EP0883607A1 - Processes and intermediates for preparing 1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine - Google Patents

Processes and intermediates for preparing 1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine

Info

Publication number
EP0883607A1
EP0883607A1 EP96931937A EP96931937A EP0883607A1 EP 0883607 A1 EP0883607 A1 EP 0883607A1 EP 96931937 A EP96931937 A EP 96931937A EP 96931937 A EP96931937 A EP 96931937A EP 0883607 A1 EP0883607 A1 EP 0883607A1
Authority
EP
European Patent Office
Prior art keywords
alkyl
compound
formula
process according
halo
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Withdrawn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
EP96931937A
Other languages
German (de)
English (en)
French (fr)
Inventor
Keith M. Devries
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.)
Pfizer Corp Belgium
Pfizer Corp SRL
Pfizer Inc
Original Assignee
Pfizer Corp Belgium
Pfizer Corp SRL
Pfizer 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 Pfizer Corp Belgium, Pfizer Corp SRL, Pfizer Inc filed Critical Pfizer Corp Belgium
Publication of EP0883607A1 publication Critical patent/EP0883607A1/en
Withdrawn legal-status Critical Current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
    • C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms

Definitions

  • DIMETHOXY-1-INDANON)-2-YL)METHYLPIPERIDINE Background of the Invention
  • This invention relates to a novel process for the preparation of 1 -benzyl-4-((5,6- d ⁇ methoxy-1- ⁇ ndanon)-2-yl)methylp ⁇ per ⁇ d ⁇ ne (E2020), the compound of the formula VII below, and to novel intermediates used in said process
  • R 2 is (C C 4 )alkyl
  • R 3 is (C ⁇ C alkyl or phenyl optionally substituted with from one to three substituents independently selected from (C,-C 4 )alkyl, (C,-C 4 )alkoxy, halo or trifluoromethyl
  • the present invention also relates to a compound of the formula
  • R 2 is (C C 4 )alkyl
  • R 3 is (C r C 4 )alkyl or phenyl optionally substituted with from one to three substituents independently selected from (C r C 4 )alkyl, (C r C 4 )alkoxy, halo or trifluoromethyl
  • the present invention also relates to a compound of the formula
  • R 2 is (C,-C 4 )alkyl
  • R 3 is (C r C 4 )alkyl or phenyl optionally substituted with from one to three substituents independently selected from (C C 4 )alkyl, (C r C 4 )alkoxy, halo or trifluoromethyl
  • the present invention also relates to a process for preparing a compound of the formula
  • R 2 is (C r C 4 )alkyl
  • R 3 is (C C 4 )alkyl or phenyl optionally substituted with from one to three substituents independently selected from (C,-C 4 )alkyl, (C r C 4 )alkoxy, halo or trifluoromethyl, comprising a) reacting a compound of the formula
  • R 2 is (C C 4 )alkyl
  • R 3 is (C C 4 )alkyl or phenyl optionally substituted with from one to three substituents independently selected from (C r C 4 )alkyl, (C,-C 4 )alkoxy, halo or trifluoromethyl, with a methenylation agent to form a compound of the formula
  • R 2 is (C C 4 )alkyl
  • R 3 is (C C 4 )alkyl or phenyl optionally substituted with from one to three substituents independently selected from (C C 4 )alkyl, (C r C 4 )alkoxy, halo or trifluoromethyl
  • said methenylation agent is tetramethyldiaminomethane in acetic anhydride More preferably said tetramethyldiaminomethane and acetic anhydride are added in excess Most preferably, said tetramethyldiaminomethane comprises 2 molar equivalents (relative to the amount of the compound of the formula III) and said acetic anhydride comprises 4 molar equivalents (relative to the amount of the compound of the formula III)
  • said strong acid is sulfuric acid More preferably said sulfuric acid is concentrated sulfuric acid Most preferably, said concentrated sulfu ⁇ c acid comprises 9 molar equivalents (relative to the amount of said compound of the formula
  • R 2 is (C.-C alkyl
  • R 3 is (C C 4 )alkyl or phenyl optionally substituted with from one to three substituents independently selected from (C 1 -C 4 )alkyl, (C C 4 )alkoxy, halo or trifluoromethyl, with hydroxide (preferably potassium hydroxide) to form a compound of the formula
  • said benzyl halide is benzyl bromide
  • said base is triethanolamine
  • the most preferred embodiment of the above invention relates to a process wherein said compound of formula I is isolated before it is converted to the compound of formula VI
  • the compound of formula I can be isolated by addition of the strongly acidic solution containing the compound of formula I to ice/water followed by extraction with an organic solvent and removal of the organic solvent
  • the present invention also related to a process for preparing a compound ofthe formula 97/22584 PC17IB96/01076
  • Scheme 1 refers to the process of preparing a compound of formula I which can be converted to a compound of the formula VII, E2020, by the methods of Scheme 2
