ATA941575A - Verfahren zur herstellung von neuen 1- substituierten-4-benzylpiperidinen und irhen saeureadditonssalzen - Google Patents

Verfahren zur herstellung von neuen 1- substituierten-4-benzylpiperidinen und irhen saeureadditonssalzen

Info

Publication number
ATA941575A
ATA941575A AT941575A AT941575A ATA941575A AT A941575 A ATA941575 A AT A941575A AT 941575 A AT941575 A AT 941575A AT 941575 A AT941575 A AT 941575A AT A941575 A ATA941575 A AT A941575A
Authority
AT
Austria
Prior art keywords
additone
benzylpiperidines
irish
salts
substituted
Prior art date
Application number
AT941575A
Other languages
English (en)
Other versions
AT352127B (de
Original Assignee
Robins Co Inc A H
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 Robins Co Inc A H filed Critical Robins Co Inc A H
Publication of ATA941575A publication Critical patent/ATA941575A/de
Application granted granted Critical
Publication of AT352127B publication Critical patent/AT352127B/de

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic 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
    • C07D211/08Heterocyclic 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
    • C07D211/18Heterocyclic 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
    • C07D211/20Heterocyclic 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 singly bound oxygen or sulphur atoms
    • C07D211/22Heterocyclic 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 singly bound oxygen or sulphur atoms by oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic 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
    • C07D211/08Heterocyclic 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
    • C07D211/10Heterocyclic 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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/12Heterocyclic 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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with only hydrogen atoms attached to the ring nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic 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
    • C07D211/08Heterocyclic 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
    • C07D211/10Heterocyclic 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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/14Heterocyclic 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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic 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
    • C07D211/08Heterocyclic 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
    • C07D211/10Heterocyclic 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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/16Heterocyclic 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 radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic 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
    • C07D211/08Heterocyclic 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
    • C07D211/18Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic 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
    • C07D211/08Heterocyclic 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
    • C07D211/18Heterocyclic 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
    • C07D211/30Heterocyclic 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
    • C07D211/32Heterocyclic 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
AT941575A 1974-12-11 1975-12-11 Verfahren zur herstellung von neuen 1- substituierten-4-benzylpiperidinen und ihren saeureadditionssalzen AT352127B (de)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US05/531,832 US3956296A (en) 1974-12-11 1974-12-11 1-Substituted-4-benzylpiperidines

Publications (2)

Publication Number Publication Date
ATA941575A true ATA941575A (de) 1979-02-15
AT352127B AT352127B (de) 1979-09-10

Family

ID=24119234

Family Applications (1)

Application Number Title Priority Date Filing Date
AT941575A AT352127B (de) 1974-12-11 1975-12-11 Verfahren zur herstellung von neuen 1- substituierten-4-benzylpiperidinen und ihren saeureadditionssalzen

Country Status (18)

