PT97507A - Processo para apreparacao de novos derivados de catecol farmacologicamente activos - Google Patents

Processo para apreparacao de novos derivados de catecol farmacologicamente activos

Info

Publication number
PT97507A
PT97507A PT97507A PT9750791A PT97507A PT 97507 A PT97507 A PT 97507A PT 97507 A PT97507 A PT 97507A PT 9750791 A PT9750791 A PT 9750791A PT 97507 A PT97507 A PT 97507A
Authority
PT
Portugal
Prior art keywords
derivatives
catecol
recreation
pharmacologically active
new pharmacologically
Prior art date
Application number
PT97507A
Other languages
English (en)
Other versions
PT97507B (pt
Inventor
Reijo Johannes Backstrom
Erkki Juhani Honkanen
Ingebritt Linden Yvonne
Erkki Aarne Olavi Nissinen
Aino Kyllikki Pippuri
Pentti Pohto
Korkolainen Tapio Juhani
Original Assignee
Orion Yhtymae Oy
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 claimed from GB909009565A external-priority patent/GB9009565D0/en
Priority claimed from GB919101563A external-priority patent/GB9101563D0/en
Application filed by Orion Yhtymae Oy filed Critical Orion Yhtymae Oy
Publication of PT97507A publication Critical patent/PT97507A/pt
Publication of PT97507B publication Critical patent/PT97507B/pt

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P37/02—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
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/96—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/38—One sulfur atom
    • C07D239/40—One sulfur atom as doubly bound sulfur atom or as unsubstituted mercapto radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/60—Three or more oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/60—Three or more oxygen or sulfur atoms
    • C07D239/62—Barbituric acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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
    • C07D263/46—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Transplantation (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Biochemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Steroid Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
PT97507A 1990-04-27 1991-04-26 Processo para apreparacao de novos derivados de catecol farmacologicamente activos PT97507B (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB909009565A GB9009565D0 (en) 1990-04-27 1990-04-27 New pharmacologically active catechol derivatives
GB919101563A GB9101563D0 (en) 1991-01-24 1991-01-24 New pharmacologically active catechol derivatives

Publications (2)

Publication Number Publication Date
PT97507A true PT97507A (pt) 1992-01-31
PT97507B PT97507B (pt) 1998-08-31

Family

ID=26297011

Family Applications (1)

Application Number Title Priority Date Filing Date
PT97507A PT97507B (pt) 1990-04-27 1991-04-26 Processo para apreparacao de novos derivados de catecol farmacologicamente activos

Country Status (17)

Country Link
US (3) US5362733A (pt)
EP (1) EP0526598B1 (pt)
JP (1) JP2972377B2 (pt)
KR (1) KR100207144B1 (pt)
AT (1) ATE146462T1 (pt)
AU (1) AU646464B2 (pt)
CA (1) CA2080917C (pt)
DE (1) DE69123738T2 (pt)
FI (1) FI95129C (pt)
HU (1) HU214872B (pt)
IE (1) IE911430A1 (pt)
LT (1) LT3137B (pt)
LV (1) LV10097B (pt)
NO (1) NO301928B1 (pt)
PL (1) PL166269B1 (pt)
PT (1) PT97507B (pt)
WO (1) WO1991017151A1 (pt)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2210566A1 (en) * 1995-01-23 1996-08-01 Eli Lilly And Company Method for treating multiple sclerosis
AU5577498A (en) * 1997-01-31 1998-08-25 Shionogi & Co., Ltd. Compounds having metalloprotease inhibitory activity
EP1006794B1 (en) * 1997-03-12 2007-11-28 Robert W. Esmond A method for treating or preventing alzheimer's disease
US20040058873A1 (en) * 1998-03-12 2004-03-25 Esmond Robert W. Method for treating or preventing Alzheimer's disease
US6191154B1 (en) 1998-11-27 2001-02-20 Case Western Reserve University Compositions and methods for the treatment of Alzheimer's disease, central nervous system injury, and inflammatory diseases
WO2001030771A1 (fr) * 1999-10-28 2001-05-03 Kyowa Hakko Kogyo Co., Ltd. Derives de thiazolidinedione
WO2002053155A1 (en) * 2000-12-30 2002-07-11 Geron Corporation Telomerase inhibitor
EP1435894A4 (en) * 2001-07-23 2005-07-06 Galileo Pharmaceuticals Inc CYTOPROTECTIVE COMPOUNDS, METHODS AND PHARMACEUTICAL AND COSMETIC FORMULATIONS
US6679051B1 (en) * 2002-07-31 2004-01-20 Ford Global Technologies, Llc Diesel engine system for use with emission control device
BRPI0416752B8 (pt) 2003-11-21 2021-05-25 Actelion Pharmaceuticals Ltd composição farmacêutica, uso de um ou mais compostos, e, compostos
USRE43833E1 (en) 2003-11-21 2012-11-27 Actelion Pharmaceuticals Ltd. Thiazolidin-4-one derivatives
US7872027B2 (en) * 2006-02-17 2011-01-18 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Low molecular weight Myc-max inhibitors
US8912340B2 (en) 2006-11-23 2014-12-16 Actelion Pharmaceuticals Ltd. Process for the preparation of 2-imino-thiazolidin-4-one derivatives
MX2009005048A (es) 2006-11-23 2009-05-25 Actelion Pharmaceuticals Ltd Nuevo proceso para la preparacion de derivados de 2-imino-tiazolidin-4-ona.
FR2919608B1 (fr) * 2007-08-01 2012-10-05 Univ Rennes Derives d'imidazolones,procede de preparation et applications biologiques
WO2010011318A2 (en) * 2008-07-23 2010-01-28 Massachusetts Institute Of Technology Activatiqn of histone deacetylase 1 (hdac1) protects against dna damage and increases neuronal survival
KR101411838B1 (ko) 2011-02-09 2014-06-27 부산대학교 산학협력단 피부미백, 항산화 및 ｐｐａｒ 활성을 갖는 신규 화합물 및 이의 의학적 용도
PL2734510T4 (pl) 2011-07-22 2019-05-31 Massachusetts Inst Technology Aktywatory deacetylaz histonowych klasy I (HDAC) i ich zastosowania
LT2885266T (lt) 2012-08-17 2020-07-10 Actelion Pharmaceuticals Ltd (2z,5z)-5-(3-chlor-4-((r)-2,3-dihidroksipropoksi)benziliden)-2-(propilimino)-3-(o-tolil)tiazolidin-4-ono gamybos būdas ir šiame procese naudojamas tarpinis junginys
CA3020161A1 (en) * 2016-04-05 2017-10-12 Immune Sensor, Llc Cgas antagonist compounds
WO2022163843A1 (ja) * 2021-02-01 2022-08-04 国立大学法人徳島大学 Ｐｉｍ２阻害剤

