HK1089964A1 - Medical use of inhibitors of glutaminyl and glutamate cyclases - Google Patents
Medical use of inhibitors of glutaminyl and glutamate cyclasesInfo
- Publication number
- HK1089964A1 HK1089964A1 HK06110737.1A HK06110737A HK1089964A1 HK 1089964 A1 HK1089964 A1 HK 1089964A1 HK 06110737 A HK06110737 A HK 06110737A HK 1089964 A1 HK1089964 A1 HK 1089964A1
- Authority
- HK
- Hong Kong
- Prior art keywords
- effectors
- inhibitors
- glutaminyl
- medical use
- modulation
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract 2
- 101710095468 Cyclase Proteins 0.000 title 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 title 1
- 229930195712 glutamate Natural products 0.000 title 1
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 title 1
- 239000012636 effector Substances 0.000 abstract 4
- 102000003642 glutaminyl-peptide cyclotransferase Human genes 0.000 abstract 2
- 108010081484 glutaminyl-peptide cyclotransferase Proteins 0.000 abstract 2
- 102000004190 Enzymes Human genes 0.000 abstract 1
- 108090000790 Enzymes Proteins 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 239000000758 substrate Substances 0.000 abstract 1
Classifications
-
- 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
-
- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- 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
- A61K31/4192—1,2,3-Triazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
-
- 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
- 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
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- 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
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic 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
- C07D405/02—Heterocyclic 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
- C07D405/06—Heterocyclic 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 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
- C07D409/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/59—Hydrogenated pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Gynecology & Obstetrics (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Nutrition Science (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US46804303P | 2003-05-05 | 2003-05-05 | |
US46801403P | 2003-05-05 | 2003-05-05 | |
US51203803P | 2003-10-15 | 2003-10-15 | |
PCT/EP2004/004778 WO2004098625A2 (en) | 2003-05-05 | 2004-05-05 | Medical use of inhibitors of glutaminyl and glutamate cyclases |
Publications (1)
Publication Number | Publication Date |
---|---|
HK1089964A1 true HK1089964A1 (en) | 2006-12-15 |
Family
ID=42827350
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HK06110737.1A HK1089964A1 (en) | 2003-05-05 | 2006-09-27 | Medical use of inhibitors of glutaminyl and glutamate cyclases |
Country Status (15)
Country | Link |
---|---|
EP (1) | EP1620082B9 (pt) |
JP (1) | JP5690463B2 (pt) |
CN (1) | CN1784220B (pt) |
AT (1) | ATE464889T1 (pt) |
AU (2) | AU2004237408C9 (pt) |
BR (1) | BRPI0410078A (pt) |
CA (1) | CA2524009C (pt) |
DK (1) | DK1620082T3 (pt) |
EA (1) | EA009291B1 (pt) |
HK (1) | HK1089964A1 (pt) |
IL (2) | IL171339A (pt) |
MX (1) | MXPA05011861A (pt) |
NZ (1) | NZ543146A (pt) |
PL (1) | PL1620082T3 (pt) |
WO (1) | WO2004098625A2 (pt) |