Country Link
US (1) US3956296A (de)
JP (1) JPS5182278A (de)
AT (1) AT352127B (de)
AU (1) AU8747675A (de)
BE (1) BE836394A (de)
BR (1) BR7508160A (de)
CA (1) CA1059512A (de)
DE (1) DE2555588A1 (de)
DK (1) DK558175A (de)
ES (1) ES443360A1 (de)
FR (1) FR2293933A1 (de)
GB (1) GB1531419A (de)
IL (1) IL48592A (de)
NL (1) NL7514460A (de)
NO (1) NO754180L (de)
NZ (1) NZ179495A (de)
SE (1) SE7513953L (de)
ZA (1) ZA757748B (de)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4163790A (en) * 1977-05-11 1979-08-07 A. H. Robins Company, Inc. Method for increasing coronary blood flow in mammals
US4246268A (en) * 1979-02-09 1981-01-20 Richardson-Merrell Inc. Neuroleptic-4-(naphthylmethyl)piperidine derivatives
US4254130A (en) * 1979-04-10 1981-03-03 Richardson-Merrell Inc. Piperidine derivatives
US4254129A (en) * 1979-04-10 1981-03-03 Richardson-Merrell Inc. Piperidine derivatives
DK159420C (da) * 1983-03-09 1991-03-11 Ciba Geigy Ag N-(piperidinyl-alkyl)-carboxamider og salte deraf, farmaceutiske praeparater indeholdende disse forbindelser samt anvendelsen af forbindelserne til fremstilling af antipsykotiske farmaceutiske praeparater
US4812452A (en) * 1984-10-19 1989-03-14 A. H. Robins Company, Incorporated 1-((aminoalkyl and aminoalkylamino) carbonyl and thiocarbonyl)-α,α-diarylpyrrolidine, piperidine and homopiperidineacetamides and acetonitriles
US4650874A (en) * 1984-11-26 1987-03-17 G. D. Searle & Co. N-(aralkoxybenzyl)-4(benzhydryl) piperidines
EP0235463A3 (de) * 1985-12-20 1990-01-17 A.H. ROBINS COMPANY, INCORPORATED (a Delaware corporation) N-substituierte Arylalkyl- und Arylalkylen-Piperidine und Anwendung als kardiovaskulär antihistaminische und antisekretorische Mittel
US4810713A (en) * 1985-12-20 1989-03-07 A. H. Robins Company, Incorporated Arylalkyl-heterocyclic amines, n-substituted by aryloxyalkyl groups used in a method for allergy treatment
DE3601048A1 (de) * 1986-01-16 1987-07-23 Hoechst Ag 1,2-disubstituierte piperidine, verfahren zu ihrer herstellung sowie ihre verwendung im pflanzenschutz
AU607735B2 (en) * 1987-05-07 1991-03-14 A.H. Robins Company, Incorporated Novel cyclic carbamate derivatives
US5057524A (en) * 1990-02-08 1991-10-15 A. H. Robins Company Incorporated 4-[diaryl)hydroxymethyl]-1-piperidinealkylcarboxylic acids, salts and esters useful in the treatment of allergic disorders
WO1992006971A1 (en) * 1990-10-10 1992-04-30 Schering Corporation Pyridine and pyridine n-oxide derivatives of diaryl methyl piperidines or piperazines, and compositions and methods of use thereof
FR2678265B1 (fr) * 1991-06-27 1994-01-14 Synthelabo Derives de 4-(2-phenylethyl)piperidine, leur preparation et leur application en therapeutique.
AU2931792A (en) * 1991-11-29 1993-06-28 Zeria Pharmaceutical Co., Ltd. Piperidine derivative and medicine containing the same
DE69303605T2 (de) * 1992-03-27 1997-01-23 Schering Corp Unverbrückte bis-aryl-carbinol-derivate, zusammensetzungen und ihre verwendung
AU3921493A (en) * 1992-03-27 1993-11-08 Schering Corporation Bridged bis-aryl carbinol derivatives, compositions and methods of use
WO1994017040A1 (en) * 1993-01-21 1994-08-04 Merrell Dow Pharmaceuticals Inc. Diarylalkyl piperidines useful as multi-drug resistant tumor agents
ES2066721B1 (es) * 1993-05-18 1996-02-16 Ferrer Int Nuevos compuestos derivados de la piridina 1,4-disustituida.
US20020007068A1 (en) 1999-07-16 2002-01-17 D'ambra Thomas E. Piperidine derivatives and process for their production
DK0703902T3 (da) * 1993-06-24 1999-08-23 Albany Molecular Res Inc Fremgangsmåde til fremstilling af piperidinderivater
US6147216A (en) * 1993-06-25 2000-11-14 Merrell Pharmaceuticals Inc. Intermediates useful for the preparation of antihistaminic piperidine derivatives
DE69431954T2 (de) 1993-06-25 2003-11-06 Merrell Pharmaceuticals Inc., Cincinnati Neue zwischenprodukte für die herstellung von antihistaminschen 4-diphenylmethyl/diphenylmethoxypiperidin-derivaten
US5670521A (en) * 1994-08-05 1997-09-23 Merrell Pharmaceuticals Inc. Reversal of multi-drug resistance by triphenyl-azacycloalkane derivatives
US6201124B1 (en) 1995-12-21 2001-03-13 Albany Molecular Research, Inc. Process for production of piperidine derivatives
US6153754A (en) * 1995-12-21 2000-11-28 Albany Molecular Research, Inc. Process for production of piperidine derivatives
US6613907B2 (en) 2000-11-08 2003-09-02 Amr Technology, Inc. Process for the production of piperidine derivatives with microorganisms
TW200517114A (en) 2003-10-15 2005-06-01 Combinatorx Inc Methods and reagents for the treatment of immunoinflammatory disorders
EP1956906A4 (de) 2005-11-09 2009-12-30 Combinatorx Inc Verfahren, zusammensetzungen und kits für die behandlung von medizinischen beschwerden
US20100092479A1 (en) * 2008-08-18 2010-04-15 Combinatorx (Singapore) Pte. Ltd. Compositions and methods for treatment of viral diseases
US20110130711A1 (en) * 2009-11-19 2011-06-02 Follica, Inc. Hair growth treatment
AU2021325024A1 (en) * 2020-08-11 2023-04-13 Board Of Trustees Of Michigan State University Proteasome enhancers and uses thereof

