WO2014013338A3 - Compounds for the treatment of alzheimer's disease - Google Patents

Compounds for the treatment of alzheimer's disease Download PDF

Info

Publication number
WO2014013338A3
WO2014013338A3 PCT/IB2013/001994 IB2013001994W WO2014013338A3 WO 2014013338 A3 WO2014013338 A3 WO 2014013338A3 IB 2013001994 W IB2013001994 W IB 2013001994W WO 2014013338 A3 WO2014013338 A3 WO 2014013338A3
Authority
WO
WIPO (PCT)
Prior art keywords
heteroaryl
aryl
relates
disease
group
Prior art date
Application number
PCT/IB2013/001994
Other languages
French (fr)
Other versions
WO2014013338A2 (en
Inventor
Jia Luo
Gregory R.J. Thatcher
Original Assignee
Sgc Pharma, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sgc Pharma, Inc. filed Critical Sgc Pharma, Inc.
Publication of WO2014013338A2 publication Critical patent/WO2014013338A2/en
Publication of WO2014013338A3 publication Critical patent/WO2014013338A3/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to the use of compounds of formula (I): wherein R1 is H, substituted or unsubstituted aryl, heteroaryl or C1-24 aliphatic group, -(CH2)1-3-aryl or -(CH2 )1-3 - heteroaryl, R2 is selected from the group consisting of H, substituted or unsubstituted aryl, heteroaryl or C1-24 aliphatic group, -ORa, halo, N(Ra)(Rb), N3, -(CH2) 1-3Ra and -(CH2)1-3-halo, wherein Ra and Rb are independently selected from the group consisting of H, C1-3 alkyl, aryl or heteroaryl, or Ra and Rb are taken together with the atom to which they are attached to form a 3 to 6 membered ring and wherein at least one of R1 and R2 is not H to provide neuroprotection via a GABAA-dependent or GABAA-indedependent pathway wherein the compound acts in a neuroprotective and/or neurorestorative manner with reduced sedative effects. In an alternate embodiment, the invention relates to the use of GT-1061 for upregulating or activating NO/cGMP/CREB pathway to provide neuroprotective and neurorestorative effects, to lower the levels of Αβ protein in the brain or to lower the level of tau, without causing sedation, hi another embodiment, the invention relates to the use of GT-1061 to treat a neurodegenerative disease or Alzheimer's disease or related disorders without causing sedative effects.
PCT/IB2013/001994 2012-07-16 2013-07-16 Compounds for the treatment of alzheimer's disease WO2014013338A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261672125P 2012-07-16 2012-07-16
US61/672,125 2012-07-16

Publications (2)

Publication Number Publication Date
WO2014013338A2 WO2014013338A2 (en) 2014-01-23
WO2014013338A3 true WO2014013338A3 (en) 2014-04-03

Family

ID=49949308

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2013/001994 WO2014013338A2 (en) 2012-07-16 2013-07-16 Compounds for the treatment of alzheimer's disease

Country Status (1)

Country Link
WO (1) WO2014013338A2 (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000054756A2 (en) * 1999-03-15 2000-09-21 Queen's University At Kingston Nitrate esters and their use for introducing neuroprotection and cognition enhancement
WO2001049275A2 (en) * 1999-12-29 2001-07-12 Queen's University At Kingston Methods and compositions for mitigating pain using nitrate esters
US20050137191A1 (en) * 1996-06-04 2005-06-23 Thatcher Gregory R. Nitrate esters and their use for mitigating cellular damage
WO2005105065A2 (en) * 2004-05-05 2005-11-10 Renopharm Ltd. Thiazole-based nitric oxide donors for treating inflammatory bowel diseases
WO2011140198A2 (en) * 2010-05-05 2011-11-10 The Board Of Trustees Of The University Of Illinois Compounds and methods of treating brain disorders
WO2012027471A1 (en) * 2010-08-24 2012-03-01 Sgc Pharma, Inc. Salt compound

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050137191A1 (en) * 1996-06-04 2005-06-23 Thatcher Gregory R. Nitrate esters and their use for mitigating cellular damage
WO2000054756A2 (en) * 1999-03-15 2000-09-21 Queen's University At Kingston Nitrate esters and their use for introducing neuroprotection and cognition enhancement
WO2001049275A2 (en) * 1999-12-29 2001-07-12 Queen's University At Kingston Methods and compositions for mitigating pain using nitrate esters
WO2005105065A2 (en) * 2004-05-05 2005-11-10 Renopharm Ltd. Thiazole-based nitric oxide donors for treating inflammatory bowel diseases
WO2011140198A2 (en) * 2010-05-05 2011-11-10 The Board Of Trustees Of The University Of Illinois Compounds and methods of treating brain disorders
WO2012027471A1 (en) * 2010-08-24 2012-03-01 Sgc Pharma, Inc. Salt compound

