AR078029A1 - Compuestos bis aromaticos inhibidores de ltc4 sintetasas, composiciones farmaceuticas que los contienen, metodo para prepararlos y uso de los mismos para el tratamiento de enfermedades respiratorias y/o inflamatorias - Google Patents
Compuestos bis aromaticos inhibidores de ltc4 sintetasas, composiciones farmaceuticas que los contienen, metodo para prepararlos y uso de los mismos para el tratamiento de enfermedades respiratorias y/o inflamatoriasInfo
- Publication number
- AR078029A1 AR078029A1 ARP100100796A ARP100100796A AR078029A1 AR 078029 A1 AR078029 A1 AR 078029A1 AR P100100796 A ARP100100796 A AR P100100796A AR P100100796 A ARP100100796 A AR P100100796A AR 078029 A1 AR078029 A1 AR 078029A1
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- AR
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- Prior art keywords
- optionally substituted
- group
- substituents selected
- independently represent
- alkyl
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Abstract
Reivindicacion 1: Un compuesto caracterizado porque responde a la formula (1), donde Y representa -C(O)- o -C(N-OR28)-, R28 representa hidrogeno o C1 alquilo opcionalmente sustituido con uno o más átomos de halo; Y se une ya sea a Da O Db; la unidad Da o Db que está directamente unida a Y representa un átomo de carbono; la unidad Da o Db que no es directamente unida a Y representa D1; cada uno de D1, D2 y D3 respectivamente representan C(R1a)=, -C(R1b)= y C(R1c)=, o, cada uno de D1, D2 y D3 puede representar de manera alternativa e independiente -N=; el anillo A representa: (2) cada uno de Ea1, Ea2, Ea3, Ea4 y Ea5 respectivamente representan -C(H)=, -C(R2b)=, -C(R2c)=, -C(R2d)= y -C(H)=, o, cada uno de Ea1, Ea2, Ea3, Ea4 y Ea5 puede representar de manera alternativa e independiente -N=; uno de R2b, R2c y R2d representa el grupo requerido -L3-Y3 grupo, y los otros representan en forma independiente hidrogeno, -L1a-Y1a o un sustituyente seleccionado entre X1; (3); Eb1 y Eb2 respectivamente representan -C(R3a)= y -C(R3b)=; Yb representa -C(R3c)= o -N=; Wb representa -N(R3d)-, -O- o -S-; uno de R3a, R3b y, si se encuentra presente, R3c y R3d, representa el grupo requerido -L3-Y3 grupo, y los restantes R3a, R3b y (si se encuentra presente) R3c sustituyentes representa hidrogeno, -L1a-Y1a o un sustituyente seleccionado entre X2, y los restantes R3d sustituyente (si se encuentra presente) representa hidrogeno o un sustituyente seleccionado entre Rz1; o (4); Ec1 y Ec2 respectivamente representan -C(R4a)= y -C(R4b)=; Yc representa -C(R4c)= o -N=; Wc representa -N(R4d)-, -O- o -S-; uno de R4a, R4b y, si se encuentra presente, R4c y R4d representa el grupo requerido -L3-Y3 grupo, y los restantes R4a, R4b y (si se encuentra presente) R4c sustituyentes representan hidrogeno, -L1a-Y1a o un sustituyente seleccionado entre X3, y los restantes R4d sustituyente (si se encuentra presente) representa hidrogeno o un sustituyente seleccionado entre Rz2; Rz1 y Rz2 representan en forma independiente un grupo seleccionado entre Z1a; R1a, R1b, R1c, representan en forma independiente hidrogeno, un grupo seleccionado entre Z2a, halo, -CN, -N(R6b)R7b, -N(R5d)C(O)R6c, -N(R5e)C(O)N(R6c)R7d, -N(R5f)C(O)OR6e, -N3, -NO2, -N(R5g)S(O)2N(R6f)R7f, -OR5h, -OC(O)N(R6g)R7g, -OS(O)2R5i, -N(R5k)S(O)2R5m, -OC(O)R5n, -OC(O)OR5p o -OS(O)2N(R6i)R7i; X1, X2 y X3 representan en forma independiente un grupo seleccionado entre Z2a, o, halo, -CN, -N(R6b)R7b, -N(R5d)C(O)R6c, -N(R5e)C(O)N(R6d)R7d, -N(R5f)C(O)OR6e, -N3, -NO2, -N(R5g)S(O)2N(R6f)R7f, -OR5h, -OC(O)N(R6g)R7g, -OS(O)2R5i, -N(R5k)S(O)2R5m, -OC(O)R5n, -OC(O)OR5p