WO2007109024A2 - Thiazolidinedione analogues for the treatment of metabolic inflammation mediated disease - Google Patents

Thiazolidinedione analogues for the treatment of metabolic inflammation mediated disease Download PDF

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Publication number
WO2007109024A2
WO2007109024A2 PCT/US2007/006321 US2007006321W WO2007109024A2 WO 2007109024 A2 WO2007109024 A2 WO 2007109024A2 US 2007006321 W US2007006321 W US 2007006321W WO 2007109024 A2 WO2007109024 A2 WO 2007109024A2
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WO
WIPO (PCT)
Prior art keywords
optionally substituted
aliphatic
hydrogen
compound
ring
Prior art date
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Ceased
Application number
PCT/US2007/006321
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English (en)
French (fr)
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WO2007109024A3 (en
Inventor
Gerard R. Colca
Rolf F. Kletzien
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Metabolic Solutions Development Co LLC
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Metabolic Solutions Development Co LLC
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
Priority to AU2007227581A priority Critical patent/AU2007227581B2/en
Priority to MX2008011871A priority patent/MX2008011871A/es
Priority to EP07752982A priority patent/EP2001468B1/en
Priority to NZ571871A priority patent/NZ571871A/en
Priority to CN2007800177654A priority patent/CN101454005B/zh
Priority to KR1020087025221A priority patent/KR101475955B1/ko
Priority to MX2012009905A priority patent/MX356584B/es
Priority to ES07752982T priority patent/ES2397944T3/es
Priority to CA2646207A priority patent/CA2646207C/en
Priority to JP2009500436A priority patent/JP5269758B2/ja
Application filed by Metabolic Solutions Development Co LLC filed Critical Metabolic Solutions Development Co LLC
Priority to PL07752982T priority patent/PL2001468T3/pl
Publication of WO2007109024A2 publication Critical patent/WO2007109024A2/en
Publication of WO2007109024A3 publication Critical patent/WO2007109024A3/en
Priority to US12/283,811 priority patent/US20090143442A1/en
Anticipated expiration legal-status Critical
Priority to US13/068,708 priority patent/US8389556B2/en
Priority to US13/751,672 priority patent/US20130203820A1/en
Priority to US14/585,619 priority patent/US9155729B2/en
Ceased legal-status Critical Current

