ES2618939T3 - Sal de camsilato - Google Patents
Sal de camsilato Download PDFInfo
- Publication number
- ES2618939T3 ES2618939T3 ES13733415.7T ES13733415T ES2618939T3 ES 2618939 T3 ES2618939 T3 ES 2618939T3 ES 13733415 T ES13733415 T ES 13733415T ES 2618939 T3 ES2618939 T3 ES 2618939T3
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- Prior art keywords
- mol
- strong
- indene
- mixture
- salt
- Prior art date
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- 229950005953 camsilate Drugs 0.000 title 1
- 150000003839 salts Chemical class 0.000 title 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 claims abstract description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims abstract 2
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 6
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
- SEQHEDQNODAFIU-UHFFFAOYSA-N 6-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=C2CCC(=O)C2=C1 SEQHEDQNODAFIU-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- GKFJEDWZQZKYHV-UHFFFAOYSA-N borane;2-methylpropan-2-amine Chemical compound B.CC(C)(C)N GKFJEDWZQZKYHV-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000005464 sample preparation method Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
Classifications
-
- 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
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or 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
- A61K31/435—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- C07D401/10—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 aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Una sal de camsilato de (1r,1'R,4R)-4-metoxi-5"-metil-6'-[5-(prop-1-in-1-il)piridin-3-il]-3'H-diespiro [ciclohexano- 1,2'-indeno-1'2"-imidazol]-4"-amina:**Fórmula**
Description
- Ángulos corregidos
- Espaciamiento d (Å) Intensidad relativa
- 12.83
- 6.89 m
- 14.07
- 6.29 w
- 15.05
- 5.88 w
- 15.24
- 5.81 m
- 15.47
- 5.72 m
- 16.24
- 5.45 w
- 16.68
- 5.31 w
- 17.17
- 5.16 m
- 17.33
- 5.11 w
- 17.62
- 5.03 vw
- 17.84
- 4.97 w
- 18.13
- 4.89 m
- 19.71
- 4.50 m
- 20.18
- 4.40 w
- 20.77
- 4.27 m
- 21.12
- 4.20 m
- 21.67
- 4.10 vw
- 21.88
- 4.06 vw
- 22.09
- 4.02 vw
- 22.29
- 3.99 w
- 22.73
- 3.91 w
- 23.11
- 3.84 vw
4
- Ángulos corregidos
- Espaciamiento d (Å) Intensidad relativa
- 23.63
- 3.76 m
- 24.50
- 3.63 m
- 26.18
- 3.40 m
- 26.54
- 3.36 m
- 27.72
- 3.22 vw
- 27.95
- 3.19 vw
- 28.80
- 3.10 vw
- 28.93
- 3.08 vw
- 29.71
- 3.00 vw
- 30.56
- 2.92 vw
- 31.14
- 2.87 vw
- 31.64
- 2.83 vw
- 31.74
- 2.82 vw
- 32.11
- 2.79 vw
- 32.84
- 2.72 vw
- 33.86
- 2.65 vw
- 34.30
- 2.61 m
- 36.78
- 2.44 m
- 37.49
- 2.40 w
- 40.23
- 2.24 vw
- 40.93
- 2.20 vw
- 41.32
- 2.18 vw
5
- Ángulos corregidos
- Espaciamiento d (Å) Intensidad relativa
- 42.43
- 2.13 w
- 44.54
- 2.03 vw
- 46.29
- 1.96 vw
- 48.32
- 1.88 vw
Otra realización de la presente invención es una sal de camsilato del compuesto (1r,1'R,4R)-4-metoxi-5"-metil-6'-[5(prop-1-in-1-il)piridin-3-il]-3'H-diespiro[ciclohexano-1,2'-indeno-1'2'-imidazole]-4"-amina, caracterizada por suministrar un patrón de difracción en polvo por rayos X, que exhibe de modo sustancial los siguientes picos muy fuertes, fuertes y medios con valores de espaciamiento d como se representan en la Tabla 2:
Tabla 2:
- Picos identificados en difracción en polvo por rayos X
- Ángulos corregidos
- Espaciamiento d (Å) Intensidad relativa
- 5.66
- 15.60 vs
- 7.72
- 11.44 m
- 11.30
- 7.83 m
- 12.35
- 7.16 s
- 12.83
- 6.89 m
- 15.24
- 5.81 m
- 15.47
- 5.72 m
- 17.17
- 5.16 m
- 18.13
- 4.89 m
- 19.71
- 4.50 m
- 20.77
- 4.27 m
- 21.12
- 4.20 m
- 23.63
- 3.76 m
6
5
10
15
20
25
30
35
40
valores de distancia en XRPD pueden variar en el intervalo ±2 en el último lugar decimal.
Las intensidades relativas se derivan de difractogramas medidos con rendijas variables.
