AR099436A1 - DERIVATIVES OF AMINO PIRIDINA AS INHIBITORS OF PHOSFATIDYLINOSITOL 3-CINASA - Google Patents

DERIVATIVES OF AMINO PIRIDINA AS INHIBITORS OF PHOSFATIDYLINOSITOL 3-CINASA

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AR099436A1
AR099436A1 ARP130102803A ARP130102803A AR099436A1 AR 099436 A1 AR099436 A1 AR 099436A1 AR P130102803 A ARP130102803 A AR P130102803A AR P130102803 A ARP130102803 A AR P130102803A AR 099436 A1 AR099436 A1 AR 099436A1
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Argentina
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alkyl
heterocyclyl
cycloalkyl
alkoxy
independently selected
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ARP130102803A
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Spanish (es)
Inventor
Charles Bloomfield Graham
Charles HALL Edward
James Culshaw Andrew
SPENDIFF Matthew
Neef James
James Watson Simon
Richard Bellenie Benjamin
Hollingworth Gregory
Bruce Ian
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Novartis Ag
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Priority to ARP130102803A priority Critical patent/AR099436A1/en
Publication of AR099436A1 publication Critical patent/AR099436A1/en

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Abstract

Los cuales inhiben la actividad de la isoforma g de la PI 3-cinasa. Reivindicación 1: Un compuesto de la fórmula (1) o una sal farmacéuticamente aceptable del mismo, en donde E se selecciona a partir de N y CRE; R¹, R² y RE se seleccionan independientemente a partir de H, halógeno, C₁₋₄ alquilo, C₁₋₄ alcoxilo, C₁₋₄ haloalquilo, C₁₋₄ haloalcoxilo, C₁₋₄ hidroxialquilo y C₃₋₇ cicloalquilo; R³ se selecciona a partir de (i) C₁₋₄ alquilo que es sustituido o no sustituido por 1 o más sustituyentes, particularmente 1 a 3 sustituyentes, independientemente seleccionados a partir de hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ haloalquilo, C₁₋₄ alcoxilo, C₁₋₄ alquilo, oxo, CN, -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ, C₃₋₇ cicloalquilo y C₃₋₇ heterociclilo, y en donde el C₃₋₇ cicloalquilo o C₃₋₇ heterociclilo es no sustituido o sustituido por 1 a 3 sustituyentes independientemente seleccionados a partir de hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ alquilo, C₁₋₄ alcoxilo, C₁₋₄ haloalquilo, oxo y -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ; (ii) C₁₋₄ alcoxilo que es sustituido o no sustituido por 1 o más sustituyentes, particularmente 1 a 3 sustituyentes, independientemente seleccionados a partir de hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ haloalquilo, C₁₋₄ alcoxilo, C₁₋₄ alquilo, oxo, CN, -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ, C₃₋₇ cicloalquilo y C₃₋₇ heterociclilo, y en donde el C₃₋₇ cicloalquilo o C₃₋₇ heterociclilo es no sustituido o sustituido por 1 a 3 sustituyentes independientemente seleccionados a partir de hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ alquilo, C₁₋₄ alcoxilo, C₁₋₄ haloalquilo, oxo y -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ; (iii) -C₃₋₇ cicloalquilo o -O-C₃₋₇ cicloalquilo en donde el C₃₋₇ cicloalquilo es no sustituido o sustituido por 1 a 3 sustituyentes independientemente seleccionados a partir de hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ alquilo, C₁₋₄ alcoxilo, C₁₋₄ haloalquilo, oxo y -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ; (iv) un -(C₀₋₃ alquilo)-C₃₋₇ cicloalquilo o -O-(C₀₋₃ alquilo)-C₃₋₇ cicloalquilo en donde el C₃₋₇ cicloalquilo es espiro condensado a un segundo C₃₋₇ cicloalquilo o C₃₋₇ heterociclilo por un átomo de carbono sencillo, y en donde el C₃₋₇ cicloalquilo o C₃₋₇ heterociclilo es no sustituido o sustituido por 1 a 3 