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    • 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
    • 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
    • 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
    • A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • 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
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • an “amido” encompasses both “aminocarbonyl” and . “carbonylamino”. These terms when used alone or in connection with another group refer to an amido group such as -N(R X )-C(O)-R Y or -C(O)-N(R X ) 2 , when used terminally, and -C(O)- N(R X )- or -N(R X )-C(O> when used internally, wherein R x and R ⁇ are defined below.
  • amino groups include alkylamino, diaikylamino, or arylamino.
  • amino is not the terminal group (e.g., alkylcarbonylamino), it is represented by -NR X -.
  • R x has the same meaning as defined above.
  • a "heterocycloalkenyl” group refers to a mono- or bicylic (e.g., 5- to 10-membered mono- or bicyclic) non-aromatic ring structure having one or more double bonds, and wherein one or more of the ring atoms is a heteroatom (e.g., N, O, or S).
  • Monocyclic and bicyclic heterocycloaliphatics are numbered according to standard chemical nomenclature.
  • a heteroaryl is optionally substituted with one or more substituents such as aliphatic [e.g., alkyl, alkenyl, or alkynyl]; cycloaliphatic; (cycloaliphatic)aliphatic; heterocycloaliphatic; (heterocycloaliphatic)aliphatic; aryl; heteroaryl; alkoxy; (cycloali ⁇ hatic)oxy; (heterocycloaliphatic)oxy; aryloxy; heteroaryloxy; (araliphatic)oxy; (heteroaraliphatic)oxy; aroyl; heteroaroyl; amino; oxo (on a non-aromatic carbocyclic or heterocyclic ring of a bicyclic or tricyclic heteroaryl); carboxy; amido; acyl [ e.g., aliphaticcarbonyl; (cycloaliphatic)carbonyl; ((cycloaliphatic)aliphatic)carbonyl; (araliphatic
  • sulfinyl refers to -S(O)-R X when used terminally and -
  • halogen or halo group refers to fluorine, chlorine, bromine or iodine.
  • Each substituent of a specific group is further optionally substituted with one to three of halo, cyano, oxo, alkoxy, hydroxy, amino, nitro, aryl, cycloaliphatic, heterocycloaliphatic, heteroaryl, haloalkyl, and alkyl.
  • an alkyl group can be substituted with alkylsulfanyl and the alkylsulfanyl can be optionally substituted with one to three of halo, cyano, oxo, alkoxy, hydroxy, amino, nitro, aryl, haloalkyl, and alkyl.
  • structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms.
  • compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a 13 C- or 14 C-enriched carbon are within the scope of this invention.
  • Such compounds are useful, for example, as analytical tools or probes in biological assays, or as therapeutic agents.
  • thiazolidinedione analogues of the present invention stem from their selective prevention of inflammation produced at the level of the mitochondria as opposed to traditional compounds that have selective direct activation of a nuclear transcription factor. Because the thiazolidinedione analogues of the present invention function via a mitochondrial mechanism, they are useful in treating or preventing all of the disease states wherein metabolic inflammation is the basis of the pathology.
  • R 3 is a methyl, ethyl, propyl, isopropyl, butyl, tert- butyl, pentyl, or hexyl, each of which is unsubstituted.
  • ring A is bound to the carbon atom adjacent to R 2 at any chemically feasible position.
  • ring A is a pyridine-2-yl, pyridine-3-yl, or pyridine-4-yl, each of which is substituted with -CH 2 -R 1 at any chemically feasible position.
  • the composition further comprises a pharmaceutically acceptable carrier.
  • Another aspect of the present invention provides a pharmaceutical composition that is useful for treating a metabolic inflammation mediated disease comprising a compound of formula V:
  • Example 2a Assays for Measuring Reduced PPAR ⁇ Receptor Activation
  • activation of the PPAR ⁇ receptor is generally believed to be a selection criteria to select for molecules that may have anti-diabetic and insulin sensitizing pharmacology
  • this invention finds that activation of this receptor should be a negative selection criterion. Molecules will be chosen from this chemical space because they have reduced, not just selective, activation of PPAR ⁇ . The optimal compounds will have at least a 10-fold reduced potency as compared to pioglitazone and less than 50% of the full activation produced by rosiglitazone in assays conducted in vitro for transactivation of the PPAR ⁇ receptor.
  • KKAy mice were dosed for 7 days with 20 rag rosigltiazone (positive control) and 100 mg/kg of compound 1 in suspension (1 % sodium methyl carboxymethyl cellulose/0.01 % Tween 80). On the 8th day, fasting, glucose, and insulin were measured, see Table D. The liver was isolated was used to measure hepatic mRNA for aP2, a biomarker for ⁇ PPAR ⁇ activation in vivo. Consistent with the poor binding of compound 1 and compound 2, which is a metabolite of compound 1, there was little activation of PPAR ⁇ as compared to the positive control. Data are mean and (SEM) for 8 mice/group.
  • Table E Physical data of several compounds of the present invention.

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  • Health & Medical Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hospice & Palliative Care (AREA)
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  • Child & Adolescent Psychology (AREA)
  • Pain & Pain Management (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
PCT/US2007/006321 2006-03-16 2007-03-14 Thiazolidinedione analogues for the treatment of metabolic inflammation mediated disease Ceased WO2007109024A2 (en)

Priority Applications (15)