  • Patent Application 08/329,352 filed October 26, 1994 also refers to the preparation of compounds of the formula V
  • R 2 is methyl
  • Suitable Lewis acids include aluminum trichloride, titanium tetrachloride or boron trichloride, preferably aluminum trichloride
  • Suitable reaction inert solvents include methylene chloride or dichloroethane, preferably methylene chloride The
  • a compound of the formula II can be prepared from a compound of the formula III by reacting said compound of the formula III with a methenylation agent
  • Suitable methenylation agents include tetramethyldiaminomethane in acetic anhydride, formaldehyde (about 37 weight % in water) in diethylamine, formaldehyde (about 37 weight % in water) in piperidine or N- methylthiomethylpiperdine
  • the methenylation agent is tetramethyldiaminomethane in acetic anhydride
  • a compound of the formula I can be prepared from a compound of the formula II by reacting said compound of the formula II with a strong acid in a reaction inert solvent
  • Suitable strong acids include concentrated sulfuric acid, aluminum trichloride or concentrated hydrochloric acid, preferably concentrated sulfuric acid
  • aluminum trichloride is the acid
  • a solvent must be used Suitable solvents include carbon disulfide, methylene chloride or dichloroethane, preferably carbon disulfide
  • the reaction is performed at a temperature from about 0°C to about 100°C, preferably at about 25°C
  • Scheme 2 refers to the conversion of compounds of the formula I into E2020, the compound of the formula Vii
  • a compound of the formula I can be converted into a compound of the formula VI by reaction with a strong base in the presence of a solvent
  • Suitable bases include potassium hydroxide and sodium hydroxide, preferably potassium hydroxide
  • Suitable solvents include lower alcohols, water or mixtures thereof, preferably a 2 1 water/methanol mixture
  • the reaction is performed at a temperature from about 25°C to about 100°C preferably at about 100°C
  • the reaction time may vary from about 6 to about 24 hours, preferably about 18 hours
  • the compound of formula I is most preferably converted into a compound of formula Vi by isolating the compound of formula I before converting it into the compound of formula VI
  • a compound of formula I is isolated by pouring the acidic solution containing the compound of formula I over an ice/water mixture and extracting the aqueous with an organic solvent Suitable solvents include methylene chloride ethyl acetate or dichlorothane, preferably methylene chloride
  • the organic layer can be concentrated and is then suitable for treatment with a strong base
  • a compound of the formula VII can be prepared from a compound of the formula VI by reacting said compound of the formula VI with a benzyl halide in a reaction inert solvent
  • Suitable halides include chloride, bromide, and iodide, preferably bromide
  • Suitable reaction inert solvents include diethyl ether, isopropyl ether, tetrahydrofuran, preferably isopropyl ether The reaction is performed at a temperature from about 0°C to about 70°C, preferably about 70°C
  • the compound of formula VII can be converted to pharmaceutically acceptable acid addition salts of the compound of the formula VII
  • the acids which are used to prepare the pharmaceutically acceptable acid addition salts of the compound of formula VII are those which form non-toxic acid addition salts, e g , salts containing pharmacologically acceptable anions, such as hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate or bisulfate, phosphate or acid phosphate, acetate, lactate, citrate or acid citrate, tartrate or bitartrate, succinate, maleate, fumarate gluconate, saccharate, benzoate, methanesulfonate and pamoate fe g , 1 ,1 '-methylene-b ⁇ s-(2- hydroxy-3-naphthoate)] salts
  • the compound of the formula VII is basic in nature and is therefore capable of forming a wide variety of different salts with va ⁇ ous inorganic and organic acids Although such salts must be pharmaceutically acceptable for administration to animals, it is often desirable in practice to initially isolate a compound of the formula VII from the reaction mixture as a pharmaceutically unacceptable salt and then simply convert the latter back to the free base compound by treatment with an alkaline reagent and subsequently convert the free base to a pharmaceutically acceptable acid addition salt
  • the acid addition salts of the base compounds of this invention are readily prepared by treating the base compound with a substantially equivalent amount of the chosen mineral or organic acid in an aqueous solvent medium or in a suitable organic solvent such as methanol or ethanol Upon careful evaporation of the solvent, the desired solid salt is obtained
