HK1091831A1 - Isoxazole compounds as inhibitors of heat shock proteins - Google Patents

Isoxazole compounds as inhibitors of heat shock proteins

Info

Publication number
HK1091831A1
HK1091831A1 HK06112447.8A HK06112447A HK1091831A1 HK 1091831 A1 HK1091831 A1 HK 1091831A1 HK 06112447 A HK06112447 A HK 06112447A HK 1091831 A1 HK1091831 A1 HK 1091831A1
Authority
HK
Hong Kong
Prior art keywords
inhibitors
heat shock
shock proteins
isoxazole compounds
isoxazole
Prior art date
Application number
HK06112447.8A
Other languages
English (en)
Inventor
Martin James Drysdale
Brian William Dymock
Harry Finch
Paul Webb
Edward Mcdonald
Karen Elizabeth James
Kwai Ming Cheung
Thomas Peter Mathews
Original Assignee
Vernalis Cambridge Ltd
Cancer Rec Tech Ltd
Cancer Res Inst
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB0303105A external-priority patent/GB0303105D0/en
Priority claimed from GBGB0306560.4A external-priority patent/GB0306560D0/en
Priority claimed from GB0313751A external-priority patent/GB0313751D0/en
Application filed by Vernalis Cambridge Ltd, Cancer Rec Tech Ltd, Cancer Res Inst filed Critical Vernalis Cambridge Ltd
Publication of HK1091831A1 publication Critical patent/HK1091831A1/xx

Links

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • 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
    • 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
    • A61K31/42—Oxazoles
    • 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
    • A61K31/42—Oxazoles
    • A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • 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
    • 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
    • A61P25/14—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
    • A61P25/28—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
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • 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
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/10—Heterocyclic 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 carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Endocrinology (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Hematology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • Psychology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Reproductive Health (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Immunology (AREA)
HK06112447.8A 2003-02-11 2006-11-10 Isoxazole compounds as inhibitors of heat shock proteins HK1091831A1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB0303105A GB0303105D0 (en) 2003-02-11 2003-02-11 Isoxazole compounds
GBGB0306560.4A GB0306560D0 (en) 2003-03-21 2003-03-21 Isoxazole compounds
GB0313751A GB0313751D0 (en) 2003-06-13 2003-06-13 Isoxazole compounds
PCT/GB2004/000506 WO2004072051A1 (en) 2003-02-11 2004-02-09 Isoxazole compounds as inhibitors of heat shock proteins

Publications (1)

Publication Number Publication Date
HK1091831A1 true HK1091831A1 (en) 2007-01-26

Family

ID=32872455

Family Applications (1)

Application Number Title Priority Date Filing Date
HK06112447.8A HK1091831A1 (en) 2003-02-11 2006-11-10 Isoxazole compounds as inhibitors of heat shock proteins

Country Status (19)

Country Link
US (6) US7705027B2 (de)
EP (1) EP1611112B1 (de)
JP (1) JP4921162B2 (de)
KR (1) KR101166749B1 (de)
CN (1) CN1771235B (de)
AU (1) AU2004210779B2 (de)
BR (1) BRPI0407403B1 (de)
CA (1) CA2515726C (de)
CY (1) CY1113761T1 (de)
DK (1) DK1611112T3 (de)
EA (1) EA009919B1 (de)
ES (1) ES2393483T3 (de)
HK (1) HK1091831A1 (de)
MX (1) MXPA05008335A (de)
NO (1) NO335001B1 (de)
NZ (1) NZ541479A (de)
PT (1) PT1611112E (de)
SI (1) SI1611112T1 (de)
WO (1) WO2004072051A1 (de)