o -OS(O)2N(R6i)R7i; Z1a y Z2a representan en forma independiente -R5a, -C(O)R5b, -C(O)OR5c, -C(O)N(R6a)R7a, -S(O)mR5j o -S(O)2N(R6h)R7h; R5b a R5h, R5j, R5k, R5n, R6a a R6i, R7a, R7b, R7d y R7f a R7i en forma independiente representan, en cada ocasion cuando se lo usa aquí, H o R5a; o cualquiera de los pares R6a y R7a, R6b y R7b, R6d y R7d, R6f y R7f, R6g y R7g, R6h y R7h o R6i y R7i se pueden unir para formar, junto con el o los átomos a los cuales se encuentran unidos, un anillo de 3 a 6 miembros, cuyo anillo contiene opcionalmente un heteroátomo adicional además del átomo de nitrogeno al cual estos sustituyentes se encuentran necesariamente unidos, y cuyo anillo se sustituye opcionalmente con uno o más sustituyentes seleccionados entre F, CI, =O, -OR5h y/o R5a; R5i, R5m y R5p representan en forma independiente R5a; R5a representa, en cada ocasion cuando se lo usa aquí, C1-6 alquilo opcionalmente sustituido con uno o más sustituyentes seleccionados entre halo, -CN, -N3, =O, -OR8a, -N(R8b)R8c, -S(O)nR8d, -S(O)2N(R8e)R8f y/o -OS(O)2N(R8g)R8h; n representa 0, 1 o 2; R8a, R8b, R8d, R8e y R8g representan en forma independiente H o C1-6 alquilo opcionalmente sustituido con uno o más sustituyentes seleccionados entre halo, =O, -OR11a, -N(R12a)R12b y/o -S(O)2-M1; R8c, R8f y R8h representan en forma independiente H, -S(O)2CH3, -S(O)2CF3 o C1-6 alquilo opcionalmente sustituido con uno o más sustituyentes seleccionados entre F, CI, =O, -OR13a, -N(R14a)R14b y/o -S(O)2-M2; o R8b y R8c, R8e y R8f o R8g y R8h se pueden unir para formar, junto con el o los átomos a los cuales se encuentran unidos, un anillo de 3 a 6 miembros, cuyo anillo contiene opcionalmente un heteroátomo adicional además del átomo de nitrogeno al cual estos sustituyentes se encuentran necesariamente unidos, y cuyo anillo se sustituye opcionalmente con uno o más sustituyentes seleccionados entre F, CI, =O y/o C1-3 alquilo opcionalmente sustituido con uno o más sustituyentes seleccionados entre =O y fluoro; M1 y M2 representan en forma independiente -N(R15a)R15b) o C1-3 alquilo opcionalmente sustituido con uno o más átomos de fluor; R11a y R13b representan en forma independiente H o C1-3 alquilo opcionalmente sustituido con uno o más átomos de fluor; R12a, R12b, R14a, R14b, R15a y R15b representan en forma independiente H, -CH3 o CH2CH3, Y1 e Y1a en forma independiente representan, en cada ocasion cuando se lo usa aquí, -C(O)OR9a o 5-tetrazolilo; R9a representa hidrogeno o C1-4- alquilo opcionalmente sustituido con uno o más átomos de halo; uno de Y2 e Y3 representa un grupo arilo o un grupo heteroarilo (de los cuales ambos grupos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre A) y el otro representa: (a) un grupo arilo o un grupo heteroarilo (de los cuales ambos grupos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre A); o (b) C1-12 alquilo o un grupo heterocicloalquilo, de los cuales ambos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre G1 y/o Z1; A representa, en cada ocasion cuando se lo usa aquí: I) un grupo arilo o un grupo heteroarilo, de los cuales ambos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre B; II) C1-8 alquilo o un grupo heterocicloalquilo, de los cuales ambos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre G1 y/o Z1; o III) un grupo G1; G1 representa, en cada ocasion cuando se lo usa aquí, halo, ciano, -N3, -NO2, -ONO-2 o -A1-R16a; donde A1 representa una union simple o un grupo separador seleccionado entre -C(O)A2-, -S-, -S(O)m1A3-, -N(R17a)A4- o -OA5-, en donde: A2 representa una union simple, -O-, -N(R17b)- o -C(O)-; A3 representa una