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3000896A (en) * 1961-09-19 Process for the manufacture of second-
NL88235C (de) * 1950-12-05
US2739969A (en) * 1952-06-09 1956-03-27 Schering Corp Substituted alkyl piperidines
US3073835A (en) * 1961-07-13 1963-01-15 Searle & Co 1-acyl-alpha, alpha-diphenyl-4-piperidinemethanols
US3576810A (en) * 1968-06-20 1971-04-27 Robins Co Inc A H 1-substituted-3-(-4)-aroylpiperidines
US3806526A (en) * 1972-01-28 1974-04-23 Richardson Merrell Inc 1-aroylalkyl-4-diphenylmethyl piperidines

Also Published As

Publication number Publication date
BR7508160A (pt) 1976-08-24
NO754180L (de) 1976-06-14
IL48592A0 (en) 1976-02-29
FR2293933B1 (de) 1979-09-28
BE836394A (fr) 1976-04-01
AU8747675A (en) 1977-06-16
ES443360A1 (es) 1977-05-01
NL7514460A (nl) 1976-06-15
FR2293933A1 (fr) 1976-07-09
AT352127B (de) 1979-09-10
IL48592A (en) 1979-01-31
DE2555588A1 (de) 1976-06-16
SE7513953L (sv) 1976-06-14
GB1531419A (en) 1978-11-08
DK558175A (da) 1976-06-12
CA1059512A (en) 1979-07-31
NZ179495A (en) 1978-06-20
US3956296A (en) 1976-05-11
ZA757748B (en) 1976-11-24
JPS5182278A (en) 1976-07-19

Similar Documents

Publication Publication Date Title
ATA941575A (de) Verfahren zur herstellung von neuen 1- substituierten-4-benzylpiperidinen und irhen saeureadditonssalzen
AT340895B (de) Verfahren zur herstellung von neuen p-trifluormethylacylophenon-o- (2-aminoathyl) -oximathern und deren saureadditionssalzen
AT344683B (de) Verfahren zur herstellung von neuen substituierten 3-phenoxy-2-hydroxy-1-aminopropanen und deren saeureadditionssalzen
AT343659B (de) Verfahren zur herstellung von neuen benzimidazol-derivaten und deren saureadditionssalzen
AT345833B (de) Verfahren zur herstellung von neuen benzimidazolinon-derivaten und ihren saeure- additionssalzen
AT352699B (de) Verfahren zur herstellung von neuen sub- stituierten 3-phenoxy-propan-2-olen und deren therapeutisch vertraeglichen salzen
AT351547B (de) Verfahren zur herstellung von neuen thieno- (1,5)-benzodiazepinen und deren saeure- additionssalzen
AT344889B (de) Verfahren zur herstellung von neuen 7-methoxy-6-thiatetracyclinen und deren salzen
AT344188B (de) Verfahren zur herstellung von neuen morpholinderivaten und von ihren saeureadditionssalzen
AT344142B (de) Verfahren zur herstellung von neuen substituierten 3-phenoxy-2-hydroxy-1-aminopropanen und deren saeureadditionssalzen
AT346303B (de) Verfahren zur herstellung von neuen 7- aminobenzocycloheptenen und deren saeure- additionssalzen
ATA513378A (de) Verfahren zur herstellung von neuen dibenzo- furanderivaten und salzen hievon
AT340912B (de) Verfahren zur herstellung von neuen amidoxim-derivaten und ihren saureadditionssalzen
ATA307175A (de) Verfahren zur herstellung von neuen prostansaeurederivaten und von ihren salzen
ATA606175A (de) Verfahren zur herstellung von neuen prostansaeurederivaten und von ihren salzen
AT344712B (de) Verfahren zur herstellung von neuen cinnolin-3-yl-carbonsaeuren und von deren salzen
AT342599B (de) Verfahren zur herstellung von neuen indolobenzazepinen und deren saureadditionssalzen
AT340896B (de) Verfahren zur herstellung von neuen p-halogen-acylophenon- o - (2-aminoathyl)-oximathern und deren saureadditionssalzen
AT345286B (de) Verfahren zur herstellung von neuen biphenylylaethern und deren saeureadditionssalzen
AT344704B (de) Verfahren zur herstellung von neuen benzylpyrimidinen und von deren salzen
AT340897B (de) Verfahren zur herstellung von neuen p-methylthioacylophenon-o- (2-aminoathyl)-oximathern und deren saureadditionssalzen
AT341529B (de) Verfahren zur herstellung von neuen azatetracyclen und ihren salzen
AT347460B (de) Verfahren zur herstellung von neuen alpha,alpha - diaryl- beta - amino-propanolen und ihren saeureadditionssalzen
AT340894B (de) Verfahren zur herstellung von neuen p-nitro-acylophenon-o- (2-aminoathyl) -oximather und deren saureadditionssalzen
AT345293B (de) Verfahren zur herstellung von neuen 1-alkenyl-3a-m-substituiertes-phenyl-decahydroisochinolinen und ihren saeureaddtionssalzen

Legal Events

Date Code Title Description
ELJ Ceased due to non-payment of the annual fee