Substrate reduction therapy

• US 9,428,541 B2
• Filed: 09/13/2013
• Issued: 08/30/2016
• Est. Priority Date: 06/27/2007
• Status: Active Grant

• Current Assignee: United States Department Of Health And Human Services
• Original Assignee: United States Department Of Health And Human Services, Chancellor Masters & Scholars of The University of Cambridge (University of Cambridge)
• Inventors: Platt, Frances Mary, Lloyd-Evans, Emyr, Porter, Forbes Dennison
• Primary Examiner(s): Lau, Jonathan S
• Application Number:
  US14/026,957
• Publication Number:
  US 20140080769A1
• Time in Patent Office: 1,082 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/431 containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61K 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/661 Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
• CPC Class Codes: A61K 31/6615 Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/7008 Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
• CPC Class Codes: A61K 31/7012 Compounds having a free or esterified carboxyl group attached, directly or through a carbon chain, to a carbon atom of the saccharide radical, e.g. glucuronic acid, neuraminic acid gluconic acid A61K31/191; ascorbic acid A61K31/375
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/708 : having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
• CPC Class Codes: A61K 45/06 : Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 17/00 : Drugs for dermatological disorders
• 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 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 211/94 : Oxygen atom, e.g. piperidine N-oxide
• CPC Class Codes: C07D 473/16 : two nitrogen atoms
• CPC Class Codes: C07H 19/06 : Pyrimidine radicals
• CPC Class Codes: C07H 19/20 : with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07J 43/003 : not condensed
• CPC Class Codes: C07J 7/009 : by only one oxygen atom doubly bound

Abstract

The present invention provides a compound which is an inhibitor of sphingolipid biosynthesis for use in the treatment of a disease which has a secondary Niemann-Pick type C disease like cellular phenotype.

Claims

1. A method of treating a subject having a disease which has a secondary Niemann-Pick type C disease like cellular phenotype, wherein the disease is inborn error of cholesterol synthesis, Tangier disease, Pelizaeus-Merzbacher disease, Mucolipidosis II (cell), or variant late infantile-Neuronal Ceroid Lipofuscinosis, and wherein the method comprises selecting the subject having the disease, and administering to the subject an effective amount of N-butyldeoxynojirimycin;

N-nonyldeoxynojirimycin;

N-butyldeoxygalactonojirimycin;

N-5adamantane-1-yl-methoxypentyl-deoxynojirimycin;

alpha-homogalactonojirimycin;

nojirimycin;

deoxynojirimycin;

N7-oxadecyl-deoxynojirimycin;

deoxygalactonojirimycin;

N-butyl-deoxygalactonojirimycin;

N-nonyl-6deoxy-DGJ;

alpha-homoallonojirimycin;

or beta-1C-butyl-deoxygalactonojirimycin.

2. The method of claim 1, wherein the disease is Tangier disease.

3. The method of claim 2, wherein the inhibitor of sphingolipid biosynthesis is N-butyldeoxynojirimycin.