DIAGNOSTIC AND REMEDY FOR DISEASE CAUSED BY AMYLOID AGGREGATION AND/OR DEPOSITION

• US 20090162283A1
• Filed: 11/30/2006
• Published: 06/25/2009
• Est. Priority Date: 11/30/2005
• Status: Active Grant

• Current Assignee: Fujifilm Ri Pharma Co., Ltd. (Fujifilm Holdings Corporation)
• Original Assignee: Daiichi Sankyo Company Limited, Fujifilm Ri Pharma Co., Ltd. (Fujifilm Holdings Corporation)
• Inventors: Taguchi, Kazumi, Bando, Kazunori
• Granted Patent: US 8,022,075 B2
• Time in Patent Office: Days
• US Class Current: 424/1.890
• CPC Class Codes: A61K 31/423 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 51/0453 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 51/0455 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 51/0459 having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 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
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 235/18 with aryl radicals directly attached in position 2
• CPC Class Codes: C07D 263/57 Aryl or substituted aryl radicals
• CPC Class Codes: C07D 277/66 with aromatic rings or ring systems directly attached in position 2
• CPC Class Codes: C07D 403/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 413/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 417/10 : linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: G01N 2333/4709 : Amyloid plaque core protein
• CPC Class Codes: G01N 2500/04 : Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)

Abstract

To provide a diagnostic drug which binds specifically to an amyloid aggregate and/or an amyloid deposit, to thereby realize imaging and quantification of a disease caused by amyloid aggregation and/or deposition.

The invention provides a compound represented by formula (1):

(wherein X¹ represents an optionally substituted bicyclic heterocyclic group;

• • X² represents a hydrogen atom, a halogen atom, or a chelate-forming group;
  • ring A represents a benzene ring or a pyridine ring; and
  • ring B represents an optionally substituted 5-membered aromatic heterocyclic group which is bonded to the benzene ring or the pyridine ring via a carbon atom of ring B), a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these, and a diagnostic, preventive, or therapeutic drug containing the same.

Claims

1. A compound represented by formula (1):

2. A compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as described in claim 1, wherein X¹, X², or ring B has at least one halogen atom.

3. A compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as described in claim 1, wherein X¹, X², or ring B has at least one radioactive nuclide.

4. A compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as described in claim 3, wherein the radioactive nuclide is selected from a radioactive halogen atom and a radioactive transition metal atom.

5. A compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as described in any one of claims 1 to 4, wherein X¹ is an optionally substituted 6-membered-5-membered bicyclic heterocyclic group.

6. A compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as described in any one of claims 1 to 5, wherein X¹ is an optionally substituted benzothiazolyl, benzoxazolyl, imidazopyridyl, imidazopyrimidyl, or benzimidazolyl group.

7. A compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as described in any one of claims 1 to 6, wherein the group X¹ which serves as a substituent of the bicyclic heterocyclic group is one to three substituents selected from among a halogen atom, a hydroxy group, an alkyl group, an alkyltin group, a halogenoalkyl group, a halogenoalkylcarbonylamino group, and a chelate-forming group.

8. A compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as described in any one of claims 1 to 7, wherein ring B is an optionally substituted 5-membered aromatic azo-heterocyclic group.

9. A compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as described in any one of claims 1 to 8, wherein ring B is an optionally substituted oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, imidazolyl, triazolyl, thiadiazolyl, oxadiazolyl, or tetrazolyl group.

10. A compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as described in any one of claims 1 to 9, wherein the substituent of ring B is one to three substituents selected from among a halogen atom, an alkyl group, an alkoxy group, and a chelate-forming group.

11. A drug containing a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10.

12. An imaging agent containing a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10.

13. An amyloid imaging agent containing a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10.

14. A preventive and/or therapeutic drug for amyloidosis, containing a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10.

15. A preventive and/or therapeutic drug for a disease caused by aggregation or deposition of amyloid, containing a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10.

16. A preventive and/or therapeutic drug for Alzheimer'"'"'s disease, Down syndrome, Creutzfeldt-Jakob disease, type-II diabetes, dialysis amyloidosis, AA amyloidosis, Gerstmann-Straeussler-Scheinker syndrome, Mucks-Wells syndrome, localized atrial amyloidosis, medullary thyroid cancer, cutaneous amyloidosis, localized nodular amyloidosis, AL amyloidosis, AH amyloidosis, familial amyloid polyneuropathy, senile systemic amyloidosis, cerebrovascular amyloidosis, familial Mediterranean fever, Parkinson disease, tauopathy, ALS, or CAG repeat disease, which drug comprises a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10.

17. A pharmaceutical composition comprising a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10, and a pharmaceutically acceptable carrier.

18. Use of a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10 for producing a drug.

19. A method for imaging an amyloid deposit, characterized in that the method comprises administering, to a subject in need thereof, a labeled compound as recited in any one of claims 1 to 10 in a detectable amount, allowing to pass a sufficient period of time for achieving binding between the labeled compound and the amyloid deposit, and detecting the labeled compound which has been bound to the amyloid deposit.

20. A method for prevention and/or treatment of a disease caused by aggregation or deposition of amyloid, characterized in that the method comprises administering, to a subject in need thereof, a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10 in an effective amount.

21. A method for prevention and/or treatment of Alzheimer'"'"'s disease, characterized in that the method comprises administering, to a subject in need thereof, a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10 in an effective amount.

23. A screening method for a preventive and/or therapeutic drug for a disease caused by aggregation or deposition of amyloid, characterized in that method comprises detecting the binding ability of a specimen to amyloid or determining the degree of aggregation and/or deposition of amyloid by use of a compound, a salt thereof, a solvate of any of these, or a transition metal coordination compound of any of these as recited in any one of claims 1 to 10.

24. A screening method as described in claim 23, wherein detecting or determining is performed in vitro or in vivo.

25. A preventive and/or therapeutic drug for a disease caused by aggregation and/or deposition of amyloid, which drug comprises a substance selected through a screening method as recited in claim 23 or 24.

22. A compound represented by formula (2):