AR065718A1 - Compuestos heterociclicos nitrogenados,utiles en el diagnostico y tratamiento de trastornos hiperproliferativos. - Google Patents
Compuestos heterociclicos nitrogenados,utiles en el diagnostico y tratamiento de trastornos hiperproliferativos.Info
- Publication number
- AR065718A1 AR065718A1 ARP080101030A ARP080101030A AR065718A1 AR 065718 A1 AR065718 A1 AR 065718A1 AR P080101030 A ARP080101030 A AR P080101030A AR P080101030 A ARP080101030 A AR P080101030A AR 065718 A1 AR065718 A1 AR 065718A1
- Authority
- AR
- Argentina
- Prior art keywords
- het
- aryl
- substituted
- alkyl
- unsubstituted
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title abstract 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title 2
- 238000003745 diagnosis Methods 0.000 title 1
- 230000003463 hyperproliferative effect Effects 0.000 title 1
- 229910052757 nitrogen Inorganic materials 0.000 title 1
- 125000003118 aryl group Chemical group 0.000 abstract 16
- 125000000217 alkyl group Chemical group 0.000 abstract 10
- -1 C (O) OR6 Chemical group 0.000 abstract 9
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 6
- 125000003545 alkoxy group Chemical group 0.000 abstract 5
- 125000004043 oxo group Chemical group O=* 0.000 abstract 5
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 4
- 125000005842 heteroatom Chemical group 0.000 abstract 4
- 229910052736 halogen Inorganic materials 0.000 abstract 3
- 150000002367 halogens Chemical class 0.000 abstract 3
- 229910052760 oxygen Inorganic materials 0.000 abstract 3
- 229910052717 sulfur Inorganic materials 0.000 abstract 3
- 125000003342 alkenyl group Chemical group 0.000 abstract 2
- 125000004429 atom Chemical group 0.000 abstract 2
- 125000000000 cycloalkoxy group Chemical group 0.000 abstract 2
- 125000002950 monocyclic group Chemical group 0.000 abstract 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 abstract 1
- 125000002252 acyl group Chemical group 0.000 abstract 1
- 125000002619 bicyclic group Chemical group 0.000 abstract 1
- 125000004432 carbon atom Chemical group C* 0.000 abstract 1
- 125000004122 cyclic group Chemical group 0.000 abstract 1
- 125000001153 fluoro group Chemical group F* 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
Classifications
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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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
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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
- A61K31/435—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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
-
- 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
-
- 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
- C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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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- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D498/14—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Steroid Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pyridine Compounds (AREA)
Abstract
Reivindicacion 1: Un compuesto de la formula (1) y las sales farmacéuticamente aceptables del mismo, en donde: R1 es fenilo que puede estar insustituido o sustituido; R2 es het, siendo N cuando menos un heteroátomo del anillo, y el cual puede estarinsustituido o sustituido; L es alquilo inferior, (CH2)1-2-A, A-(CH2)1-2, o CH2-A-CH2, y A es O, S, NH, o N-aIquilo, en donde alquilo inferior puede estar insustituido o sustituido con alquilo inferior, o uno o más átomos de fluor; X es N o CH, ycuando menos un X es N; Y es un enlace, CH2, C(O), o SO2; R3 es arilo o het, el cual está sustituido, Z es H, alquilo inferior, alcoxilo inferior, oxo, C(O)OR6, o -CN; en donde alquilo inferior y alcoxilo inferior pueden estar insustituidos osustituidos con uno o más de halogeno, -OH, -CN, -NH2, u oxo, y dos Z conectados al mismo átomo pueden formar un anillo de cicloalquilo, y m es de 0 a 3, las sustituciones de fenilo, arilo o het de R1, R2, o R3 pueden ser uno o más de alquilo,cicloalquilo, alcoxilo, cicloalcoxilo, halogeno, -CN, oxo, arilo, carbalcoxilo, OCF3, CF3, OH, -C(O)N(R6)2, C(O)R6, -C(O)OR6, -N(R6)2, -NHC(O)R6, -SO2(R6), -SO2N(R6)2, CH2OC(O)N(R6)2, -CH2N(R6)2, -NHC(O)OR6, NHC(O)N(R6)2, -CH2NHC(O)R6,CH2NHC(O)N(R6)2, CH2NHSO2(R6), CHNHC(O)OR6, -OC(O)R6, NHC(O)R6, O-arilo, het, u O-het, en donde alquilo, het, cicloalquilo, cicloalcoxilo, N(R6)2, arilo, carbalcoxilo, y alcoxilo pueden estar insustituidos o sustituidos con uno o más de halogeno, -OCH3, -OCF3, -OH, -NH2, alquilo, OR6, oxo, N(H)0-2-R6, -CN, -C(O)N(R6)2, C(O)R6, C(O)OR6, -N(R6)2, NHC(O)R6, -SO2(R6), -SO2N(R6)2, OSO2R6, -CH2N(R6)2, -CH2NHC(O)R6, -OC(O)R6, arilo, NHC(O)-(R6), O-arilo, het, O-het, o cicloalquilo; R6 es H, alquilo,alquenilo, arilo, het, o dos R6 sobre un átomo pueden formar cicloalquilo, arilo, o het; y alquilo, alquenilo, arilo, het, cicloalquilo, o het pueden estar insustituidos o sustituidos por OH, oxo, alcoxilo, NR6, N-alquilo, acilo, arilo