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EP2195294A1 - Nouveau procédé de préparation - Google Patents

Nouveau procédé de préparation

Info

Publication number
EP2195294A1
EP2195294A1 EP08803003A EP08803003A EP2195294A1 EP 2195294 A1 EP2195294 A1 EP 2195294A1 EP 08803003 A EP08803003 A EP 08803003A EP 08803003 A EP08803003 A EP 08803003A EP 2195294 A1 EP2195294 A1 EP 2195294A1
Authority
EP
European Patent Office
Prior art keywords
general formula
group
solvent
compound
alkyl
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.)
Withdrawn
Application number
EP08803003A
Other languages
German (de)
English (en)
Inventor
Kathrin Pachur
Stefan Goepper
Günther HUCHLER
Michael Konrad
Kathrin Maier
Werner Rall
Uwe Jörg RIES
Andreas Zopf
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.)
Boehringer Ingelheim International GmbH
Original Assignee
Boehringer Ingelheim International GmbH
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 Boehringer Ingelheim International GmbH filed Critical Boehringer Ingelheim International GmbH
Publication of EP2195294A1 publication Critical patent/EP2195294A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/56—Nitrogen atoms
    • C07D211/58—Nitrogen atoms attached in position 4
    • 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
    • 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
    • C07C229/40—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/42—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Definitions

