AR045238A1 - Compuestos utiles como inhibidores de canales ionicos regulados por voltaje - Google Patents

Compuestos utiles como inhibidores de canales ionicos regulados por voltaje

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Publication number
AR045238A1
AR045238A1 ARP040102855A ARP040102855A AR045238A1 AR 045238 A1 AR045238 A1 AR 045238A1 AR P040102855 A ARP040102855 A AR P040102855A AR P040102855 A ARP040102855 A AR P040102855A AR 045238 A1 AR045238 A1 AR 045238A1
Authority
AR
Argentina
Prior art keywords
aliphatic
nr6c
nr5c
optionally comprises
independently selected
Prior art date
Application number
ARP040102855A
Other languages
English (en)
Inventor
Jesus E Gonzales Iii
Andreas Peter Termin
Ester Martinborough
Nicole Zimmermann
Original Assignee
Vertex Pharma
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Publication date
Application filed by Vertex Pharma filed Critical Vertex Pharma
Publication of AR045238A1 publication Critical patent/AR045238A1/es

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Abstract

Reivindicación 1: Un compuesto de la fórmula (1), en donde: cada RN es independientemente hidrógeno o C1-4 alifático opcionalmente sustituido con hasta dos sustituyentes seleccionados de R1, R4, o R5; X1 es O, S o NRx; p es 0 o 1; Rx es H o R2; X2 es alifático C1-3, opcionalmente sustituido con hasta 2 sustituyentes seleccionados, de modo independiente, de R1, R4 o R5; Z se selecciona de un resto de grupo de fórmula (2), T es un anillo bicíclico o tricíclico aromático o no aromático de 8-14 miembros, que tiene 0-5 heteroátomos seleccionados de O, S, N, NH, S(O) o SO2; en donde el anillo T está unido al resto de la molécula a través de un átomo del anillo de carbono; en donde cada uno de Z y T comprende opcionalmente hasta 4 sustituyentes seleccionados, de modo independiente, de R1, R2, R3, R4 o R5; R1 es oxo, =NN(R6)2, =NN(R7)2, =NN(R6R7), R6 o (CH2)n-Y; n es 0, 1 ó 2; Y es halo, CN, NO2, CF3, OCF3, OH, SR6, S(O)R6, SO2R6, NH2, NHR6, N(R6)2, NR6R8, COOH, COOR6 u OR6; o dos R1 en átomos de anillo adyacentes, tomados juntos, forman 1,2-metilendioxi o 1,2-etilendioxi; R2 es alifático, en donde cada R2 comprende opcionalmente hasta 2 sustituyentes seleccionados, de modo independiente, de R1, R4 o R5; R3 es un anillo cicloalifático, arilo, heterocíclico o heteroarilo que opcionalmente comprende hasta 3 sustituyentes seleccionados, de modo independiente, de R1, R2, R4 o R5; R4 es OR5, OR6, OC(O)R6, OC(O)R5, OC(O)OR6, OC(O)OR5, OC(O)N(R6)2, OC(O)N(R5)2, OC(O)N(R6R5), OP(O)(OR6)2, OP(O)(OR5)2, OP(O)(OR6)(OR5), SR6, SR5, S(O)R6, S(O)R5, SO2R6, SO2R5, SO2N(R6)2, SO2N(R5)2, SO2NR5R6, SO3R6, SO3R5, C(O)R5, C(O)OR5, C(O)R6, C(O)OR6, C(O)N(R6)2, C(O)N(R5)2, C(O)N(R5R6), C(O)N(OR6)R6, C(O)N(OR5)R6, C(O)N(OR6)R5, C(O)N(OR5)R5, C(NOR6)R6, C(NOR6)R5, C(NOR5)R6, C(NOR5)R5, N(R6)2, N(R5)2, N(R5R6), NR5C(O)R5, NR6C(O)R6, NR6C(O)R5, NR6C(O)OR6, NR5C(O)OR6, NR6C(O)OR5, NR5C(O)OR5, NR6C(O)N(R6)2, NR6C(O)NR5R6, NR6C(O)N(R5)2, NR5C(O)N(R6)2, NR5C(O)NR5R6, NR5C(O)N(R5)2, NR6SO2R6, NR6SO2R5, NR5SO2R5, NR6SO2N(R6)2, NR6SO2NR5R6, NR6SO2N(R5)2, NR5SO2NR5R6, NR5SO2N(R5)2, N(OR6)R6, N(OR6)R5, N(OR5)R5, N(OR5)R6, P(O)(OR6)N(R6)2, P(O)(OR6)N(R5R6), P(O)(OR6)N(R5)2, P(O)(OR5)N(R5R6), P(O)(OR5)N(R6)2, P(O)(OR5)N(R5)2, P(O)(OR6)2, P(O)(OR5)2 o P(O)(OR6)(OR5); R5 es un anillo cicloalifático, arilo, heterocíclico o heteroarilo que opcionalmente comprende hasta 3 sustituyentes R1; R6 es H o alifático, en donde R6 comprende opcionalmente un sustituyente R7; R7 es un anillo cicloalifático, arilo, heterocíclico o heteroarilo y cada R7 comprende opcionalmente hasta 2 sustituyentes seleccionados, de modo independiente, de H, alifático o (CH2)n-Z'; Z' se selecciona de halo, CN, NO2, CF3, OCF3, OH, S-alifático, S(O)-alifático, SO2-alifático, NH2, N-alifático, N(alifático)2, N(alifático)R8, COOH, C(O)O(-alifático u O-alifático); y R8 es un grupo de protección amino; con la condición de que: i) cuando: X2, X1, q, y p son juntos -CH2-O-, entonces: T no sea ninguno de los restos de grupo de fórmula (3), ii) cuando: X2, X1, q y p son juntos -CH2-S-, entonces: T no sea ninguno de los restos de grupos de fórmula (4), en donde B es hidrógeno, metilo, n-propilo, isopropilo, alilo, bencilo o feniletilo.
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