HUP0000090A3 - 1,4-disubstituted piperazines, pharmaceutical compositions containing them, process for producing them and their use - Google Patents

1,4-disubstituted piperazines, pharmaceutical compositions containing them, process for producing them and their use

Info

Publication number
HUP0000090A3
HUP0000090A3 HU0000090A HUP0000090A HUP0000090A3 HU P0000090 A3 HUP0000090 A3 HU P0000090A3 HU 0000090 A HU0000090 A HU 0000090A HU P0000090 A HUP0000090 A HU P0000090A HU P0000090 A3 HUP0000090 A3 HU P0000090A3
Authority
HU
Hungary
Prior art keywords
producing
pharmaceutical compositions
compositions containing
disubstituted piperazines
piperazines
Prior art date
Application number
HU0000090A
Other languages
English (en)
Original Assignee
Novo Nordisk As
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 Novo Nordisk As filed Critical Novo Nordisk As
Publication of HUP0000090A2 publication Critical patent/HUP0000090A2/hu
Publication of HUP0000090A3 publication Critical patent/HUP0000090A3/hu

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72Nitrogen atoms
    • C07D213/74Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/04Antipruritics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/06Antimigraine agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/78Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79Acids; Esters
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/06Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals
    • C07D295/073Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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 chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2603/00Systems containing at least three condensed rings
    • C07C2603/56Ring systems containing bridged rings
    • C07C2603/58Ring systems containing bridged rings containing three rings
    • C07C2603/76Ring systems containing bridged rings containing three rings containing at least one ring with more than six ring members
    • C07C2603/78Ring systems containing bridged rings containing three rings containing at least one ring with more than six ring members containing seven-membered rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Pain & Pain Management (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
HU0000090A 1996-10-04 1997-10-02 1,4-disubstituted piperazines, pharmaceutical compositions containing them, process for producing them and their use HUP0000090A3 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DK109096 1996-10-04
PCT/DK1997/000422 WO1998015548A1 (en) 1996-10-04 1997-10-02 1,4-disubstituted piperazines

Publications (2)

Publication Number Publication Date
HUP0000090A2 HUP0000090A2 (hu) 2001-04-28
HUP0000090A3 true HUP0000090A3 (en) 2002-01-28

Family

ID=8100883

Family Applications (1)

Application Number Title Priority Date Filing Date
HU0000090A HUP0000090A3 (en) 1996-10-04 1997-10-02 1,4-disubstituted piperazines, pharmaceutical compositions containing them, process for producing them and their use

Country Status (20)

Country Link
US (4) US5916889A (hu)
EP (1) EP0934312B1 (hu)
JP (1) JP2001502307A (hu)
KR (1) KR20000048899A (hu)
CN (1) CN1088459C (hu)
AT (1) ATE234831T1 (hu)
AU (1) AU740662B2 (hu)
BR (1) BR9712196A (hu)
CA (1) CA2267835A1 (hu)
CZ (1) CZ114099A3 (hu)
DE (1) DE69720021T2 (hu)
DK (1) DK0934312T3 (hu)
ES (1) ES2194217T3 (hu)
HU (1) HUP0000090A3 (hu)
IL (1) IL129123A (hu)
NO (1) NO991565L (hu)
PL (1) PL188338B1 (hu)
RU (1) RU2188197C2 (hu)
WO (1) WO1998015548A1 (hu)
ZA (1) ZA978864B (hu)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001501629A (ja) * 1996-10-04 2001-02-06 ノボ ノルディスク アクティーゼルスカブ N―置換アザ複素環式化合物
US6613905B1 (en) * 1998-01-21 2003-09-02 Millennium Pharmaceuticals, Inc. Chemokine receptor antagonists and methods of use therefor
US7045519B2 (en) * 1998-06-19 2006-05-16 Chiron Corporation Inhibitors of glycogen synthase kinase 3
JP4533534B2 (ja) 1998-06-19 2010-09-01 ノバルティス バクシンズ アンド ダイアグノスティックス,インコーポレーテッド グリコーゲンシンターゼキナーゼ3のインヒビター
US7541365B2 (en) 2001-11-21 2009-06-02 Millennium Pharmaceuticals, Inc. Chemokine receptor antagonists and methods of use therefor
US20040038861A1 (en) * 2001-11-26 2004-02-26 Cooper Garth J. S. Methods and compositions for normalizing lipid levels in mammalian tissues
TWI291467B (en) 2002-11-13 2007-12-21 Millennium Pharm Inc CCR1 antagonists and methods of use therefor
AU2005286593A1 (en) * 2004-09-23 2006-03-30 Reddy Us Therapeutics, Inc. Novel pyridine compounds, process for their preparation and compositions containing them
FR2885616B1 (fr) * 2005-05-12 2007-06-22 Servier Lab Nouveaux derives de phenylpyridinylpiperazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
FR2885615B1 (fr) * 2005-05-12 2007-06-22 Servier Lab Nouveaux derives de phenylpyridinylpiperazine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
JP2009514969A (ja) 2005-11-09 2009-04-09 コンビナトアールエックス インコーポレーティッド 医学的状態を治療するための方法、組成物、およびキット
EP2420239B1 (en) * 2007-04-13 2015-01-14 Southern Research Institute Clomipramine as anti-angiogenic agent
CN103086898B (zh) * 2012-07-11 2015-04-08 山东道可化学有限公司 二苯胺或其环上取代的衍生物的制备方法