  • the present invention is a process for the preparation of compounds of general formula I.
  • R 1 1 , R 1 2 , R 1 3 and R 2 are defined as mentioned below, their pharmaceutically acceptable salts and the solvates thereof, starting from compounds of the general formula II
  • R 1 1 , R 1 2 and R 1 3 are defined as mentioned below can be prepared.
  • the present invention relates to a process for the preparation of compounds of general formula I, which is based on the stepwise construction starting from compounds of general formulas III and IV. Furthermore, the invention relates to the compounds of the general formulas III per se, since these are particularly suitable for the preparation of the compounds of general formula I, which possess CGRP antagonistic properties.
  • the compounds of the general formulas II and III are valuable starting materials for the synthesis of the compounds of the general formula I which possess CGRP-antagonistic properties.
  • the isolated intermediates are obtained as crystalline solids, which is for the purification and the separation of any resulting enantiomeric mixtures of great advantage.
  • a first subject of the present invention relates to a process for the preparation of compounds of general formula II
  • R 1 1 .3 J is CH 3 , CF 3 , F, Cl or Br, comprising the steps:
  • R 3 is an imidazole or triazole radical, preferably an imidazole radical, which is bonded via a nitrogen atom;
  • step (b) isolating the compound of general formula II obtained in step (a) by crystallization from a solvent and
  • step (c) optionally recrystallizing a solid obtained in step (b) from a suitable solvent.
  • 1.0 equivalents of a compound of general formula III can be reacted with 1.0 to 1.5 equivalents, preferably 1.1 equivalents, of a compound of general formula IV in a solvent in the presence of a strong base.
  • a solvent tert As a solvent tert. Amyl alcohol, te / f.-butanol or tetrahydrofuran be used.
  • the solvent is preferably added in an amount of 2 to 3 L / mol of the compound of general formula III, preferably in an amount of 2.2 to 2.5 L / mol of the compound of general formula III used.
  • the base can be added in an amount of from 2.0 to 2.5 equivalents, preferably in an amount of 2.2 equivalents, in each case based on the amount of compound of the general formula III used.
  • Potassium te / t-butylate can be used, - A -
  • step (b) and the recrystallization in step (c) can be carried out independently of one another in a polar solvent.
  • polar solvent As polar
  • Solvents may be, for example, water, acetone, ethanol, isopropanol or n-butyl acetate and mixtures of these solvents.
  • the crystallization in step (b) preferably takes place from a mixture of acetone and water in the ratio 1: 1.
  • a second subject of the present invention relates to a process for the preparation of compounds of general formula I.
  • R 1 - 1 - 1 H de-alkyl, O-benzyl, O-tert-butyl
  • R 3 is an imidazole or triazole radical, preferably an imidazole radical, which is bonded via a nitrogen atom;
  • step (b) reaction of a product of general formula II formed in step (a)
  • R 1 1 , R 1 2 and R 1 3 are defined as mentioned above, with a compound of general formula V HN N- (N ⁇ x R 2
  • step (c) optionally recrystallizing a solid obtained in step (b) from a suitable solvent.
  • step (a) 1.0 equivalents of a compound of general formula II and 1.0 to 1.5 equivalents of a compound of general formula III can be suspended in a polar solvent and reacted at elevated temperature in the presence of a strong base.
  • te / t -amyl alcohol As polar solvents, it is preferable to use te / t -amyl alcohol, te / f.-butanol or tetrahydrofuran.
  • the base used may be selected from the group consisting of potassium te / f.butylate, sodium te / t-butylate, lithium te / t-butylate and sodium te / f.amylate.
  • the reaction is preferably carried out at a temperature between 40 0 C and 80 0 C.
  • step (b) 1.0 equivalents of a compound of general formula II and 1.1 to 1.5 equivalents of a compound of general formula V can be used.
  • the reaction is preferably carried out at a low temperature in the presence of an amine and a condensing agent in a polar solvent.
  • the amine used can be selected from the group consisting of triethylamine, diisopropylethylamine, ethyldiisopropylamine and tributylamine and is used in an amount of 5 to 7 equivalents, based on the amount of compound of general formula II used.
  • the condensing agent can be selected from the group consisting of propanephosphonic anhydride, dicyclohexylcarbodiimide, carbonyldiimidazole, carbonylditriazole, 2- (1 / - / - benzotriazol-1-yl) -1,3,3-tetramethyluronium tetrafluoroborate, 1-ethyl-3- (3 ' -dimethylamino-propyl) -carbodiimide and chlordimethoxy-triazine, optionally in the presence of hydroxysuccinimide, hydroxybenzotriazole, p-nitrophenol and pentafluorophenol and is used in an amount of 2 to 3 equivalents, based on the amount of compound of the general formula II.