sustituyentes independientemente seleccionados a partir de hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ alquilo, C₁₋₄ alcoxilo, C₁₋₄ haloalquilo, oxo y -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ; (v) un -(C₀₋₃ alquilo)-C₃₋₇ heterociclilo o -O-(C₀₋₃ alquilo)-C₃₋₇ heterociclilo, y en donde dicho C₃₋₇ heterociclilo es no sustituido o sustituido por 1 a 3 sustituyentes independientemente seleccionados a partir de hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ alquilo, C₁₋₄ alcoxilo, C₁₋₄ haloalquilo, oxo y -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ; (vi) un -(C₀₋₃ alquilo)-C₃₋₇ heterociclilo o -O-(C₀₋₃ alquilo)-C₃₋₇ heterociclilo, y en donde dicho C₃₋₇ heterociclilo es espiro condensado a un segundo C₃₋₇ heterociclilo o un C₃₋₇ cicloalquilo por un átomo de carbono sencillo, y en donde el C₃₋₇ heterociclilo o C₃₋₇ cicloalquilo es no sustituido o sustituido por 1 a 3 sustituyentes independientemente seleccionados a partir de hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ alquilo, C₁₋₄ alcoxilo, C₁₋₄ haloalquilo, oxo y -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ; (vii) un piridilo en donde el piridilo es no sustituido o sustituido por 1 a 3 sustituyentes seleccionados independientemente a partir de C₁₋₄ alquilo, C₁₋₄ alcoxilo, hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ haloalquilo y -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ; y (viii) H; R⁴ se selecciona a partir de H y C₁₋₄ alquilo; o R³ y R⁴ junto con el átomo de nitrógeno al que se fijan forman un C₃₋₇ heterociclilo, tal C₃₋₇ heterociclilo es opcionalmente espiro condensado a un segundo C₃₋₇ heterociclilo o un C₃₋₇ cicloalquilo por un átomo de carbono sencillo, y tal C₃₋₇ heterociclilo y C₃₋₇ cicloalquilo son no sustituidos o sustituidos por 1 a 3 sustituyentes independientemente seleccionados a partir de hidroxilo, C₁₋₄ hidroxialquilo, halógeno, C₁₋₄ alquilo, C₁₋₄ alcoxilo, C₁₋₄ haloalquilo, oxo y -(C₀₋₃ alquilo)-NR³ᵃR³ᵇ; R³ᵃ y R³ᵇ se seleccionan independientemente a partir de H, C₁₋₄ alquilo y C₁₋₄ haloalquilo; Y es un heteroarilo de 5 - 6 miembros, tal heteroarilo es no sustituido o sustituido por 1 a 3 sustituyentes seleccionados independientemente a partir de C₁₋₄ alquilo, C₁₋₄ haloalquilo, C₁₋₄ alcoxi-C₁₋₄ alquilo, C₁₋₄ hidroxialquilo, C₁₋₄ alcoxilo, C₁₋₄ haloalcoxilo, halógeno, -(C₀₋₃ alquilo)-NRR, -(C₀₋₃ alquilo)-C₃₋₇ cicloalquilo, -(C₀₋₃ alquilo)-C₃₋₇ heterociclilo, -(C=O)-C₃₋₇ heterociclilo, -(C=O)-NRR, -(C₀₋₃ alquilo)-fenilo y (C₀₋₃ alquilo)-heteroarilo de 5 - 6 miembros; R y R se seleccionan independientemente a partir de H y C₁₋₄ alquilo.Which inhibit the activity of the isoform g of PI 3-kinase. Claim 1: A compound of the formula (1) or a pharmaceutically acceptable salt thereof, wherein E is selected from N and CRE; R¹, R² and RE are independently selected from H, halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, C₁₋₄ haloalkoxy, C₁₋₄ hydroxyalkyl and C₃₋₇ cycloalkyl; R³ is selected from (i) C₁₋₄ alkyl which is substituted or unsubstituted by 1 or more substituents, particularly 1 to 3 substituents, independently selected from hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁₋₄ alkyl, oxo, CN, - (C₀₋₃ alkyl) -NR³ᵃR³ᵇ, C₃₋₇ cycloalkyl and C₃₋₇ heterocyclyl, and wherein C₃₋₇ cycloalkyl or C₃₋₇ heterocyclyl is unsubstituted or substituted by 1 to 3 substituents independently selected from hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, oxo and - (C₀₋₃ alkyl) -NR³ᵃR³ᵇ; (ii) C₁₋₄ alkoxy which is substituted or unsubstituted by 1 or more substituents, particularly 1 to 3 substituents, independently selected from hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ haloalkyl, C₁₋₄ alkoxy, C₁ ₋₄ alkyl, oxo, CN, - (C₀₋₃ alkyl) -NR³ᵃR³ᵇ, C₃₋₇ cycloalkyl and C₃₋₇ heterocyclyl, and wherein the C₃₋₇ cycloalkyl or C₃₋₇ heterocyclyl is unsubstituted or substituted by 1 to 3 substituents independently selected from hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, oxo and - (C₀₋₃ alkyl) -NR³ᵃR³ᵇ; (iii) -C₃₋₇ cycloalkyl or -O-C₃₋₇ cycloalkyl wherein C₃₋₇ cycloalkyl is unsubstituted or substituted by 1 to 3 substituents independently selected from hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, oxo and - (C₀₋₃ alkyl) -NR³ᵃR³ᵇ; (iv) a - (C₀₋₃ alkyl) -C₃₋₇ cycloalkyl or -O- (C₀₋₃ alkyl) -C₃₋₇ cycloalkyl where C₃₋₇ cycloalkyl is a condensed spiro to a second C₃₋₇ cycloalkyl or C₃ ₋₇ heterocyclyl by a single carbon atom, and wherein the C₃₋₇ cycloalkyl or C₃₋₇ heterocyclyl is unsubstituted or substituted by 1 to 3 substituents independently selected from hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, oxo and - (C₀₋₃ alkyl) -NR³ᵃR³ᵇ; (v) a - (C₀₋₃ alkyl) -C₃₋₇ heterocyclyl or -O- (C₀₋₃ alkyl) -C₃₋₇ heterocyclyl, and wherein said C₃₋₇ heterocyclyl is unsubstituted or substituted by 1 to 3 substituents independently selected from hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, oxo and - (C₀₋₃ alkyl) -NR³ᵃR³ᵇ; (vi) a - (C₀₋₃ alkyl) -C₃₋₇ heterocyclyl or -O- (C₀₋₃ alkyl) -C₃₋₇ heterocyclyl, and wherein said C₃₋₇ heterocyclyl is spiro condensed to a second C₃₋₇ heterocyclyl or a C₃₋₇ cycloalkyl by a single carbon atom, and wherein the C₃₋₇ heterocyclyl or C₃₋₇ cycloalkyl is unsubstituted or substituted by 1 to 3 substituents independently selected from hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, oxo and - (C₀₋₃ alkyl) -NR³ᵃR³ᵇ; (vii) a pyridyl wherein pyridyl is unsubstituted or substituted by 1 to 3 substituents independently selected from C₁₋₄ alkyl, C₁₋₄ alkoxy, hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ haloalkyl and - ( C₀₋₃ alkyl) -NR³ᵃR³ᵇ; and (viii) H; R⁴ is selected from H and C₁₋₄ alkyl; or R³ and R⁴ together with the nitrogen atom to which they are attached form a C₃₋₇ heterocyclyl, such C₃₋₇ heterocyclyl is optionally spiro condensed to a second C₃₋₇ heterocyclyl or a C₃₋₇ cycloalkyl by a single carbon atom, and such C₃₋₇ heterocyclyl and C₃₋₇ cycloalkyl are unsubstituted or substituted by 1 to 3 substituents independently selected from hydroxyl, C₁₋₄ hydroxyalkyl, halogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkyl, oxo and - (C₀₋₃ alkyl) -NR³ᵃR³ᵇ; R³ᵃ and R³ᵇ are independently selected from H, C₁₋₄ alkyl and C₁₋₄ haloalkyl; Y is a 5-6 membered heteroaryl, such heteroaryl is unsubstituted or substituted by 1 to 3 substituents independently selected from C₁₋₄ alkyl, C₁₋₄ haloalkyl, C₁₋₄ alkoxy-C₁₋₄ alkyl, C₁₋₄ hydroxyalkyl, C₁₋₄ alkoxy, C₁₋₄ haloalkoxy, halogen, - (C₀₋₃ alkyl) -NRR, - (C₀₋₃ alkyl) -C₃₋₇ cycloalkyl, - (C₀₋₃ alkyl) -C₃₋₇ heterocyclyl, - (C = O) -C₃₋₇ heterocyclyl, - (C = O) -NRR, - (C₀₋₃ alkyl) -phenyl and 5-6 membered (Che alkyl) -heteroaryl; R and R are independently selected from H and C₁₋₄ alkyl.

ARP130102803A 2013-08-07 2013-08-07 DERIVATIVES OF AMINO PIRIDINA AS INHIBITORS OF PHOSFATIDYLINOSITOL 3-CINASA AR099436A1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11306079B2 (en) 2017-12-21 2022-04-19 Incyte Corporation 3-(5-amino-pyrazin-2-yl)-benzenesulfonamide derivatives and related compounds as PI3K-gamma kinase inhibitors

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11306079B2 (en) 2017-12-21 2022-04-19 Incyte Corporation 3-(5-amino-pyrazin-2-yl)-benzenesulfonamide derivatives and related compounds as PI3K-gamma kinase inhibitors

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