AR074506A1 - Moduladores de los receptores tipo toll - Google Patents

Moduladores de los receptores tipo toll

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Publication number
AR074506A1
AR074506A1 ARP090104738A AR074506A1 AR 074506 A1 AR074506 A1 AR 074506A1 AR P090104738 A ARP090104738 A AR P090104738A AR 074506 A1 AR074506 A1 AR 074506A1
Authority
AR
Argentina
Prior art keywords
substituted
heteroalkyl
heterocyclyl
carbocyclyl
alkyl
Prior art date
Application number
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English (en)
Original Assignee
Gilead Sciences Inc
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Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=41621203&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR074506(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc
Publication of AR074506A1 publication Critical patent/AR074506A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D475/00—Heterocyclic compounds containing pteridine ring systems
    • C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/527—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim spiro-condensed
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
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    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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    • 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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    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
    • A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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    • 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
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • A61K31/708—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
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    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D475/08—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
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Abstract

Sus sales aceptables desde el punto de vista farmacéutico, composiciones que contienen compuestos, y métodos terapéuticos que incluyen la administración de dichos compuestos. Reivindicación 1: Un compuesto de fórmula (1), o una de sus sales o ésteres aceptables desde el punto de vista farmacéutico, en los cuales: Y-Z es -CR4R5-, -CR4R5-CR4R5-, -C(O)CR4R5-, -CR4R5C(O)-, -NR8C(O)-, -C(O)NR8-, -CR4R5S(O)2-, o -CR5=CR5-; L1 es -NR8-, -O-, -S-, -N(R8)C(O)-, -S(O)2-, -S(O)-, -C(O)N(R8)-, -N(R8)S(O)2-, -S(O)2N(R8)- o un enlace covalente; R1 es alquilo, alquilo sustituido, haloalquilo, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, heteroalquilo, heteroalquilo sustituido, carbociclilo, carbociclilo sustituido, carbociclilalquilo, carbociclilalquilo sustituido, heterociclilo, heterociclilo sustituido, heterociclilalquilo, o heterociclilalquilo sustituido, arilalquilo, arilalquilo sustituido, heteroarilalquilo, heteroarilalquilo sustituido, carbociclilheteroalquilo, carbociclilheteroalquilo sustituido, heterociclil heteroalquilo, heterociclil heteroalquilo sustituido, aril heteroalquilo, aril heteroalquilo sustituido, heteroaril heteroalquilo, o heteroaril heteroalquilo sustituido; X1 es alquileno, alquileno sustituido, hetero alquileno, hetero alquileno sustituido, alquenileno, alquenileno sustituido, alquinileno, alquinileno sustituido, carbociclileno, carbociclileno sustituido, heterociclileno, heterociclileno sustituido, -NR8-, -O-, -C(O)-, -S(O)-, -S(O)2-, o un enlace; D es carbociclilo, carbociclilo sustituido, heterociclilo o heterociclilo sustituido, en el cual dicho carbociclilo, carbociclilo sustituido, heterociclilo o heterociclilo sustituido, está sustituido con uno o dos -L2-NR6R7; o D es heterociclilo, heterociclilo sustituido, heteroarilo o heteroarilo sustituido en el cual dicho heterociclilo, heterociclilo sustituido, heteroarilo o heteroarilo sustituido comprende 1 a 4 átomos de N; cada L2 es en forma independiente alquileno, alquileno sustituido, hetero alquileno, hetero alquileno sustituido, o un enlace covalente; cada R3 es en forma independiente halógeno, ciano, azido, nitro, alquilo, alquilo sustituido, hidroxilo, amino, heteroalquilo, heteroalquilo sustituido, alcoxi, haloalquilo, haloalcoxi, -CH, -C(O)OR8, -S(O)R8, -S(O)2R8, -C(O)NR9R10, -N(R9)C(O)R8, carbociclilo, carbociclilo sustituido, carbociclilalquilo, carbociclilalquilo sustituido, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, -S(O)2NR9R10, -N(R9)S(O)2R8, -N(R9)S(O)2OR10, -OS(O)2NR9R10; n es 0, 1, 2, 3, 4 o 5; R4 y R5 son cada uno en forma independiente H, alquilo, alquilo sustituido, haloalquilo, heteroalquilo, heteroalquilo sustituido, carbociclilo, carbociclilo sustituido, carbociclilalquilo, carbociclilalquilo sustituido, heterociclilo, heterociclilo sustituido, heterociclilalquilo, heterociclilalquilo sustituido, arilalquilo, arilalquilo