Las intensidades relativas medidas vs. el pico más fuerte son dados como muy fuerte (vs) por encima de 50%, como fuerte (s) entre 25 y 50%, como media (m) entre 10 y 25%, como débil (w) entre 5 y 10% y como muy débil (vw) por debajo de 5% de altura relativa de pico. Una persona experta en la técnica notará que las intensidades de XRPD pueden variar entre diferentes muestras y diferentes preparaciones de muestra por una variedad de razones, incluyendo la orientación preferida. También una persona experta en la técnica notará que pueden ocurrir desplazamientos más pequeños en el ángulo medido y por ello en el espaciamiento d, por una variedad de razones incluyendo variación del nivel de superficie de la muestra en el difractómetro.
Ejemplos
Ejemplo 1
6'-bromoespiro[ciclohexano-1,2'-indeno]-1',4(3'H)-diona
Se cargó tert-butóxido de potasio (223 g, 1.99 mol) a un reactor de 100 L que contenía una mezcla agitada de 6bromo-1-indanona (8.38 kg, 39.7 mol) en THF (16.75 L) a 20-30 °C. Se cargó entonces metil acrilato (2.33 L, 25.8 mol) a la mezcla durante 15 minutos manteniendo la temperatura entre 20-30 °C. Se añadió una solución de tertbutóxido de potasio (89.1 g, 0.79 mol) disuelto en THF (400 mL) después se añadió metil acrilato (2.33 L, 25.8 mol) durante 20 minutos a 20-30 °C. Se añadió entonces una tercera porción de tert-butóxido de potasio (90 g, 0.80 mol) disuelto en THF (400 mL), seguido por una tercera adición de metil acrilato (2.33 L, 25.8 mol) durante 20 minutos a 20-30 °C. Se cargó al reactor tert-butóxido de potasio (4.86 kg, 43.3 mol) disuelto en THF (21.9 L), durante 1 hora a 20-30 °C. Se calentó la reacción a aproximadamente 65 °C y se retiraron por destilación 23 L de solvente. Se redujo la temperatura de reacción a 60 °C y se añadió a la mezcla hidróxido de potasio acuoso al 50% (2.42 L, 31.7 mol) disuelto en agua (51.1 L), durante 30 minutos a 55-60 °C después se agitó la mezcla por 6 horas a 60 °C, se enfrió a 20 °C durante 2 horas. Después de agitar por 12 horas a 20 °C se separó por filtración el material sólido, se lavó dos veces con una mezcla de agua (8.4 L) y THF (4.2 L) y luego se secó a 50 °C bajo vacío para dar 6'bromoespiro[ciclohexano-1,2'-indeno]-1',4(3'H)-diona (7.78 kg; 26.6 mol). 1H RMN (500 MHz, DMSO-d6) δ ppm 1.78 -1.84 (m, 2 H), 1.95 (td, 2 H), 2.32 -2.38 (m, 2 H), 2.51 -2.59 (m, 2 H), 3.27 (s, 2 H), 7.60 (d, 1 H), 7.81 (m, 1 H),
7.89 (m, 1 H).
Ejemplo 2
(1r,4r)-6'-bromo-4-metoxiespiro[ciclohexano-1,2'-indeno]-1'(3'H)-ona
Se cargó complejo de borano tert-butilamina (845 g, 9.7 mol) disuelto en DCM (3.8 L) a una pasta de 6'bromoespiro[ciclohexano-1,2'-indeno]-1',4(3'H)-diona (7.7 kg, 26.3 mol) en DCM (42.4 L) a aproximadamente 0-5 °C durante aproximadamente 25 minutos. Se dejó la reacción con agitación a 0-5°C por 1 hora, después de análisis se confirmó que la conversión era >98%. Se cargó una solución preparada de cloruro de sodio (2.77 kg), agua (13.3 L) y ácido clorhídrico al 37% (2.61 L, 32 mol). Se calentó la mezcla a aproximadamente 15 °C y se separaron las fases después de decantarse en capas. Se devolvió la fase orgánica al reactor, junto con metil metanosulfonato (2.68 L,
31.6 mol) y cloruro de tetrabutilamonio (131 g, 0.47 mol) y se agitó vigorosamente la mezcla a 20 °C. Se cargó entonces hidróxido de sodio al 50% (12.5 L, 236 mol) a la mezcla de reacción agitada vigorosamente, durante aproximadamente 1 hora y se dejó la reacción con agitación vigorosa durante la noche a 20 °C. Se añadió agua (19 L) y después de la separación se descartó la fase acuosa. Se calentó la capa orgánica a aproximadamente 40 °C y se separaron por destilación 33 L de solvente. Se cargó etanol (21 L) y se reanudó la destilación aumentando la
11
Claims (17)
- REIVINDICACIONES
- 1.
- Una sal de camsilato de (1r,1'R,4R)-4-metoxi-5"-metil-6'-[5-(prop-1-in-1-il)piridin-3-il]-3'H-diespiro [ciclohexano1,2'-indeno-1'2"-imidazol]-4"-amina:
-
- 2.
