Treatment of diseases related to alpha subunits of sodium channels, voltage-gated (SCNxA) with small molecules

• US 10,583,128 B2
• Filed: 08/28/2012
• Issued: 03/10/2020
• Est. Priority Date: 09/06/2011
• Status: Active Grant

• Current Assignee: CURNA, Inc. (Opko Health, Inc.)
• Original Assignee: CURNA, Inc. (Opko Health, Inc.)
• Inventors: Collard, Joseph, Khorkova Sherman, Olga, Hsiao, Jane H.
• Primary Examiner(s): Krishnan, Ganapathy
• Application Number:
  US14/343,890
• Publication Number:
  US 20140309181A1
• Time in Patent Office: 2,751 Days
• Field of Search: 514 27, 514176, 514221, 514237, 5142378, 514250, 51425405, 51425407, 51425504, 514291, 514318
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/41 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 31/4245 Oxadiazoles
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4409 only substituted in position 4, e.g. isoniazid, iproniazid
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• 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 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/5375 1,4-Oxazines, e.g. morpholine
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/64 Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/08 : of the prostate
• CPC Class Codes: A61P 13/12 : of the kidneys
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/10 : for impotence
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Small compounds that modulate the expression of and/or function of sodium channel, voltage-gated, alpha subunit (SCNxA) are presented. Pharmaceutical compositions containing such small molecules and their use in treating diseases and disorders associated with the expression of SCNxA are also presented.

Claims

1. A method of treating a patient having Dravet Syndrome comprising:

contacting said patient with at least one compound selected from the group consisting of milnacipran, torsemide, pinacidil, benidipine, ketoconazole, ebselen, tadalafil, zeranol, nefazadone, lomerizine, icariin, omeprazole, esomeprazole, 2-[5-[3-(4-Methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine, nitrendipine, amlexanox, mosapride, or stanozolol or pharmaceutically acceptable salts, isomers, enantiomers, isoforms, polymorphs, hydrates, solvates thereof wherein said treatment results in the upregulation of the expression of a sodium channel, voltage-gated, alpha subunit (SCN1A) polynucleotide and treats said patient having Dravet Syndrome.

2. A method of treating a patient having generalized epilepsy with febrile seizure plus (GEFS+) with a therapeutically effective dose of at least one compound selected from the group consisting of milnacipran, torsemide, pinacidil, benidipine, ketoconazole, ebselen, tadalafil, zeranol, nefazadone, lomerizine, icariin, omeprazole, esomeprazole, 2-[5-[3-(4-Methylsulfonylamino)benzyl-1,2,4-oxadiazol-5-yl]-1H-indol-3-yl]ethanamine, nitrendipine, amlexanox, mosapride, or stanozolol or pharmaceutically acceptable salts, isomers, enantiomers, isoforms, polymorphs, hydrates or solvates thereof that upregulates the expression of a sodium channel, voltage-gated, alpha subunit (SCN 1A), and wherein the administration of said compound relieves or causes regression of said disease.