WO2007005404A1 - AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR ß-SECRETASE MODULATION - Google Patents
AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR ß-SECRETASE MODULATION Download PDFInfo
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- WO2007005404A1 WO2007005404A1 PCT/US2006/024912 US2006024912W WO2007005404A1 WO 2007005404 A1 WO2007005404 A1 WO 2007005404A1 US 2006024912 W US2006024912 W US 2006024912W WO 2007005404 A1 WO2007005404 A1 WO 2007005404A1
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- WIPO (PCT)
- Prior art keywords
- amino
- methyl
- imidazol
- dihydro
- pyridin
- Prior art date
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- 0 C1C*C*C1 Chemical compound C1C*C*C1 0.000 description 4
- NYPYPOZNGOXYSU-UHFFFAOYSA-N Brc1cnccc1 Chemical compound Brc1cnccc1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
- JFBMFWHEXBLFCR-UHFFFAOYSA-N Cc1cc(Br)ccn1 Chemical compound Cc1cc(Br)ccn1 JFBMFWHEXBLFCR-UHFFFAOYSA-N 0.000 description 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
- C07D401/04—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
-
- 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
- A61P25/28—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
-
- 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
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Definitions
- the present invention relates to 2-amino-5-heteroaryl-5-phenylimidazolone compounds and to methods for using them to modulate (and, preferably, inhibit) ⁇ - secretase (BACE) and to treat ⁇ -amyloid deposits and neurofibrillary tangles.
- BACE ⁇ - secretase
- BACE activity is correlated directly to the generation of A ⁇ peptide from APP (Sinha, et al, Nature, 1999, 402, 537-540), and studies increasingly indicate that the inhibition of BACE inhibits the production of A ⁇ peptide (Roberds, S. L., et al, Human Molecular Genetics, 2001 , 10, 1317-1324).
- the present invention provides a compound of formi
- Ri and R 2 are each independently H, COR 34 , CO 2 R 12 or an optionally substituted C r C 4 alkyl group;
- R 3 is H, OR 13 or a C r C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl,
- R 4 and R 5 are each independently H, halogen, NO 2 , CN, OR 14 , CO 2 R 15 , COR 16 , NR 17 R 18 , SOpNR 19 R 20 or a C r C 6 alkyl, C-i-Cehaloalkyl, C 2 - C 6 alkenyl, C 2 -C 6 alkynyl or C 3 -C 8 cycloalkyl group each optionally substituted;
- Ri 1 , R 12 , R 13 , R 14 , R 15 , R 16 , R 21 , R 24 , R 2 7, R28 and R 29 are each independently H or a Ci-C 6 alkyl, CrCehaloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 - C 8 cycloalkyl, cycloheteroalkyl or aryl group each optionally substituted;
- R-17, R18, R19, R2 0 , R22, R23, R25, R26, R3C R31 , R32 3nd R 33 are each independently H, COR 34 , SO p R 35 or a C r C 4 alkyl, C 2 -C 6 alkenyl, C 2 - C 6 alkynyl, C 3 -C 8 cycloalkyl, cycloheteroalkyl, aryl or heteroaryl group each optionally substituted or R 17 , R 18 ; or R 19 , R 20 , or R 22 , R 23 , or R 25 , R 26 , or R 30 , R 31 , or R 32 , R 33 may be taken together with the atom to which they are attached to form an optionally substituted 5- to 7- membered ring optionally containing an additional heteroatom selected from O, N or S; R 34 is H, or a C r C 6 alkyl, C r C 6 haloalkyl, C 2
- the present invention also relates to the use of the formula I heteroarylimidazolone compound for the treatment of ⁇ -amyloid deposits and neurofibrillary tangles.
- the compound of the invention is particularly useful for treating Alzheimer's disease, cognitive impairment, Down's Syndrome, HCHWA-D, cognitive decline, senile dementia, cerebral amyloid angiopathy, degenerative dementia, or other neurodegenerative disorders.
- BACE1 amyloid precursor protein
- W is CO, CS or CH 2 ;
- X is N, NO or CR;
- Y is N, NO or CR 10 ;
- Z is N, NO or CRi 1 with the proviso that at least one of X, Y or Z must be N or NO;
- R 1 and R 2 are each independently H, COR 34 , CO 2 Ri 2 or an optionally substituted C r C 4 alkyl group;
- R 35 is a Ci-C 6 alkyl, C r C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -
- each alkyl, alkenyl, alkynyl, cycloalkyl cycloheteroalkyl, aryl or heteroaryl group is contemplated as being optionally substituted.