- Una sal de camsilato de acuerdo con la reivindicación 1 que tiene un patrón de difracción de rayos X en polvo (XRPD) que exhibe sustancialmente los siguientes picos muy fuerte, fuerte y medio con valores d:
imagen1 - Ángulos corregidos
- Espaciamiento d (Å) Intensidad relativa
-
- 5.66
- 15.60 vs
-
- 7.72
- 11.44 m
-
- 11.30
- 7.83 m
-
- 12.35
- 7.16 s
-
- 12.83
- 6.89 m
-
- 15.24
- 5.81 m
-
- 15.47
- 5.72 m
-
- 17.17
- 5.16 m
-
- 18.13
- 4.89 m
-
- 19.71
- 4.50 m
-
- 20.77
- 4.27 m
-
- 21.12
- 4.20 m
-
- 23.63
- 3.76 m
-
- 24.50
- 3.63 m
-
- 26.18
- 3.40 m
16imagen2
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261662592P | 2012-06-21 | 2012-06-21 | |
| US201261662592P | 2012-06-21 | ||
| PCT/GB2013/051606 WO2013190302A1 (en) | 2012-06-21 | 2013-06-20 | Camsylate salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2618939T3 true ES2618939T3 (es) | 2017-06-22 |
Family
ID=48746084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13733415.7T Active ES2618939T3 (es) | 2012-06-21 | 2013-06-20 | Sal de camsilato |
Country Status (42)
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8415483B2 (en) | 2010-12-22 | 2013-04-09 | Astrazeneca Ab | Compounds and their use as BACE inhibitors |
| ES2566373T3 (es) | 2011-10-10 | 2016-04-12 | Astrazeneca Ab | Inhibidores monofluoro beta-secretasa |
| US9000182B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | 2H-imidazol-4-amine compounds and their use as BACE inhibitors |
| US9000185B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cycloalkyl ether compounds and their use as BACE inhibitors |
| US9000184B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cyclohexane-1,2′-naphthalene-1′,2″-imidazol compounds and their use as BACE inhibitors |
| US9000183B2 (en) | 2012-06-20 | 2015-04-07 | Astrazeneca Ab | Cyclohexane-1,2′-indene-1′,2″-imidazol compounds and their use as BACE inhibitors |
| US10053453B2 (en) | 2014-10-07 | 2018-08-21 | Astrazeneca Ab | Compounds and their use as BACE inhibitors |
| JP6546410B2 (ja) * | 2015-02-23 | 2019-07-17 | ローム株式会社 | 電力供給装置、ａｃアダプタ、ａｃチャージャ、電子機器および電力供給システム |
| AR107893A1 (es) * | 2016-03-15 | 2018-06-28 | Astrazeneca Ab | TERAPIAS COMBINADAS, COMBINACIÓN DE UN INHIBIDOR DE BACE Y UN ANTICUERPO O UN FRAGMENTO DE UNIÓN AL ANTÍGENO PARA EL TRATAMIENTO DE UN TRASTORNO ASOCIADO CON LA ACUMULACIÓN DE b AMILOIDE |
| TW201740944A (zh) | 2016-03-15 | 2017-12-01 | 美國禮來大藥廠 | 組合療法 |
| MX2021011105A (es) * | 2019-03-14 | 2021-10-22 | Astrazeneca Ab | Lanabecestat para la perdida de peso. |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100452491B1 (ko) * | 2001-03-29 | 2004-10-12 | 한미약품 주식회사 | 신규한 결정형 암로디핀 캠실레이트 염 및 그의 제조방법 |
| JP4273406B2 (ja) | 2001-06-01 | 2009-06-03 | 小野薬品工業株式会社 | アルドース還元酵素阻害剤を有効成分とする脱髄性疾患または脱髄を伴う疾患治療剤 |
| US7592348B2 (en) | 2003-12-15 | 2009-09-22 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| ES2332184T3 (es) | 2004-03-22 | 2010-01-28 | ELI LILLY & COMPANY | Derivados de piridilo y su uso como antagonistas del receptor mglu5. |
| WO2006138264A2 (en) | 2005-06-14 | 2006-12-28 | Schering Corporation | Aspartyl protease inhibitors |
| TW200734311A (en) | 2005-11-21 | 2007-09-16 | Astrazeneca Ab | New compounds |
| CN101360716A (zh) | 2005-11-21 | 2009-02-04 | 阿斯利康(瑞典)有限公司 | 新颖的2-氨基-咪唑-4-酮化合物及其在制备用于治疗认知缺损、阿尔茨海默病、神经变性和痴呆的药物中的用途 |
| JP2009521488A (ja) | 2005-12-21 | 2009-06-04 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｐｋｃ−シータのインヒビターとして有益なピリミジン誘導体 |
| WO2007100536A1 (en) | 2006-02-24 | 2007-09-07 | Wyeth | DIHYDROSPIRO[DIBENZO[A,D][7]ANNULENE-5,4'-IMIDAZOL] COMPOUNDS FOR THE INHIBITION OF β-SECRETASE |
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| WO2008076043A1 (en) | 2006-12-20 | 2008-06-26 | Astrazeneca Ab | Novel 2-amino-5,5-diaryl-imidazol-4-ones |
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