Families Citing this family (113)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI297335B (en) 2001-07-10 2008-06-01 Synta Pharmaceuticals Corp Taxol enhancer compounds
TWI332943B (en) 2001-07-10 2010-11-11 Synta Pharmaceuticals Corp Taxol enhancer compounds
TWI252847B (en) 2001-07-10 2006-04-11 Synta Pharmaceuticals Corp Synthesis of taxol enhancers
TWI330079B (en) 2003-01-15 2010-09-11 Synta Pharmaceuticals Corp Treatment for cancers
SI1611112T1 (sl) 2003-02-11 2012-12-31 Vernalis (R&D) Limited Izoksazolne spojine kot inhibitorji vroäśinskih ĺ ok proteinov
GB0315111D0 (en) * 2003-06-27 2003-07-30 Cancer Rec Tech Ltd Substituted 5-membered ring compounds and their use
WO2005063222A1 (ja) * 2003-12-26 2005-07-14 Kyowa Hakko Kogyo Co., Ltd. Hsp90ファミリー蛋白質阻害剤
EP1748767B1 (de) 2004-05-28 2011-12-28 Unigen, Inc. 1-(3-methyl-2,4-dimethoxyphenyl)-3-(2',4'-dihydroxyphenyl)-propan als hochwirksamer tyrosinase-inhibitor
GB0412769D0 (en) 2004-06-08 2004-07-07 Novartis Ag Organic compounds
RS52999B (en) 2004-06-23 2014-02-28 Synta Pharmaceuticals Corp. BIS (AMIDIDA TIO-HYDRAZIDE) Salts for Cancer Treatment
CA2581125C (en) 2004-09-22 2013-04-23 Nippon Kayaku Kabushiki Kaisha Modified poly(ethylene oxide-amino acid) copolymer, micelle preparation, and anticancer agent containing the same
US7781485B2 (en) 2004-11-09 2010-08-24 Kyowa Hakko Kirin Co., Ltd. Hsp90 family protein inhibitors
NZ555158A (en) 2004-11-18 2010-09-30 Synta Pharmaceuticals Corp Triazole compounds that modulate Hsp90 activity
KR101364762B1 (ko) * 2005-02-17 2014-02-17 신타 파마슈티칼스 코프. 증식성 장애의 치료를 위한 화합물
DE102005007304A1 (de) * 2005-02-17 2006-08-24 Merck Patent Gmbh Triazolderivate
FR2882361A1 (fr) * 2005-02-22 2006-08-25 Aventis Pharma Sa Nouveaux derives de 3-aryl-1,2-benzisoxazole, compositions les contenant et leur utilisation
JP4956737B2 (ja) * 2005-02-23 2012-06-20 国立大学法人名古屋大学 抗ポリグルタミン病剤
US8399464B2 (en) 2005-03-09 2013-03-19 Nippon Kayaku Kabushiki Kaisha HSP90 inhibitor
CN1834095B (zh) 2005-03-18 2011-04-20 中国科学院上海药物研究所 一类非核苷类抗病毒抑制剂及其制备方法和用途
JP2008137894A (ja) * 2005-03-22 2008-06-19 Nippon Kayaku Co Ltd 新規なアセチレン誘導体
FR2884252B1 (fr) 2005-04-08 2007-05-18 Aventis Pharma Sa Nouveaux derives d'isoindoles, compositions les contenant, leur preparation et leurs utilisations pharmaceutiques notamment en tant qu'inhibiteurs d'activites de la proteine chaperone hsp90
WO2006109085A1 (en) * 2005-04-13 2006-10-19 Astex Therapeutics Limited Hydroxybenzamide derivatives and their use as inhibitors of hsp90
CA2604907A1 (en) 2005-04-15 2006-10-26 Synta Pharmaceuticals Corp. Combination cancer therapy with bis(thiohydrazide) amide compounds
FR2885904B1 (fr) 2005-05-19 2007-07-06 Aventis Pharma Sa Nouveaux derives du fluorene, compositions les contenant et utilisation
WO2006126751A1 (en) * 2005-05-25 2006-11-30 Korea Research Institute Of Bioscience And Biotechnology New diaryl-isoxazole derivatives, and pharmaceutical compositions containing the same for the prevention and the treatment of cancers
AU2006338265B2 (en) 2005-08-18 2011-04-14 Synta Pharmaceuticals Corp. Triazole compounds that modulate HSP90 activity
GB0603880D0 (en) * 2006-02-27 2006-04-05 Novartis Ag Organic compounds
