˣ, -SRˣ, -NRˣRʸ, C alquilo alkyl, C₆₋₁₄ heterocyclyl or alkylheterocyclyl, wherein C₁₋₈ alkyl and heterocyclyl is optionally substituted with one or more of Rᵇ; Rˣ and Rʸ in each occurrence are independently hydrogen, C₁₋₈ alkyl, C₆₋₁₄ aryl or heteroaryl, wherein each of C₁₋₈ alkyl, C₆₋₁₄ aryl or heteroaryl are optionally substituted with Rᵇ; and Rᵇ in each occurrence is halogen, -CN or -NH₂; or its pharmaceutically acceptable salts or solvates; and one or more anti-proliferative agents. Claim 37: A pharmaceutical composition comprising a therapeutically effective amount of a Pl3K / mTOR inhibitor selected from the compounds of the formula (1); and a therapeutically effective amount of one or more anti-proliferative agents; in association with one or more pharmaceutically acceptable vehicle, diluent or excipient.

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