- cycloheteroalkyl or heteroaryl or cycloalkyl groups, preferably halogen atoms or lower alkyl or lower alkoxy groups.
- typically, 0-4 substituents may be present. When more than one substituent is present they may be the same of different.
- any of the foregoing substituents represents or contains an alkyl substituent group, this may be linear or branched and may contain up to 12 carbon atoms, preferably up to 6 carbon atoms, more preferably up to 4 carbon atoms.
- alkyl includes both (C 1 -C 10 ) straight chain and (C 3 - C 12 ) branched-chain (unless defined otherwise) monovalent saturated hydrocarbon moiety.
- saturated hydrocarbon alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, ⁇ -butyl, tert- butyl, isobutyl, sec-butyl; higher homologs such as n-pentyl, ⁇ -hexyl, and the like.
- alkyl include those alkyl groups that are optionally substituted.
- Suitable alkyl substitutions include, but are not limited to, CN, OH, halogen, phenyl, carbamoyl, carbonyl, alkoxy or aryloxy.
- haloalkyl designates a C n H 2n+ -: group having from one to 2n+1 halogen atoms which may be the same or different. Examples of haloalkyl groups include CF 3 , CH 2 CI, C 2 H 3 BrCI, C 3 H 5 F 2 , or the like.
- alkenyl refers to either a (C 2 -C 8 ) straight chain or (C 3 -C 10 ) branched-chain monovalent hydrocarbon moiety containing at least one double bond. Such hydrocarbon alkenyl moieties may be mono or polyunsaturated, and may exist in the E or Z configurations. The compounds of this invention are meant to include all possible E and Z configurations.
- alkynyl moiety may be mono or polyunsaturated. Examples include ethynyl.
- cycloalkyl refers to a monocyclic, bicyclic, tricyclic, fused, bridged, or spiro monovalent saturated hydrocarbon moiety of 3-10 carbon atoms, unless otherwise specified, wherein the carbon atoms are located inside or outside of the ring system. Any suitable ring position of the cycloalkyl moiety may be covalently linked to the defined chemical structure.
- cycloalkyl moieties include, but are not limited to, chemical groups such as cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cycloheptyl, norbornyl, adamantyl, spiro[4.5]decanyl, and homologs, isomers, or the like.
- aryl refers to an aromatic carbocyclic moiety of up to 20 carbon atoms, e.g. 6-20 carbon atoms, which may be a single ring (monocyclic) or multiple rings (bicyclic, up to three rings) fused together or linked covalently. Any suitable ring position of the aryl moiety may be covalently linked to the defined chemical structure.
- heteroaryl moieties include, but are not limited to, heterocycles such as furan, thiophene, pyrrole, N-methylpyrrole, pyrazole, N- methylpyrazole, imidazole, N-methylimidazole, oxazole, isoxazole, thiazole, isothiazole, 1 H-tetrazole, 1-methyltetrazole, 1 ,3,4-oxadiazole, 1 H-1 ,2,4-triazole, 1- methyl-1 ,2,4-triazole 1 ,3,4-triazole, 1-methyl-1 ,3,4-triazole, pyridine, pyrimidine, pyrazine, pyridazine, benzoxazole, benzisoxazole, benzothiazole, benzofuran, benzothiophene, thianthrene, dibenzo[b,d]furan, dibenzo[b,d]thiophene, benzimid
- Suitable salts with bases are, for example, metal salts, such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, thiomorpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower alkylamine, for example ethyl-tert- butyl-, diethyl-, diisopropyl-, triethyl-, tributyl- or dimethylpropylamine, or a mono-, di-, or trihydroxy lower alkylamine, for example mono-, di- or triethanolamine, where lower denotes 1-6 carbon atoms.
- metal salts such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts
- salts with ammonia or an organic amine such as morpholine, thiomorpholine, piperidine, pyrrolidine, a mono
- Tautomers often exist in equilibrium with each other. As these tautomers interconvert under environmental and physiological conditions, they provide the same useful biological effects.
- the present invention includes mixtures of such tautomers as well as the individual tautomers of Formula I and Formula It.