union simple, -O- o -N(R17c)-; A4 y A5 representan en forma independiente una union simple, -C(O)-, -C(O)N(R17d)-, -C(O)O-, -S(O)2- o -S(O)2N(R17e)-; Z1 representa, en cada ocasion cuando se lo usa aquí, =O, =S, -NOR16b, =NS(O)2N(R17f)R16c, =NCN o =C(H)NO2; B representa, en cada ocasion cuando se lo usa aquí: I) un grupo arilo o un grupo heteroarilo, de los cuales ambos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre G2; II) C1-8 alquilo o un grupo heterocicloalquilo, de los cuales ambos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre G2 y/o Z2; o III) un grupo G2; G2 representa, en cada ocasion cuando se lo usa aquí, halo, ciano, -N3, -NO2, -ONO-2 o -A6-R18a; donde A6 representa una union simple o un grupo separador seleccionado entre -C(O)A7-, -S-, -S(O)m1A8-, -N(R19a)A9- o -OA10-, en donde: A7 representa una union simple, -O-, -N(R19b)- o -C(O)-; A8 representa una union simple, -O- o -N(R19c)-; A9 y A10 representan en forma independiente una union simple, -C(O)-, -C(O)N(R19d)-, -C(O)O-, -S(O)2- o -S(O)2N(R19e)-; Z2 representa, en cada ocasion cuando se lo usa aquí, =O, =S, =NOR18b, =NS(O)2N(R19f)R18c, =NCN o =C(H)NO2; R16a, R16b, R16c, R17a, R17b, R17c, R17d, R17e, R17f, R18a, R18b, R18c, R19a, R19b, R19c, R19d, R19e y R19f se seleccionan en forma independiente entre: i) hidrogeno; ii) un grupo arilo o un grupo heteroarilo, de los cuales ambos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre G3; iii) C1-8 alquilo o un grupo heterocicloalquilo, de los cuales ambos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre G3 y/o Z3; o cualquier par de R16a a R16c y R17a a R17f, y/o R18a a R18c y R19a a R19f, pueden estar unidos para formar con ellos o con otros átomos relevantes otro anillo de 3 a 8 miembros, que opcionalmente contienen 1 a 3 heteroátomos y/o 1 a 3 dobles ligaduras, cuyo anillo se sustituye opcionalmente con uno o más sustituyentes seleccionados entre G3 y/o Z3; G3 representa, en cada ocasion cuando se lo usa aquí, halo, ciano, -N3, -NO2, -ONO-2 o -A11-R20a; donde A11 representa una union simple o un grupo separador seleccionado entre -C(O)A12-, -S-, -S(O)m1A13-, -N(R21a)A14- o -OA15-, en donde: A12 representa una union simple, -O-, -N(R21b)- o -C(O)-; A13 representa una union simple, -O- o -N(21c)-; A14 y A15 representan en forma independiente una union simple, -C(O)-, -C(O)N(R21d)-, -C(O)O-, -S(O)2- o -S(O)2N(R21e)-; Z3 representa, en cada ocasion cuando se lo usa aquí, =O, =S, =NOR20b, =NS(O)2N(R21f)R20c, =NCN o =C(H)NO2; R20a, R20b, R20c, R21a, R21b, R21c, R21d, R21e y R21f se seleccionan en forma independiente entre: i) hidrogeno; ii) C1-6 alquilo o un grupo heterocicloalquilo, de los cuales ambos grupos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre halo, C1-4 alquilo, -N(R22a)R23a, -OR22b y =O; y iii) un grupo arilo o heteroarilo, de los cuales ambos se sustituyen opcionalmente con uno o más sustituyentes seleccionados entre halo, C1-4 alquilo (opcionalmente sustituido con uno o más sustituyentes seleccionados entre =O, fluoro y cloro), -N(R22c)R23b y -OR22d; cualquier par de R20a a R2Oc y R21a a R21f pueden estar unidos para formar con ellos o con otros átomos relevantes otro anillo de 3 a 8 miembros, que opcionalmente contienen 1 a 3 heteroátomos y/o 1 o 2 dobles ligaduras, cuyo anillo se sustituye opcionalmente con uno o más sustituyentes seleccionados entre halo, C1-4 alquilo, -N(R22e)R23c, -OR22f y =O; L1 y L1a representan en forma independiente una union simple o -(CH2)p-Q-(CH2)q-; p y q en forma independiente representan, en cada ocasion cua
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