AR077025A1 - Compuestos tetraciclicos - Google Patents

Compuestos tetraciclicos

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Publication number
AR077025A1
AR077025A1 ARP100102015A ARP100102015A AR077025A1 AR 077025 A1 AR077025 A1 AR 077025A1 AR P100102015 A ARP100102015 A AR P100102015A AR P100102015 A ARP100102015 A AR P100102015A AR 077025 A1 AR077025 A1 AR 077025A1
Authority
AR
Argentina
Prior art keywords
group
alkyl
substituted
groups
amino
Prior art date
Application number
ARP100102015A
Other languages
English (en)
Inventor
Kazutomo Kinoshita
Kohsuke Asoh
Noriyuki Furuichi
Toshiya Ito
Hatsuo Kawada
Nobuya Ishii
Hiroshi Sakamoto
Woo Sang Hong
Min Jeong Park
Yoshiyuki Ono
Yasuharu Kato
Kenji Morikami
Takashi Emura
Nobuhiro Oikawa
Original Assignee
Chugai Pharmaceutical Co Ltd
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=43308919&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR077025(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Chugai Pharmaceutical Co Ltd filed Critical Chugai Pharmaceutical Co Ltd
Publication of AR077025A1 publication Critical patent/AR077025A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/58—[b]- or [c]-condensed
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A—HUMAN NECESSITIES
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
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    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
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    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
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    • C07D209/80—[b, c]- or [b, d]-condensed
    • C07D209/82—Carbazoles; Hydrogenated carbazoles
    • C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
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Abstract

Es de utilidad como un inhibidor de ALK, y util para la profilaxis o el tratamiento de una enfermedad acompanada de anomalías de ALk, por ejemplo, cáncer, metástasis de cáncer, depresion o un trastorno de la funcion cognitiva. Reivindicacion 1: A compuesto o su sal o solvato caracterizado porque se representa con la formula (1) [donde, A1, A2, A3, A4, A7, A8, A9 y A10 todos representan C, o cualquiera de A2, A3, A4, A7, A8 y A9 representa N (con la salvedad de que, cuando representa N, no existe un grupo sustituyente para el mismo) y los restantes representan C; A5 se selecciona entre NR5, O y S; R1 y R10 representa cada uno en forma independiente [1] un átomo de hidrogeno, [2] un grupo ciano, [3] un átomo de halogeno o [4] un grupo heterocicloalquilo de entre 4 y 10 miembros que puede estar sustituido con uno o más grupos heterocicloalquilo de entre 4 y 10 miembros; R2 se selecciona entre el grupo que consiste en: (1) un átomo de hidrogeno, (2) un grupo alquilo C1-8, (3) un grupo alquenilo C2-8, (4) un grupo alquinilo C2-8, (5) un grupo ciano, (6) un átomo de halogeno, (7) un grupo (alquilo C1-8) m2-amino que puede estar sustituido con uno o más grupos alquilsulfonilo C1-8, m2: 0-2, y (8) un grupo nitro; R3 se selecciona entre el grupo que consiste en: (1) un átomo de hidrogeno, (2) un grupo alquilo C1-8 que puede estar sustituido con [1] uno o más átomos de halogeno, [2] uno o más grupos hidroxilo o [3] uno o más grupos alcoxilo C1-8, (3) un grupo arilo C6-10, (4) un grupo ciano, (5) un grupo alcanoilo C1-8 que puede estar sustituido con uno o más grupos arilo C6-10, (6) un grupo (alquil C1-8)m3a-aminocarboniIo que puede estar sustituido con uno o más R3A, R3A: [1] un grupo arilo C6-10, [2] un grupo alcoxilo C1-8, [3] un grupo heteroarilo de entre 5 y 14 miembros, o [4] un grupo arilsulfonilo C6-10, m3a: 0-2, (7) un grupo hidroxicarbonilo, (8) un grupo alcoxicarbonilo C1-8 que puede estar sustituido con [1] uno o más grupos hidroxilo o [2] uno o más grupos alcoxilo C1-8, (9) un átomo de halogeno, (10) un grupo (alquil C1-8)m3b-amino que puede estar sustituido con uno o más grupos arilo C6-10, m3b: 