Compounds to treat Alzheimer's disease

• US 7,553,831 B2
• Filed: 01/25/2005
• Issued: 06/30/2009
• Est. Priority Date: 06/30/2000
• Status: Expired due to Fees

• Current Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Original Assignee: Elan Pharmaceuticals Incorporated (Perrigo Company PLC)
• Inventors: Gailunas, Andrea, Jagodinska, Barbara, Maillaird, Michael, Beck, James, John, Varghese, Hom, Roy
• Primary Examiner(s): Wilson; James O.
• Assistant Examiner(s): Ward; Paul V.
• Application Number:
  US11/042,695
• Publication Number:
  US 20050203096A1
• Time in Patent Office: 1,617 Days
• Field of Search: 514/183, 514/252.12, 514/616, 514/617, 544/358, 544/398, 544/402
• US Class Current: 514/183
• 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: C07C 215/28 and containing six-membered aromatic rings
• CPC Class Codes: C07C 233/78 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
• CPC Class Codes: C07C 235/84 with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 239/20 having oxygen atoms of hydroxylamino groups etherified
• CPC Class Codes: C07C 243/22 having nitrogen atoms of hydrazine groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 243/28 to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
• CPC Class Codes: C07C 271/16 to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 271/18 to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms
• CPC Class Codes: C07C 275/24 containing six-membered aromatic rings
• CPC Class Codes: C07C 311/03 having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 311/08 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 311/13 the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 311/16 having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
• CPC Class Codes: C07C 311/37 having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 317/44 having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
• CPC Class Codes: C07C 323/60 with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
• CPC Class Codes: C07D 211/60 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 215/12 with substituted hydrocarbon radicals attached to ring carbon atoms
• CPC Class Codes: C07D 223/10 attached in position 2
• CPC Class Codes: C07D 277/04 : having no double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 295/13 : to an acyclic saturated chain
• CPC Class Codes: C07D 303/36 : with hydrocarbon radicals, substituted by nitrogen atoms nitro, nitroso radicals C07D303/08
• CPC Class Codes: C07D 307/52 : Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 307/54 : Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/24 : Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

The present invention is disubstituted amines of formula (I)

and disubstituted amines of formula (II)

useful in treating Alzheimer'"'"'s disease and other similar diseases.

Claims

1. A compound of formula I

2. A compound according to claim 1, wherein R₁ is:

—

(CH₂)_0-1—

(R_1-aryl), or

—

(CH₂)_n-1—

(R_1-heteroaryl).

3. A compound according to claim 2, wherein R₁ is:

—

(CH₂)—

(R_1-aryl), or

—

(CH₂)—

(R_1-heteroaryl).

4. A compound according to claim 3, wherein R₁ is —

(CH₂)—

(R_1-aryl) where R_1-aryl is phenyl.

5. A compound according to claim 4, wherein R₁ is substituted with two —

F.

6. A compound according to claim 1, wherein R₂ and R₃ are both —

H.

7. A compound according to claim 1, wherein R_C is:

—

C₁-C₈ alkyl,

—

(CH₂)_0-3—

(C₃-C₇) cycloalkyl,

—

(CR_C-xR_C-y)_0-4—

R_C-aryl,

—

(CR_C-xR_C-y)_0-4—

R_C-heteroary,

—

(CR_C-xR_C-y)_0-4—

R_{C-heterocycle}, or

-cyclopentyl or -cyclohexyl ring fused to R_C-aryl or R_C-heteroaryl or R_{C-heterocycle}.

8. A compound according to claim 7, wherein R_C is:

—

(CH₂)_0-3—

(C₃-C₇) cycloalkyl,

—

(CR_C-xR_C-y)_0-4—

R_C-aryl,

—

(CR_C-xR_C-y)_0-4R_C-heteroaryl,

—

(CR_C-xR_C-y)_0-4R_{C-heterocycle},

-cyclopentyl or -cyclohexyl ring fused to a R_C-aryl R_C-heteroaryl or R_{C-heterocycle}.

9. A compound according to claim 8, wherein R_C is:

—

(CR_C-xR_C-y)_0-4—

R_C-aryl,

—

(CR_C-xR_C-y)_0-4—

R_C-heteroaryl,

-cyclopentyl or -cyclohexyl ring fused to a R_C-aryl R_C-heteroaryl or R_{C-heterocycle}.

10. A compound according to claim 9, wherein R_C is:

—

(CR_C-xR_C-y)_0-4—

R_C-aryl where R_C-aryl is phenyl.

11. A compound according to claim 10, wherein said phenyl is substituted in the 3-position or 3,5-positions.

12. A compound according to claim 1, wherein R_C-A is:

-methyl, or

-ethyl.

13. A compound according to claim 1, wherein Z is:

—

C(O)—

, or

—

C(O)—

X_N-1-where X_N-1 is selected from the group consisting of —

O—

, —

S—

and —

NR′

—

.

14. A composition comprising a compound according to claim 1, and a binder, excipient, disintegrating agent, lubricant, or glidant.