Families Citing this family (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE602004026712D1 (de) | 2003-05-05 | 2010-06-02 | Probiodrug Ag | Medizinische verwendung von hemmern von glutaminyl und glutamatcyclasen |
MXPA06003998A (es) | 2003-10-15 | 2006-06-27 | Probiodrug Ag | Uso de efectores de ciclasas de glutamato y glutaminil. |
US20050137142A1 (en) * | 2003-11-03 | 2005-06-23 | Probiodrug Ag | Combinations useful for the treatment of neuronal disorders |
AU2005210004B2 (en) * | 2004-02-05 | 2010-10-28 | Probiodrug Ag | Novel inhibitors of glutaminyl cyclase |
EA013790B1 (ru) * | 2004-02-05 | 2010-06-30 | Пробиодруг Аг | Новые ингибиторы глутаминилциклазы |
SI1942898T2 (sl) | 2005-09-14 | 2014-08-29 | Takeda Pharmaceutical Company Limited | Dipeptidil-peptidazni inhibitorji za zdravljenje diabetesa |
CN102675221A (zh) | 2005-09-16 | 2012-09-19 | 武田药品工业株式会社 | 用于制备嘧啶二酮衍生物的方法中的中间体 |
US7572614B2 (en) | 2006-02-24 | 2009-08-11 | Academia Sinica | Crystal structure of soluble glutaminyl cyclase |
WO2007112347A1 (en) | 2006-03-28 | 2007-10-04 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
TW200808773A (en) | 2006-06-23 | 2008-02-16 | Abbott Lab | Cyclopropyl amine derivatives |
US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
US8889709B2 (en) | 2006-09-21 | 2014-11-18 | Probiodrug Ag | Use of isoQC inhibitors in the treatment and prevention of inflammatory diseases or conditions |
US9277737B2 (en) | 2006-09-21 | 2016-03-08 | Probiodrug Ag | Mouse models carrying a knock-out mutation of the QPCTL-gene |
NZ590631A (en) * | 2006-09-21 | 2011-12-22 | Probiodrug Ag | Novel genes related to glutaminyl cyclase |
EP2089383B1 (en) | 2006-11-09 | 2015-09-16 | Probiodrug AG | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
NZ578513A (en) | 2007-01-19 | 2012-01-12 | Probiodrug Ag | In vivo screening models for treatment of alzheimer's disease and other qpct-related disorders |
US20120070444A1 (en) | 2007-01-19 | 2012-03-22 | Probiodrug Ag | IN VIVO SCREENING MODELS FOR TREATMENT OF isoQC-RELATED DISORDERS |
AU2008220785B2 (en) | 2007-03-01 | 2013-02-21 | Vivoryon Therapeutics N.V. | New use of glutaminyl cyclase inhibitors |
EP2118101B1 (en) | 2007-03-09 | 2012-09-26 | Probiodrug AG | Imidazo [1,5-a] pyridine derivatives as inhibitors of glutaminyl cyclase |
US9656991B2 (en) | 2007-04-18 | 2017-05-23 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
WO2009034158A2 (en) | 2007-09-12 | 2009-03-19 | Probiodrug Ag | Transgenic mice |
AU2009204864A1 (en) | 2008-01-14 | 2009-07-23 | Probiodrug Ag | Mouse models carrying a knock-out mutation of the glutaminyl cyclase gene |
SG193148A1 (en) * | 2008-07-31 | 2013-09-30 | Probiodrug Ag | Glutaminyl cyclase as a diagnostic / prognostic indicator for neurodegenerative diseases |
US8288591B2 (en) | 2008-11-20 | 2012-10-16 | Designer Molecules, Inc. | Curing agents for epoxy resins |
US8563735B2 (en) * | 2008-12-05 | 2013-10-22 | Abbvie Inc. | Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases |
US9186353B2 (en) | 2009-04-27 | 2015-11-17 | Abbvie Inc. | Treatment of osteoarthritis pain |
PL2475428T3 (pl) | 2009-09-11 | 2015-12-31 | Probiodrug Ag | Pochodne heterocykliczne jako inhibitory cyklazy glutaminowej |
JP2013505438A (ja) * | 2009-09-18 | 2013-02-14 | プロビオドルグ エージー | アミロイドβペプチドの検出のための新規アッセイ |
WO2011076854A1 (en) * | 2009-12-22 | 2011-06-30 | Probiodrug Ag | CLEAVAGE OF β-AMYLOID PRECURSOR PROTEIN |
CN102947705A (zh) * | 2010-02-18 | 2013-02-27 | 前体生物药物股份公司 | 通过确定焦谷氨酸修饰的mcp-1诊断炎性疾病的方法和谷氨酰胺酰基环化酶抑制剂的筛选方法 |