- the compounds of this invention may contain an asymmetric carbon atom and some of the compounds of this invention may contain one or more asymmetric centers and may thus give rise to optical isomers and diastereomers. While shown without respect to stereochemistry in Formula I, the present invention includes such optical isomers and diastereomers; as well as the racemic and resolved, enantiomerically pure R and S stereoisomers; as well as other mixtures of the R and S stereoisomers and pharmaceutically acceptable salts thereof. Where a stereoisomer is preferred, it may in some embodiments be provided substantially free of the corresponding enantiomer.
- an enantiomer substantially free of the corresponding enantiomer refers to a compound that is isolated or separated via separation techniques or prepared free of the corresponding enantiomer.
- substantially free means that the compound is made up of a significantly greater proportion of one steriosomer, preferably less than about 50%, more preferably less than about 75%, and even more preferably less than about 90%.
- Preferred compounds of formula I are those compounds wherein W is CO; X is N; Y is CRi 0 and Z is CR 11 .
- Another group of preferred compounds is those compounds of formula I wherein W is CO and R 7 is phenyl or heteroaryl. Also preferred are those compounds of formula I wherein W is CO; R 1 and R 2 are H and R 3 is CrC 3 alkyl.
- R 7 are optionally substituted phenyl and heteroaryl groups as defined herein, including pyrimidinyl (such as pyrimid-5-yl) and pyridyl (such as pyrid-
- More preferred compounds of the invention are those compounds of formula I wherein W is CO; X is N; Y is CR-ioi Z is CR 11 ; and R 7 is phenyl or heteroaryl.
- Another group of more preferred compounds of the invention are those compounds of formula I wherein W is CO; X is N; Y is CRi 0 ; Z is CR 11 ; R 7 is phenyl or heteroaryl; and R 1 and R 2 are H
- a further group of more preferred compounds of the invention are those compounds of formula I wherein W is CO; X is N; Y is CR 10 ; Z is CR 11 ; R 7 is phenyl or heteroaryl; R 1 and R 2 are H; and R 3 is methyl.
- Preferred compounds of the invention include: (5S)-2-amino-5-[4-fluoro-3-(2-fluoropyridin-3-yl)phenyl]-3-methyl-5-pyridin-4-yl-3,5- dihydro-4H-imidazol-4-one;
- Compounds of the invention may be prepared employing conventional methods that utilize readily available reagents and starting materials.
- the reagents used in the preparation of the compounds of this invention can be either commercially obtained or can be prepared by standard procedures described in the literature.
- Representative compounds of the present invention can be prepared using the following synthetic schemes. The skilled practitioner will know how to make use of variants of these reaction sequences, which in themselves are well known in the art.
- compounds of formula I wherein W is CO (Ia) may be prepared by reacting a diketone of formula Il with an aminoguanidine derivative of formula III in the presence of a base such as a metal carbonate to give the desired formula Ia compound. The reaction is shown in flow diagram I.
- the compounds of formula I act as BACE inhibitors for the treatment of ⁇ -amyloid deposits and neurofibrillary tangles associated with such diseases as Alzheimer's disease, Trisomy 21 (Down's Syndrome), Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch-type (HCHWA-D), and other neurodegenerative disorders.
- the present invention also provides methods for modulating (and, preferably, inhibiting) the activity of BACE, comprising administering to a patient and/or contacting a receptor thereof with an effective amount of at least one compound of Formula I. Certain methods further comprise determining BACE activity, either before or after said contacting step.
- the term "providing,” with respect to providing a compound or substance covered by this invention means either directly administering such a compound or substance, or administering a prodrug, derivative, or analog which will form the effective amount of the compound or substance within the body.
- This invention also covers providing the compounds of this invention to treat the disease states disclosed herein that the compounds are useful for treating.
- patient refers to a mammal, preferably a human.
- administered refers to either directly administering a compound or composition to a patient, or administering a prodrug derivative or analog of the compound to the patient, which will form an equivalent amount of the active compound or substance within the patient's body.
- effective amount refers to the amount of a compound that, when administered to a patient, is effective to at least partially ameliorate (and, in preferred embodiments, cure) a condition from which the patient is suspected to suffer.
- the effective dosage of the active compounds of this invention may vary depending upon the particular compound utilized, the mode of administration, the condition, and severity thereof, of the condition being treated, as well as the various physical factors related to the individual being treated.
- a daily dosage of from about 0.1 mg to about 1 mg per kilogram of body weight, preferably administered in divided doses two to six times per day, or in a sustained release form.
- the total daily dosage is from about 3.5 mg to about 140 mg preferably from about 3.5 to about 5 mg.
