AR096846A1 - Dihidroquinoxalinonas y dihidropiridopirazinonas modificadas como inhibidores de la proteína bet - Google Patents
Dihidroquinoxalinonas y dihidropiridopirazinonas modificadas como inhibidores de la proteína betInfo
- Publication number
- AR096846A1 AR096846A1 ARP140102526A ARP140102526A AR096846A1 AR 096846 A1 AR096846 A1 AR 096846A1 AR P140102526 A ARP140102526 A AR P140102526A AR P140102526 A ARP140102526 A AR P140102526A AR 096846 A1 AR096846 A1 AR 096846A1
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- Prior art keywords
- alkyl
- optionally
- heterocycloalkyl
- monosubstituted
- cycloalkyl
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract 2
- 102000004169 proteins and genes Human genes 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 title 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 23
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract 12
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 8
- 125000004043 oxo group Chemical group O=* 0.000 abstract 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 6
- 229910052739 hydrogen Inorganic materials 0.000 abstract 6
- 239000001257 hydrogen Substances 0.000 abstract 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract 5
- 229910052731 fluorine Inorganic materials 0.000 abstract 5
- 239000011737 fluorine Substances 0.000 abstract 5
- 229910052736 halogen Inorganic materials 0.000 abstract 5
- 150000002367 halogens Chemical class 0.000 abstract 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 abstract 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 3
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 abstract 3
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 3
- 125000004366 heterocycloalkenyl group Chemical group 0.000 abstract 3
- 229910052799 carbon Inorganic materials 0.000 abstract 2
- 150000001721 carbon Chemical group 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 150000002431 hydrogen Chemical group 0.000 abstract 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 abstract 1
- 229940088617 BET protein inhibitor Drugs 0.000 abstract 1
- 108091005625 BRD4 Proteins 0.000 abstract 1
- 102100029895 Bromodomain-containing protein 4 Human genes 0.000 abstract 1
- -1 C4−8-cycloalkenyl Chemical group 0.000 abstract 1
- 208000036142 Viral infection Diseases 0.000 abstract 1
- 230000003143 atherosclerotic effect Effects 0.000 abstract 1
- CPPKAGUPTKIMNP-UHFFFAOYSA-N cyanogen fluoride Chemical compound FC#N CPPKAGUPTKIMNP-UHFFFAOYSA-N 0.000 abstract 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 1
- 230000035558 fertility Effects 0.000 abstract 1
- 125000001072 heteroaryl group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 230000003463 hyperproliferative effect Effects 0.000 abstract 1
- 208000027866 inflammatory disease Diseases 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 1
- 230000001613 neoplastic effect Effects 0.000 abstract 1
- 208000015122 neurodegenerative disease Diseases 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 230000000069 prophylactic effect Effects 0.000 abstract 1