US7754725B2 (en) 2006-03-01 2010-07-13 Astex Therapeutics Ltd. Dihydroxyphenyl isoindolymethanones
US8323669B2 (en) 2006-03-28 2012-12-04 Nippon Kayaku Kabushiki Kaisha Polymer conjugate of taxane
US20070259820A1 (en) * 2006-05-03 2007-11-08 The Regents Of The University Of Michigan Methods and reagents for activating heat shock protein 70
US8940332B2 (en) 2006-05-18 2015-01-27 Nippon Kayaku Kabushiki Kaisha High-molecular weight conjugate of podophyllotoxins
KR20090045354A (ko) 2006-08-21 2009-05-07 신타 파마슈티칼스 코프. 증식성 장애를 치료하기 위한 화합물
AU2007290490B2 (en) 2006-08-31 2011-09-08 Synta Pharmaceuticals Corp. Combination with bis(thiohydrazide amides) for treating cancer
AU2007294752A1 (en) * 2006-09-14 2008-03-20 Synta Pharmaceuticals Corp. Compounds for the treatment of angiogenesis
CA2664852A1 (en) * 2006-10-03 2008-04-10 Nippon Kayaku Kabushiki Kaisha High-molecular weight conjugate of resorcinol derivatives
GB0620259D0 (en) 2006-10-12 2006-11-22 Astex Therapeutics Ltd Pharmaceutical compounds
WO2008044045A1 (en) 2006-10-12 2008-04-17 Astex Therapeutics Limited Pharmaceutical combinations
WO2008044029A1 (en) 2006-10-12 2008-04-17 Astex Therapeutics Limited Pharmaceutical combinations
EP2081891A2 (de) 2006-10-12 2009-07-29 Astex Therapeutics Limited Pharmazeutische verbindungen mit hsp90-hemmender oder modulierender wirkung
JP5518478B2 (ja) 2006-10-12 2014-06-11 アステックス、セラピューティックス、リミテッド 医薬化合物
US8916552B2 (en) 2006-10-12 2014-12-23 Astex Therapeutics Limited Pharmaceutical combinations
US8334364B2 (en) 2006-11-06 2012-12-18 Nipon Kayaku Kabushiki Kaisha High-molecular weight derivative of nucleic acid antimetabolite
US8188222B2 (en) 2006-11-08 2012-05-29 Nippon Kayaku Kabushiki Kaisha High molecular weight derivative of nucleic acid antimetabolite
US7799954B2 (en) 2006-11-17 2010-09-21 Abraxis Bioscience, Llc Dicarbonyl derivatives and methods of use
EA017075B1 (ru) 2007-03-01 2012-09-28 Новартис Аг Мезилат, гидраты и полиморфные формы этиламида 5-(2,4-дигидрокси-5-изопропилфенил)-4-(4-морфолин-4-илметилфенил)изоксазол-3-карбоновой кислоты и препараты, содержащие эти формы
BRPI0814532A2 (pt) 2007-07-25 2015-01-27 Hoffmann La Roche Compostos, processo para a sua manufatura, composições farmacêuticas que os compreendem, método para o tratamento e/ou prevenção de enfermidades que estão associadas com a modulação dos receptores de h3, e uso desses compostos para a preparação de medicamentos.
MX2010002258A (es) 2007-08-27 2010-04-22 Helicon Therapeutics Inc Compuestos terapeuticos de isoxazol.
WO2009026658A1 (en) * 2007-08-29 2009-03-05 The University Of Sydney Ppar agonists
JP5349318B2 (ja) 2007-09-28 2013-11-20 日本化薬株式会社 ステロイド類の高分子結合体
TW200922595A (en) * 2007-10-12 2009-06-01 Novartis Ag Organic compounds
JP4792128B2 (ja) 2007-10-12 2011-10-12 アークル インコーポレイテッド 癌に対するｈｓｐ９０阻害剤としての５−（２−ヒドロキシフェニル）テトラゾール
WO2009055917A1 (en) * 2007-11-02 2009-05-07 Methylgene Inc. Inhibitors of histone deacetylase
GB0722680D0 (en) * 2007-11-19 2007-12-27 Topotarget As Therapeutic compounds and their use
WO2009116509A1 (ja) 2008-03-18 2009-09-24 日本化薬株式会社 生理活性物質の高分子結合体
GB0806527D0 (en) 2008-04-11 2008-05-14 Astex Therapeutics Ltd Pharmaceutical compounds