  • Compounds of the formula VII, E2020, and its pharmaceutically acceptable salts can be used to treat a disease caused by acetylcholinesterase activity, such as Alzheimers' Disease, according to the methods described in United States Patent 4,895,841 , issued January 23, 1990
  • United States Patent 4,895,841 states that the in vitro acetyl cho nesterase activity of 1-benzyl-4-((5,6-d ⁇ ethyoxy-1- ⁇ ndanon)-2yl)methyl piperidine, E2020 , or a pharmaceutically acceptable salt thereof can be determined according to the method of Ellman et al Biochem Pharmacol , 7, 88-95 (1961 )
  • the acetylcholinesterase inhibitory activity of 1-benzyl-4-((5,6-d ⁇ ethyoxy-1 - ⁇ ndanon)-2yl)methyl piperidine, determined according to the method of Ellman et a , expressed in terms of 50% inhibitory concentration (IC 50 ) is 0 0053 ⁇ M
  • 1-Benzyl-4-((5,6-d ⁇ methoxy-1- ⁇ ndanon)-2yl)methylp ⁇ per ⁇ d ⁇ ne is effective for treatment, prevention, remission, improvement, etc of various kinds of senile dementia particularly senile dementia of the Alzheimer's type, cerebrovascular disease accompanying cerebral apoplexy, e g cerebral hemorrhage or cerebral infarcts, cerebral arteriosclerosis, head injury, etc , and aprosexia, disturbance of speech, hypobu a, emotional changes, recent memory disturbance, hallucinatory-paranoid syndrome, behavioral changes, etc accompanying encephalitis, cerebral palsy, etc
  • 1-benzyl-4-((5,6-d ⁇ methoxy-1- ⁇ ndanon)-2yl)methylp ⁇ per ⁇ d ⁇ ne has a strong and highly selective anticholinesterase action, which also renders the compound useful as a pharmaceutical based on this mode of action
  • 1-benzyl-4-((5,6-d ⁇ methoxy-1- ⁇ ndanon)-2yl)methyl-p ⁇ pe ⁇ d ⁇ ne is effective for, for example, Huntington's chorea, Pick's disease and delayed ataxia or tardive dyskinesia other than senile dementia of the Alzheimer type
  • 1-benzyl-4-((5,6-d ⁇ methoxy-1- ⁇ ndanon)-2yl)methylp ⁇ per ⁇ dine is used as a pharmaceutical for these diseases, it may be orally or parenterally administered In general, it is parenterally administered in the form of injections, such as intravenous, subcutaneous, and intramuscular injections, suppositories, or sublingual tablets
  • injections such as intravenous, subcutaneous, and intramuscular injections, suppositories, or sublingual tablets
  • the dose will vary depending upon the symptom; age, sex, weight, and sensitivity of patients, method of administration, time and intervals of administration and properties, dispensing, and kind
  • the compound may be administered in a dose of about 0 1 to 300 mg, preferably 1 to 100 mg, per day per adult, ordinarily in one to four portions
  • Pharmaceutical preparations in the dosage form of e g , injections, suppositories, sublingual tablets, tablets, and capsules are prepared according to methods which are commonly accepted in the art ln preparing injections, the effective ingredient is blended, if necessary, with a pH modifier, a buffer, a suspending agent, a solubilizing agent, a stabilizer, a tonicity agent, a preservative, etc , followed by preparation of an intravenous, subcutaneous, or intramuscular injection according to an ordinary method In this case, if necessary, it is possible to lyophilize these preparations accordmg to an ordinary method
  • suspending agents examples include methylcellulose Polysorbate 80® hydroxyethylcellulose, acacis, powdered tragacanth, sodium carboxymethylcellulose, and polyoxyethylene sorbitan monolaurate
  • solubilizing agent examples include polyoxyethylene hydrogenated castor oil, Polysorbate 80®, nicotinamide, polyoxyethylene sorbitan monolaurate, Macrogol®, and an ethyl ester of castor oil fatty acid
  • Examples of stabilizer include sodium sulfite, sodium metasulfite, and ether, and examples of the preservative include methyl p-hydroxybenzoate ethyl p- hydroxybenzoate, sorbic acid, phenol, cresol, and chlorocresol
  • Examples of stabilizer include sodium sulfite, sodium metasulfite, and ether
  • examples of the preservative include methyl p-hydroxybenzoate ethyl p- hydroxybenzoate, sorbic acid, phenol, cresol, and chlorocresol
  • Example 6 2-(1 -Benzyl-piperidin-4-ylmethv ⁇ -5,6-dimethoxy-indan-1 -one
  • benzylbromide (0 75 mL, 6 3 mmol)
  • triethanolamine 940 mg, 6 3 mmol
  • the slurry was stirred overnight, at 70°C, at which time high pressure liquid chromatography indicated that the starting material was mostly consumed
  • the reaction mixture was then filtered to remove precipitated triethanolamine hydrobromide
  • To the remaining solution was added ether saturated with hydrochloric acid (1 0 mL, 12 mmol), and the solvent was removed in vacuo
  • the residue was dissolved in 20 mL of hot isopropanol and allowed to cool to room temperature
  • the precipitated solid was filtered to provide 1 60 gm (61 %) of the title compound as a white solid