- 229940121649 protein inhibitor Drugs 0.000 abstract 1
- 239000012268 protein inhibitor Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 230000009385 viral infection Effects 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- 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
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61K31/535—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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/44—Benzopyrazines 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 hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Gynecology & Obstetrics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Virology (AREA)
- Pregnancy & Childbirth (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Dihidroquinoxalinonas y dihidropiridopirazinonas inhibidoras de la proteína BET, en especial inhibidoras de BRD4, composiciones farmacéuticas que comprenden a éstos compuestos de la presente y el uso profiláctico y terapéutico de los mismos para casos de trastornos hiperproliferativos, en especial para casos de trastornos neoplásicos. Uso de inhibidores de la proteína BET en infecciones virales, en trastornos neurodegenerativos, en enfermedades inflamatorias, en trastornos ateroescleróticos y en el control de la fertilidad masculina. Reivindicación 1: Compuestos caracterizados porque son de la fórmula general (1) en donde A es -NH-, -N(C₁₋₃-alquilo) o -O-; X es -N- o -CH-; n es 0, 1 ó 2; R¹ es un grupo -C(=O)NR⁷R⁸ o -S(=O)₂NR⁷R⁸, o es heteroarilo monocíclico de 5 miembros que opcionalmente puede estar monosustituido, disustituido o trisustituido en forma idéntica o diferente con halógeno, ciano, C₁₋₄-alquilo, C₂₋₄-alquenilo, C₂₋₄ alquinilo, halo-C₁₋₄-alquilo, C₁₋₄-alcoxi, halo-C₁₋₄-alcoxi, C₁₋₄-alquiltio, halo-C₁₋₄-alquiltio, -NR⁹R¹⁰, -C(=O)OR¹¹, -C(=O)NR⁹R¹⁰, -C(=O)R¹¹, -S(=O)₂R¹¹, -S(=O)₂NR⁹R¹⁰; R² es hidrógeno, halógeno, ciano, C₁₋₃-alquilo, C₂₋₄-alquenilo, C₂₋₄-alquinilo, halo-C₁₋₄-alquilo, C₁₋₄-alcoxi, halo-C₁₋₄-alcoxi, C₁₋₄-alquiltio o halo-C₁₋₄-alquiltio, y, si n es 2, R² puede ser igual o diferente; o R¹ y R² juntos son un grupo *-S(=O)₂NR⁸-CH₂-**, *-S(=O)₂-NR⁸-CH₂-CH₂-**, *-C(=O)-NR⁸-CH₂-** o *-C(=O)-NR⁸-CH₂-CH₂-** en donde "*" denota el punto de unión de R¹ al anillo fenilo en la fórmula (1), y en donde "**" denota un átomo de carbono de este anillo fenilo adyacente a este punto de unión; R³ es metilo o etilo; R⁴ es hidrógeno o C₁₋₃-alquilo; R⁵ es hidrógeno o C₁₋₃-alquilo; o R⁴ y R⁵ junto con el átomo de carbono al cual están unidos son C₃₋₆-cicloalquileno; R⁶ es C₁₋₆alquilo que opcionalmente puede estar monosustituido con C₁₋₃alcoxi, fenilo, C₃₋₈-cicloalquilo, o heterocicloalquilo de entre 4 y 8 miembros, en donde fenilo a su vez puede estar opcionalmente monosustituido, disustituido o trisustituido en forma idéntica o diferente con: halógeno, ciano, C₁₋₄-alquilo, C₂₋₄-alquenilo, C₂₋₄-alquinilo, C₁₋₄-alcoxi, halo-C₁₋₄-alquilo, halo-C₁₋₄-alcoxi, y en donde C₃₋₈-cicloalquilo y heterocicloalquilo de entre 4 y 8 miembros a su vez pueden estar opcionalmente monosustituidos o disustituidos en forma idéntica o diferente con C₁₋₃-alquilo, o es C₃₋₈-cicloalquilo