LT5623B (lt) 2008-04-30 2010-01-25 Biotechnologijos Institutas, , 5-aril-4-(5-pakeistieji 2,4-dihidroksifenil)-1,2,3-tiadiazolai kaip hsp90 šaperono slopikliai ir tarpiniai junginiai jiems gauti
WO2009136572A1 (ja) 2008-05-08 2009-11-12 日本化薬株式会社 葉酸若しくは葉酸誘導体の高分子結合体
CN102098918A (zh) * 2008-05-13 2011-06-15 帕纳德制药公司 用于治疗癌症和神经退行性疾病的生物活性化合物
TWI450898B (zh) 2008-07-04 2014-09-01 Sigma Tau Res Switzerland Sa 具有抗腫瘤活性之芳基異唑化合物
PL3542780T3 (pl) 2008-07-21 2022-05-02 Unigen, Inc. Szereg związków wybielających (rozjaśniających)
NZ592890A (en) * 2008-11-28 2013-09-27 Novartis Ag Pharmaceutical combination comprising a hsp 90 inhibitor and a mtor inhibitor
EP2370103B1 (de) * 2008-11-28 2016-03-23 Novartis AG Arzneimittelkombinationen, enthaltend einen von isoxazol abgeleiteten hsp90-hemmer und den her2-hemmer trastuzumab
EP2421833B1 (de) 2009-04-21 2015-01-14 Nerviano Medical Sciences S.r.l. Resorcinol derivate als hsp90-inhibitoren
CN102421827B (zh) 2009-05-15 2014-07-30 日本化药株式会社 具有羟基的生理活性物质的高分子结合体
EP2471918A4 (de) 2009-09-29 2013-06-05 Takeda Pharmaceutical Screening-verfahren
HUE026447T2 (en) 2009-10-16 2016-05-30 Novartis Ag Pharmacodynamic tumor response biomarkers
US20120309750A1 (en) * 2010-02-17 2012-12-06 Ildong Pharm Co., Ltd. 5-membered heterocycle derivatives and manufacturing process thereof
US9205086B2 (en) 2010-04-19 2015-12-08 Synta Pharmaceuticals Corp. Cancer therapy using a combination of a Hsp90 inhibitory compounds and a EGFR inhibitor
CA2816997A1 (en) 2010-11-17 2012-05-24 Nippon Kayaku Kabushiki Kaisha Novel polymer derivative of cytidine metabolic antagonist
ES2859700T3 (es) 2011-03-24 2021-10-04 Unigen Inc Compuestos y métodos para la preparación de diarilpropanos
WO2013015661A2 (en) * 2011-07-28 2013-01-31 Ildong Pharm Co.,Ltd. Novel prodrugs of 5-(2,4-dihydroxy-5-isopropylphenyl)-n-ethyl-4-(5-methyl1-1,2,4-oxadiazol-3-yl)isoxazole-3-carboxamide
CN102351655A (zh) * 2011-08-18 2012-02-15 杭州澳赛诺化工有限公司 一种4-异丙基间苯二酚的合成方法
BR112014005452B1 (pt) 2011-09-11 2021-03-16 Nippon Kayaku Kabushiki Kaisha método de produção de copolímero de bloco
CA2851383A1 (en) 2011-10-14 2013-04-18 Xizhong Huang 2 - carboxamide cycloamino urea derivatives in combination with hsp90 inhibitors for the treatment of proliferative diseases
CN103086994A (zh) * 2011-10-31 2013-05-08 上海壹志医药科技有限公司 异噁唑衍生物的盐
WO2013067162A1 (en) 2011-11-02 2013-05-10 Synta Pharmaceuticals Corp. Cancer therapy using a combination of hsp90 inhibitors with topoisomerase i inhibitors
US20140286902A1 (en) 2011-11-02 2014-09-25 Synta Pharmaceuticals Corp. Combination therapy of hsp90 inhibitors with platinum-containing agents
JP2014533299A (ja) 2011-11-14 2014-12-11 シンタ ファーマシューティカルズ コーポレーション Ｂｒａｆ阻害剤とｈｓｐ９０阻害剤の組合せ療法
RU2015121424A (ru) 2012-11-07 2016-12-27 Новартис Аг Комбинированная терапия
EP2917200A1 (de) 2012-11-09 2015-09-16 Jacobus Pharmaceutical Company, Inc. Arylderivate und verwendungen davon
DK2917181T3 (da) * 2012-11-09 2020-01-13 Medicines For Malaria Venture Mmv Heteroarylderivater og anvendelser deraf
EP2968349A2 (de) * 2013-03-15 2016-01-20 Novartis AG Biomarker für pharmakodynamische tumorreaktionen
CA2915975A1 (en) * 2013-06-26 2014-12-31 Proteostasis Therapeutics, Inc. Methods of modulating cftr activity
JOP20200094A1 (ar) 2014-01-24 2017-06-16 Dana Farber Cancer Inst Inc جزيئات جسم مضاد لـ pd-1 واستخداماتها
JOP20200096A1 (ar) 2014-01-31 2017-06-16 Children’S Medical Center Corp جزيئات جسم مضاد لـ tim-3 واستخداماتها
US20150259420A1 (en) 2014-03-14 2015-09-17 Novartis Ag Antibody molecules to lag-3 and uses thereof
EP3157917B1 (de) * 2014-06-19 2020-03-18 Proteostasis Therapeutics, Inc. Verbindungen, zusammensetzungen und verfahren zur steigerung der cftr-aktivität
PT3202766T (pt) 2014-10-01 2020-03-25 Daiichi Sankyo Co Ltd Derivado de isoxazol como inibidor de isocitrato desidrogenase 1 mutante
MA41044A (fr) 2014-10-08 2017-08-15 Novartis Ag Compositions et procédés d'utilisation pour une réponse immunitaire accrue et traitement contre le cancer
CR20170143A (es) 2014-10-14 2017-06-19 Dana Farber Cancer Inst Inc Moléculas de anticuerpo que se unen a pd-l1 y usos de las mismas
WO2016100882A1 (en) 2014-12-19 2016-06-23 Novartis Ag Combination therapies
CN104725329B (zh) * 2015-01-13 2017-01-18 陕西科技大学 一种具有抗肿瘤活性的异恶唑羧酸类化合物及其合成方法
CN107108591B (zh) * 2015-01-22 2020-05-05 正大天晴药业集团股份有限公司 作为hsp90抑制剂的间苯二酚类衍生物
SG11201706756VA (en) 2015-03-10 2017-09-28 Aduro Biotech Inc Compositions and methods for activating "stimulator of interferon gene" -dependent signalling
CN106349180B (zh) * 2015-07-14 2020-05-19 上海翰森生物医药科技有限公司 4,5-二苯基异噁唑衍生物及其制备方法和应用
DK3317301T3 (da) 2015-07-29 2021-06-28 Immutep Sas Kombinationsterapier omfattende antistofmolekyler mod lag-3
EP4378957A2 (de) 2015-07-29 2024-06-05 Novartis AG Kombinationstherapien mit antikörpermolekülen gegen pd-1
WO2017019897A1 (en) 2015-07-29 2017-02-02 Novartis Ag Combination therapies comprising antibody molecules to tim-3
EP3370768B9 (de) 2015-11-03 2022-03-16 Janssen Biotech, Inc. Spezifisch an pd-1 bindende antikörper und deren verwendung
CN108495651A (zh) 2015-12-17 2018-09-04 诺华股份有限公司 抗pd-1的抗体分子及其用途
CN107540624B (zh) * 2016-06-29 2020-06-16 广州市恒诺康医药科技有限公司 热休克蛋白抑制剂及其制备方法和应用
CN106146466A (zh) * 2016-06-30 2016-11-23 珠海赛隆药业股份有限公司（长沙）医药研发中心 富马酸沃诺拉赞中间体、其制备方法和制备富马酸沃诺拉赞的方法
EP3507367A4 (de) 2016-07-05 2020-03-25 Aduro BioTech, Inc. Cyclisches dinukleotidverbindungen mit eingeschlossenen nukleinsäuren und verwendungen davon
CN109641858B (zh) * 2016-07-21 2021-06-25 正大天晴药业集团股份有限公司 间苯二酚类衍生物的结晶、盐及其制备方法
UY37695A (es) 2017-04-28 2018-11-30 Novartis Ag Compuesto dinucleótido cíclico bis 2’-5’-rr-(3’f-a)(3’f-a) y usos del mismo
CN111217762B (zh) * 2018-11-23 2021-08-20 华中师范大学 多卤代5-(2-羟基苯基)异噁唑类化合物及其制备方法和应用
WO2020231979A1 (en) * 2019-05-13 2020-11-19 The Trustees Of Princeton University Small molecule inhibitors of viral replication
CN110283080A (zh) * 2019-07-05 2019-09-27 山西大学 一种含氟的二苯甲酮衍生物及其制备方法和应用
WO2021152113A1 (en) 2020-01-31 2021-08-05 Bayer Aktiengesellschaft Substituted 2,3-benzodiazepines derivatives
CN115160250B (zh) * 2021-04-02 2024-06-04 沈阳药科大学 4,6-联苯二酚类衍生物及其用途
US11324737B1 (en) * 2021-05-25 2022-05-10 Louis Habash Modulating expression level of a gene encoding a heat shock protein by treating a human subject with a nitroxide
US11729925B2 (en) 2021-06-15 2023-08-15 Erico International Corporation Mounting bracket with angled mounting openings for electrical boxes
CN114751870B (zh) * 2022-02-28 2023-10-20 贵州医科大学 一种2-(异噁唑-5-基)苯基-3,4-二羟基苯甲酸酯及其衍生物及合成方法和应用

