ATE255564T1 - Imidazolderivat - Google Patents

Imidazolderivat

Info

Publication number
ATE255564T1
ATE255564T1 AT95932231T AT95932231T ATE255564T1 AT E255564 T1 ATE255564 T1 AT E255564T1 AT 95932231 T AT95932231 T AT 95932231T AT 95932231 T AT95932231 T AT 95932231T AT E255564 T1 ATE255564 T1 AT E255564T1
Authority
AT
Austria
Prior art keywords
alkyl
imidazole derivative
halogeno
formula
hydrogen
Prior art date
Application number
AT95932231T
Other languages
English (en)
Inventor
Hirohiko Sugimoto
Tamio Fujiwara
Original Assignee
Shionogi & Co
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 Shionogi & Co filed Critical Shionogi & Co
Application granted granted Critical
Publication of ATE255564T1 publication Critical patent/ATE255564T1/de

Links

Classifications

    • 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
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
    • C07D233/84—Sulfur atoms
    • 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
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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
    • 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
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C07D233/58—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring nitrogen atoms
    • 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
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • 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
    • C07D401/02—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
    • C07D401/06—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 linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Communicable Diseases (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Dental Preparations (AREA)
  • Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
  • Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
AT95932231T 1994-09-26 1995-09-25 Imidazolderivat ATE255564T1 (de)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP25749094 1994-09-26
JP8469095 1995-03-15
JP22720595 1995-08-12
PCT/JP1995/001936 WO1996010019A1 (en) 1994-09-26 1995-09-25 Imidazole derivative

Publications (1)

Publication Number Publication Date
ATE255564T1 true ATE255564T1 (de) 2003-12-15

Family

ID=27304632

Family Applications (1)

Application Number Title Priority Date Filing Date
AT95932231T ATE255564T1 (de) 1994-09-26 1995-09-25 Imidazolderivat

Country Status (20)

Country Link
US (2) US5910506A (de)
EP (1) EP0786455B1 (de)
JP (1) JP3155009B2 (de)
KR (1) KR100387157B1 (de)
CN (1) CN1093535C (de)
AT (1) ATE255564T1 (de)
BR (1) BR9509024A (de)
CA (1) CA2200316C (de)
DE (1) DE69532245T2 (de)
DK (1) DK0786455T3 (de)
ES (1) ES2211917T3 (de)
FI (1) FI971234A7 (de)
HU (1) HUT77357A (de)
MX (1) MX9702030A (de)
NO (1) NO308739B1 (de)
PL (1) PL183931B1 (de)
PT (1) PT786455E (de)
RU (1) RU2157368C2 (de)
TW (1) TW401404B (de)
WO (1) WO1996010019A1 (de)

Families Citing this family (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6054591A (en) * 1996-03-28 2000-04-25 Shionogi & Co., Ltd. Lymph-absorbable aryl substituted imidazole derivatives
MXPA98008158A (es) * 1996-04-04 2002-02-08 Shionogi & Co Composicion anti-vih que contiene derivados de imidazol.
RU2188638C2 (ru) * 1996-04-04 2002-09-10 Шионоги Энд Ко., Лтд. Анти-вич-композиция, содержащая имидазольные производные
DE69728180T2 (de) * 1996-12-26 2005-03-17 Shionogi & Co., Ltd. Verfahren zur herstellung von carbamoylsubstituierten imidazolderivaten
EP0949249B1 (de) * 1996-12-26 2005-07-13 Shionogi & Co., Ltd. Verfahren zur herstellung von imidazolderivaten
TWI232214B (en) 1998-04-16 2005-05-11 Shionogi & Co Preparation of aryl sulfenyl halide
WO2000061109A1 (fr) 1999-04-12 2000-10-19 Shionogi & Co., Ltd. Procede de production de composition medicamenteuse renfermant un compose medicamenteux hydrophobe basique
GB0016787D0 (en) * 2000-07-07 2000-08-30 Pfizer Ltd Compounds useful in therapy
PL363321A1 (en) 2001-01-31 2004-11-15 Warner-Lambert Company Llc Method for carbamoylating alcohols
DK1370539T3 (da) 2001-02-23 2012-02-13 Leuven K U Res & Dev HIV-inhiberende N-aminoimidazolderivater
SI1762567T1 (sl) 2001-04-10 2012-08-31 Pfizer Derivati pirazola za zdravljenje HIV-a
GB0113524D0 (en) * 2001-06-04 2001-07-25 Hoffmann La Roche Pyrazole derivatives
FR2825926A1 (fr) * 2001-06-14 2002-12-20 Sod Conseils Rech Applic Derives d'imidazoles modulant les canaux sodiques
EP1501817A1 (de) * 2002-04-23 2005-02-02 F. Hoffmann-La Roche Ag Imidazolinylmethyl aralkylsulfonamide
TW200408645A (en) 2002-04-26 2004-06-01 Gilead Sciences Inc Non nucleoside reverse transcriptase inhibitors
TW200423930A (en) 2003-02-18 2004-11-16 Hoffmann La Roche Non-nucleoside reverse transcriptase inhibitors
WO2004085406A1 (en) 2003-03-24 2004-10-07 F. Hoffmann-La Roche Ag Benzyl-pyridazinons as reverse transcriptase inhibitors
US7452901B2 (en) 2003-04-25 2008-11-18 Gilead Sciences, Inc. Anti-cancer phosphonate analogs
EP1620109A2 (de) 2003-04-25 2006-02-01 Gilead Sciences, Inc. Kinase inhbitor phosphonat konjugate
US7470724B2 (en) 2003-04-25 2008-12-30 Gilead Sciences, Inc. Phosphonate compounds having immuno-modulatory activity
US7427636B2 (en) 2003-04-25 2008-09-23 Gilead Sciences, Inc. Inosine monophosphate dehydrogenase inhibitory phosphonate compounds
US7432261B2 (en) 2003-04-25 2008-10-07 Gilead Sciences, Inc. Anti-inflammatory phosphonate compounds
WO2004096285A2 (en) 2003-04-25 2004-11-11 Gilead Sciences, Inc. Anti-infective phosphonate conjugates
US7407965B2 (en) 2003-04-25 2008-08-05 Gilead Sciences, Inc. Phosphonate analogs for treating metabolic diseases
SG182849A1 (en) 2003-04-25 2012-08-30 Gilead Sciences Inc Antiviral phosphonate analogs
WO2005002626A2 (en) 2003-04-25 2005-01-13 Gilead Sciences, Inc. Therapeutic phosphonate compounds
WO2005016912A1 (en) * 2003-08-19 2005-02-24 Pfizer Inc. An efficient microbial preparation of capravirine metabolites m4 and m5
US7432273B2 (en) 2003-10-24 2008-10-07 Gilead Sciences, Inc. Phosphonate analogs of antimetabolites
WO2005042773A1 (en) 2003-10-24 2005-05-12 Gilead Sciences, Inc. Methods and compositions for identifying therapeutic compounds
WO2005044279A1 (en) 2003-10-24 2005-05-19 Gilead Sciences, Inc. Purine nucleoside phosphonate conjugates
CA2548388A1 (en) * 2003-12-15 2005-06-30 Schering Corporation Heterocyclic aspartyl protease inhibitors
BRPI0417988A (pt) 2003-12-22 2007-04-27 Gilead Sciences Inc análogos de fosfonato antivirais
EP1740550A1 (de) * 2004-04-14 2007-01-10 Pfizer Limited Schwefelgebundene imidazolverbindungen zur behandlung von hiv
KR100749566B1 (ko) * 2004-04-21 2007-08-16 이화여자대학교 산학협력단 Alk5 및/또는 alk4 억제제로 유효한 2-피리딜이치환된 이미다졸 유도체
US7893278B2 (en) * 2004-06-17 2011-02-22 Hoffman-La Roche Inc. CIS-imidazolines
PT2258376T (pt) 2004-07-27 2019-05-31 Gilead Sciences Inc Análogos fosfonatados de compostos inibidores do vih
JP4993407B2 (ja) 2004-08-04 2012-08-08 大正製薬株式会社 トリアゾール誘導体
CA2592909A1 (en) * 2005-01-06 2006-07-13 Pfizer Limited Imidazole derivatives as enzyme reverse transcriptase modulators
KR101139263B1 (ko) * 2005-03-16 2012-05-16 에프. 호프만-라 로슈 아게 시스-2,4,5-트리아릴-이미다졸린 및 항암 약제로서의그의 용도
CN101316823B (zh) * 2005-12-01 2013-05-22 霍夫曼-拉罗奇有限公司 用作抗癌剂的作为p53和MDM2蛋白之间相互作用的抑制剂的2,4,5-三苯基咪唑啉衍生物
PL1988083T3 (pl) 2006-02-03 2014-08-29 Taisho Pharmaceutical Co Ltd Pochodna triazolowa
RU2395499C2 (ru) * 2006-02-06 2010-07-27 Тайсо Фармасьютикал Ко., Лтд. Ингибитор связывания сфингозин-1-фосфата
US7649098B2 (en) * 2006-02-24 2010-01-19 Lexicon Pharmaceuticals, Inc. Imidazole-based compounds, compositions comprising them and methods of their use
US7994205B2 (en) * 2006-03-31 2011-08-09 Takeda Pharmaceutical Company Limited Aryl-or heteroaryl-sulfonyl compounds as acid secretion inhibitors
PE20080948A1 (es) * 2006-07-25 2008-09-10 Irm Llc Derivados de imidazol como moduladores de la senda de hedgehog
DE602007013573D1 (de) 2006-08-16 2011-05-12 Hoffmann La Roche Nicht-nukleosidische reverse-transkriptase-hemmer
ATE554070T1 (de) 2007-08-01 2012-05-15 Taisho Pharmaceutical Co Ltd Hemmer der s1p1-bindung
TW200920355A (en) * 2007-09-06 2009-05-16 Lexicon Pharmaceuticals Inc Compositions and methods for treating immunological and inflammatory diseases and disorders
JP5345140B2 (ja) * 2007-09-28 2013-11-20 武田薬品工業株式会社 プロトンポンプ阻害剤としての5員複素環化合物
AU2008340422B2 (en) 2007-12-21 2014-06-19 F. Hoffmann-La Roche Ag Heterocyclic antiviral compounds
BRPI0915878A2 (pt) 2008-07-08 2015-11-03 Gilead Sciences Inc sais ou hidratos de compostos inibidores de hiv, seu uso e composição farmacêutica que os compreende
JP2012517479A (ja) * 2009-02-12 2012-08-02 エグゼリクシス, インコーポレイテッド 糖尿病および肥満の処置においてtgr5アゴニストとして使用するためのトリアゾールおよびイミダゾール誘導体
WO2010110378A1 (ja) 2009-03-26 2010-09-30 武田薬品工業株式会社 ピラゾール化合物
EP2508511A1 (de) * 2011-04-07 2012-10-10 Laboratoire Biodim Inhibitoren der Virenreplikation, Verfahren zu deren Herstellung und deren therapeutische Verwendung
CA2879726A1 (en) * 2012-07-24 2014-01-30 Bial- Portela & Ca, S.A. Urea compounds and their use as enzyme inhibitors
EP2716632A1 (de) 2012-10-05 2014-04-09 Laboratoire Biodim Inhibitoren der Virenreplikation, Verfahren zu deren Herstellung und deren therapeutische Verwendung
EP2716639A1 (de) 2012-10-05 2014-04-09 Laboratoire Biodim Inhibitoren der Virenreplikation, Verfahren zu deren Herstellung und deren therapeutische Verwendung
GB201602934D0 (en) 2016-02-19 2016-04-06 Cancer Res Inst Royal Compounds
EP3381905A1 (de) * 2017-03-30 2018-10-03 Institut National de la Sante et de la Recherche Medicale (INSERM) Neuartige antivirale verbindungen
PT3661937T (pt) 2017-08-01 2021-09-24 Gilead Sciences Inc Formas cristalinas de ((s)-((((2r,5r)-5-(6-amino-9h-purin-9-il)-4-fluoro-2,5-dihidrofurano-2-il)oxi)metil)(fenoxi)fosforil)-l-alaninato de etil (gs-9131) para tratamento de infeções virais

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE428686B (sv) * 1975-08-11 1983-07-18 Du Pont Forfarande for framstellning av antiinflammatoriskt aktiva imidazoler
JPS63150266A (ja) * 1986-12-12 1988-06-22 Mitsui Petrochem Ind Ltd ベンジルイミダゾ−ル誘導体
JPH0283373A (ja) * 1988-05-19 1990-03-23 Nippon Soda Co Ltd 5員環の複素環化合物及びその製造方法
IL98319A (en) * 1990-07-05 1997-04-15 Roussel Uclaf Sulphurous derivatives of imidazole, their preparation process, and pharmaceutical compositions containing them
TW235963B (de) * 1992-01-16 1994-12-11 Shionogi & Co
DE10230797C2 (de) * 2001-07-16 2003-09-25 Dieter Reif Befestigungsklammer zur Verbindung von Holzbauteilen

Also Published As

Publication number Publication date
EP0786455A4 (de) 1998-12-30
CA2200316C (en) 2004-09-21
EP0786455A1 (de) 1997-07-30
TW401404B (en) 2000-08-11
PL183931B1 (pl) 2002-08-30
RU2157368C2 (ru) 2000-10-10
CN1158609A (zh) 1997-09-03
DE69532245D1 (en) 2004-01-15
BR9509024A (pt) 1997-09-30
US6147097A (en) 2000-11-14
KR970706260A (ko) 1997-11-03
PL320009A1 (en) 1997-09-01
JP3155009B2 (ja) 2001-04-09
NO971306L (no) 1997-05-21
FI971234L (fi) 1997-05-23
PT786455E (pt) 2004-02-27
FI971234A0 (fi) 1997-03-25
CA2200316A1 (en) 1996-04-04
NO971306D0 (no) 1997-03-20
HUT77357A (hu) 1998-03-30
US5910506A (en) 1999-06-08
AU4788896A (en) 1996-04-19
WO1996010019A1 (en) 1996-04-04
DK0786455T3 (da) 2004-03-29
FI971234A7 (fi) 1997-05-23
CN1093535C (zh) 2002-10-30
ES2211917T3 (es) 2004-07-16
NO308739B1 (no) 2000-10-23
EP0786455B1 (de) 2003-12-03
DE69532245T2 (de) 2004-09-16
AU706095B2 (en) 1999-06-10
MX9702030A (es) 1997-06-28
KR100387157B1 (ko) 2003-09-29

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