AR049437A1 - PIRAZOL DERIVATIVES AS PROTEIN QUINASA MODULATORS - Google Patents

PIRAZOL DERIVATIVES AS PROTEIN QUINASA MODULATORS

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Publication number
AR049437A1
AR049437A1 ARP050102341A ARP050102341A AR049437A1 AR 049437 A1 AR049437 A1 AR 049437A1 AR P050102341 A ARP050102341 A AR P050102341A AR P050102341 A ARP050102341 A AR P050102341A AR 049437 A1 AR049437 A1 AR 049437A1
Authority
AR
Argentina
Prior art keywords
group
hydrocarbyl
saturated
heterocyclic
nr2r3
Prior art date
Application number
ARP050102341A
Other languages
Spanish (es)
Inventor
Valerio Berdini
Gordon Saxty
Marinus Leendert Verdonk
Steven John Woodhead
Paul Graham Wyatt
Robert George Boyle
Hannah Fiona Sore
David Winter Walker
Robert Downham
Robin Arthur Ellis Carr
Ian Collins
Original Assignee
Astex Technology Ltd
Cancer Res Inst Royal
Cancer Rec Tech 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
Priority claimed from PCT/GB2004/005464 external-priority patent/WO2005061463A1/en
Application filed by Astex Technology Ltd, Cancer Res Inst Royal, Cancer Rec Tech Ltd filed Critical Astex Technology Ltd
Publication of AR049437A1 publication Critical patent/AR049437A1/en

