AR071452A1 - Inhibidores de hsp90 - Google Patents

Inhibidores de hsp90

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Publication number
AR071452A1
AR071452A1 ARP090100342A ARP090100342A AR071452A1 AR 071452 A1 AR071452 A1 AR 071452A1 AR P090100342 A ARP090100342 A AR P090100342A AR P090100342 A ARP090100342 A AR P090100342A AR 071452 A1 AR071452 A1 AR 071452A1
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AR
Argentina
Prior art keywords
alkyl
cycloalkyl
heterobicycloaryl
bicycloaryl
heteroaryl
Prior art date
Application number
ARP090100342A
Other languages
English (en)
Inventor
Wolfgang Reinhard Lu Notz
Young K Chen
Jeffrey A Stafford
Erick W Co
Prasuna Guntupalli
Huong-Thu Ton-Nu
John D Lawson
Original Assignee
Takeda Pharmaceutical
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Publication date
Application filed by Takeda Pharmaceutical filed Critical Takeda Pharmaceutical
Publication of AR071452A1 publication Critical patent/AR071452A1/es

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    • A61K31/57Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
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Abstract

Composiciones farmacéuticas, kits y artículos de fabricacion que comprenden dichos compuestos; métodos e intermediarios utiles para producir los compuestos; y métodos de uso de dichos compuestos. Reivindicacion 1: Un compuesto de la formula seleccionada del grupo que consiste en formulas (1), (2), (3) o (4), o uno de sus tautomeros, estereoisomeros o sales aceptables desde el punto de vista farmacéutico, en los cuales X es O, NR8 o CR9R9'; R1 se selecciona del grupo que consiste en hidrogeno, carbonilo, hidroxicarbonilo, oxicarbonilo, aminocarbonilo, sulfonilo, sulfinilo, alquilo C1-10, haloalquilo C1-10, heteroalquilo C1-10, hidroxialquilo C1-10, alcoxialquilo C1-10, aminoalquilo C1-10, iminoalquilo C1-10, carbonilalquilo C1-10, sulfonilalquilo C1-10, sulfinilalquilo C1-10, carbonilaminoalquilo C1-10, tiocarbonilalquilo C1-10, hidroxilcarbonilalquilo C1-10, aminocarbonilalquilo C1-10, aminosulfonilalquilo C1-10, sulfonilaminoalquilo C1-10, alquilsulfonilamino C1-6-alquilo C1-10, cicloalquil C3-12-alquilo C1-5, hetero cicloalquil C3-12-alquilo C1-10, arilalquilo C1-10, heteroaril C1-10-alquilo C1-5, bicicloaril C9-12-alquilo C1-5, heterobicicloaril C8-12-alquilo C1-5, heteroalquilo C1-10, cicloalquilo C3-12, heterocicloalquilo C3-12, bicicloalquilo C9-12, heterobicicloalquilo C3-12, arilo C4-12, heteroarilo C1-10, bicicloarilo C9-12 y heterobicicloarilo C4-12, cada uno no sustituido o sustituido; R2 se selecciona del grupo que consiste en hidrogeno, halo, ciano, tio, hidroxi, carboniloxi, alcoxi C1-10, ariloxi C4-12, heteroariloxi C1-10, carbonilo, oxicarbonilo, aminocarbonilo, amino, alquilamino C1-10, sulfonilamino, aminosulfonilo, sulfonilo, sulfinilo, alquilo C1-10, hetero alquilo C1-10, haloalquilo C1-10, hidroxialquilo C1-10, carbonilalquilo C1-10, tiocarbonilalquilo C1-10, sulfonilalquilo C1-10, sulfinilalquilo C1-10, iminoalquilo C1-10, cicloalquil C3-12-alquilo C1-5, hetero cicloalquil C3-12-alquilo C1-10, arilalquilo C1-10, heteroaril C1-10-alquilo C1-5, bicicloaril C9-12-alquilo C1-5, heterobicicloaril C8-12-alquilo C1-5, heteroalquilo C1-10, cicloalquilo C3-12, heterocicloalquilo C3-12, bicicloalquilo C9-12, heterobicicloalquilo C3-12, arilo C4-12, heteroarilo C1-10, bicicloarilo C9-12 y heterobicicloarilo C4-12 cada uno sustituido o no sustituido; R3 se selecciona del grupo que consiste en hidrogeno, halo, nitro, ciano, tio, oxi, hidroxi, carboniloxi, alcoxi C1-10, ariloxi C4-12, heteroariloxi C1-10, carbonilo, oxicarbonilo, aminocarbonilo, amino, alquilamino C1-10, sulfonilamino, aminosulfonilo, sulfonilo, sulfinilo, alquilo C1-10, alquenilo C1-10, haloalquilo C1-10, hidroxialquilo C1-10, carbonilalquilo C1-10, tiocarbonilalquilo C1-10, sulfonilalquilo C1-10, sulfinilalquilo C1-10, heteroalquilo C1-10, iminoalquilo C1-10, cicloalquil C3-12-alquilo C1-5, hetero cicloalquil C3-12-alquilo C1-10, arilalquilo C1-10, heteroaril C1-10-alquilo C1-5, bicicloaril C9-12-alquilo C1-5, heterobicicloaril C8-12-alquilo C1-5, heteroalquilo C1-10, cicloalquilo C3-15, heteroC1-14cicloalquilo, bicicloalquilo C9-12, heterobicicloalquilo C3-12, arilo C4-15, heteroC1-14arilo, bicicloarilo