Methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid

• US 9,499,480 B2
• Filed: 04/07/2014
• Issued: 11/22/2016
• Est. Priority Date: 10/12/2006
• Status: Active Grant

• Current Assignee: BELLUS Health, Inc. (GSK plc)
• Original Assignee: BHI Limited Partnership
• Inventors: Kong, Xianqi, Atfani, Mohamed, Bachand, Benoit, Bouzide, Abderrahim, Ciblat, Stephane, Levesque, Sophie, Migneault, David, Valade, Isabelle, Wu, Xinfu, Delorme, Daniel
• Primary Examiner(s): Lau, Jonathan S
• Application Number:
  US14/246,894
• Publication Number:
  US 20140220122A1
• Time in Patent Office: 960 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/145 having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) isothiourea A61K31/155
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/542 Carboxylic acids, e.g. a fatty acid or an amino acid
• CPC Class Codes: A61K 47/545 Heterocyclic compounds A61K47/558 takes precedence
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61K 47/554 the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
• CPC Class Codes: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: C07C 309/15 the nitrogen atom of at least one of the amino groups being part of any of the groups , X being a hetero atom, Y being any atom
• CPC Class Codes: C07C 309/18 containing amino groups bound to the same carbon skeleton
• CPC Class Codes: C07C 309/19 of a saturated carbon skeleton containing rings
• CPC Class Codes: C07C 309/24 of a carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07D 207/16 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 209/20 substituted additionally by nitrogen atoms, e.g. tryptophane
• CPC Class Codes: C07D 217/24 Oxygen atoms
• CPC Class Codes: C07D 233/64 with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
• CPC Class Codes: C07D 285/36 Seven-membered rings
• CPC Class Codes: C07D 285/38 Eight-membered rings
• CPC Class Codes: C07D 291/02 not condensed with other rings
• CPC Class Codes: C07D 317/40 Vinylene carbonate; Substituted vinylene carbonates
• CPC Class Codes: C07D 323/02 Five-membered rings
• 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
• CPC Class Codes: C07H 15/12 : attached to a nitrogen atom of the saccharide radical
• CPC Class Codes: C07H 7/02 : Acyclic radicals
• CPC Class Codes: C07J 9/005 : containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
• CPC Class Codes: C07K 5/06026 : the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
• CPC Class Codes: C07K 5/06052 : Val-amino acid
• CPC Class Codes: C07K 5/0606 : the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr
• CPC Class Codes: C07K 5/06069 : Ser-amino acid
• CPC Class Codes: C07K 5/06086 : with the first amino acid being basic
• CPC Class Codes: C07K 5/0806 : the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
• CPC Class Codes: C07K 5/081 : the side chain containing O or S as heteroatoms, e.g. Cys, Ser
• CPC Class Codes: C12P 11/00 : Preparation of sulfur-containing organic compounds
• CPC Class Codes: C12P 13/001 : Amines; Imines
• CPC Class Codes: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compound that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to the prevention and treatment of Alzheimer'"'"'s disease.

Claims

1. A compound of Formula XII:

2. The compound of claim 1, wherein D is a carbonyl.

3. The compound of claim 1, wherein D is a substituted methylene group.

4. The compound of claim 1, wherein X is an oxygen atom.

5. The compound of claim 1, wherein Xis a NH group.

6. The compound of claim 1, wherein X is a sulfur atom.

7. The compound claim 1, wherein said compound is of Formula XII-A:

8. The compound of claim 7, wherein said R¹⁴ is a substituted or unsubstituted C₁-C₁₂alkyl group.

9. The compound of claim 8, wherein said R¹⁴ is a substituted or unsubstituted C₁-C₆alkyl group.

10. A pharmaceutical composition comprising a compound of claim 1 together with a pharmaceutically acceptable carrier.

11. The pharmaceutical composition of claim 10 which is suitable for oral administration.

12. The pharmaceutical composition of claim 10, which is in the form of a hard shell gelatin capsule, soft shell gelatin capsule, cachet, pill, tablet, lozenge, powder, granule, pellet, dragee, which is optionally enteric coated, a solution, an aqueous liquid suspension, a non-aqueous liquid suspension, an oil-in-water liquid emulsion, a water-in-oil liquid emulsion, an elixir, a syrup, or a pastille.

13. A compound selected from: