WO1999059957A1 - Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase - Google Patents

Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase Download PDF

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Publication number
WO1999059957A1
WO1999059957A1 PCT/IT1999/000126 IT9900126W WO9959957A1 WO 1999059957 A1 WO1999059957 A1 WO 1999059957A1 IT 9900126 W IT9900126 W IT 9900126W WO 9959957 A1 WO9959957 A1 WO 9959957A1
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WO
WIPO (PCT)
Prior art keywords
trimethylammonium
group
aminobutyrate
alkyl
compounds
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/IT1999/000126
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English (en)
French (fr)
Other versions
WO1999059957A9 (en
Inventor
Fabio Giannessi
Mauro Marzi
Patrizia Minetti
Francesco De Angelis
Maria Ornella Tinti
Piero Chiodi
Arduino Arduini
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.)
Sigma Tau Industrie Farmaceutiche Riunite SpA
Original Assignee
Sigma Tau Industrie Farmaceutiche Riunite SpA
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 EP99921135A priority Critical patent/EP1077925B1/en
Application filed by Sigma Tau Industrie Farmaceutiche Riunite SpA filed Critical Sigma Tau Industrie Farmaceutiche Riunite SpA
Priority to AU38473/99A priority patent/AU3847399A/en
Priority to DK99921135T priority patent/DK1077925T3/da
Priority to DE69920208T priority patent/DE69920208T2/de
Priority to HK01102605.2A priority patent/HK1033573B/en
Priority to CA2329930A priority patent/CA2329930C/en
Priority to JP2000549576A priority patent/JP5127093B2/ja
Priority to AT99921135T priority patent/ATE276230T1/de
Publication of WO1999059957A1 publication Critical patent/WO1999059957A1/en
Priority to US09/677,328 priority patent/US6369073B1/en
Anticipated expiration legal-status Critical
Priority to US09/986,327 priority patent/US6444701B1/en
Publication of WO1999059957A9 publication Critical patent/WO1999059957A9/en
Priority to US11/606,322 priority patent/USRE40861E1/en
Priority to US11/607,078 priority patent/USRE41226E1/en
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • 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
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/26—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one amino group bound to the carbon skeleton, e.g. lysine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/12—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/04—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms
    • C07C275/06—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton
    • C07C275/16—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to acyclic carbon atoms of an acyclic and saturated carbon skeleton being further substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
    • C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C311/06—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C335/00—Thioureas, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C335/04—Derivatives of thiourea
    • C07C335/06—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms
    • C07C335/08—Derivatives of thiourea having nitrogen atoms of thiourea groups bound to acyclic carbon atoms of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds
    • C07F9/5407—Acyclic saturated phosphonium compounds

Definitions

  • the present invention relates to compounds having inhibiting
  • palmitoyl-transferase in particular hyperglycaemic states, such as
  • hypoglycaemic therapy is based on the use of drugs
  • Insulin and its analogues represent the most used therapy
  • Hyperglycaemia is also treated with gluconeogenesis inhibitors
  • CPT carnitine palmitoyltransf erase
  • acetyl-coenzyme A which activates a key gluconeogenetic enzyme:
  • Emeriamine and its analogues are disclosed in EP 0 127 098
  • hyperglycaemia do not exist.
  • some products such as tetradecyl
  • hyperglycaemia still remains.
  • X + is selected from the group consisting of N + (Ri,R2,R3)
  • -R4 is a Ci-C2o saturated or unsaturated, straight or
  • Ai is selected from the group consisting of halogen atom
  • heteroaryl aryloxy or heteroaryloxy groups being optionally
  • Y- is selected from the group consisting of -COO, PO3H-, -
  • R4 is not Ci-C ⁇ alkyl.
  • the present invention further comprises the use of the
  • palmitoyl carnitine such as and in particular hyperglycemic states, diabetes and related pathologies, congestive heart failure and
  • the present invention comprises pharmaceutical compositions
  • the present invention comprises also processes for the
  • Examples of (C6-C14) aryl group are phenyl, 1 - or 2-naphthyl,
  • heterocyclic groups thienyl, quinolyl, pyridyl, N-
  • halogen atom it is intended fluorine, chlorine, bromine,
  • the compounds of formula (I) can be also in the form of inner
  • a first group of preferred compounds comprises the
  • a second group of preferred compounds comprises the
  • a third group of preferred compounds comprises the
  • R4 group is preferably a C -C 2 o saturated or unsaturated, straight or
  • alkyl chain R 4 significantly increases the selectivity against CPT.
  • Preferred R4 groups are selected from the group consisting of heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl,
  • Z group are ureido (-NHCONHR4)
  • Z is ureido (-NHCONHR4) or
  • R4 is a C7-C20, preferably a C 9 -
  • Ci8 saturated or unsaturated, straight or branched alkyl group are
  • the compounds of formula (I) have an asymmetry center on
  • each compound of formula (I) can exist both as R,S,
  • the compounds of formula (I) are quaternary ammonium or
  • X + is salified with a
  • inorganic and organic such as for example, hydrochloric acid
  • carboxyl the salts with pharmaceutically acceptable bases, both inorganic and organic, such as for example, alkaline and alkaline-
  • a first group of particularly preferred compounds comprises:
  • phenoxydecylcarbamoyl)aminobutyrate R-4-trimethylammonium-3-(tr ⁇ ns- ⁇ -styrenesulfonyl)aminobutyrate.
  • the compounds of formula (I) can be prepared with reactions
  • Z is -NHR 4 comprising the reaction of X + -CH 2 -CH(NH 2 )-CH 2 -Y-,
  • alkane carbaldheydes wherein the alkyl moiety is a one-term lower
  • alkyl chloroformates alkyl isocyanates, alkyl isothiocyanates,
  • alkyl thiochloroformates containing the desired R4 alkyl group.
  • NHSO2NHR4 are obtained by reacting X + -CH 2 -CH(NH 2 )-CH2-Y-,
  • alkyl sulfamoyl chlorides or SO2CI2 and alkyl amines
  • Hal is a halogen atom, preferably
  • R' is the residue of a suitable ester, such as for
  • nucleophilic group such as azido, phthalimido, nitro
  • Hal atom is substituted with a (Ri,R 2 ,R3)- substituted phosphine
  • alkane carbaldheydes wherein the alkyl moiety is a one-term lower homologue of R4, and subsequent
  • reactives these reactives are available in the market, or can be
  • CPT carnitine palmitoyl-transferase
  • hyperglycaemia diabetes and disorders related thereto, such as, for example
  • cardiovascular disorders such as cardiovascular disorders
  • ketonic states wherein it is intended the pathological conditions
  • Inhibiting activity mainly occurs on the isoform I of palmitoyl
  • CPT-I carnitine transferase
  • compositions comprising at least a compound of
  • compositions according to the present invention are provided.
  • compositions shall be in solid or liquid
  • compositions according to the present invention comprise
  • solubilizing, dispersing, suspending, emulsionating agents for example solubilizing, dispersing, suspending, emulsionating agents
  • compositions are capsules, tablets, granulates, powders, syrups,
  • compositions are solutions, emulsions, suspensions.
  • suitable transdermal pharmaceutical compositions are patches,
  • the dose of the active ingredients will vary depending on the
  • the dosage and posology shall be determined by the clinic expert or the physician. Generally, a therapeutic effect can be obtained at
  • dosages comprised between 1 and 100 mg/kg body weight.
  • present invention is the preparation of a pharmaceutical
  • composition comprising admixing at least a compound of formula (I)
  • the azide solution was kept between 10 and 15°C. after one hour,
  • phase (the aqueous one) was eliminated.
  • the higher phase was
  • Nonyl isocyanate (15.42 g, 91.12 mmoles) was added to a
  • Nonyl isocyanate (7.39 g, 43.36 mmoles) was added to a
  • Nonyl isocyanate (4.04 g, 23.86 mmoles) was added to the
  • step A The ester obtained in step A was hydrolysed on Amberlyst IRA
  • Step B The product was prepared as disclosed in Example 6, step B.
  • ammonium bromide were added to a solution of 1 1.4 g (0.041 moles)
  • the product was prepared as in example 8, step B.
  • the product was prepared as in example 8, step B.
  • the product was prepared as in example 8, step C.
  • Step D The product was prepared as in example 8, step D.
  • the product was prepared as in example 8, step F.
  • the product was prepared as in example 8, step F.
  • step C were dissolved in 10 ml of methanol and 10ml of 4N NaOH
  • Step E The product obtained in step D (1.19 g, 2.56 mmoles) was
  • step E The product obtained in step E (0.969 g, 1.97 mmoles) was
  • step F The product obtained in step F (2.78 g, 7.1 mmoles) was
  • step F were suspended in 18 ml water and 1.47 ml HCOOH and
  • step I The product obtained in step I (2.99 g, 5.33 mmoles) was