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE59009528D1 (de) * 1989-09-22 1995-09-21 Basf Ag Carbonsäureamide.
CA2102209C (en) * 1991-05-01 1997-11-18 Takashi Shindo Novel isoxazole derivative and salt thereof
WO1994024095A1 (en) 1993-04-16 1994-10-27 Abbott Laboratories Immunosuppressive agents
DE69729946T2 (de) * 1996-10-15 2005-01-20 G.D. Searle Llc Verwendung von cyclooxygenase-2 inhibitoren zur behandlung und verbeugung von neoplasia
ATE236890T1 (de) * 1996-12-23 2003-04-15 Bristol Myers Squibb Pharma Co Sauerstoff oder schwefel enthaltende 5-gliedrige heteroaromatishe derivative als factor xa hemmer
US6187797B1 (en) * 1996-12-23 2001-02-13 Dupont Pharmaceuticals Company Phenyl-isoxazoles as factor XA Inhibitors
ATE315033T1 (de) * 1998-08-07 2006-02-15 Chiron Corp Subtituierte isoxazole derivate als estrogen rezeptor modulatore
CA2343027A1 (en) * 1998-09-09 2000-03-16 Metabasis Therapeutics, Inc. Novel heteroaromatic inhibitors of fructose 1,6-bisphosphatase
ATE300288T1 (de) * 1998-12-24 2005-08-15 Metabasis Therapeutics Inc Zusammensetzung enthaltend insulin- sensibilisierenden wirkstoffe und inhibitoren der fruktose-1,6-bisphosphatase (fbpase) zur behandlung von diabetes
WO2001012621A1 (en) * 1999-08-13 2001-02-22 Vertex Pharmaceuticals Incorporated INHIBITORS OF c-JUN N-TERMINAL KINASES (JNK) AND OTHER PROTEIN KINASES
US6965033B2 (en) * 1999-12-22 2005-11-15 Metabasis Therapeutics, Inc. Bisamidate phosphonate prodrugs
US6673818B2 (en) * 2001-04-20 2004-01-06 Pharmacia Corporation Fluoro-substituted benzenesulfonyl compounds for the treatment of inflammation
JP2002363079A (ja) * 2001-05-31 2002-12-18 National Cancer Center-Japan モフェゾラクを有効成分とする、消化管ポリープおよび／または消化管がんの予防または治療のための薬剤
JP4399265B2 (ja) * 2001-12-21 2010-01-13 ヴァーナリス（ケンブリッジ）リミテッド ３，４−ジアリールピラゾール、および癌の治療におけるそれらの使用
SI1611112T1 (sl) * 2003-02-11 2012-12-31 Vernalis (R&D) Limited Izoksazolne spojine kot inhibitorji vroäśinskih ĺ ok proteinov
US20110201587A1 (en) * 2010-02-16 2011-08-18 Bio Holding, Inc. Hsp90 inhibitors and methods of use