Application Number Priority Date Filing Date Title
MX2008011871A MX2008011871A (es) 2006-03-16 2007-03-14 Analogos de tiazolidindiona para el tratamiento de enfermedad mediada por inflamacion metabolica.
EP07752982A EP2001468B1 (en) 2006-03-16 2007-03-14 Thiazolidinedione analogues
NZ571871A NZ571871A (en) 2006-03-16 2007-03-14 Thiazolidinedione analogues for the treatment of metabolic inflammation mediated disease
CN2007800177654A CN101454005B (zh) 2006-03-16 2007-03-14 用于治疗代谢性炎症介导的疾病的噻唑烷二酮类似物
KR1020087025221A KR101475955B1 (ko) 2006-03-16 2007-03-14 티아졸리딘디온 유사체
MX2012009905A MX356584B (es) 2006-03-16 2007-03-14 Analogos de tiazolidindiona para el tratamiento de enfermedad mediada por inflamacion metabolica.
ES07752982T ES2397944T3 (es) 2006-03-16 2007-03-14 Análogos de tiazolidindiona
JP2009500436A JP5269758B2 (ja) 2006-03-16 2007-03-14 代謝性炎症によって媒介される疾患を処置するためのチアゾリジンジオン類似体
CA2646207A CA2646207C (en) 2006-03-16 2007-03-14 Thiazolidinedione analogues for the treatment of metabolic inflammation mediated disease
AU2007227581A AU2007227581B2 (en) 2006-03-16 2007-03-14 Thiazolidinedione analogues for the treatment of metabolic inflammation mediated disease
PL07752982T PL2001468T3 (pl) 2006-03-16 2007-03-14 Analogi tiazolidynodionu
US12/283,811 US20090143442A1 (en) 2006-03-16 2008-09-16 Thiazolidinedione analogues
US13/068,708 US8389556B2 (en) 2006-03-16 2011-05-18 Thiazolidinedione analogues
US13/751,672 US20130203820A1 (en) 2006-03-16 2013-01-28 Thiazolidinedione analogues
US14/585,619 US9155729B2 (en) 2006-03-16 2014-12-30 Thiazolidinedione analogues

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US78289406P 2006-03-16 2006-03-16
US60/782,894 2006-03-16

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12/283,811 Continuation-In-Part US20090143442A1 (en) 2006-03-16 2008-09-16 Thiazolidinedione analogues

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WO2007109024A2 true WO2007109024A2 (en) 2007-09-27
WO2007109024A3 WO2007109024A3 (en) 2007-11-15

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PCT/US2007/006321 Ceased WO2007109024A2 (en) 2006-03-16 2007-03-14 Thiazolidinedione analogues for the treatment of metabolic inflammation mediated disease

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US (4) US20090143442A1 (enExample)
EP (3) EP2902026B1 (enExample)
JP (2) JP5269758B2 (enExample)
KR (1) KR101475955B1 (enExample)
CN (1) CN101454005B (enExample)
AU (1) AU2007227581B2 (enExample)
CA (1) CA2646207C (enExample)
ES (2) ES2654908T3 (enExample)
HU (1) HUE035314T2 (enExample)
MX (2) MX356584B (enExample)
NZ (1) NZ571871A (enExample)
PL (2) PL2001468T3 (enExample)
RU (1) RU2445957C2 (enExample)
UA (1) UA96441C2 (enExample)
WO (1) WO2007109024A2 (enExample)

Cited By (24)