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1038050B (de) * 1955-11-17 1958-09-04 Farmaceutici Italia S A Soc Verfahren zur Herstellung von 5-(3', 4'-Dioxybenzyliden)-Derivaten heterocyclischer Verbindungen
US4264617A (en) * 1972-06-16 1981-04-28 Canada Packers, Limited Antiviral 5-(substituted benzal) hydantoins
GB1439318A (en) * 1972-06-16 1976-06-16 Canada Packers Ltd 5-substituted benzal- hydantoins derivatives
US4013770A (en) * 1972-06-16 1977-03-22 Canada Packers Limited Antiviral 5-(substituted benzal) hydantoins
GB1601310A (en) * 1978-05-23 1981-10-28 Lilly Industries Ltd Aryl hydantoins
JPS5697277A (en) * 1980-01-07 1981-08-05 Takeda Chem Ind Ltd Thiazolidine derivative
DE3013626C2 (de) * 1980-04-09 1985-06-27 Degussa Ag, 6000 Frankfurt Verfahren zur Herstellung von 5-Arylidenhydantoinen (A)
DE3013647C2 (de) * 1980-04-09 1985-07-11 Degussa Ag, 6000 Frankfurt Verfahren zur Herstellung von 5-Arylidenhydantoinen (B)
JPS60233063A (ja) * 1984-05-02 1985-11-19 Showa Denko Kk ５−ベンジリデンヒダントインの製造法
US4582903A (en) * 1984-08-17 1986-04-15 Stauffer Chemical Company Synthesis of unsaturated hydantoins with an inexpensive catalyst
US4650876A (en) * 1984-08-17 1987-03-17 Stauffer Chemical Company Hydrogenation of substituted, unsaturated hydantoins to substituted, saturated hydantoins
IL79648A (en) * 1985-08-09 1991-12-12 Lilly Co Eli Pharmaceutical anti-inflammatory and ischemia preventing compositions containing di-t-butylphenol derivatives,some such novel compounds and process for their preparation
IE940525L (en) * 1988-05-25 1989-11-25 Warner Lambert Co Known and selected novel arylmethylenyl derivatives of¹thiazolidinones, imidazolidinones and oxazolidinones useful¹as antiallergy agents and antiinflammatory agents
US5208250A (en) * 1988-05-25 1993-05-04 Warner-Lambert Company Known and selected novel arylmethylenyl derivatives of thiazolidinones, imidazolidinones and oxazolidinones useful as antiallergy agents and anti-inflammatory agents
US5306822A (en) * 1988-05-25 1994-04-26 Warner-Lambert Company Arylmethylenyl derivatives of oxazolidinone
GB8911073D0 (en) * 1989-05-15 1989-06-28 Fujisawa Pharmaceutical Co New benzofuran derivatives,a process for the preparation thereof and pharmaceutical composition comprising the same
JPH1052765A (ja) 1996-08-09 1998-02-24 Sukematsu Iwashita 鉄筋材の圧接装置

Also Published As

Publication number Publication date
HU214872B (hu) 1998-07-28
JP2972377B2 (ja) 1999-11-08
NO301928B1 (no) 1997-12-29
AU7761891A (en) 1991-11-27
EP0526598A1 (en) 1993-02-10
JPH05331148A (ja) 1993-12-14
HUT65662A (en) 1994-07-28
CA2080917A1 (en) 1991-10-28
CA2080917C (en) 2001-06-12
FI924838A (fi) 1992-10-23
US5362733A (en) 1994-11-08
AU646464B2 (en) 1994-02-24
DE69123738T2 (de) 1997-07-03
WO1991017151A1 (en) 1991-11-14
LV10097A (lv) 1994-05-10
FI924838A0 (fi) 1992-10-23
KR930700468A (ko) 1993-03-15
US5614541A (en) 1997-03-25
ATE146462T1 (de) 1997-01-15
NO924132D0 (no) 1992-10-26
LT3137B (en) 1995-01-31
FI95129C (fi) 1995-12-27
DE69123738D1 (en) 1997-01-30
HU9203369D0 (en) 1993-01-28
US5889037A (en) 1999-03-30
PT97507B (pt) 1998-08-31
PL166269B1 (pl) 1995-04-28
FI95129B (fi) 1995-09-15
IE911430A1 (en) 1991-11-06
KR100207144B1 (en) 1999-07-15
NO924132L (no) 1992-12-23
EP0526598B1 (en) 1996-12-18
LTIP227A (lt) 1994-08-25
LV10097B (en) 1995-02-20

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Effective date: 19910913

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Effective date: 19980514

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Free format text: LAPSE DUE TO NON-PAYMENT OF FEES

Effective date: 20031130