o heterocicloalquilo de entre 4 y 8 miembros, que opcionalmente puede estar monosustituido o disustituido en forma idéntica o diferente con C₁₋₃-alquilo o C₁₋₄-alcoxicarbonilo, o es fenilo que opcionalmente puede estar monosustituido o disustituido en forma idéntica o diferente con halógeno, C₁₋₃-alquilo o heterocicloalquilo de entre 4 y 8 miembros, en donde el heterocicloalquilo de entre 4 y 8 miembros a su vez puede estar opcionalmente monosustituido o disustituido en forma idéntica o diferente con C₁₋₃-alquilo o C₁₋₄-alcoxicarbonilo; R⁷ es hidrógeno, o es C₁₋₆-alquilo que opcionalmente puede estar monosustituido, disustituido o trisustituido en forma idéntica o diferente con: hidroxilo, oxo, flúor, ciano, C₁₋₄-alcoxi, halo-C₁₋₄-alcoxi, -NR⁹R¹⁰, C₃₋₈-cicloalquilo, C₄₋₈-cicloalquenilo, heterocicloalquilo de entre 4 y 8 miembros, heterocicloalquenilo de entre 4 y 8 miembros, -C₅₋₁₁-espirocicloalquilo, C₅₋₁₁-heteroespirocicloalquilo, C₆₋₁₂-cicloalquilo en puente, C₆₋₁₂-heterocicloalquilo en puente, C₆₋₁₂-bicicloalquilo, C₆₋₁₂-heterobicicloalquilo, fenilo, heteroarilo de 5 ó 6 miembros, en donde C₃₋₈-cicloalquilo, C₄₋₈-cicloalquenilo, heterocicloalquilo de entre 4 y 8 miembros, heterocicloalquenilo de entre 4 y 8 miembros, C₅₋₁₁-espirocicloalquilo, C₅₋₁₁-heteroespirocicloalquilo, C₆₋₁₂-cicloalquilo en puente, C₆₋₁₂-heterocicloalquilo en puente, C₆₋₁₂-bicicloalquilo, C₆₋₁₂-heterobicicloalquilo a su vez puede estar opcionalmente monosustituido o disustituido en forma idéntica o diferente con: hidroxilo, flúor, oxo, ciano, C₁₋₃-alquilo, fluoro-C₁₋₃-alquilo, C₃₋₆-cicloalquilo, ciclopropilmetilo, C₁₋₃-alquilcarbonilo, C₁₋₄-alcoxicarbonilo o -NR⁹R¹⁰, y en donde fenilo y heteroarilo de 5 ó 6 miembros opcionalmente puede estar monosustituido o disustituido en forma idéntica o diferente con: halógeno, ciano, trifluorometilo, C₁₋₃-alquilo, C₁₋₃-alcoxi, o es C₃₋₆-alquenilo o C₃₋₆-alquinilo, o es C₃₋₈-cicloalquilo, C₄₋₈-cicloalquenilo, C₅₋₁₁-espirocicloalquilo, C₆₋₁₂-cicloalquilo en puente o C₆₋₁₂-bicicloalquilo, que opcionalmente puede estar monosustituido o disustituido en forma idéntica o diferente con: hidroxilo, oxo, ciano, flúor, C₁₋₃-alquilo, C₁₋₃-alcoxi, trifluorometilo, -NR⁹-R¹⁰, o es heterocicloalquilo de entre 4 y 8 miembros, heterocicloalquenilo de entre 4 y 8 miembros, C₅₋₁₁-heteroespirocicloalquilo, C₆₋₁₂-heterocicloalquilo en puente o C₆₋₁₂-heterobicicloalquilo, que opcionalmente puede estar monosustituido o disustituido en forma idéntica o diferente con: hidroxilo, flúor, oxo, ciano, C₁₋₃-alquilo, fluoro-C₁₋₃-alquilo, C₃₋₆-cicloalquilo, ciclopropilmetilo, C₁₋₃-alquilcarbonilo, C₁₋₄-alcoxicarbonilo o -NR⁹R¹⁰; R⁸ es hidrógeno o C₁₋₃-alquilo opcionalmente sustituido con hidroxilo, oxo o C₁₋₃-alcoxi una o dos veces, en forma idéntica o diferente, o fluoro-C₁₋₃-alquilo; o R⁷ y R⁸ junto con el átomo de nitrógeno al cual están unidos son heterocicloalquilo de entre 4 y 8 miembros, heterocicloalquenilo de entre 4 y 8 miembros, C₅₋₁₁-heteroespirocicloalquilo, C₆₋₁₂-heterocicloalquilo en puente o C₆₋₁₂-heterobicicloalquilo, que opcionalmente puede estar monosustituido o