  • the polar solvent THF or ethyl acetate can be used. According to the invention, the reaction is preferably carried out at a temperature between 0 and 10 ° C.
  • a third object of the present invention relates to the compounds of general formula III
  • R 1 - 1 - 1 H de-alkyl, O-benzyl, O-tert-butyl
  • R 1 - 1 - 2 H de-alkyl, O-benzyl, O-tert-butyl
  • R 1 - 2 - 1 H de-alkyl, O-benzyl, O-tert-butyl
  • R 1 - 2 - 2 H de-alkyl, O-benzyl, O-tert-butyl
  • R 2 de-alkyl
  • a preferred third article comprises the following compounds of the formula IIIa:
  • a further preferred third object relates to the compound (R) -3- (4-amino-3-chloro-5-trifluoromethyl-phenyl) -2-hydroxy-propionic acid of the formula IIIa
  • the listed value was determined by means of differential scanning calorimetry (DSC: evaluation via onset, heating rate: 10 ° C./min) (DSC 821 from Mettler Toledo).
  • a fourth subject of the present invention relates to a process for the preparation of compounds of the general formula Hl
  • R 1 - 1 - 2 H de-alkyl, O-benzyl, O-tert-butyl
  • R 1 - 2 - 1 H de-alkyl, O-benzyl, O-tert-butyl
  • R 1 - 2 - 2 H de-alkyl, O-benzyl, O-te / tButyl and
  • R 4 is a Ci -6 alkyl group represents, independently, in a solvent and in the presence of a strong base
  • step (b) cleavage of the ester group of a compound of general formula VII obtained in step (a)
  • R 1 1, R 1 2 and R 1 3 are as hereinbefore defined and R 4 represents a Ci -6 alkyl group, by adding an inorganic base;
  • step (c) optionally isolating a compound of general formula VIII obtained in step (b)
  • R 1 1, R 1 2 and R 1 3 are as hereinbefore defined and R 4 represents a Ci -6 alkyl group;
  • step (d) cleaving the protecting group of a compound of general formula VIII obtained under step (b) or (c) by adding a strong inorganic acid;
  • step (e) optionally isolating a compound of general formula IX obtained in step (d)
  • step (f) mixing a compound of general formula IX obtained in step (e) with a solvent and reducing the double bond by adding a reducing agent and in the presence of a base;
  • step (G) isolating a compound of general formula III obtained in step (f) and optionally recrystallization from a solvent.
  • a further subject matter comprises in step (a) the reaction of a compound of the general formula V in which
  • R 1 - 3 Cl means
  • step (a) 1.0 equivalents of a compound of general formula V are reacted with 1.8 to 2.5 equivalents, preferably 1.9 to 2.1 equivalents, more preferably 2 equivalents, of a compound of general formula VI.
  • the solvent te / f.-butanol or tetrahydrofuran or mixtures of these solvents can be used.
  • the solvent is added in an amount of 0.5 to 0.8 L / mol, preferably in an amount of 0.6 to 0.7 L / mol of the compound of general formula V used.
  • the base is preferably added in an amount of 1.0 to 1.5 equivalents, preferably in an amount of 1.25 equivalents, based on the amount of the compound of the general formula used V.
  • a further subject in step (b) comprises the cleavage of the ester group of a compound of general formula VII in which »1.1 CF 3
  • R 4 is CH 3 .
  • the inorganic base may be selected from
  • Group consisting of lithium hydroxide, sodium hydroxide and potassium hydroxide. It may be added in an amount of 1.5 to 2.5 equivalents, preferably 2 equivalents, based on the amount of compound of general formula VII used.
  • step (c) The isolation of a compound of the general formula VIII described in step (c) can be carried out, for example, by means of crystallization.
  • step (d) 1.0 equivalent of a compound of general formula VIII is reacted with 8 to 12 equivalents, preferably 10 equivalents, of an inorganic acid.
  • the inorganic acid may be selected from the group consisting of hydrochloric acid, hydrobromic acid, hydroiodic acid and sulfuric acid; hydrobromic acid is preferably used.
  • step (f) may be selected from among
  • the base may be selected from the group consisting of triethylamine, diisopropylethylamine and pyridine.
  • the reducing agent likewise described under step (f) may be selected from the group consisting of diisopinocampheylboron chloride, ⁇ -chlorodiisopinocampheylborane,
  • step (g) may be selected from the group consisting of n-butyl acetate, isopropyl acetate, ethyl acetate and tetrahydrofuran.
  • R 3 is an imidazole or triazole radical, preferably an imidazole radical which is bonded via a nitrogen atom, is carried out by a process comprising the steps:
  • step (b) crystallizing the crude product formed in step (a) by adding another polar aprotic solvent when R 3 represents an imidazole group.