C9-12 y heterobicicloarilo C4-12, cada uno no sustituido o sustituido; R4 se selecciona del grupo que consiste en hidrogeno, carbonilo, oxicarbonilo, amino, alquilamino C1-10, sulfonilamino, aminosulfonilo, sulfonilo, sulfinilo, alquilo C1-10, haloalquilo C1-10, hidroxialquilo C1-10, carbonilalquilo C1-10, tiocarbonilalquilo C1-10, sulfonilalquilo C1-10, sulfinilalquilo C1-10, azaalquilo C1-10, iminoalquilo C1-10, cicloalquil C3-12-alquilo C1-5, heterocicloalquil C3-12-alquilo C1-10, arilalquilo C1-10, heteroaril C1-10-alquilo C1-5, bicicloaril C9-12-alquilo C1-5, heterobicicloaril C8-12- alquilo C1-5, heteroalquilo C1-10, cicloalquilo C3-12, heterocicloalquilo C3-12 , bicicloalquilo C9-12, heterobicicloalquilo C3-12, arilo C4-12, heteroarilo C1-10, bicicloarilo C9-12 y heterobicicloarilo C4-12, cada uno sustituido o no sustituido; R5 y R5' se seleccionan cada uno en forma independiente del grupo que consiste en hidrogeno, ciano, carbonilo, oxicarbonilo, aminocarbonilo, sulfonilo, sulfinilo, alquilo C1-10, haloalquilo C1-10, hidroxialquilo C1-10, carbonilalquilo C1-10, tiocarbonilalquilo C1-10, sulfonilalquilo C1-10, sulfinilalquilo C1-10, heteroalquilo C1-10, iminoalquilo C1-10, cicloalquil C3-12-alquilo C1-5, hetero cicloalquil C3-12-alquilo C1-10, arilalquilo C1-10, heteroaril C1-10-alquilo C1-5, bicicloaril C9-12-alquilo C1-5, heterobicicloaril C8-12-alquilo C1-5, heteroalquilo C1-10, cicloalquilo C3-12, heterocicloalquilo C3-12, bicicloalquilo C9-12, heterobicicloalquilo C3-12, arilo C4-12, heteroarilo C1-10, bicicloarilo C9-12 y heterobicicloarilo C4-12, cada uno sustituido o no sustituido; R6 y R6' se seleccionan cada uno en forma independiente del grupo que consiste en hidrogeno, halogeno, ciano, alquilo C1-10, sulfonilalquilo C1-10, sulfinilalquilo C1-10, heteroalquilo C1-10, cicloalquil C3-12-alquilo C1-5, hetero cicloalquil C3-12-alquilo C1-10, arilalquilo C1-10, heteroaril C1-10-alquilo C1-5, bicicloaril C9-12-alquilo C1-5, heterobicicloaril C8-12-alquilo C1-5, heteroalquilo C1-10, cicloalquilo C3-12, heterocicloalquilo C3-12, bicicloalquilo C9-12, heterobicicloalquilo C3-12, arilo C4-12, heteroarilo C1-10, bicicloarilo C9-12 y heterobicicloarilo C4-12, cada uno sustituido o no sustituido, siempre que R6' esté ausente cuando A es CR5R5'; R7 se selecciona del grupo que consiste en hidrogeno, ciano, sulfonilo, sulfinilo, alquilo C1-10, sulfonilalquilo C1-10, sulfinilalquilo C1-10, azaalquilo C1-10, oxaalquilo C1-10, cicloalquil C3-12-alquilo C1-5, heterocicloalquil C3-12-alquilo C1-10, arilalquilo C1-10, heteroaril C1-10-alquilo C1-5, bicicloaril C9-12-alquilo C1-5, heterobicicloaril C8-12- alquilo C1-5, heteroalquilo C1-10, cicloalquilo C3-12, heterocicloalquilo C3-12 , bicicloalquilo C9-12, heterobicicloalquilo C3-12, arilo C4-12, heteroarilo C1-10, bicicloarilo C9-12 y heterobicicloarilo C4-12, cada uno sustituido o no sustituido; R8 se selecciona del grupo que consiste en hidrogeno, alquilo C1-10, hidroxialquilo C1-10, sulfonilalquilo C1-10, sulfinilalquilo C1-10, cicloalquil C3-12-alquilo C1-5, hetero cicloalquil C3- 12-alquilo C1-10, arilalquilo C1-10, heteroaril C1-10-alquilo C1-5, bicicloaril C9-12-alquilo C1-5, heterobicicloaril C8-12-alquilo C1-5, heteroalquilo C1-10, cicloalquilo C3-12, heterocicloalquilo C3-12, bicicloalquilo C9-12, heterobicicloalquilo C3-12, arilo C4-12, heteroarilo C1-10, bicicloarilo C9-12 y heterobicicloarilo C4-12, cada uno sustituido o no sustituido; y R9 y R9' se seleccionan cada uno en forma independiente del grupo que consiste en hidrogeno, sulfonilamino, aminosulfonilo, sulfonilo, sulfinilo, alquilo C1-10, hidroxialquilo C1-10, sulfonilalquilo C1-10, sulfinilalquilo C1-10, heteroalquilo C1-10, cicloalquil C3-12, alquilo C1-5, hetero cicloalquil C3-12-alquilo C1-10, arilalquilo C1-10, heteroaril C1-10-alquilo C1-5, bicicloaril C9-12-alquilo C1-5, heterobicicloaril C8-12-alquilo C1-5, heteroalquilo C1-10, cicloalquilo C3-12, heterocicloalquilo C3-12, bicicloalquilo C9-12, heterobicicloalquilo C3-12, arilo C4-12, heteroarilo C1-10, bicicloarilo C9-12 y heterobicicloarilo C4-12, cada un sustituido o no sustituido; siempre que para la Formula 2, cuando X es O, R1 es alquilo C1-6 sustituido con por lo menos dos grupos hidroxilo.
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