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
BENNET ET AL.: "Cognitive Deficits in Rats after Forebrain Cholinergic Depletion are Reversed by a Novel NO Mimetic Nitrate Ester", NEUROPSYCHOPHARMACOLOGY, vol. 32/3, 2007, pages 505 - 513 *
IQBAL ET AL.: "Tau Pathology in Alzheimer Disease and other tauopathies", BIOCHIM. BIOPHYS. ACTA, vol. 1739/2-3, 2005, pages 198 - 210 *
NELSON ET AL.: "Neuroprotective efficacy of AR-A008055, a clomethiazole analogue, in a global model of acute ischaemic stroke and its effect on ischaemia- induced glutamate and GABA efflux in vitro", NEUROPHARMACOLOGY, vol. 41/2, 2001, pages 159 - 166 *
QIN ET AL.: "Design and Synthesis ofNeuroprotective Methylthiazoles and Modification as NO-Chimeras for Neurodegenerative Therapy", J. MED. CHEM., vol. 55/15, 2012, pages 6784 - 6801 *
THATCHER ET AL.: "Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimer's Disease", CURRRENT ALZHEIMER RESEARCH, vol. 2, 2005, pages 171 - 182 *
THATCHER ET AL.: "NO Chimerase as Therapeutic Agents in Alzheimer's Disease", CURRRENT ALZHEIMER RESEARCH, vol. 3, 2006, pages 237 - 245 *
THATCHER ET AL.: "Novel nitrates as NO mimetics directed at Alzheimer's disease", J. ALZHEIMER'S DISEASE, vol. 6, 2004, pages S75 - S84 *

Also Published As

Publication number Publication date
WO2014013338A2 (en) 2014-01-23

Similar Documents

Publication Publication Date Title
WO2014031438A3 (en) SUBSTITUTED PHENYL SPLEEN TYROSINE KINASE (Syk) INHIBITORS
UY37845A (en) SULFONYLUREAS AND SULPHONYLTIOUREAS USEFUL AS INHIBITORS OF NLRP3
TN2013000285A1 (en) Novel heterocyclic derivatives and their use in the treatment of neurological disorders
EA201791011A1 (en) 3-SUBSTITUTED 5-AMINO-6H-TIAZOLO [4,5-d] Pyrimidine-2,7-DION COMPOUNDS FOR THE TREATMENT AND PREVENTION OF VIRAL INFECTIONS
GEP201706608B (en) 1 - arylcarbonyl - 4 - oxy – piperidine compounds useful for the treatment of neurodegenerative diseases
WO2010068483A3 (en) Mlk inhibitors and methods of use
WO2011149950A3 (en) Bicyclic heteroaryl kinase inhibitors and methods of use
MX2013012776A (en) Amino-pyridine-containing spleen tyrosine kinase (syk) inhibitors.
IN2014DN09805A (en)
WO2015039612A8 (en) Compound inhibiting activities of btk and/or jak3 kinases
WO2014070991A3 (en) Galactopyranosyl-cyclohexyl derivatives as e-selectin antagonists
BR112013022813B1 (en) Diaminocarbonitrile pyrimidines and substituted diaminocarboxamide, compositions thereof and methods of treatment therewith
MX2014004479A (en) Novel oxazine derivatives and their use in the treatment of disease.
WO2012048129A3 (en) Inhibitors of polo-like kinase
BR112017022568A2 (en) compounds and their uses as bace1 inhibitors
IN2014MN02082A (en)
WO2014125408A3 (en) Substituted 1h-pyrrolopyridinone derivatives as kinase inhibitors
EA201500182A1 (en) 4-METHYL-2,3,5,9,9b-PENTAASACYCLOPENT [a] NAFTAIL
LT3609886T (en) Benzoazepine analogs as inhibiting agents for bruton's tyrosine kinase
RU2014121205A (en) ASOLES DERIVATIVES
SI3386991T1 (en) Polycyclic compounds as inhibitors of bruton's tyrosine kinase
EP2898923A3 (en) Isoflavones for regulating sirtuin gene expression
WO2013040227A3 (en) Therapeutic compounds
MX2018006636A (en) Cyclic phosphates and cyclic phosphoramidates for the treatment of neurologic disorders.
SG10201907291QA (en) Monomethylfumarate prodrug compositions

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 13819594

Country of ref document: EP

Kind code of ref document: A2

122 Ep: pct application non-entry in european phase

Ref document number: 13819594

Country of ref document: EP

Kind code of ref document: A2