Also Published As

Publication number Publication date
KR101166749B1 (ko) 2012-07-27
NZ541479A (en) 2008-11-28
US20190358241A1 (en) 2019-11-28
AU2004210779A1 (en) 2004-08-26
US7705027B2 (en) 2010-04-27
BRPI0407403B1 (pt) 2022-07-19
US20120252797A1 (en) 2012-10-04
US8450310B2 (en) 2013-05-28
WO2004072051A1 (en) 2004-08-26
US20060241106A1 (en) 2006-10-26
CA2515726A1 (en) 2004-08-26
US9718793B2 (en) 2017-08-01
US20130289026A1 (en) 2013-10-31
DK1611112T3 (da) 2012-11-19
ES2393483T3 (es) 2012-12-21
JP2006517572A (ja) 2006-07-27
MXPA05008335A (es) 2006-05-04
EP1611112B1 (de) 2012-08-22
CN1771235B (zh) 2010-04-28
EA009919B1 (ru) 2008-04-28
JP4921162B2 (ja) 2012-04-25
CA2515726C (en) 2012-07-10
US20100179138A1 (en) 2010-07-15
US8507480B2 (en) 2013-08-13
BRPI0407403A (pt) 2006-10-03
NO335001B1 (no) 2014-08-18
EA200501272A1 (ru) 2006-02-24
KR20050103925A (ko) 2005-11-01
PT1611112E (pt) 2012-11-02
US10413550B2 (en) 2019-09-17
AU2004210779B2 (en) 2010-06-10
NO20054195D0 (no) 2005-09-09
EP1611112A1 (de) 2006-01-04
US20170326152A1 (en) 2017-11-16
NO20054195L (no) 2005-11-09
SI1611112T1 (sl) 2012-12-31
US11234987B2 (en) 2022-02-01
CN1771235A (zh) 2006-05-10
CY1113761T1 (el) 2016-07-27

Similar Documents

Publication Publication Date Title
HK1091831A1 (en) Isoxazole compounds as inhibitors of heat shock proteins
GB0318343D0 (en) No title
DE60112974D1 (en) Carbolinderivate
IL165434A0 (en) Compounds having DPP-IV inhibitory activity
MXPA04002931A (es) Heterociclos que contienen nitrogeno de 5 miembros sustituidos con fenilo para el tratamiento de la obesidad.
DE60317198D1 (de) Proteinkinaseinhibitoren
HK1096549A1 (en) Imidazopyridine-derivatives as inducible no-synthase inhibitors
MY135477A (en) 2-(2,6-dichlorophenyl)-diarylimidazoles
DE60216233D1 (en) Carbolinderivate
PH12009500610A1 (en) 4-imidazolin-2-one compounds
WO2007062308A3 (en) Homo- and heterocyclic compounds suitable as cetp inhibitors
AU2001266575A1 (en) Chemical compounds
NO20044526L (no) Hemisterlinderivater og anvendelser derav
BRPI0407841A (pt) inibidores heterocìclicos de quinase
MXPA04006041A (es) Antivirales de piridoquinoxalina.
HK1096548A1 (en) Imidazopyridine-derivatives as inductible no-synthase inhibitors
AU2001263278A1 (en) Cyclic gmp-specific phosphodiesterase inhibitors
DE602004005881D1 (de) Substituierte pyrazinonverbindungen zur behandlung von entzündungen
RS20060206A (en) Aminopyridine-derivatives as inducible no-synthase inhibitors
RS20060195A (en) Imidazopyridine-derivatives as inducible no-synthase inhibitors
EP1476149A4 (de) Substituierte hydrazone als hemmer von cyclooxygenase-2
NO20001751L (no) Nye forbindelser til bruk som neuroprotektive midler
MY136854A (en) Crystalline n-formyl hydroxylamine compounds
ATE279113T1 (de) Hypoxanthin- und thiohypxanthin-verbindungen
SG145572A1 (en) Intermediates useful in the synthesis of hiv-protease inhibitors and methods for preparing the same

Legal Events

Date Code Title Description
PE Patent expired

Effective date: 20240212