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Child & Adolescent Psychology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
PCT/IT1999/000126 1998-05-15 1999-05-11 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase Ceased WO1999059957A1 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
AT99921135T ATE276230T1 (de) 1998-05-15 1999-05-11 Verbindungen, die als reversible inhibitoren der carnitin palmitoyltransferase wirsam sind
AU38473/99A AU3847399A (en) 1998-05-15 1999-05-11 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase
DK99921135T DK1077925T3 (da) 1998-05-15 1999-05-11 Forbindelser med reversibel inhiberende aktivitet af carnitinpalmitoyltransferase
DE69920208T DE69920208T2 (de) 1998-05-15 1999-05-11 Verbindungen, die als reversible inhibitoren der carnitin palmitoyltransferase wirsam sind
HK01102605.2A HK1033573B (en) 1998-05-15 1999-05-11 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase
CA2329930A CA2329930C (en) 1998-05-15 1999-05-11 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase
JP2000549576A JP5127093B2 (ja) 1998-05-15 1999-05-11 カルニチンパルミトイル−トランスフェラーゼの可逆的阻害活性を有する化合物
EP99921135A EP1077925B1 (en) 1998-05-15 1999-05-11 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase
US09/677,328 US6369073B1 (en) 1998-05-15 2000-10-02 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase
US09/986,327 US6444701B1 (en) 1998-05-15 2001-11-08 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase
US11/606,322 USRE40861E1 (en) 1998-05-15 2006-11-30 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase
US11/607,078 USRE41226E1 (en) 1998-05-15 2006-12-01 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ITMI98A001075 1998-05-15
IT98MI001075A IT1299266B1 (it) 1998-05-15 1998-05-15 Inibitori reversibili della carnitina palmitoil trasferasi

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/677,328 Continuation US6369073B1 (en) 1998-05-15 2000-10-02 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase

Publications (2)

Publication Number Publication Date
WO1999059957A1 true WO1999059957A1 (en) 1999-11-25
WO1999059957A9 WO1999059957A9 (en) 2002-06-13

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PCT/IT1999/000126 Ceased WO1999059957A1 (en) 1998-05-15 1999-05-11 Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase

Country Status (14)

Country Link
US (4) US6369073B1 (https=)
EP (2) EP1077925B1 (https=)
JP (1) JP5127093B2 (https=)
KR (1) KR100585443B1 (https=)
AT (2) ATE465988T1 (https=)
AU (1) AU3847399A (https=)
CA (1) CA2329930C (https=)
CY (1) CY1110200T1 (https=)
DE (2) DE69942315D1 (https=)
DK (2) DK1077925T3 (https=)
ES (2) ES2345100T3 (https=)
IT (1) IT1299266B1 (https=)
PT (2) PT1077925E (https=)
WO (1) WO1999059957A1 (https=)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002009682A3 (en) * 2000-08-01 2002-04-18 Sigma Tau Ind Farmaceuti Use of fibrates for the preparation of a medicament useful in the treatment of congestive heart failure
WO2004063143A1 (en) * 2003-01-08 2004-07-29 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Synthesis fo (r) and (s)-aminocarnitine and derivatives thereof from d-and l-aspartic acid
WO2004069239A1 (en) * 2003-02-10 2004-08-19 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Combination of antidiabetic drugs
WO2005077354A1 (en) * 2004-02-12 2005-08-25 Defiante Farmaceutica Lda. Compounds having antitumor activity
US6953865B2 (en) * 2001-07-26 2005-10-11 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Process for the preparation of (r)- or (s)-aminocarnitine inner salt, the salts and derivatives thereof
WO2006092204A1 (en) * 2005-03-02 2006-09-08 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Derivatives of aminobutanoic acid inhibiting cpt
WO2008015081A1 (en) 2006-08-02 2008-02-07 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Derivatives of 4-trimethylammonium-3-aminobutyrate and 4-trimethylphosphonium-3-aminobutyrate as cpt-inhibitors
WO2008109991A1 (en) * 2007-03-09 2008-09-18 University Health Network Inhibitors of carnitine palmitoyltransferase and treating cancer
WO2009132979A1 (en) 2008-04-29 2009-11-05 F. Hoffmann-La Roche Ag 4-trimethylammonio-butyrates as cpt2 inhibitors
WO2009132978A1 (en) 2008-04-29 2009-11-05 F. Hoffmann-La Roche Ag 4-dimethylaminobutyric acid derivatives
WO2010014943A3 (en) * 2008-08-01 2011-01-13 Bioxiness Pharmaceutics, Inc. Methionine analogs and methods of using same
US20110136905A1 (en) * 2007-08-07 2011-06-09 Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. Crystalline teglicar
US8314144B2 (en) 2004-02-12 2012-11-20 Defiante Farmaceutica, S.A. Compounds having antitumor activity
US8680282B2 (en) 2007-08-01 2014-03-25 University Health Network Cyclic inhibitors of carnitine palmitoyltransferase and treating cancer

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