  • the solvent mentioned above under step (a) may be selected from the group consisting of acetone, acetonitrile, tert./b.butyl methyl ether, ⁇ /, ⁇ / -dimethylacetamide, dimethylformamide, dimethyl sulfoxide, pyridine and ⁇ / -methylpyrrolidone.
  • the polar, aprotic solvent mentioned above under step (b) may be selected from the group consisting of tert-butyl methyl ether and dimethylformamide.
  • a fifth subject of the present invention relates to a process for the preparation of compounds of general formula V
  • R 2 denotes de-alkyl, comprising the steps:
  • R 2 represents a C 1-6 -alkyl group, in a solvent and in the presence of a base
  • 1.0 equivalents of piperidone 4-hydrate hydrochloride can be reacted with 1.0 to 1.2 equivalents of a chloroacetic acid ester of general formula X.
  • the abovementioned solvent can be selected from the group consisting of acetone, acetonitrile, tert.-butylmethyl ether, .alpha.,. Omega.-dimethylacetamide, dimethylformamide, dimethyl sulfoxide, pyridine and .omega.-methylpyrrolidone, acetonitrile being of particular importance.
  • the solvent may be used in an amount of 0.8 to 1.5 L / mol of piperidone 4-hydrate hydrochloride, preferably 0.9 to 1.1 L / mol of piperidone 4-hydrate hydrochloride used.
  • the base may be selected from the group consisting of sodium carbonate, potassium carbonate, sodium hydride and potassium hydride. It may be added in an amount of 2.0 to 2.5 equivalents, based on the amount of piperidone 4-hydrate hydrochloride employed.
  • step (b) 1.0 equivalents of 1-benzyl-piperazine can be reacted with 1.1 to 1.7 equivalents of a compound of general formula XI.
  • the mentioned solvent may be selected from the group consisting of te / f-butylmethyl ether, tetrahydrofuran, toluene and 2-methyltetrahydrofuran.
  • the solvent can be used in an amount of 1.0 to 2.0 L / mol of 1-benzyl-piperazine used.
  • sodium borohydride or sodium triacetoxyborohydride may be used, which is added in an amount of 1.0 to 2.0 equivalents based on the amount of 1-benzyl-piperazine used.
  • 1.0 equivalents of a compound of general formula XII can be reacted with 1.1 to 5 equivalents of hydrochloric acid.
  • the mentioned solvent may be selected from the group consisting of methanol, ethanol and isopropanol.
  • the solvent can be used in an amount of 2.5 to 4.0 L / mol of 1-benzyl-piperazine used.
  • the removal of a benzyl protective group from a compound of general formula XII described above under step (d) can be carried out in a polar solvent such as, for example, methanol, ethanol, propanol, tert-butanol, water, acetone, tetrahydrofuran, dimethylformamide or mixtures of these solvents.
  • a polar solvent such as, for example, methanol, ethanol, propanol, tert-butanol, water, acetone, tetrahydrofuran, dimethylformamide or mixtures of these solvents.
  • the solvent may be added in an amount of 4.0 to 7.0 L / mol of the compound of general formula XII used.
  • Advantageous conditions for the hydrogenation are temperatures of 40 to 80 0 C and a hydrogen pressure of at most 5 bar.
  • catalyst palladium / carbon or palladium hydroxide / carbon can be used.
  • the compounds of the invention including their salts, in which one or more hydrogen atoms, for example one, two, three, four or five hydrogen atoms, are replaced by deuterium.
  • Ci 6 alkyl the term (including those which are part of other groups) are meant branched and unbranched alkyl groups having 1 to 6 carbon atoms. Examples include: methyl, ethyl, n-propyl, / so-propyl, n-butyl, sec-butyl, te / t-butyl, pentyl or hexyl. If appropriate, the abbreviations Me, Et, n-Pr, / -P, etc. are also used for the abovementioned groups.
  • the compounds of general formula I may contain basic groups such as e.g. Possess amino functions. They can therefore be used as internal salts, as salts with pharmaceutically usable inorganic acids such as hydrobromic acid, phosphoric acid, nitric acid, hydrochloric acid, sulfuric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid or organic acids such as, for example, malic acid, succinic acid, acetic acid, fumaric acid, Maleic acid, mandelic acid, lactic acid, tartaric acid or citric acid.
  • pharmaceutically usable inorganic acids such as hydrobromic acid, phosphoric acid, nitric acid, hydrochloric acid, sulfuric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid or organic acids such as, for example,
  • the invention relates to the respective compounds optionally in the form of the individual optical isomers, mixtures of the individual enantiomers or racemates, in the form of tautomers and in the form of the free bases or the corresponding acid addition salts with pharmacologically acceptable acids.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