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Abstract

Compuestos de formula (1) con actividad inhibidora de proteína quinasa B, composiciones farmacéuticas que contienen los compuestos, métodos para preparar los compuestos y su uso como agentes anticancerosos. Reivindicacion 1: Un compuesto caracterizado porque responde a la formula (1), o una sal, solvato, tautomero o N-oxido del mismo; donde A es un grupo conector hidrocarburo saturado que contiene entre 1 y 7 átomos de carbono, donde el grupo conector que se extiende entre R1 y NR2R3 tiene una longitud máxima de cadena de 5 átomos y el que se extiende entre E y NR2R3 tiene una longitud máxima de cadena de 4 átomos, donde uno de los átomos de carbono en el grupo conector se puede reemplazar opcionalmente por un átomo de oxígeno o de nitrogeno; y donde los átomos de carbono del grupo conector A pueden llevar opcionalmente uno o más sustituyentes que se seleccionan entre oxo, fluor e hidroxi, siempre y cuando, cuando esté presente, el grupo hidroxi no esté localizado en un átomo de carbono a con respecto al grupo NR2R3 y siempre y cuando, si está presente, el grupo oxo esté localizado en un átomo de carbono a con respecto al grupo NR2R3; E es un grupo carbocíclico monocíclico o bicíclico o heterocíclico; R1 es un grupo arilo o heteroarilo; R2 y R3 se seleccionan de manera independiente entre hidrogeno, hidrocarbilo C1-4 y acilo C1-4 donde las unidades hidrocarbilo y acilo están sustituidas opcionalmente con uno o más sustituyentes que se seleccionan entre fluor, hidroxi, amino, metilamino, dimetilamino y metoxi; o R2 y R3 junto con el átomo de nitrogeno al que están unidos forman un grupo cíclico que se selecciona entre un grupo imidazol y un grupo monocíclico heterocíclico saturado con 4-7 miembros en el anillo y que opcionalmente contienen un segundo miembro heteroátomo en el anillo que se selecciona entre O y N; o uno de R2 y R3 junto con el átomo de nitrogeno al que están unidos y uno o más átomos del grupo conector A forman un grupo monocíclico heterocíclico saturado con 4-7 miembros en el anillo y que opcionalmente contienen un segundo miembro heteroátomo en el anillo que se selecciona entre O y N; o NR2R3 y el átomo de carbono del grupo conector A al cual está unido forman juntos un grupo ciano; R4 se selecciona entre hidrogeno, halogeno, hidrocarbilo saturado C1-5, hidrocarbiloxi saturado C1-5, ciano, y CF3; y R5 se selecciona entre hidrogeno, halogeno, hidrocarbilo saturado C1-5, hidrocarbiloxi saturado C1-5, ciano, CONH2, CONHR9, CF3, NH2, NHCOR9 o NHCONHR9; R9 es un grupo R9a o (CH2)R9a, donde R9a es un grupo monocíclico o bicíclico que puede ser carbocíclico o heterocíclico; el grupo carbocíclico o heterocíclico R9 está sustituido opcionalmente con uno o más sustituyentes que se seleccionan entre halogeno, hidroxi, trifluorometilo, ciano, nitro, carboxi, amino, mono- o di-hidrocarbilamino C1-4; un grupo Ra-Rb donde Ra es un anion, O, CO, X1C(X2), C(X2)X1, X1C(X2)X1, S, SO, SO2, NRc, SO2NRc o NRcSO2; y Rb se selecciona entre hidrogeno, grupos heterocíclicos con entre 3 y 12 miembros en el anillo, y un grupo hidrocarbilo C1-8 sustituido opcionalmente con uno o más sustituyentes que se seleccionan entre hidroxi, oxo, halogeno, ciano, nitro, carboxi, amino, mono- o di-hidrocarbilamino C1-4, grupos carbocíclicos y heterocíclicos con entre 3 y 12 miembros en el anillo y donde uno o más átomos de carbono del grupo hidrocarbilo C1-8 se pueden reemplazar opcionalmente por O, S, SO, SO2, NRc, X1C(X2), C(X2)X1 o X1C(X2)X1; Rc se selecciona entre hidrogeno e hidrocarbilo C1-4; y X1 es O, S o NRc y X2 es =O, =S o =NRc.Compounds of formula (1) with protein kinase B inhibitory activity, pharmaceutical compositions containing the compounds, methods for preparing the compounds and their use as anti-cancer agents. Claim 1: A compound characterized in that it responds to formula (1), or a salt, solvate, tautomer or N-oxide thereof; where A is a saturated hydrocarbon linker group containing between 1 and 7 carbon atoms, where the linker group that extends between R1 and NR2R3 has a maximum chain length of 5 atoms and the one that extends between E and NR2R3 has a length chain maximum of 4 atoms, where one of the carbon atoms in the linker group can optionally be replaced by an oxygen or nitrogen atom; and where the carbon atoms of the linker group A may optionally carry one or more substituents that are selected from oxo, fluorine and hydroxy, as long as, when present, the hydroxy group is not located on a carbon atom a with respect to the NR2R3 group and as long as, if present, the oxo group is located on a carbon atom with respect to the NR2R3 group; E is a monocyclic or bicyclic or heterocyclic carbocyclic group; R1 is an aryl or heteroaryl group; R2 and R3 are independently selected from hydrogen, C1-4 hydrocarbyl and C1-4 acyl where the hydrocarbyl and acyl units are optionally substituted with one or more substituents that are selected from fluorine, hydroxy, amino, methylamino, dimethylamino and methoxy; or R2 and R3 together with the nitrogen atom to which they are attached form a cyclic group that is selected from an imidazole group and a saturated heterocyclic monocyclic group with 4-7 ring members and optionally contain a second ring heteroatom member which is selected between O and N; or one of R2 and R3 together with the nitrogen atom to which they are attached and one or more atoms of the linker group A form a saturated heterocyclic monocyclic group with 4-7 ring members and optionally contain a second ring heteroatom member which is selected between O and N; or NR2R3 and the carbon atom of the linker group A to which it is attached together form a cyano group; R4 is selected from hydrogen, halogen, C1-5 saturated hydrocarbyl, C1-5 saturated hydrocarbyloxy, cyano, and CF3; and R5 is selected from hydrogen, halogen, C1-5 saturated hydrocarbyl, C1-5 saturated hydrocarbyloxy, cyano, CONH2, CONHR9, CF3, NH2, NHCOR9 or NHCONHR9; R9 is a R9a or (CH2) R9a group, where R9a is a monocyclic or bicyclic group that can be carbocyclic or heterocyclic; the carbocyclic or heterocyclic group R9 is optionally substituted with one or more substituents that are selected from halogen, hydroxy, trifluoromethyl, cyano, nitro, carboxy, amino, mono- or di-hydrocarbonylamino C1-4; a Ra-Rb group where Ra is an anion, O, CO, X1C (X2), C (X2) X1, X1C (X2) X1, S, SO, SO2, NRc, SO2NRc or NRcSO2; and Rb is selected from hydrogen, heterocyclic groups with between 3 and 12 ring members, and a C1-8 hydrocarbyl group optionally substituted with one or more substituents that are selected from hydroxy, oxo, halogen, cyano, nitro, carboxy, amino , mono- or di-hydrocarbonylamino C1-4, carbocyclic and heterocyclic groups with between 3 and 12 ring members and where one or more carbon atoms of the C1-8 hydrocarbyl group can optionally be replaced by O, S, SO, SO2 , NRc, X1C (X2), C (X2) X1 or X1C (X2) X1; Rc is selected from hydrogen and C1-4 hydrocarbyl; and X1 is O, S or NRc and X2 is = O, = S or = NRc.

ARP050102341A 2004-06-08 2005-06-08 PIRAZOL DERIVATIVES AS PROTEIN QUINASA MODULATORS AR049437A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US57784304P 2004-06-08 2004-06-08
PCT/GB2004/005464 WO2005061463A1 (en) 2003-12-23 2004-12-23 Pyrazole derivatives as protein kinase modulators

Publications (1)

Publication Number Publication Date
AR049437A1 true AR049437A1 (en) 2006-08-02

Family

ID=36940507

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP050102341A AR049437A1 (en) 2004-06-08 2005-06-08 PIRAZOL DERIVATIVES AS PROTEIN QUINASA MODULATORS

Country Status (4)

Country Link
AR (1) AR049437A1 (en)
MY (1) MY144464A (en)
SA (1) SA05260179B1 (en)
TW (1) TWI363622B (en)

Also Published As

Publication number Publication date
MY144464A (en) 2011-09-30
TW200602046A (en) 2006-01-16
SA05260179B1 (en) 2009-06-14
TWI363622B (en) 2012-05-11

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