AR089667A1 - PYRIMIDINE PIRROLO DERIVATIVES AS SELECTIVE BTK INHIBITORS - Google Patents

PYRIMIDINE PIRROLO DERIVATIVES AS SELECTIVE BTK INHIBITORS

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Publication number
AR089667A1
AR089667A1 ARP130100040A AR089667A1 AR 089667 A1 AR089667 A1 AR 089667A1 AR P130100040 A ARP130100040 A AR P130100040A AR 089667 A1 AR089667 A1 AR 089667A1
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AR
Argentina
Prior art keywords
halogen
hydroxy
optionally substituted
alkyl
hydrogen
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Spanish (es)
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Novartis Ag
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.)
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Application filed by Novartis Ag filed Critical Novartis Ag
Priority to ARP130100040 priority Critical patent/AR089667A1/en
Publication of AR089667A1 publication Critical patent/AR089667A1/en

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Abstract

La presente descripción describe derivados pirrolo pirimidina y sus sales farmacéuticamente aceptables las cuales parece que interactúan con tirosina quinasa de Bruton (Btk). Por consiguiente, estas pirrolo pirimidinas pueden ser eficaces en el tratamiento de enfermedades autoinmunes, enfermedades inflamatorias, enfermedades alérgicas, enfermedades de las vías respiratorias, tal como asma y enfermedad pulmonar obstructiva crónica (EPOC), rechazo de trasplante, cánceres por ej. de origen hematopoyético o tumores sólidos. Reivindicación 1: Un compuesto de fórmula (1) o una sal farmacéuticamente aceptable del mismo; donde, R¹ es hidrógeno, alquilo C₁₋₆ opcionalmente sustituido por hidroxi; R² es hidrógeno o halógeno; R³ es hidrógeno o halógeno; R⁴ es hidrógeno, R⁵ es fenilo opcionalmente sustituido por halógeno; SF₅; NR⁶R⁷; hidroxi; alcoxi C₁₋₆; alquenilo C₁₋₆; alquil C₁₋₆carbonilo; alquilo C₁₋₆ opcionalmente sustituido por hidroxi, halógeno, o alcoxi C₁₋₆; o cicloalquilo C₃₋₆ opcionalmente sustituido por halógeno, hidroxi, o alquilo C₁₋₆ opcionalmente sustituido por halógeno; o R⁵ es un sistema anular mono o bicíclico de 4 - 14 miembros heterociclilo o heteroarilo que comprende 1, 2 ó 3 heteroátomos seleccionados entre N, S y O estando ese anillo opcionalmente sustituido por halógeno; hidroxi; alcoxi C₁₋₆ opcionalmente sustituido por hidroxi o halógeno; o alquilo C₁₋₆ opcionalmente sustituido por hidroxi o halógeno; o R⁴ y R⁵ junto con los átomos a los cuales están unidos forman un anillo piperidona, que opcionalmente comprende un anillo fenilo anular, estando cualquiera de dichos anillos opcionalmente sustituido por alquilo C₁₋₆, alcoxi C₁₋₆, o cicloalquilo C₃₋₆ cada uno de los cuales miembros de sustitución puede opcionalmente ser sustituido por halógeno o hidroxi; R⁶ y R⁷ se seleccionan independientemente entre hidrógeno o alquilo C₁₋₆; o R⁶ y R⁷ junto con el átomo de nitrógeno al cual están unidos forman un anillo azacicloalcano saturado de 4 - 8 miembros, opcionalmente sustituido por halógeno, hidroxi o alquilo C₁₋₆; X es O, S(O)ₙ donde n es 0, 1 ó 2, o un resto de fórmula (2) donde q es 2 ó 3, y R¹⁰ está ausente; o X es CH o N; y R¹⁰ es hidrógeno, hidroxi, -NR⁶R⁷, -CO-R¹¹, -S(O)ₚ-R¹² donde p es 1 ó 2, R¹¹ es alquilo C₁₋₆ opcionalmente sustituido por hidroxi, ciano, halógeno, carboxi o alcoxi C₁₋₆carboniloxi; o NR⁶R⁷; y R¹² es alquilo C₁₋₆ o NR⁶R⁷.The present description describes pyrrolo pyrimidine derivatives and their pharmaceutically acceptable salts which appear to interact with Bruton tyrosine kinase (Btk). Consequently, these pyrrolo pyrimidines can be effective in the treatment of autoimmune diseases, inflammatory diseases, allergic diseases, respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), transplant rejection, cancers e.g. Hematopoietic origin or solid tumors. Claim 1: A compound of formula (1) or a pharmaceutically acceptable salt thereof; where, R¹ is hydrogen, C₁₋₆ alkyl optionally substituted by hydroxy; R² is hydrogen or halogen; R³ is hydrogen or halogen; R⁴ is hydrogen, R⁵ is phenyl optionally substituted by halogen; SF₅; NR⁶R⁷; hydroxy; C₁₋₆ alkoxy; C₁₋₆ alkenyl; C₁₋₆carbonyl alkyl; C₁₋₆ alkyl optionally substituted by hydroxy, halogen, or C₁₋₆ alkoxy; or C₃₋₆ cycloalkyl optionally substituted by halogen, hydroxy, or C₁₋₆ alkyl optionally substituted by halogen; or R⁵ is a 4- or 14-membered heterocyclyl or heteroaryl mono or bicyclic ring system comprising 1, 2 or 3 heteroatoms selected from N, S and O with that ring being optionally substituted by halogen; hydroxy; C₁₋₆ alkoxy optionally substituted by hydroxy or halogen; or C₁₋₆ alkyl optionally substituted by hydroxy or halogen; or R⁴ and R⁵ together with the atoms to which they are attached form a piperidone ring, which optionally comprises an annular phenyl ring, any of said rings being optionally substituted by C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₃₋₆ cycloalkyl each one of which substitution members may optionally be substituted by halogen or hydroxy; R⁶ and R⁷ are independently selected from hydrogen or C₁₋₆ alkyl; or R⁶ and R⁷ together with the nitrogen atom to which they are attached form a 4-8 membered saturated azacycloalkane ring, optionally substituted by halogen, hydroxy or C₁₋₆ alkyl; X is O, S (O) ₙ where n is 0, 1 or 2, or a remainder of formula (2) where q is 2 or 3, and R¹⁰ is absent; or X is CH or N; and R¹⁰ is hydrogen, hydroxy, -NR⁶R⁷, -CO-R¹¹, -S (O) ₚ-R¹² where p is 1 or 2, R¹¹ is C₁₋₆ alkyl optionally substituted by hydroxy, cyano, halogen, carboxy or C₁₋ alkoxy Boncarbonyloxy; or NR⁶R⁷; and R¹² is C₁₋₆ or NR⁶R⁷ alkyl.

ARP130100040 2013-01-04 2013-01-04 PYRIMIDINE PIRROLO DERIVATIVES AS SELECTIVE BTK INHIBITORS AR089667A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
ARP130100040 AR089667A1 (en) 2013-01-04 2013-01-04 PYRIMIDINE PIRROLO DERIVATIVES AS SELECTIVE BTK INHIBITORS

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ARP130100040 AR089667A1 (en) 2013-01-04 2013-01-04 PYRIMIDINE PIRROLO DERIVATIVES AS SELECTIVE BTK INHIBITORS

Publications (1)

Publication Number Publication Date
AR089667A1 true AR089667A1 (en) 2014-09-10

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ARP130100040 AR089667A1 (en) 2013-01-04 2013-01-04 PYRIMIDINE PIRROLO DERIVATIVES AS SELECTIVE BTK INHIBITORS

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