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL102488C (hu) * 1957-07-18
GB1013901A (en) * 1962-01-26 1965-12-22 Kefalas As Dihydroanthracene, dibenzocycloheptadiene and dibenzocycloheptatriene derivatives
FR88751E (hu) * 1963-07-09 1967-06-07
US3435073A (en) * 1966-04-19 1969-03-25 Colgate Palmolive Co 5-(n-benzyl-n-lower alkylaminoalkylene)-5h-dibenzo(a,d)cycloheptenes
GB1347935A (en) * 1971-04-10 1974-02-27 Yoshitomi Pharmaceutical Piperazine derivatives methods for their production and phar maceutical compositions containing them
FR2186249A1 (en) * 1972-05-31 1974-01-11 Synthelabo Phenyl piperazinoalkyl (dihydro)dibenzazepines - antidepressants having low toxicity
HU174126B (hu) * 1977-08-02 1979-11-28 Egyt Gyogyszervegyeszeti Gyar Sposob poluchenija novykh proizvodnykh dibenzo-kvadratnaja skobka-d,g-kvadratnaja skobka zakryta-kvadratnaja skobka-1,3,6-kvadratnaja skobka zakryta-dioksazocina
ES524680A0 (es) * 1983-08-02 1984-12-16 Espanola Farma Therapeut Procedimiento de obtencion de nuevos compuestos derivados de la difenil-metilen-etilamina.
AU612437B2 (en) * 1987-12-14 1991-07-11 Kyowa Hakko Kogyo Co. Ltd. Tricyclic compounds
ZA914764B (en) * 1990-06-22 1992-03-25 Schering Corp Bis-benzo or benzopyrido cyclohepta piperidene,piperidylidene and piperazine compounds,compositions and methods of use
MY113463A (en) * 1994-01-04 2002-03-30 Novo Nordisk As Novel heterocyclic compounds
UA54385C2 (uk) * 1995-04-07 2003-03-17 Ново Нордіск А/С N-заміщені азагетероциклічні карбонові кислоти та їх ефіри, спосіб їх одержання, фармацевтична композиція та спосіб лікування
EP0851865B1 (en) * 1995-09-19 2002-07-17 Novo Nordisk A/S 12H-Dibenzo[d,g][1,3]dioxocine derivatives

Also Published As

Publication number Publication date
DE69720021D1 (de) 2003-04-24
US5916889A (en) 1999-06-29
DK0934312T3 (da) 2003-07-21
KR20000048899A (ko) 2000-07-25
ATE234831T1 (de) 2003-04-15
PL332597A1 (en) 1999-09-27
IL129123A0 (en) 2000-02-17
AU740662B2 (en) 2001-11-08
CN1088459C (zh) 2002-07-31
HUP0000090A2 (hu) 2001-04-28
RU2188197C2 (ru) 2002-08-27
BR9712196A (pt) 1999-08-31
IL129123A (en) 2004-07-25
EP0934312A1 (en) 1999-08-11
US6040302A (en) 2000-03-21
US6004961A (en) 1999-12-21
WO1998015548A1 (en) 1998-04-16
ZA978864B (en) 1998-04-06
CA2267835A1 (en) 1998-04-16
NO991565D0 (no) 1999-03-30
US6133268A (en) 2000-10-17
AU4377297A (en) 1998-05-05
NO991565L (no) 1999-06-04
JP2001502307A (ja) 2001-02-20
PL188338B1 (pl) 2005-01-31
CZ114099A3 (cs) 1999-09-15
CN1234799A (zh) 1999-11-10
EP0934312B1 (en) 2003-03-19
ES2194217T3 (es) 2003-11-16
DE69720021T2 (de) 2004-02-05