US9181233B2 (en) | 2010-03-03 | 2015-11-10 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
DK2545047T3 (da) | 2010-03-10 | 2014-07-28 | Probiodrug Ag | Heterocycliske inhibitorer af glutaminylcyclase (QC, EC 2.3.2.5) |
US20130012620A1 (en) * | 2010-03-17 | 2013-01-10 | Designer Molecules, Inc. | Curing agents for epoxy resins |
WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
ES2540467T3 (es) | 2010-08-19 | 2015-07-09 | Probiodrug Ag | Estructura cristalina de glutaminil ciclasa |
US8853390B2 (en) | 2010-09-16 | 2014-10-07 | Abbvie Inc. | Processes for preparing 1,2-substituted cyclopropyl derivatives |
RU2650778C2 (ru) * | 2011-02-17 | 2018-04-17 | Фуджиребио Диагностикс, Инк | Композиции и способы применения для определения не4а |
EP2686313B1 (en) | 2011-03-16 | 2016-02-03 | Probiodrug AG | Benzimidazole derivatives as inhibitors of glutaminyl cyclase |
EP2742062A2 (en) | 2011-08-12 | 2014-06-18 | Probiodrug AG | In vivo screening models for treatment of qc-related disorders |
US9138393B2 (en) * | 2013-02-08 | 2015-09-22 | The Procter & Gamble Company | Cosmetic compositions containing substituted azole and methods for improving the appearance of aging skin |
US9512115B2 (en) * | 2013-03-15 | 2016-12-06 | Probiodrug Ag | Inhibitors |
JP6902416B2 (ja) * | 2016-07-05 | 2021-07-14 | ライオン株式会社 | 睡眠評価用マーカー及びその用途 |
FI3658141T3 (fi) | 2017-07-24 | 2023-03-02 | Patologisten tilojen hoitaminen suoralla tai epäsuoralla siralfa-cd47-vuorovaikutukseen kohdentamisella | |
PL3461819T3 (pl) | 2017-09-29 | 2020-11-30 | Probiodrug Ag | Inhibitory cyklazy glutaminylowej |
IT202100012173A1 (it) * | 2021-05-12 | 2022-11-12 | Univ Degli Studi Roma La Sapienza | Composizioni per l’uso nel trattamento di disabilità intellettiva e di malattie neurodegenerative in un soggetto con Sindrome di Down |
EP4359405A1 (en) | 2021-06-24 | 2024-05-01 | Insilico Medicine IP Limited | Beta-lactam derivatives for the treatment of diseases |
Family Cites Families (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0633882A1 (en) * | 1992-04-01 | 1995-01-18 | The University Of Toledo | 4- 4'-piperidinyl or 3'-pirrolidinyl] substituted imidazoles as h3-receptor antagonists and therapeutic uses thereof |
IL111785A0 (en) | 1993-12-03 | 1995-01-24 | Ferring Bv | Dp-iv inhibitors and pharmaceutical compositions containing them |
WO1995022327A1 (en) * | 1994-02-22 | 1995-08-24 | Knoll Ag | Use of 1-(arylalkylaminoalkyl) imidazoles for treating neurological damage |
US5552426A (en) * | 1994-04-29 | 1996-09-03 | Eli Lilly And Company | Methods for treating a physiological disorder associated with β-amyloid peptide |
DE69619381T2 (de) * | 1995-05-30 | 2002-11-21 | Gliatech Inc | 1h-4(5)substituierte imidazolderivate |
DE19616486C5 (de) | 1996-04-25 | 2016-06-30 | Royalty Pharma Collection Trust | Verfahren zur Senkung des Blutglukosespiegels in Säugern |
TW492957B (en) | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
US6011155A (en) | 1996-11-07 | 2000-01-04 | Novartis Ag | N-(substituted glycyl)-2-cyanopyrrolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
EP2574336A1 (en) | 1998-02-02 | 2013-04-03 | Trustees Of Tufts College | Use of dipeptidylpeptidase inhibitors to regulate glucose metabolism |
US5994379A (en) * | 1998-02-13 | 1999-11-30 | Merck Frosst Canada, Inc. | Bisaryl COX-2 inhibiting compounds, compositions and methods of use |
