Aminodihydrothiazine derivatives substituted with a cyclic group

• US 8,168,630 B2
• Filed: 04/23/2008
• Issued: 05/01/2012
• Est. Priority Date: 04/24/2007
• Status: Expired due to Fees

• Current Assignee: Shionogi & Co., Ltd.
• Original Assignee: Shionogi & Co., Ltd.
• Inventors: Tamura, Yuusuke, Suzuki, Shinji, Tada, Yukio, Fujikoshi, Chiaki, Matsumoto, Sae, Kooriyama, Yuuji, Ueno, Tatsuhiko, Yonezawa, Shuji
• Primary Examiner(s): HABTE, KAHSAY
• Application Number:
  US12/596,796
• Publication Number:
  US 20100075957A1
• Time in Patent Office: 1,469 Days
• Field of Search: 514/227.2, 544/53, 544/55
• US Class Current: 514/227.2
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 215/20 the carbon skeleton being saturated and containing rings
• CPC Class Codes: C07D 279/06 not condensed with other rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 493/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 Ortho-condensed systems
• CPC Class Codes: C07D 513/04 Ortho-condensed systems

Abstract

This invention provides a compound of the formula (I):

wherein the ring A is an optionally substituted carbocyclic group or an optionally substituted heterocyclic group; R¹ is optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl; R^2a and R^2b are each independently hydrogen, optionally substituted lower alkyl or optionally substituted acyl; R^3a, R^3b, R^3c and R^3d are each independently hydrogen, halogen, hydroxy or optionally substituted lower alkyl etc.;
a pharmaceutically acceptable salt or solvate thereof,
which is useful for treating diseases induced by production, secretion and/or deposition of amyloid β protein.

Claims

1. A compound of the formula (I):

2. The compound of claim 1,

wherein the ring A is

3. The compound of claim 2, wherein the ring A′

is phenyl or a nitrogen-containing aromatic heterocyclic group;

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 2, wherein the ring A′

is a nitrogen-containing aromatic monocyclic heterocyclic group;

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1, wherein R¹ is C1-C3 alkyl;

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1, wherein both of R^2a and R^2b are hydrogen;

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1, wherein all of R^3a, R^3b, R^3cand R^3d are hydrogen;

or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1, wherein R^3a and R^3b are the same substituent selected from halogen and optionally substituted lower alkyl wherein the substituent(s) is selected from the substituent group α

;

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1, wherein R^3c and R^3d are the same substituent selected from halogen and optionally substituted lower alkyl wherein the substituent(s) is selected from the substituent group α

;

or a pharmaceutically acceptable salt thereof.

10. The compound of claim 1, wherein R^3a and R^3b, or R^3c and R^3d form a carbocyclic ring together with a linked carbon atom;

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof as an active ingredient, and a pharmaceutically acceptable carrier.

12. A method for treating a condition selected from the group consisting of Down'"'"'s disease, prion disease, mild cognitive impairment (MCI), Dutch-type hereditary cerebral hemorrhage with amyloidosis, cerebral amyloid angiopathy, degenerated dementia, vascular degenerated mixed dementia, dementia associated with Parkinson'"'"'s disease, dementia associated with progressive supranuclear paralysis, dementia associated with corticobasal degeneration, diffuse Lewy Bodies Alzheimer'"'"'s disease, age-related macular degeneration, Parkinson'"'"'s disease, or amyloid angiopathy in a subject in need thereof, comprising administering to the subject an effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.