Similar Documents

Publication Publication Date Title
HUP9904521A3 (en) Piperazine derivatives, process for producing them and pharmaceutical compositions containing them
HUP9902471A3 (en) Piperazine and piperidine compounds, process for their preparation and pharmaceutical compositions containing the same
HUP0004334A2 (en) Substituted 1,2,3,4-tetrahydronaphthalene derivatives, process for producing them and pharmaceutical compositions containing them
HUP9900055A3 (en) 4-aryl-1-phenylalkyl-1,2,3,6-tetrahydropyridin -derivatives, process for producing them and pharmaceutical compositions containing them
HUT53362A (en) Process for producing substituted 1,3-oxathiolans and pharmaceutical compositions comprising same
HU9602489D0 (en) New piperazine derivatives, process for producing them and pharmaceutical compositions containing them
HUP0000068A3 (en) Process for producing ecteinascidin compounds, their use and pharmaceutical compositions containing them
HUT76286A (en) Quinoline derivatives, pharmaceutical compositions containing them, process for producing them and their use
HUP9601529A3 (en) Pyrimidinedion-, pyrimidinetrion-, triazinedion-, tetrahydro-quinazolinedion- derivatives, pharmaceutical compositions containing them, process for producing them and their use
IL119488A0 (en) Substituted 2,4-imidazolidinediones their production and pharmaceutical compositions containing them
HUP9904167A3 (en) 1,4-disubstituted piperazine and piperidine derivatives, their use and pharmaceutical compositions containing the same
HUP9901739A3 (en) Aminoisoquinolines and aminothienopyridine derivatives, process for producing thereof and pharmaceutical compositions containing them
HUP9901473A3 (en) 2,3-benzodiazepine derivatives, process for producing them and pharmaceutical compositions containing them
HUP0000090A3 (en) 1,4-disubstituted piperazines, pharmaceutical compositions containing them, process for producing them and their use
AU4134297A (en) 2,4-disubstituted pyrimidine derivatives, process for producing the same, and medicinal compositions containing the same
HUP9701660A3 (en) 10,13,15-trioxatricyclo[9.2.1.1.9.6]pentadekanon derivatives, process for producing them, and pharmaceutical compositions containing them
HUP0001827A3 (en) Colchicine derivatives, process for producing them, pharmaceutical compositions containing them, and use thereof for producing pharmaceutical compositions
IL134572A (en) Substituted 1,2,3,4,5,6-hexahydro-2, 6-methano-3-benzazocin - 10 -ols, methods for their production and use thereof as medicaments
HUT77375A (hu) Enterokinetikus hatású benzamidszármazékok, az ezeket tartalmazó gyógyszerkészítmények és eljárás a vegyületek előállítására
HU9503801D0 (en) Substituted 4-phenyl-thiazol derviatives, process for producing them and pharmaceutical compositions containing them
HU9503366D0 (en) Novel n-arylaliphatic-n-alkyl-functionalised amides, method for their preparation and pharmaceutical compositions containing same
HUT74615A (en) 2,3-cyclic-condensed-1,4-dihydro-pyridine derivatives, process for producing them and pharmaceutical compositions containing the same
HU9601331D0 (en) New piperazine- and homeopiperazine-derivatives, process for producing them and pharmaceutical compositions containing them
HUP9702227A3 (en) New benzopirane compounds, process for producing them and pharmaceutical composition containing them
HUT73975A (en) Substituted benzol-sulfonyl-ureas and-thioureas, process for producing them, pharmaceutical compositions containing them and their use

Legal Events

Date Code Title Description
FD9A Lapse of provisional protection due to non-payment of fees