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AR104865A1 - THYROSINE KINASE INHIBITORS - Google Patents

THYROSINE KINASE INHIBITORS

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Publication number
AR104865A1
AR104865A1 ARP160101618A ARP160101618A AR104865A1 AR 104865 A1 AR104865 A1 AR 104865A1 AR P160101618 A ARP160101618 A AR P160101618A AR P160101618 A ARP160101618 A AR P160101618A AR 104865 A1 AR104865 A1 AR 104865A1
Authority
AR
Argentina
Prior art keywords
alkyl
heterocyclyl
hydrogen
halo
independently selected
Prior art date
Application number
ARP160101618A
Other languages
Spanish (es)
Inventor
d owens Timothy
Goldstein David
Original Assignee
Principia Biopharma Inc
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
Application filed by Principia Biopharma Inc filed Critical Principia Biopharma Inc
Publication of AR104865A1 publication Critical patent/AR104865A1/en

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Abstract

Reivindicación 1: Un compuesto de la fórmula (1), caracterizado porque: R¹ y R² son, independientemente, hidrógeno, alquilo, alcoxilo, haloalquilo o halo; X es -O-, -CONR-, -NRCO-, o -NR-CO-NR donde R y R son, independientemente, hidrógeno o alquilo; Ar heteroarilo o fenilo donde el heteroarilo y fenilo están opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados independientemente entre alquilo, halo, haloalquilo, alcoxilo e hidroxilo; A es -N- o -CR³- donde R³ es hidrógeno, alquilo, ciclopropilo, halo, haloalquilo, haloalcoxilo, alcoxilo o ciano; Y es un enlace o alquileno; el anillo Z es heterocicloamino opcionalmente sustituido con uno o dos sustituyentes independientemente seleccionados entre alquilo, hidroxilo, alcoxilo y fluoro; R⁵ es un grupo de la fórmula (i), (ii), (iii) ó (iv) seleccionado del grupo de fórmulas (2), donde: Rᵃ es hidrógeno, fluoro o ciano; con la condición de que, cuando Rᵃ es ciano, entonces Rᵇ es hidrógeno y Rᶜ no es hidrógeno; Rᵇ es hidrógeno o alquilo; y Rᶜ es hidrógeno, hidroxialquilo, alcoxialquilo, alquilo (opcionalmente sustituido con uno o dos sustituyentes seleccionados independientemente entre hidroxilo, hidroxialquilo, heteroarilo (opcionalmente sustituido con uno o dos sustituyentes seleccionados independientemente entre alquilo y heterociclilo donde heterociclilo está opcionalmente sustituido con uno o dos sustituyentes independientemente seleccionados entre halo y alquilo), y -CONR⁹R¹⁰ (donde R⁹ y R¹⁰ son, independientemente, hidrógeno o alquilo, o R⁹ y R¹⁰ junto con el átomo de nitrógeno al que están ligados forman un heterociclilo opcionalmente sustituido con uno o dos sustituyentes seleccionados entre alquilo y heterociclilo)), cicloalquilo (opcionalmente sustituido con uno o dos sustituyentes seleccionados independientemente entre halo, alquilo, alcoxialquilo y arilo; o donde dos sustituyentes adyacentes del cicloalquilo junto con los átomos de carbono a los que están ligados forman un grupo heterociclilo), heterociclilalquilo, heterociclilo (donde heterociclilo y heterociclilo en heterociclilalquilo están opcionalmente sustituidos con uno, dos o tres sustituyentes, donde dos de los sustituyentes opcionales se seleccionan, independientemente entre alquilo, alcoxilo, hidroxilo, halo, amino y oxo, y uno de los sustituyentes opcionales es alquilo, hidroxialquilo, alcoxilo, alcoxialquilo, acilo, haloalquilo, alquilsulfonilo, alcoxicarbonilo o heterociclilo donde el heterociclilo está sustituido con uno o dos sustituyentes independientemente seleccionados entre hidrógeno, alquilo, halo, hidroxilo y alcoxilo), o -(alquilén)-NR⁶R⁷ (donde R⁶ y R⁷ son, independientemente, hidrógeno, alquilo, haloalquilo, hidroxialquilo, alcoxialquilo, cicloalquilo o heterociclilo donde el heterociclilo está opcionalmente sustituido con uno o dos sustituyentes seleccionados independientemente entre alquilo, halo, hidroxilo, hidroxialquilo, alcoxialquilo, acilo y alcoxicarbonilo; o R⁶ y R⁷ junto con el átomo de nitrógeno al que están ligados forman un resto de fórmula (3) ó (4) donde uno o dos de X¹, X² y X³ son nitrógeno y el resto son carbono, y el anillo está opcionalmente sustituido con uno o dos sustituyentes seleccionados independientemente entre alquilo, haloalquilo, y halo); y/o una sal farmacéuticamente aceptable del mismo con la condición de que: cuando A es -N-, entonces Rᵃ es ciano y Rᶜ es heterocicloaminoalquilo donde el heterocicloamino en heterocicloaminoalquilo está opcionalmente sustituido con uno o dos sustituyentes seleccionados independientemente entre