o un grupohet; het es un anillo heterocíclico monocíclico de 5 a 7 miembros, el cual puede ser aromático o no aromático, que contiene de 1 a 4 heteroátomos del anillo seleccionados a partir de N, O, y S; o un sistema de anillos fusionados de 8 a 12 miembrosque incluye cuando menos un anillo heterocíclico de 5 a 7 miembros, el cual puede ser aromático o no aromático, que contiene 1, 2, o 3 heteroátomos de anillo seleccionados a partir de N, O y S, cuyo het está insustituido o sustituido; arilo es unradical aromático que tiene de 6 a 14 átomos de carbono del anillo, y ningun heteroátomo del anillo, en donde este grupo arilo puede ser monocíclico o bicíclico o tricíclico fusionado, que puede estar insustituido o sustituido por uno o mássustituyentes; y n es 0, 1, 2, o 3.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US89499107P | 2007-03-15 | 2007-03-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR065718A1 true AR065718A1 (es) | 2009-06-24 |
Family
ID=39472520
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP080101030A AR065718A1 (es) | 2007-03-15 | 2008-03-13 | Compuestos heterociclicos nitrogenados,utiles en el diagnostico y tratamiento de trastornos hiperproliferativos. |
Country Status (33)
| Country | Link |
|---|---|
| US (1) | US8536168B2 (es) |
| EP (1) | EP2137162B1 (es) |
| JP (1) | JP5550352B2 (es) |
| KR (1) | KR101473504B1 (es) |
| CN (1) | CN101657430B (es) |
| AR (1) | AR065718A1 (es) |
| AU (1) | AU2008225766B2 (es) |
| BR (1) | BRPI0809193A2 (es) |
| CA (1) | CA2681162C (es) |
| CL (1) | CL2008000754A1 (es) |
| CO (1) | CO6220967A2 (es) |
| CR (1) | CR11016A (es) |
| CU (1) | CU23769B7 (es) |
| DK (1) | DK2137162T3 (es) |
| DO (1) | DOP2009000217A (es) |
| EA (1) | EA016564B1 (es) |
| EC (1) | ECSP099636A (es) |
| GE (1) | GEP20125487B (es) |
| GT (1) | GT200900244A (es) |
| IL (1) | IL200654A (es) |
| MA (1) | MA31258B1 (es) |
| MX (1) | MX2009009873A (es) |
| MY (1) | MY156814A (es) |
| NI (1) | NI200900168A (es) |
| NZ (1) | NZ579402A (es) |
| PE (1) | PE20090188A1 (es) |
| SG (1) | SG182205A1 (es) |
| SM (1) | SMP200900082B (es) |
| TN (1) | TN2009000373A1 (es) |
| TW (1) | TWI406857B (es) |
| UA (1) | UA100684C2 (es) |
| WO (1) | WO2008110611A1 (es) |
| ZA (1) | ZA200905949B (es) |
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| TWI433674B (zh) | 2006-12-28 | 2014-04-11 | Infinity Discovery Inc | 環杷明(cyclopamine)類似物類 |
| SG182205A1 (en) | 2007-03-15 | 2012-07-30 | Novartis Ag | Organic compounds and their uses |
| EP2197873B1 (en) | 2007-09-20 | 2014-07-16 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
| CN104059124A (zh) | 2007-12-27 | 2014-09-24 | 无限药品股份有限公司 | 立体选择性还原的方法 |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| AU2009217982B2 (en) * | 2008-02-26 | 2013-04-11 | Takeda Pharmaceutical Company Limited | Fused heterocyclic derivative and use thereof |
| CA2723042A1 (en) | 2008-04-29 | 2009-11-05 | Eli Lilly And Company | Disubstituted phthalazine hedgehog pathway antagonists |
| US20100041663A1 (en) * | 2008-07-18 | 2010-02-18 | Novartis Ag | Organic Compounds as Smo Inhibitors |
| WO2010037715A1 (en) * | 2008-10-01 | 2010-04-08 | Novartis Ag | Smoothened antagonism for the treatment of hedgehog pathway-related disorders |
| HRP20130527T1 (en) | 2008-11-03 | 2013-07-31 | Eli Lilly And Company | Disubstituted phthalazine hedgehog pathway antagonists |
| ES2446307T3 (es) | 2008-11-17 | 2014-03-07 | Eli Lilly And Company | Piridazinas tetrasustituidas antagonistas de la ruta de Hedgehog |
| HRP20120762T1 (hr) * | 2008-11-17 | 2012-10-31 | Eli Lilly And Company | Tetrasupstituirani piridazini kao inhibitori hedgehog puta |
| AR077014A1 (es) | 2009-06-19 | 2011-07-27 | Lilly Co Eli | Compuesto derivado de ftalazina 1,4-disustituida, composicion farmaceutica que lo comprende y uso para preparar un medicamento util para el tratamiento de cancer |
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| US20110039850A1 (en) * | 2009-08-12 | 2011-02-17 | Mhairi Copland | Leukemia Treatment |
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| US9006450B2 (en) | 2010-07-01 | 2015-04-14 | Boehringer Ingelheim International Gmbh | Compounds, pharmaceutical compositions and uses thereof |
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| PE20180318A1 (es) | 2011-01-10 | 2018-02-09 | Infinity Pharmaceuticals Inc | Procedimiento para preparar isoquinolinonas y formas solidas de isoquinolinonas |
| WO2013012918A1 (en) | 2011-07-19 | 2013-01-24 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| WO2013012915A1 (en) | 2011-07-19 | 2013-01-24 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
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| US9630979B2 (en) | 2011-09-29 | 2017-04-25 | Infinity Pharmaceuticals, Inc. | Inhibitors of monoacylglycerol lipase and methods of their use |
| EP2785690B1 (en) * | 2011-12-02 | 2016-07-13 | Boehringer Ingelheim International GmbH | Piperidine derivatives, pharmaceutical compositions and uses thereof |
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