sustituido, heteroarilalquilo, heteroarilalquilo sustituido, carbociclilheteroalquilo, carbociclilheteroalquilo sustituido, heterociclil heteroalquilo, heterociclil heteroalquilo sustituido, aril heteroalquilo, aril heteroalquilo sustituido, heteroaril heteroalquilo, o heteroaril heteroalquilo sustituido, ciano, azido, OR8, -C(O)H, C(O)R8, -S(O)R8, -S(O)2R8, -C(O)OR8, o -C(O)NR9R10; o R4 y R5, tomados junto con el carbono al cual ambos están unidos, forman un carbociclo, carbociclo sustituido, heterociclo o heterociclo sustituido; o R4 y R5, cuando están en el mismo átomo de carbono, tomados junto con el carbono al cual están unidos son -C(O)- o -C(NR8)-; o dos R4 o dos R5 en átomos de carbono adyacentes cuando se los toma junto con los carbonos a los cuales están unidos forman un carbociclo de 3 a 6 miembros, carbociclo sustituido, heterociclo o heterociclo sustituido; R6 y R7 son cada uno en forma Independiente H, alquilo, alquilo sustituido, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, haloalquilo, heteroalquilo, heteroalquilo sustituido, carbociclilo, carbociclilo sustituido, carbociclilalquilo, carbociclilalquilo sustituido, heterociclilo, heterociclilo sustituido, heterociclilalquilo, heterociclilalquilo sustituido, arilalquilo, arilalquilo sustituido, heteroarilalquilo, heteroarilalquilo sustituido, carbociclilheteroalquilo, carbociclilheteroalquilo sustituido, heterociclil heteroalquilo, heterociclil heteroalquilo sustituido, aril heteroalquilo, aril heteroalquilo sustituido, heteroaril heteroalquilo, o heteroaril heteroalquilo sustituido, -C(O)H, -C(O)R8, -S(O)R8, -S(O)2R8, -C(O)OR8, o -C(O)NR9R10, -S(O)2NR9R10; o R6 y R7, tomados junto con el nitrógeno al cual ambos están unidos, forman un heterociclo sustituido o no sustituido, que puede contener uno o más heteroátomos adicionales seleccionados de N, O, P, o S; o R7 tomados junto con L2, y el N al cual ambos están unidos, forma un heterociclo de 3 a 8 miembros sustituido o no sustituido que puede contener uno o más heteroátomos adicionales seleccionados de N, O, S, o P; R8 es H, alquilo, alquilo sustituido, haloalquilo, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, heteroalquilo, heteroalquilo sustituido, carbociclilo, carbociclilo sustituido, carbociclilalquilo, carbociclilalquilo sustituido, heterociclilo, heterociclilo sustituido, heterociclilalquilo, heterociclilalquilo sustituido, arilalquilo, arilalquilo sustituido, heteroarilalquilo, heteroarilalquilo sustituido, carbociclilheteroalquilo, carbociclilheteroalquilo sustituido, heterociclil heteroalquilo, heterociclil heteroalquilo sustituido, aril heteroalquilo, aril heteroalquilo sustituido, heteroaril heteroalquilo, o heteroaril heteroalquilo sustituido; y R9 y R10 son cada uno en forma independiente H, alquilo, alquilo sustituido, alquenilo, alquenilo sustituido, alquinilo, alquinilo sustituido, haloalquilo, heteroalquilo, heteroalquilo sustituido, carbociclilo, carbociclilo sustituido, carbociclilalquilo, carbociclilalquilo sustituido, heterociclilo, heterociclilo sustituido, heterociclilalquilo, heterociclilalquilo sustituido, arilalquilo, arilalquilo sustituido, heteroarilalquilo, heteroarilalquilo sustituido, carbociclilheteroalquilo, carbociclilheteroalquilo sustituido, heterociclil heteroalquilo, heterociclil heteroalquilo sustituido, aril heteroalquilo, aril heteroalquilo sustituido, heteroaril heteroalquilo, o heteroaril heteroalquilo sustituido; o R9 y R10, tomados junto con el nitrógeno al cual ambos están unidos forman un heterociclo sustituido o no sustituido; en el cual cada alquilo sustituido, alquenilo sustituido, alquinilo sustituido, heteroalquilo sustituido, carbociclilo sustituido, carbociclilalquilo sustituido, heterociclilo sustituido, heterociclilalquilo sustituido, arilalquilo sustituido, heteroarilalquilo sustituido, carbociclilheteroalquilo sustituido, heterociclil heteroalquilo sustituido, aril heteroalquilo sustituido, heteroaril heteroalquilo sustituido, alquileno sustituido, hetero alquileno sustituido, alquenileno sustituido, alquinileno sustituido, carbociclileno sustituido, o heterociclileno sustituido está sustituido en forma independiente con uno a cuatro sustituyentes seleccionados del grupo que consiste en -halógeno, -R, -O- , =O, -OR. -SR, -S-, -NR2, -N(+)R3, =NR, -C(halógeno)3, -CR(halógeno)2, -CR2(halógeno), -CN, -OCN, -SCN, -N=C=O, -NCS, -NO, -NO2, =N2, -N3, -NRC(=O)R, -NRC(=O)OR, -NRC(=O)NRR, -C(=O)NRR, -C(=O)OR, -OC(=O)NRR, -OC(=O)OR, -C(=O)R, -S(=O)2OR, -S(=O)2R, -OS(=O)2OR, -S(=O)2NR, -S(=O)R, -NRS(=O)2R, -NRS(=O)2NRR. -NRS(=O)2OR, -OP(=O)(OR)2, -P(=O)(OR)2, -P(O)(OR)(O)R, -C(=O)R, -C(=S)R, -C(=O)OR, -C(=S)OR, -C(=O)SR, -C(=S)SR, -C(=O)NRR, -C(=S)NRR, -C(=NR)NRR, y -NRC(=NR)NRR; en el cual cada R es en forma independiente H, alquilo, cicloalquilo, arilo, arilalquilo, o heterociclilo.
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