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
EP96931937A 1995-12-15 1996-10-11 Processes and intermediates for preparing 1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine Withdrawn EP0883607A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US875395P 1995-12-15 1995-12-15
US8753P 1995-12-15
PCT/IB1996/001076 WO1997022584A1 (en) 1995-12-15 1996-10-11 Processes and intermediates for preparing 1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine

Publications (1)

Publication Number Publication Date
EP0883607A1 true EP0883607A1 (en) 1998-12-16

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ID=21733469

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EP96931937A Withdrawn EP0883607A1 (en) 1995-12-15 1996-10-11 Processes and intermediates for preparing 1-benzyl-4-((5,6-dimethoxy-1-indanon)-2-yl)methylpiperidine

Country Status (33)

Country Link
EP (1) EP0883607A1 (cs)
JP (1) JP3066083B2 (cs)
KR (1) KR20000064387A (cs)
AP (1) AP708A (cs)
AR (1) AR004368A1 (cs)
AU (1) AU716462B2 (cs)
BG (1) BG102525A (cs)
BR (1) BR9612018A (cs)
CA (1) CA2237647A1 (cs)
CO (1) CO4750831A1 (cs)
CZ (1) CZ180898A3 (cs)
DZ (1) DZ2141A1 (cs)
GT (1) GT199600092A (cs)
HN (1) HN1996000065A (cs)
HR (1) HRP960592A2 (cs)
HU (1) HUP9904275A3 (cs)
IL (3) IL124452A0 (cs)
IS (1) IS4752A (cs)
MA (1) MA24032A1 (cs)
NO (1) NO982712L (cs)
NZ (1) NZ318843A (cs)
OA (1) OA10694A (cs)
PE (1) PE25698A1 (cs)
PL (1) PL197306B1 (cs)
RO (1) RO121382B1 (cs)
RU (1) RU2160731C2 (cs)
SK (1) SK75498A3 (cs)
TN (1) TNSN96153A1 (cs)
TW (1) TW414787B (cs)
UY (1) UY24401A1 (cs)
WO (1) WO1997022584A1 (cs)
YU (1) YU49486B (cs)
ZA (1) ZA9610533B (cs)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2316360C (en) 1998-01-16 2007-09-18 Eisai Co., Ltd. Process for production of donepezil derivative
IL125809A (en) * 1998-08-17 2005-08-31 Finetech Lab Ltd Process and intermediates for production of donepezil and related compounds
US7148354B2 (en) * 2002-07-24 2006-12-12 Dr. Reddy's Laboratories Limited Process for preparation of donepezil
IL150982A (en) 2002-07-30 2007-02-11 Ori Lerman Process for making Donafzil
IL151253A0 (en) * 2002-08-14 2003-04-10 Finetech Lab Ltd Process for production of highly pure donepezil hydrochloride
US6649765B1 (en) 2003-02-12 2003-11-18 Usv Limited, Bsd Marg. Process for the preparation of 1-benzyl-4(5,6-dimethoxy-1-indanon)-2-yl) methyl piperidine hydrochloride (Donepezil HCL)
US6953856B2 (en) 2003-02-12 2005-10-11 Usv, Limited Process for the preparation of 1-benzyl-4-(5,6-dimethoxy-1-indanon)-2-yl) methyl piperidine hydrochloride (Donepezil HCI)
EP1608371A1 (en) * 2003-03-21 2005-12-28 Ranbaxy Laboratories, Ltd. Process for the preparation of donepezil and derivatives thereof
WO2004099142A1 (en) * 2003-05-05 2004-11-18 Ranbaxy Laboratories Limited Hydrobromide salt of benzyl-piperidylmethyl-indanone and its polymorphs
EP1654230A1 (en) 2003-07-01 2006-05-10 Hetero Drugs Limited Preparation of intermediates for acetyl cholinesterase inhibitors
CN1280273C (zh) 2003-11-05 2006-10-18 天津和美生物技术有限公司 合成多奈哌齐及其衍生物的方法
US7592459B2 (en) 2004-09-29 2009-09-22 Chemagis Ltd. Use of purified donepezil maleate for preparing pharmaceutically pure amorphous donepezil hydrochloride
CN100436416C (zh) * 2005-07-29 2008-11-26 西南合成制药股份有限公司 盐酸多奈哌齐合成工艺
GB0515803D0 (en) 2005-07-30 2005-09-07 Pliva Hrvatska D O O Intermediate compounds
AR057910A1 (es) 2005-11-18 2007-12-26 Synthon Bv Proceso para preparar donepezilo
US8030491B2 (en) 2006-01-04 2011-10-04 Cipla Limited Process and intermediate for preparation of donepezil
EP2114166A4 (en) 2006-12-11 2011-05-25 Reviva Pharmaceuticals Inc COMPOSITIONS, SYNTHESIS, AND METHODS OF USING INDANONE-BASED CHOLINESTERASE INHIBITORS
WO2013078608A1 (en) 2011-11-29 2013-06-06 Ziqiang Gu Donepezil pamoate and methods of making and using the same
AU2014307803A1 (en) 2013-08-16 2016-03-10 Universiteit Maastricht Treatment of cognitive impairment with PDE4 inhibitor

