FI913503A - BENSIMIDAZOLER, DESSA FOERENINGAR INNEHAOLLANDE CEILING MODEL OCH FOERFARANDE FOER DERAS FRAMSTAELLNING. - Google Patents

BENSIMIDAZOLER, DESSA FOERENINGAR INNEHAOLLANDE CEILING MODEL OCH FOERFARANDE FOER DERAS FRAMSTAELLNING. Download PDF

Info

Publication number
FI913503A
FI913503A FI913503A FI913503A FI913503A FI 913503 A FI913503 A FI 913503A FI 913503 A FI913503 A FI 913503A FI 913503 A FI913503 A FI 913503A FI 913503 A FI913503 A FI 913503A
Authority
FI
Finland
Prior art keywords
bensimidazoler
foerfarande foer
och foerfarande
deras framstaellning
foer deras
Prior art date
Application number
FI913503A
Other languages
Finnish (fi)
Other versions
FI913503A0 (en
FI105811B (en
Inventor
Berthold Narr
Norbert Hauel
Meel Jacques Van
Wolfgang Wienen
Michael Entzeroth
Uwe Ries
Original Assignee
Thomae Gmbh Dr K
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 DE4023369A external-priority patent/DE4023369A1/en
Application filed by Thomae Gmbh Dr K filed Critical Thomae Gmbh Dr K
Publication of FI913503A0 publication Critical patent/FI913503A0/en
Publication of FI913503A publication Critical patent/FI913503A/en
Application granted granted Critical
Publication of FI105811B publication Critical patent/FI105811B/en

Links

Classifications

    • 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
    • C07D403/02Heterocyclic 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
    • C07D403/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/26Psychostimulants, e.g. nicotine, cocaine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/06Antiglaucoma agents or miotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/08Radicals containing only hydrogen and carbon atoms
    • 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
    • C07D403/02Heterocyclic 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
    • C07D403/10Heterocyclic 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 aromatic rings
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Psychiatry (AREA)
  • Ophthalmology & Optometry (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Child & Adolescent Psychology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Obesity (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Toys (AREA)
  • Instructional Devices (AREA)
  • Steroid Compounds (AREA)

Abstract

The invention relates to benzimidazoles of the general formula <IMAGE> in which R1 to R4 are as defined in Claim 1, mixtures of their 1-, 3-isomers, and their salts, which have valuable properties. The novel compounds are, in particular, angiotensin antagonists.
FI913503A 1990-07-23 1991-07-22 The method provides pharmacologically useful benzimidazoles FI105811B (en)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
DE4023369 1990-07-23
DE4023369A DE4023369A1 (en) 1990-07-23 1990-07-23 New 1-bi:phenylyl:methyl benzimidazole derivs.
DE4031287A DE4031287A1 (en) 1990-07-23 1990-10-04 New 1-bi:phenylyl:methyl benzimidazole derivs.
DE4031287 1990-10-04
DE4105324A DE4105324A1 (en) 1990-07-23 1991-02-20 New 1-bi:phenylyl:methyl benzimidazole derivs.
DE4105324 1991-02-20

Publications (3)

Publication Number Publication Date
FI913503A0 FI913503A0 (en) 1991-07-22
FI913503A true FI913503A (en) 1992-01-24
FI105811B FI105811B (en) 2000-10-13

Family

ID=27201487

Family Applications (1)

Application Number Title Priority Date Filing Date
FI913503A FI105811B (en) 1990-07-23 1991-07-22 The method provides pharmacologically useful benzimidazoles

Country Status (18)