* Cited by examiner, † Cited by third party
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WO2011075514A1 (en) * 2009-12-15 2011-06-23 Metabolic Solutions Development Company Ppar-sparing thiazolidinediones and combinations for the treatment of neurodegenerative diseases
WO2011084456A1 (en) * 2009-12-15 2011-07-14 Metabolic Solutions Development Company Ppar-sparing thiazolidinediones and combinations for the treatment of diabetes mellitus and other metabolic diseases
GB2477743A (en) * 2010-02-10 2011-08-17 Argenta Therapeutics Ltd Enantiomers of 5-methyl-thiazolidine-2,4-dione glitazone compounds
WO2011098799A2 (en) 2010-02-10 2011-08-18 Pulmagen Therapeutics (Inflammation) Limited Respiratory disease treatment
US8067450B2 (en) 2007-09-14 2011-11-29 Metabolic Solutions Development Company Thiazolidinedione analogues for the treatment of metabolic diseases
WO2012021467A1 (en) * 2010-08-10 2012-02-16 Metabolic Solutions Development Company, Llc Synthesis for thiazolidinedione compounds
WO2012149083A1 (en) * 2011-04-28 2012-11-01 Metabolic Solutions Development Company, Llc Ppar-sparing thiazolidinediones for the treatment of kidney related diseases
US8304441B2 (en) 2007-09-14 2012-11-06 Metabolic Solutions Development Company, Llc Thiazolidinedione analogues for the treatment of metabolic diseases
US8389556B2 (en) 2006-03-16 2013-03-05 Metabolic Soultions Development Company, LLC Thiazolidinedione analogues
WO2012114204A3 (en) * 2011-02-15 2013-06-27 Ecole Polytechnique Federale De Lausanne (Epfl) Epfl-Tto Methods of treating mitochondrial dysfunction
US8629159B2 (en) 2006-03-16 2014-01-14 Metabolic Solutions Development Company, Llc Thiazolidinedione analogues
US8815508B2 (en) 2008-08-12 2014-08-26 Zinfandel Pharmaceuticals, Inc. Method of identifying disease risk factors
US8846315B2 (en) 2008-08-12 2014-09-30 Zinfandel Pharmaceuticals, Inc. Disease risk factors and methods of use
US8912335B2 (en) 2009-12-15 2014-12-16 Metabolic Solutions Development Company, Llc PPAR-sparing thiazolidinedione salts for the treatment of metabolic diseases
US8933240B2 (en) 2010-08-10 2015-01-13 Metabolic Solutions Development Company, Llc Synthesis for thiazolidinedione compounds
US8969581B2 (en) 2013-03-14 2015-03-03 Deuterx, Llc 5-deutero-2,4-thiazolidinedione derivatives and compositions comprising and methods of using the same
US9102666B2 (en) 2011-01-10 2015-08-11 Zinfandel Pharmaceuticals, Inc. Methods and drug products for treating Alzheimer's disease
AU2014202074B2 (en) * 2009-12-15 2016-01-07 Cirius Therapeutics, Inc. PPAR-sparing thiazolidinediones and combinations for the treatment of neurodegenerative diseases
US20160051529A1 (en) * 2012-12-11 2016-02-25 Metabolic Solutions Development Company Llc Ppar-sparing thiazolidinediones and combinations for the treatment of neurodegenerative and other metabolic diseases
US9925175B2 (en) 2007-09-26 2018-03-27 Deuterx, Llc Deuterium-enriched pioglitazone
US10188639B2 (en) 2014-01-15 2019-01-29 Deuterx, Llc Methods of treating neurological, metabolic, and other disorders using enantiopure deuterium-enriched pioglitazone
US11319313B2 (en) 2020-06-30 2022-05-03 Poxel Sa Crystalline forms of deuterium-enriched pioglitazone
US11767317B1 (en) 2020-06-30 2023-09-26 Poxel Sa Methods of synthesizing enantiopure deuterium-enriched pioglitazone
WO2024017851A1 (en) 2022-07-18 2024-01-25 The University Court Of The University Of Glasgow Mitochondrial pyruvate metabolism inhibitors for treating chronic myeloid leukemia

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CA2646170A1 (en) * 2006-03-16 2007-09-27 Metabolic Solutions Development Company Combination therapies of thiazolidinedione analogues and glucocorticoid agonists
CN103153972A (zh) * 2010-04-19 2013-06-12 新陈代谢解决方案开发公司 噻唑烷二酮化合物的新的合成方法
PL2560956T3 (pl) 2010-04-19 2017-03-31 Octeta Therapeutics, Llc Nowa synteza związków tiazolidynodionowych
KR20130015932A (ko) * 2011-08-05 2013-02-14 연세대학교 산학협력단 저용량의 치아졸리딘다이온을 포함하는 알츠하이머 병 치료용 약학조성물
WO2014046474A2 (ko) * 2012-09-21 2014-03-27 가톨릭대학교 산학협력단 메트포민을 유효성분으로 함유하는 염증성 장질환의 예방 또는 치료용 조성물
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