disustituido en forma idéntica o diferente con: hidroxilo, flúor, oxo, ciano, C₁₋₃-alquilo, fluoro-C₁₋₃-alquilo, C₃₋₆-cicloalquilo, ciclopropilmetilo, C₁₋₃-alquilcarbonilo, C₁₋₄-alcoxicarbonilo o -NR⁹R¹⁰; R⁹ y R¹⁰ es cada uno en forma independiente hidrógeno o C₁₋₃-alquilo opcionalmente sustituido con hidroxilo, oxo o C₁₋₃-alcoxi una o dos veces, en forma idéntica o diferente, o fluoro-C₁₋₃-alquilo, o heterocicloalquilo de entre 4 y 8 miembros, en donde el heterocicloalquilo de entre 4 y 8 miembros a su vez puede estar opcionalmente monosustituido o disustituido en forma idéntica o diferente con C₁₋₃-alquilo; o R⁹ y R¹⁰ junto con el átomo de nitrógeno al cual están unidos son heterocicloalquilo de entre 4 y 8 miembros que opcionalmente puede estar monosustituido o disustituido en forma idéntica o diferente con: hidroxilo, flúor, oxo, ciano, C₁₋₃-alquilo, fluoro-C₁₋₃-alquilo, C₃₋₆-cicloalquilo, ciclopropilmetilo, C₁₋₃-alquilcarbonilo o C₁₋₄-alcoxicarbonilo; R¹¹ es C₁₋₆-alquilo o fenil-C₁₋₃-alquilo; y los diasterómeros, racematos, polimorfos y sales fisiológicamente aceptables de los mismos.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13175767 | 2013-07-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR096846A1 true AR096846A1 (es) | 2016-02-03 |
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ID=48747457
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP140102526A AR096846A1 (es) | 2013-07-09 | 2014-07-08 | Dihidroquinoxalinonas y dihidropiridopirazinonas modificadas como inhibidores de la proteína bet |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20160176867A1 (es) |
| EP (1) | EP3019493B1 (es) |
| JP (1) | JP2016523941A (es) |
| CN (1) | CN105518001A (es) |
| AR (1) | AR096846A1 (es) |
| CA (1) | CA2917562A1 (es) |
| ES (1) | ES2635003T3 (es) |
| HK (1) | HK1221721A1 (es) |
| TW (1) | TW201542533A (es) |
| UY (1) | UY35654A (es) |
| WO (1) | WO2015004075A1 (es) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2952526A1 (en) * | 2014-06-18 | 2015-12-23 | Bayer Pharma Aktiengesellschaft | Bet-protein inhibiting 3,4-dihydropyrido[2,3-b]pyrazinones with meta-substituted aromatic amino- or ether groups |
| GB201504694D0 (en) | 2015-03-19 | 2015-05-06 | Glaxosmithkline Ip Dev Ltd | Covalent conjugates |
| US10836742B2 (en) | 2015-08-11 | 2020-11-17 | Neomed Institute | N-substituted bicyclic lactams, their preparation and their use as pharmaceuticals |
| CN108290856A (zh) * | 2015-08-11 | 2018-07-17 | 尼奥迈德研究所 | 芳基-取代的二氢喹诺酮、它们的制备和它们作为药物的用途 |
| KR102784592B1 (ko) | 2015-08-12 | 2025-03-19 | 에피제네틱스, 인크. | 치환된 벤즈이미다졸, 그의 제조법 및 제약으로서의 그의 용도 |
| WO2017066876A1 (en) | 2015-10-21 | 2017-04-27 | Neomed Institute | Substituted imidazopyridines, their preparation and their use as pharmaceuticals |
| US10519151B2 (en) | 2016-01-28 | 2019-12-31 | Neomed Institute | Substituted [1,2,4]triazolo[4,3-A]pyridines, their preparation and their use as pharmaceuticals |
| DE102017005089A1 (de) | 2016-05-30 | 2017-11-30 | Bayer Pharma Aktiengesellschaft | Substitulerte 3,4-Dihydrochinoxalin-2(1H)-one |