AU3034299A (en) | 1998-03-09 | 1999-09-27 | Fondatech Benelux N.V. | Serine peptidase modulators |
DE19823831A1 (de) | 1998-05-28 | 1999-12-02 | Probiodrug Ges Fuer Arzneim | Neue pharmazeutische Verwendung von Isoleucyl Thiazolidid und seinen Salzen |
DE19828114A1 (de) | 1998-06-24 | 2000-01-27 | Probiodrug Ges Fuer Arzneim | Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV |
DE19828113A1 (de) | 1998-06-24 | 2000-01-05 | Probiodrug Ges Fuer Arzneim | Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV |
DE19834591A1 (de) | 1998-07-31 | 2000-02-03 | Probiodrug Ges Fuer Arzneim | Verfahren zur Steigerung des Blutglukosespiegels in Säugern |
EP1932535A3 (en) | 1998-07-31 | 2008-10-29 | Novo Nordisk A/S | Stimulation of beta cell profileration |
US6110949A (en) | 1999-06-24 | 2000-08-29 | Novartis Ag | N-(substituted glycyl)-4-cyanothiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
US6107317A (en) | 1999-06-24 | 2000-08-22 | Novartis Ag | N-(substituted glycyl)-thiazolidines, pharmaceutical compositions containing them and their use in inhibiting dipeptidyl peptidase-IV |
US6172081B1 (en) | 1999-06-24 | 2001-01-09 | Novartis Ag | Tetrahydroisoquinoline 3-carboxamide derivatives |
WO2001034594A1 (en) * | 1999-11-12 | 2001-05-17 | Guilford Pharmaceuticals, Inc. | Dipeptidyl peptidase iv inhibitors and methods of making and using dipeptidyl peptidase iv inhibitors |
GB9928330D0 (en) | 1999-11-30 | 2000-01-26 | Ferring Bv | Novel antidiabetic agents |
US6380398B2 (en) | 2000-01-04 | 2002-04-30 | Novo Nordisk A/S | Therapeutically active and selective heterocyclic compounds that are inhibitors of the enzyme DPP-IV |
AU2001228309A1 (en) | 2000-01-24 | 2001-08-07 | Novo-Nordisk A/S | N-substituted 2-cyanopyroles and -pyrrolines which are inhibitors of the enzyme dpp-iv |
US6395767B2 (en) | 2000-03-10 | 2002-05-28 | Bristol-Myers Squibb Company | Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method |
GB0010183D0 (en) | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
GB0010188D0 (en) | 2000-04-26 | 2000-06-14 | Ferring Bv | Inhibitors of dipeptidyl peptidase IV |
JP2004502690A (ja) | 2000-07-04 | 2004-01-29 | ノボ ノルディスク アクティーゼルスカブ | 酵素dpp−ivのインヒビターである複素環式化合物 |
WO2002004610A2 (en) | 2000-07-10 | 2002-01-17 | Bayer Aktiengesellschaft | Regulation of human dipeptidyl-peptidase iv-like enzyme |
WO2002014271A1 (fr) | 2000-08-10 | 2002-02-21 | Mitsubishi Pharma Corporation | Dérivés de proline et leur utilisation comme médicaments |
CA2419073A1 (en) * | 2000-08-17 | 2002-02-21 | Gliatech, Inc. | Novel alicyclic imidazoles as h3 agents |
BR0114924A (pt) | 2000-10-27 | 2003-12-23 | Probiodrug Ag | Método para o tratamento de distúrbios neurológicos e neuropsicológicos |
TWI243162B (en) | 2000-11-10 | 2005-11-11 | Taisho Pharmaceutical Co Ltd | Cyanopyrrolidine derivatives |
JPWO2002051836A1 (ja) | 2000-12-27 | 2004-04-22 | 協和醗酵工業株式会社 | ジペプチジルペプチダーゼ−iv阻害剤 |
AU2002234640B8 (en) | 2001-02-24 | 2009-11-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Xanthine derivative, production and use thereof as a medicament |
JP2004525929A (ja) | 2001-03-27 | 2004-08-26 | メルク エンド カムパニー インコーポレーテッド | 糖尿病の治療または予防用のジペプチジルペプチダーゼ阻害薬 |
US6573287B2 (en) | 2001-04-12 | 2003-06-03 | Bristo-Myers Squibb Company | 2,1-oxazoline and 1,2-pyrazoline-based inhibitors of dipeptidyl peptidase IV and method |