alquilo, alcoxilo, hidroxilo, halo, amino y oxo, y el átomo de nitrógeno del heterocicloamino está sustituido con heterociclilo donde el heterociclilo está sustituido con uno o dos sustituyentes seleccionados independientemente entre hidrógeno, alquilo, halo, hidroxilo y alcoxilo.Claim 1: A compound of the formula (1), characterized in that: R¹ and R² are, independently, hydrogen, alkyl, alkoxy, haloalkyl or halo; X is -O-, -CONR-, -NRCO-, or -NR-CO-NR where R and R are independently hydrogen or alkyl; Ar heteroaryl or phenyl wherein the heteroaryl and phenyl are optionally substituted with one, two or three substituents independently selected from alkyl, halo, haloalkyl, alkoxy and hydroxyl; A is -N- or -CR³- where R³ is hydrogen, alkyl, cyclopropyl, halo, haloalkyl, haloalkoxy, alkoxy or cyano; And it is a bond or alkylene; the Z ring is heterocycloamino optionally substituted with one or two substituents independently selected from alkyl, hydroxyl, alkoxy and fluoro; R⁵ is a group of the formula (i), (ii), (iii) or (iv) selected from the group of formulas (2), where: Rᵃ is hydrogen, fluoro or cyano; with the proviso that, when Rᵃ is cyano, then Rᵇ is hydrogen and Rᶜ is not hydrogen; Rᵇ is hydrogen or alkyl; and Rᶜ is hydrogen, hydroxyalkyl, alkoxyalkyl, alkyl (optionally substituted with one or two substituents independently selected from hydroxyl, hydroxyalkyl, heteroaryl (optionally substituted with one or two substituents independently selected from alkyl and heterocyclyl where heterocyclyl is optionally substituted with one or two substituents independently selected from halo and alkyl), and -CONR⁹R¹⁰ (where R⁹ and R¹⁰ are, independently, hydrogen or alkyl, or R⁹ and R¹⁰ together with the nitrogen atom to which they are attached form a heterocyclyl optionally substituted with one or two substituents selected from alkyl and heterocyclyl)), cycloalkyl (optionally substituted with one or two substituents independently selected from halo, alkyl, alkoxyalkyl and aryl; or where two adjacent cycloalkyl substituents together with the carbon atoms to which they are attached form a he group tert-cyclyl), heterocyclylalkyl, heterocyclyl (where heterocyclyl and heterocyclyl in heterocyclylalkyl are optionally substituted with one, two or three substituents, where two of the optional substituents are independently selected from alkyl, alkoxy, hydroxyl, halo, amino and oxo, and one of Optional substituents are alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, acyl, haloalkyl, alkylsulfonyl, alkoxycarbonyl or heterocyclyl where the heterocyclyl is substituted with one or two substituents independently selected from hydrogen, alkyl, halo, hydroxyl and alkoxy), or - (alkylene) -NR⁶R⁷ (where R⁶ and R⁷ are independently hydrogen, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl or heterocyclyl where the heterocyclyl is optionally substituted with one or two substituents independently selected from alkyl, halo, hydroxyl, hydroxyalkyl, alkoxyalkyl, acyl and alkoxycarbonyl; or R⁶ and R⁷ together with the nitrogen atom to which they are attached form a residue of formula (3) or (4) where one or two of X¹, X² and X³ are nitrogen and the rest are carbon, and the ring is optionally substituted with one or two substituents independently selected from alkyl, haloalkyl, and halo); and / or a pharmaceutically acceptable salt thereof with the proviso that: when A is -N-, then Rᵃ is cyano and Rᶜ is heterocycloaminoalkyl where the heterocyclocycloinoino in heterocycloaminoalkyl is optionally substituted with one or two substituents independently selected from alkyl, alkoxy, hydroxyl, halo, amino and oxo, and the heterocycle cycloamine nitrogen atom is substituted with heterocyclyl where the heterocyclyl is substituted with one or two substituents independently selected from hydrogen, alkyl, halo, hydroxyl and alkoxy.

ARP160101618A 2015-06-03 2016-06-02 THYROSINE KINASE INHIBITORS AR104865A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201562170547P 2015-06-03 2015-06-03

Publications (1)

Publication Number Publication Date
AR104865A1 true AR104865A1 (en) 2017-08-23

Family

ID=59724528

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP160101618A AR104865A1 (en) 2015-06-03 2016-06-02 THYROSINE KINASE INHIBITORS

Country Status (3)

Country Link
AR (1) AR104865A1 (en)
EC (1) ECSP18000097A (en)
MA (1) MA45367B1 (en)

Also Published As

Publication number Publication date
ECSP18000097A (en) 2018-10-31
MA45367B1 (en) 2021-09-30

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