0-2, (11) un grupo alquilcarbonil C1-8(alquil C0-8)amino que puede estar sustituido con [1] uno o más grupos arilo C6-10 o [2] uno más grupos ariloxi C6-10, (12) un grupo arilcarbonil c6-10(alquil C0-8)amino que puede estar sustituido con uno o más grupos alquilo C1-8 que puede estar sustituido con uno o más átomos de halogeno, (13) un grupo (alquil C1-8)m3c-aminocarbonil (alquil C0-8) amino que puede estar sustituido con uno o más grupos arilo C6-10, m3c: 0-2, (14) un grupo nitro, (15) un grupo hidroxilo, (16) un grupo alcoxilo C1-8 que puede estar sustituido con uno o más R3B, R3B [1] un grupo hidroxilo, [2] un grupo alcoxilo C1-8, [3] un grupo arilo C6-10(alquil C0-8) aminocarbonilo, [4] un grupo (alquil C1-8)m3d-amino, o [5] un átomo de halogeno, m3d: 0-2, (17) un grupo heterocicloalquiloxi de entre 4 y 10 miembros, (18) un grupo heteroariloxi de entre 4 y 14 miembros, (19) un grupo (alquil C1-8)m3e-aminocarboniloxi que puede estar sustituido con uno o más grupos arilo C6-10, m3e: 0-2, (20) un grupo heterocicloalquilcarbonilo de entre 4 y 10 miembros con contenido de nitrogeno, (21) un grupo alquilsulfoniloxi C1-8 que puede estar sustituido con uno o más átomos de halogeno, (22) un grupo alquiltio C1-8, (23) un grupo alquilsulfonilo C1-8que puede estar sustituido con uno o más grupos arilo C6-10, (24) un grupo heteroarilo de entre 5 y 14 miembros que puede estar sustituido con uno o más grupos alquilo C1-8que puede estar sustituido con uno o más grupos alcoxilo C1-8, (25) un grupo alcoxicarbonil C1-8(alquil C0-8) amino que puede estar sustituido con uno o más grupos alcoxilo C1-8, (26) un grupo ariloxicarbonil C6-10(alquil C0-8) amino que puede estar sustituido con uno o más grupos alquilo C1-8 que puede estar sustituido con uno o más átomos de halogeno, (27) un grupo arilo C6-10(alquil C0-8) aminocarbonil (alquil C0-8) amino que puede estar sustituido con uno o más R3c, R3c: [1] un grupo alquilo C1-8que puede estar sustituido con uno o más átomos de halogeno, o [2] un grupo alcoxilo C1-8, (28) un grupo cicloalquilo C3-8(alquil C0-8) aminocarboniloxi, y (29) un grupo arilo C6-10(alquil C0-8) aminocarboniloxi que puede estar sustituido con uno o más sustituyentes seleccionados del grupo que consiste en [1] un grupo alquilo C1-8 y [2] un grupo alcoxi C1-8; R4 se selecciona entre el grupo que consiste en: (1) un átomo de hidrogeno, (2) un grupo alquilo C1-8 que puede estar sustituido con uno o más átomos de halogeno, (3) un grupo alquenilo C2-8, (4) un grupo alquinilo C2-8, (5) un grupo cicloalquilo C3-8, (6) un grupo ciano, (7) un grupo aminocarbonilo, (8) un grupo (alquil c1-8)m4a-aminocarbonilo, m4a: 1-2, (9) un grupo hidroxicarbonilo, (10) un grupo alcoxicarbonilo C1-8, (11) un átomo de halogeno, (12) un grupo (alquil C1-8)m4b-amino, m4b: 0-2, (13) un grupo hidroxilo, y (14) un grupo alcoxilo C1-8 que puede estar sustituido con uno o más grupos hidroxilo; R5 se selecciona entre el grupo que consiste en: (1) un átomo de hidrogeno, (2) un grupo alquilo C1-8 que puede estar sustituido con uno o más R5A, R5A: [1] un grupo hidroxicarbonilo, [2] un grupo alcoxicarbonilo C1-8, [3] un grupo hidroxilo, [4] un grupo alcoxilo C1-8, [5] un grupo (alquil C1-8)m5-amino, [6] un grupo arilo C6-10, o [7] un grupo alquiltio C1-8, m5: 0-2, (3) un grupo alquenilo C2-8, (4) un grupo alquinilo C2-8, (5) un grupo cicloalquilo C3-8, y (6) un grupo alquilsulfonilo C1-8; R6 y R6' se seleccionan en forma independiente entre sí entre el grupo que consiste en: (1) un grupo alquilo C1-8 que puede estar sustituido con uno o más átomos de halogeno, (2) un grupo alquenilo C2-8, y (3) un grupo alquinilo C2-8; o R6 y R6' se toman junto con los átomos de carbono a los cuales están unidos para formar: (4) un grupo cicloalquilo C3-8, o (5) un grupo heterocicloalquilo de entre 4 y 10 miembros que puede estar sustituido con uno o más grupos alquilo C1-8-aril C6-10 sulfonilo que puede estar sustituido con uno o más grupos