US20030013177A1 (en) * | 2001-05-23 | 2003-01-16 | Ebens Allen J. | Polynucleotides encoding insect glutaminyl cyclase and uses thereof |
AU2002310465B2 (en) | 2001-06-20 | 2006-06-15 | Merck & Co., Inc. | Dipeptidyl peptidase inhibitors for the treatment of diabetes |
EP1406872B1 (en) | 2001-06-20 | 2007-12-19 | Merck & Co., Inc. | Dipeptidyl peptidase inhibitors for the treatment of diabetes |
GB0115517D0 (en) | 2001-06-25 | 2001-08-15 | Ferring Bv | Novel antidiabetic agents |
NZ529973A (en) | 2001-06-27 | 2006-01-27 | Smithkline Beecham Corp | Fluoropyrrolidines as dipeptidyl peptidase inhibitors |
DE10150203A1 (de) | 2001-10-12 | 2003-04-17 | Probiodrug Ag | Peptidylketone als Inhibitoren der DPIV |
DE10154689A1 (de) * | 2001-11-09 | 2003-05-22 | Probiodrug Ag | Substituierte Aminoketonverbindungen |
CN1688599A (zh) | 2001-06-27 | 2005-10-26 | 前体生物药物股份有限公司 | 二肽基肽酶iv抑制剂的新用途 |
EP1399433B1 (en) | 2001-06-27 | 2007-08-22 | Smithkline Beecham Corporation | Fluoropyrrolidines as dipeptidyl peptidase inhibitors |
JP4300108B2 (ja) | 2001-06-27 | 2009-07-22 | スミスクライン ビーチャム コーポレーション | ジペプチジルペプチダーゼ阻害剤としてのピロリジン類 |
WO2003002595A2 (en) | 2001-06-27 | 2003-01-09 | Probiodrug Ag | Dipeptidyl peptidase iv inhibitors and their uses as anti-cancer agents |
EP1404675B1 (en) | 2001-07-03 | 2008-03-12 | Novo Nordisk A/S | Dpp-iv-inhibiting purine derivatives for the treatment of diabetes |
US20040259883A1 (en) | 2001-09-14 | 2004-12-23 | Hiroshi Sakashita | Thiazolidine derivative and medicinal use thereof |
EP1463727A2 (en) | 2001-09-19 | 2004-10-06 | Novo Nordisk A/S | Heterocyclic compounds that are inhibitors of the enzyme dpp-iv |
EP1615636A1 (en) * | 2003-04-10 | 2006-01-18 | Pfizer Inc. | Bicyclic compounds as nr2b receptor antagonists |
GB0704100D0 (en) | 2006-03-17 | 2007-04-11 | Vodafone Plc | Improvements in an ehspa architecture |
US8593773B2 (en) | 2008-11-05 | 2013-11-26 | Osram Gesellschaft Mit Berschraenkter Haftung | Half-bridge circuit protected against short circuits and having semiconductor switches |
US8049427B2 (en) | 2008-11-25 | 2011-11-01 | Lutron Electronics Co., Inc. | Load control device having a visual indication of energy savings and usage information |
-
2004
- 2004-05-05 AT AT04731150T patent/ATE464889T1/de active
- 2004-05-05 MX MXPA05011861A patent/MXPA05011861A/es active IP Right Grant
- 2004-05-05 CA CA2524009A patent/CA2524009C/en not_active Expired - Lifetime
- 2004-05-05 NZ NZ543146A patent/NZ543146A/en not_active IP Right Cessation
- 2004-05-05 WO PCT/EP2004/004778 patent/WO2004098625A2/en active Application Filing
- 2004-05-05 EP EP04731150A patent/EP1620082B9/en not_active Expired - Lifetime
- 2004-05-05 CN CN2004800123862A patent/CN1784220B/zh not_active Expired - Fee Related
- 2004-05-05 PL PL04731150T patent/PL1620082T3/pl unknown
- 2004-05-05 DK DK04731150.1T patent/DK1620082T3/da active
- 2004-05-05 AU AU2004237408A patent/AU2004237408C9/en not_active Ceased
- 2004-05-05 JP JP2006505377A patent/JP5690463B2/ja not_active Expired - Fee Related
- 2004-05-05 BR BRPI0410078-6A patent/BRPI0410078A/pt not_active Application Discontinuation
- 2004-05-05 EA EA200501700A patent/EA009291B1/ru not_active IP Right Cessation
-
2005
- 2005-10-10 IL IL171339A patent/IL171339A/en active IP Right Grant
-
2006
- 2006-09-27 HK HK06110737.1A patent/HK1089964A1/xx not_active IP Right Cessation
-
2009
- 2009-10-23 AU AU2009227925A patent/AU2009227925B2/en not_active Ceased