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FI95572C (fi) * 1987-06-22 1996-02-26 Eisai Co Ltd Menetelmä lääkeaineena käyttökelpoisen piperidiinijohdannaisten tai sen farmaseuttisen suolan valmistamiseksi
FR2642069B1 (fr) * 1989-01-20 1991-04-12 Rhone Poulenc Sante Nouveaux derives du benzopyranne, leur preparation et les compositions pharmaceutiques qui les contiennent
DE4439822A1 (de) * 1994-11-08 1996-08-29 Bayer Ag Verfahren zur Herstellung von Benzyl-piperidylmethyl-indanonen

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Also Published As

Publication number Publication date
AP9600892A0 (en) 1997-01-31
WO1997022584A1 (en) 1997-06-26
HRP960592A2 (en) 1998-06-30
AP708A (en) 1998-12-04
NZ318843A (en) 2000-01-28
IS4752A (is) 1998-05-22
RO121382B1 (ro) 2007-04-30
CO4750831A1 (es) 1999-03-31
YU49486B (sh) 2006-08-17
KR20000064387A (ko) 2000-11-06
HN1996000065A (es) 1997-06-26
IL136420A0 (en) 2001-06-14
IL136421A0 (en) 2001-06-14
IL124452A0 (en) 1998-12-06
TNSN96153A1 (fr) 2005-03-15
YU66096A (en) 1999-11-22
HUP9904275A3 (en) 2001-05-28
CA2237647A1 (en) 1997-06-26
PL327512A1 (en) 1998-12-21
GT199600092A (es) 1998-05-12
MA24032A1 (fr) 1997-07-01
CZ180898A3 (cs) 1999-05-12
JPH11500756A (ja) 1999-01-19
UY24401A1 (es) 1997-06-09
AR004368A1 (es) 1998-11-04
AU7092596A (en) 1997-07-14
SK75498A3 (en) 1999-08-06
NO982712D0 (no) 1998-06-12
MX9804820A (es) 1998-10-31
RU2160731C2 (ru) 2000-12-20
DZ2141A1 (fr) 2002-07-23
HUP9904275A2 (hu) 2000-05-28
BR9612018A (pt) 1999-02-17
OA10694A (en) 2001-05-04
PL197306B1 (pl) 2008-03-31
JP3066083B2 (ja) 2000-07-17
PE25698A1 (es) 1998-05-21
NO982712L (no) 1998-06-12
BG102525A (en) 1999-05-31
TW414787B (en) 2000-12-11
AU716462B2 (en) 2000-02-24
ZA9610533B (en) 1998-06-15

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