alquilo C1-8; R7 se selecciona entre el grupo que consiste en: (1) un átomo de hidrogeno, (2) un átomo de halogeno, (3) un grupo alcoxilo C1-8 que puede estar sustituido con uno o más R7A, R7A: [1] un grupo (alquil C1-8){3m7a-amino, [2] un hidroxilo, [3] un grupo heterocicloalquilo de entre 4 y 10 miembros que puede estar sustituido con uno o más grupos alquilo C1-8, m7a: 0-2, (4) un grupo alquilsulfonilo C4-8, (5) un grupo nitro, y (6) un grupo hidroxilo; R8 se selecciona entre el grupo que consiste en: (1) un átomo de hidrogeno, (2) un grupo alquilo C1-8 que puede estar sustituido con uno o más R8A, R8A: [1] un grupo heterocicloalquilo de entre 4 y 10 miembros que puede estar sustituido con uno o más R8A1, [2] un grupo (alquil C1-8)m8a-amino que puede estar sustituido con un átomo de halogeno, o [3] un grupo hidroxilo, m8a:0-2, R8A1: [1] un grupo alquilo C1-8, [2] un grupo alquilsulfonilo C1-8, [3] un grupo (alquil C1-8)m8b- aminosulfonilo, [4] un grupo oxo, [5] un grupo alcoxicarbonilo C1-8, o [6] un grupo alcoxicarbonil C1-8 (alquil C0-8) aminosulfonilo, m8b: 0-2, (3) un grupo alquenilo C2-8, (4) un grupo heterocicloalquilo de entre 4 y 10 miembros que puede estar sustituido con uno o más R8B, R8B: un grupo alquilo C1-8 que puede estar sustituido con uno o más R8B1, un grupo alquenilo C2-8, un grupo alquinilo C2-8, un grupo cicloalquilo C3-8 que puede estar sustituido con [1] uno o más grupos ciano o [2] uno o más grupos alquilo C1-8, un grupo heterocicloalquilo de entre 4 y 10 miembros que puede estar sustituido con uno o más R8B2, un grupo alcoxilo C1-8 que puede estar sustituido con uno o más sustituyentes seleccionados del grupo que consiste en [1] un grupo alcoxilo C1-8 y [2] un grupo cicloalquilo C3-8, un grupo alcoxicarbonilo C1-8, un grupo alquilsulfonilo C1-8, un grupo heteroarilsulfonilo de entre 5 y 14 miembros, un grupo oxo, un grupo ciano, un grupo alcanoilo C1-8 que puede estar sustituido con uno o más R8B3, un grupo cicloalquilcarbonilo C3-8, un grupo (alquil C1-8)m8c-aminosulfonilo, un grupo alquilsulfonil C1-8(alquil C0-8) amino, un grupo (alquil C1-8)m8d-amino que puede estar sustituido con uno o más R8B4, un grupo hidroxilo, un grupo (alquil C1-8)m8e-aminocarbonilo, o un grupo alcoxicarbonil C1-8(alquil C0-8) amino m8c: 0-2, m8d: 0-2, m8e 0-2, R8B1: [1] un grupo cicloalquilo C3-8, [2] un grupo hidroxilo, o [3] uno o más grupos alcoxi C1-8, R882: [1] un átomo de halogeno, [2] un grupo alquilo C1-8, [3] un grupo oxo, [4] un grupo hidroxilo, o [5] un átomo de deuterio, R8B3: un grupo (alquil C1-8)m8f-amino, m8f: 0-2, R8B4: [1] un grupo cicloalquilo C3-8, o [2] un grupo hidroxilo, (5) un grupo heteroarilo de entre 5 y 14 miembros que puede estar sustituido con un grupo alquilo C1-8, (6) un grupo ( alquil C1-8)m8g-aminocarbonilo que puede estar sustituido con uno o más R8C, m8g: 0-2, R8C:[1] un grupo hidroxilo, [2] un grupo (alquil C1-8)m8h-amino que puede estar sustituido con uno o más sustituyentes seleccionados del grupo que consiste en un grupo (alquil C1-8)m8j-aminosulfonilo, un grupo alquilsulfonilo C1-8, un grupo alcoxicarbonilo C1-8 y un grupo alcoxicarbonil C1-8(alquil C0-8) aminosulfonilo, [3] un grupo alquilsulfonilo C1-8, o [4] un grupo alcoxilo C1-8 que puede estar sustituido con un grupo hidroxilo, m8h: 0-2, m8i: 0-2, (7) un grupo heterocicloalquilo (alquil C0-8) aminocarbonilo de entre 4 y 10 miembros que puede estar sustituido con uno o más grupos oxo, (8) un grupo heterocicloalquilcarbonilo de entre 4 y 10 miembros con contenido de nitrogeno que puede estar sustituido con uno o más R8D, R8D: [1] un grupo alquilo C1-8 que puede estar sustituido con uno o más R8D1, [2] un grupo hidroxilo, [3] un grupo alquilsulfonilo C1-8, o [4] un grupo alcoxicarbonilo C1-8, R8D1: [1] un grupo hidroxilo, o [2] un grupo alcoxilo C1-8, (9) un grupo hidroxicarbonilo, (10) un grupo alcoxi C0-8 (alquil C0-8) aminocarbon
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