| DE102017005091A1 (de) | 2016-05-30 | 2017-11-30 | Bayer Pharma Aktiengesellschaft | Substituierte 3,4-Dihydropyrido[2,3-b]pyrazin-2(1H)-one |
| CN107793371B (zh) * | 2016-09-05 | 2020-12-15 | 中国科学院上海药物研究所 | 一类溴结构域识别蛋白抑制剂及其制备方法和用途 |
| EP3725768A1 (en) * | 2019-04-17 | 2020-10-21 | Newron Pharmaceuticals S.p.A. | Process for the production of substituted 2-[2-(phenyl) ethylamino]alkaneamide derivatives |
| EP4039333A4 (en) | 2019-09-30 | 2024-02-14 | Kyowa Kirin Co., Ltd. | BET DEGRADATION AGENT |
| US12527741B2 (en) | 2021-06-17 | 2026-01-20 | Wisconsin Alumni Research Foundation | Modular dendron micelles for treatment of pulmonary diseases related to fibrosis and viral infection including COVID-19 |
| CN115947728B (zh) * | 2021-10-09 | 2024-01-09 | 沈阳药科大学 | 含磺酰基的二氢喋啶酮衍生物及其应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20040213A2 (en) * | 2001-09-04 | 2005-02-28 | Boehringer Ingelheim Pharma Gmbh & Co.Kg | Novel dihydropteridinones, method for producing the same and the use thereof as medicaments |
| US6861422B2 (en) * | 2003-02-26 | 2005-03-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions |
| WO2007022638A1 (en) * | 2005-08-26 | 2007-03-01 | Methylgene Inc. | Benzodiazepine and benzopiperazine analog inhibitors of histone deacetylase |
| WO2009071480A2 (en) * | 2007-12-04 | 2009-06-11 | Nerviano Medical Sciences S.R.L. | Substituted dihydropteridin-6-one derivatives, process for their preparation and their use as kinase inhibitors |
| CA2750106A1 (en) * | 2009-01-23 | 2010-07-29 | Takeda Pharmaceutical Company Limited | Poly (adp-ribose) polymerase (parp) inhibitors |
| JP2012197231A (ja) * | 2009-08-06 | 2012-10-18 | Oncotherapy Science Ltd | Ｔｔｋ阻害作用を有するピリジンおよびピリミジン誘導体 |
| WO2013027168A1 (en) * | 2011-08-22 | 2013-02-28 | Pfizer Inc. | Novel heterocyclic compounds as bromodomain inhibitors |
| CA2895404A1 (en) * | 2012-12-20 | 2014-06-26 | Bayer Pharma Aktiengesellschaft | Bet-protein-inhibiting dihydropyridopyrazinones |
-
2014
- 2014-07-07 CA CA2917562A patent/CA2917562A1/en not_active Abandoned
- 2014-07-07 WO PCT/EP2014/064486 patent/WO2015004075A1/de not_active Ceased
- 2014-07-07 US US14/903,549 patent/US20160176867A1/en not_active Abandoned
- 2014-07-07 JP JP2016524782A patent/JP2016523941A/ja active Pending
- 2014-07-07 EP EP14737225.4A patent/EP3019493B1/de not_active Not-in-force
- 2014-07-07 ES ES14737225.4T patent/ES2635003T3/es active Active
- 2014-07-07 HK HK16109965.4A patent/HK1221721A1/zh unknown
- 2014-07-07 CN CN201480049697.XA patent/CN105518001A/zh active Pending
- 2014-07-08 AR ARP140102526A patent/AR096846A1/es unknown
- 2014-07-09 TW TW103123703A patent/TW201542533A/zh unknown
- 2014-07-09 UY UY35654A patent/UY35654A/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CN105518001A (zh) | 2016-04-20 |
| CA2917562A1 (en) | 2015-01-15 |
| ES2635003T3 (es) | 2017-10-02 |
| TW201542533A (zh) | 2015-11-16 |
| HK1221721A1 (zh) | 2017-06-09 |
| US20160176867A1 (en) | 2016-06-23 |
| EP3019493B1 (de) | 2017-06-14 |
| JP2016523941A (ja) | 2016-08-12 |
| UY35654A (es) | 2015-02-27 |
| EP3019493A1 (de) | 2016-05-18 |
| WO2015004075A1 (de) | 2015-01-15 |
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