- the total daily dose will generally be from about 7 mg to about 70 mg and may be adjusted to provide the optimal therapeutic result.
- This regimen may be adjusted to provide the optimal therapeutic response.
- the present invention is directed to compositions comprising one or more compounds of formula I and one or more pharmaceutically acceptable carriers.
- the compounds of this invention may be administered orally or parenterally, neat or in combination with conventional pharmaceutical carriers.
- Applicable solid carriers can include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintegrating agents or encapsulating materials. They are formulated in conventional manner, for example, in a manner similar to that used for known antihypertensive agents, diuretics and ⁇ -blocking agents.
- Oral formulations containing the active compounds of this invention may comprise any conventionally used oral forms, including tablets, capsules, buccal forms, troches, lozenges and oral liquids, suspensions or solutions.
- Liquid carriers may be used in preparing solutions, suspensions, emulsions, syrups and elixirs.
- the active ingredient of this invention can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fat.
- the liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators.
- suitable examples of liquid carriers for oral and parenteral administration include water (particularly containing additives as above, e.g.
- cellulose derivatives preferably sodium carboxymethyl cellulose solution
- alcohols including monohydric alcohols and polyhydric alcohols, e.g. glycols) and their derivatives, and oils (e.g. fractionated coconut oil and arachis oil).
- the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate.
- Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration.
- the liquid carrier for pressurized compositions can be halogenated hydrocarbon or other pharmaceutically acceptable propellant.
- the effective dosage may vary depending upon the particular compound utilized, the mode of administration, the condition, and severity thereof, of the condition being treated, as well as the various physical factors related to the individual being treated.
- compounds of the present invention are provided to a patient already suffering from a disease in an amount sufficient to cure or at least partially ameliorate the symptoms of the disease and its complications. An amount adequate to accomplish this is defined as a "therapeutically effective amount".
- the dosage to be used in the treatment of a specific case must be subjectively determined by the attending physician. The variables involved include the specific condition and the size, age and response pattern of the patient. In some cases it may be desirable to administer the compounds directly to the airways in the form of an aerosol.
- the compounds of this invention may be formulated into an aqueous or partially aqueous solution.
- the compounds of this invention may be administered parenterally or intraperitoneally.
- Solutions or suspensions of these active compounds as a free base or pharmaceutically acceptable salt may be prepared in water suitably mixed with a surfactant such as hydroxyl-propylcellulose.
- Dispersions may also be prepared in glycerol, liquid polyethylene glycols and mixtures thereof in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to inhibit the growth of microorganisms.
- the pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions.
- the form must be sterile and must be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi.
- the carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils.
- the compounds of this invention can be administered transdermal ⁇ through the use of a transdermal patch.
- thransdermal administrations are understood to include all administrations across the surface of the body and the inner linings of bodily passages including epithelial and mucosal tissues. Such administrations may be carried out using the present compounds, or pharmaceutically acceptable salts thereof, in lotions, creams, foams, patches, suspensions, solutions, and suppositories (rectal and vaginal).
- Transdermal administration may be accomplished through the use of a transdermal patch containing the active compound and a carrier that is inert to the active compound, is non-toxic to the skin, and allows delivery of the agent for systemic absorption into the blood stream via the skin.
- the carrier may take any number of forms such as creams and ointments, pastes, gels and occlusive devices.
- the creams and ointments may be viscous liquid or semisolid emulsions of either the oil-in-water or water-in-oil type. Pastes comprised of absorptive powders dispersed in petroleum or hydrophilic petroleum containing the active ingredient may also be suitable.
- occlusive devices may be used to release the active ingredient into the blood stream, such as a semi-permeable membrane covering a reservoir containing the active ingredient with or without a carrier, or a matrix containing the active ingredient.
- Other occlusive devices are known in the literature.
- the compounds of this invention may be administered rectally or vaginally in the form of a conventional suppository.
- Suppository formulations may be made from traditional materials, including cocoa butter, with or without the addition of waxes to alter the suppository's melting point, and glycerin.
- Water soluble suppository bases such as polyethylene glycols of various molecular weights, may also be used.
- the dosage, regimen and mode of administration of these compounds will vary according to the malady and the individual being treated and will be subject to the judgment of the medical practitioner involved. It is preferred that the administration of one or more of the compounds herein begin at a low dose and be increased until the desired effects are achieved.