-
2010
- 2010-05-27 IL IL206009A patent/IL206009A/en active IP Right Grant
Also Published As
Publication number | Publication date |
---|---|
ATE464889T1 (de) | 2010-05-15 |
WO2004098625A3 (en) | 2005-06-23 |
JP5690463B2 (ja) | 2015-03-25 |
EA200501700A1 (ru) | 2006-06-30 |
CN1784220B (zh) | 2011-08-03 |
BRPI0410078A (pt) | 2006-05-16 |
IL206009A0 (en) | 2010-11-30 |
EA009291B1 (ru) | 2007-12-28 |
CA2524009C (en) | 2014-04-29 |
AU2004237408C1 (en) | 2010-04-01 |
JP2006525278A (ja) | 2006-11-09 |
NZ543146A (en) | 2008-09-26 |
MXPA05011861A (es) | 2006-02-17 |
IL206009A (en) | 2017-09-28 |
DK1620082T3 (da) | 2010-08-16 |
EP1620082B9 (en) | 2010-08-25 |
CN1784220A (zh) | 2006-06-07 |
AU2009227925A1 (en) | 2009-11-12 |
AU2004237408C9 (en) | 2010-04-15 |
AU2004237408B2 (en) | 2009-10-01 |
EP1620082A2 (en) | 2006-02-01 |
IL171339A (en) | 2011-11-30 |
PL1620082T3 (pl) | 2010-10-29 |
EP1620082B1 (en) | 2010-04-21 |
AU2009227925B2 (en) | 2011-12-15 |
CA2524009A1 (en) | 2004-11-18 |
AU2004237408A1 (en) | 2004-11-18 |
WO2004098625A2 (en) | 2004-11-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
HK1089964A1 (en) | Medical use of inhibitors of glutaminyl and glutamate cyclases | |
CY1110171T1 (el) | Ιατρικη χρηση αναστολεων γλουταμινικων και γλουταμικων κυκλασων για θεραπεια της ασθενειας του alzheimer και του συνδρομου down | |
WO2005039548A3 (en) | Use of effectors of glutaminyl and glutamate cyclases | |
MY142589A (en) | Benzimidazole derivatives : preparation and pharmaceutical applications | |
EP1562897A4 (en) | PHENYL ACARBOXAMIDE AS A BETA SEKRETASE INHIBITOR FOR THE TREATMENT OF ALZHEIMER | |
MY147647A (en) | Imidazo [1,2-a] pyridine derivatives : preparation and pharmaceutical applications | |
TW200626601A (en) | Novel compounds | |
MXPA05005223A (es) | Diaminotriazoles utiles como inhibidores de proteinas cinasas. | |
GEP20094845B (en) | Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors | |
AU2003218215A1 (en) | Azolylaminoazines as inhibitors of protein kinases | |
AU2003220300A1 (en) | Compositions useful as inhibitors of protein kinases | |
HK1087700A1 (en) | Triazolopyridazines as protein kinases inhibitors | |
NO20050514L (no) | Sammensetning og antiviral aktivitet til substituerte azaindoloksoeddikpiperazinderivater | |
EP1765335A4 (en) | PYRAZOLAMIDE DERIVATIVES, COMPOSITIONS AND METHODS OF APPLYING THESE COMPOUNDS | |
MY140840A (en) | Acylated, heteroaryl-condensed cycloalkenylamines and their use as pharmaceuticals | |
CY1109245T1 (el) | Ενωσεις χρησιμες στην θεραπεια ανθρακα και στην αναστολη θανατηφορου παραγοντα | |
MXPA05004621A (es) | Derivados de anilinopirazol utiles en el tratamiento de la diabetes. | |
MXPA04004372A (es) | Derivados heterociclicos de glicinamida y su uso medico. | |
MX2022001933A (es) | Inhibidores de enzimas. | |
WO2004052236A3 (en) | Methods and compositions for treatment of otitis media | |
SE0302756D0 (sv) | Novel Compounds | |
MXPA03010205A (es) | Derivados de acido oxalico. | |
AU2003270470A1 (en) | Vitreoretinal tamponades based on fluorosilicone fluids | |
CY1110156T1 (el) | Υποκατεστημενες ενωσεις 4,5,6,7-τετραϋδρο-βενζοθειαζολ-2-υλαμινης | |
ATE334209T1 (de) | Inaktivierung von genen des mep-wegs |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PC | Patent ceased (i.e. patent has lapsed due to the failure to pay the renewal fee) |
Effective date: 20190505 |