La présente invention concerne un procédé de préparation de composés de formule générale (I), dans laquelle R1.1, R1.2, R1.3 et R2 ont les définitions indiquées dans la description, de leurs sels pharmaceutiquement acceptables et des solvates de ces sels, qui peuvent être préparés à partir des composés de formule générale (II), dans laquelle R1.1, R1.2 et R1.3 ont les définitions indiquées dans la description.
EP08803003A 2007-08-13 2008-08-12 Nouveau procédé de préparation Withdrawn EP2195294A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102007038250A DE102007038250A1 (de) 2007-08-13 2007-08-13 Neues Herstellverfahren
PCT/EP2008/060559 WO2009021942A1 (fr) 2007-08-13 2008-08-12 Nouveau procédé de préparation

Publications (1)

Publication Number Publication Date
EP2195294A1 true EP2195294A1 (fr) 2010-06-16

Family

ID=39877761

Family Applications (1)

Application Number Title Priority Date Filing Date
EP08803003A Withdrawn EP2195294A1 (fr) 2007-08-13 2008-08-12 Nouveau procédé de préparation

Country Status (16)

Country Link
US (1) US8222402B2 (fr)
EP (1) EP2195294A1 (fr)
JP (1) JP2010535837A (fr)
KR (1) KR20100053651A (fr)
CN (1) CN101821237A (fr)
AR (1) AR068806A1 (fr)
AU (1) AU2008288429A1 (fr)
BR (1) BRPI0815498A2 (fr)
CA (1) CA2696205A1 (fr)
CL (1) CL2008002376A1 (fr)
DE (1) DE102007038250A1 (fr)
MX (1) MX2010001600A (fr)
PE (1) PE20090901A1 (fr)
TW (1) TW200916461A (fr)
UY (1) UY31283A1 (fr)
WO (1) WO2009021942A1 (fr)

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH07501063A (ja) 1991-11-14 1995-02-02 グラクソ、グループ、リミテッド フィブリノーゲン依存性血小板凝集阻害剤としてのピペリジン酢酸誘導体
CZ119398A3 (cs) * 1995-10-17 1998-09-16 Astra Aktiebolag Farmaceuticky účinné sloučeniny na bázi chinazolinu
BR9612381A (pt) * 1995-12-29 1999-07-13 Smithkline Beecham Corp Antagonistas receptores vitronectina
DE10250080A1 (de) 2002-10-25 2004-05-13 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
DE102004015723A1 (de) * 2004-03-29 2005-10-20 Boehringer Ingelheim Pharma Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
DE102004018795A1 (de) 2004-04-15 2005-10-27 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
EP1770091A1 (fr) 2005-09-29 2007-04-04 Boehringer Ingelheim Pharma GmbH & Co. KG Antagonistes CGRP, leur procédé de préparation ansi que leur utilisation comme médicaments
DE102005038831A1 (de) * 2005-08-17 2007-02-22 Boehringer Ingelheim Pharma Gmbh & Co. Kg Ausgewählte CGRP-Antagonisten, Verfahren zu deren Herstellung sowie deren Verwendung als Arzneimittel
DE102007038251A1 (de) * 2007-08-13 2009-02-19 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neues Herstellverfahren

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2009021942A1 *

Also Published As

Publication number Publication date
TW200916461A (en) 2009-04-16
KR20100053651A (ko) 2010-05-20
CA2696205A1 (fr) 2009-02-19
CN101821237A (zh) 2010-09-01
DE102007038250A1 (de) 2009-02-19
PE20090901A1 (es) 2009-08-06
UY31283A1 (es) 2009-03-31
WO2009021942A1 (fr) 2009-02-19
AU2008288429A1 (en) 2009-02-19
JP2010535837A (ja) 2010-11-25
US8222402B2 (en) 2012-07-17
MX2010001600A (es) 2010-03-15
CL2008002376A1 (es) 2009-09-11
BRPI0815498A2 (pt) 2015-02-10
US20110071286A1 (en) 2011-03-24
AR068806A1 (es) 2009-12-09

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