- Example 30 Using essentially the same procedure described in Example 30 and employing the appropriate boronic acid and suitable 5-(3-bromophenyl)imidazolone substrate, the compounds shown in Table VII were obtained and identified by NMR and mass spectral analyses.
- Table VII the term /-Pr designates isopropyl.
- Fluorescence Readings Readings at ⁇ ex 320 nm and ⁇ em 420 nm are taken every 40 sec for 30 min at room temperature and the linear slope for substrate cleavage rate (Vi) determined.
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Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BRPI0613578-1A BRPI0613578A2 (en) | 2005-06-30 | 2006-06-26 | a compound of formula i; use of a compound of formula i; and pharmaceutical composition |
MX2008000212A MX2008000212A (en) | 2005-06-30 | 2006-06-26 | Amino-5-(6-membered)heteroarylimidazolone compounds and the use thereof for beta-secretase modulation. |
AU2006266167A AU2006266167A1 (en) | 2005-06-30 | 2006-06-26 | Amino-5-(6-membered)heteroarylimidazolone compounds and the use thereof for beta-secretase modulation |
EP06774065A EP1896448A1 (en) | 2005-06-30 | 2006-06-26 | AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR ß-SECRETASE MODULATION |
JP2008519470A JP2009500329A (en) | 2005-06-30 | 2006-06-26 | Amino-5- (6 membered) heteroarylimidazolone compounds and their use for β-selectase modulation |
CA002613435A CA2613435A1 (en) | 2005-06-30 | 2006-06-26 | Amino-5-(6-membered)heteroarylimidazolone compounds and the use thereof for .beta.-secretase modulation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US69530505P | 2005-06-30 | 2005-06-30 | |
US60/695,305 | 2005-06-30 |
Publications (1)
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WO2007005404A1 true WO2007005404A1 (en) | 2007-01-11 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US2006/024912 WO2007005404A1 (en) | 2005-06-30 | 2006-06-26 | AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR ß-SECRETASE MODULATION |
Country Status (9)
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US (2) | US7452885B2 (en) |
EP (1) | EP1896448A1 (en) |
JP (1) | JP2009500329A (en) |
CN (1) | CN101213183A (en) |
AU (1) | AU2006266167A1 (en) |
BR (1) | BRPI0613578A2 (en) |
CA (1) | CA2613435A1 (en) |
MX (1) | MX2008000212A (en) |
WO (1) | WO2007005404A1 (en) |
Cited By (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007058601A1 (en) * | 2005-11-21 | 2007-05-24 | Astrazeneca Ab | Novel 2-amino-imidazole-4-one compounds and their use in the manufacture of a medicament to be used in the treatment of cognitive impairment, alzheimer’s disease, neurodegeneration and dementia |
WO2007058602A3 (en) * | 2005-11-21 | 2007-07-05 | Astrazeneca Ab | Novel 2-amino-imidazole-4-one compounds and their use in the manufacture of a medicament to be used in the treatment of cognitive impairment, alzheimer’s disease, neurodegeneration and dementia. |
WO2007078813A2 (en) * | 2005-12-19 | 2007-07-12 | Wyeth | 2-AMINO-5-PIPERIDINYLIMIDAZOLONE COMPOUNDS AND USE THEREOF FOR β-SECRETASE MODULATION |
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 |
WO2008022024A2 (en) * | 2006-08-17 | 2008-02-21 | Wyeth | Imidazole amines as inhibitors of beta-secretase |
WO2008076043A1 (en) * | 2006-12-20 | 2008-06-26 | Astrazeneca Ab | Novel 2-amino-5,5-diaryl-imidazol-4-ones |
US7417047B2 (en) | 2005-06-30 | 2008-08-26 | Wyeth | Amino-5-(5-membered)hetero-arylimidazolone compounds and the use thereof for β-secretase modulation |
US7423158B2 (en) | 2005-09-26 | 2008-09-09 | Wyeth | Amino-5-[4-(difluoromethoxy)phenyl]-5-phenylimidazolone compounds for the inhibition of β-secretase |
US7452885B2 (en) | 2005-06-30 | 2008-11-18 | Wyeth | Amino-5-(6-membered)heteroarylimidazolone compounds and the use thereof for β-secretase modulation |
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CA2613435A1 (en) | 2007-01-11 |
BRPI0613578A2 (en) | 2012-01-17 |
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US20090042908A1 (en) | 2009-02-12 |
US20070004730A1 (en) | 2007-01-04 |
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