Country Link
EP (1) EP0468470B1 (en)
JP (1) JP2539113B2 (en)
AT (1) ATE151766T1 (en)
AU (1) AU640505B2 (en)
CA (1) CA2047496C (en)
CS (1) CS230491A3 (en)
DE (1) DE59108658D1 (en)
DK (1) DK0468470T3 (en)
ES (1) ES2100907T3 (en)
FI (1) FI105811B (en)
GR (1) GR3024027T3 (en)
HU (1) HUT58298A (en)
IE (1) IE912563A1 (en)
IL (1) IL98933A (en)
NO (1) NO178927C (en)
NZ (1) NZ239089A (en)
PT (1) PT98414B (en)
RU (1) RU1836357C (en)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8904174D0 (en) * 1989-02-23 1989-04-05 British Bio Technology Compounds
NZ232785A (en) * 1989-03-15 1991-03-26 Janssen Pharmaceutica Nv 5-(1,2 benzisoxazol-, benzimidazol and benzisothiazol-3- yl)-1h-benzimadazol-2-yl carbamic acid ester derivatives preparatory processes, intermediates and anthelmintic compositions
IE70593B1 (en) * 1989-09-29 1996-12-11 Eisai Co Ltd Biphenylmethane derivative the use of it and pharmacological compositions containing same
SI9210098B (en) * 1991-02-06 2000-06-30 Dr. Karl Thomae Benzimidazoles, drugs with this compounds, and process for their preparation
US5602127A (en) * 1991-02-06 1997-02-11 Karl Thomae Gmbh (Alkanesultam-1-yl)-benzimidazol-1-yl)-1yl)-methyl-biphenyls useful as angiotensin-II antagonists
DE4225756A1 (en) * 1992-01-22 1994-03-10 Thomae Gmbh Dr K Benzimidazoles, medicaments containing these compounds and process for their preparation
US5594003A (en) * 1991-02-06 1997-01-14 Dr. Karl Thomae Gmbh Tetrahydroimidazo[1,2-a]pyridin-2-yl-(benzimidazol-1-yl)-methyl-biphenyls useful as angiotensin-II antagonists
DE4224752A1 (en) * 1992-04-11 1994-02-03 Thomae Gmbh Dr K Benzimidazoles, medicaments containing these compounds and process for their preparation
DE4224133A1 (en) * 1992-07-22 1994-01-27 Thomae Gmbh Dr K Benzimidazoles, medicaments containing these compounds and process for their preparation
US5614519A (en) * 1991-02-06 1997-03-25 Karl Thomae Gmbh (1-(2,3 or 4-N-morpholinoalkyl)-imidazol-4-yl)-benizimidazol-1-yl-methyl]-biphenyls useful as angiotensin-II antagonists
US5798364A (en) * 1992-03-26 1998-08-25 Merck Patent Gesellschaft Mit Beschrankter Haftung Imidazopyridines
SG42942A1 (en) * 1991-09-10 1997-10-17 Tanabe Seiyaku Co Imidazopyridine derivatives and process for preparation thereof
EP0543263A3 (en) * 1991-11-16 1993-08-25 Dr. Karl Thomae Gmbh Benziimidazoles, pharmaceuticals containing them and process for their preparation
DE4219534A1 (en) * 1992-02-19 1993-12-16 Thomae Gmbh Dr K Substituted biphenylyl derivatives, pharmaceutical compositions containing them and methods for their preparation
DE4207904A1 (en) * 1992-03-12 1993-09-16 Thomae Gmbh Dr K SUBSTITUTED BENZIMIDAZOLYL DERIVATIVES, MEDICAMENTS CONTAINING SUCH COMPOUNDS AND METHOD FOR THE PRODUCTION THEREOF
US5612360A (en) * 1992-06-03 1997-03-18 Eli Lilly And Company Angiotensin II antagonists
DE4237656A1 (en) * 1992-06-13 1993-12-16 Merck Patent Gmbh benzimidazole derivatives
GB9218449D0 (en) 1992-08-29 1992-10-14 Boots Co Plc Therapeutic agents
DE4304455A1 (en) * 1993-02-15 1994-08-18 Bayer Ag Heterocyclic substituted phenyl-cyclohexane-carboxylic acid derivatives
DE4408497A1 (en) * 1994-03-14 1995-09-21 Thomae Gmbh Dr K New bi:phenyl-methyl-benzimidazole derivs.
US5753672A (en) * 1994-04-19 1998-05-19 Tanabe Seiyaku Co., Ltd. Imidazopyridine derivatives and process for preparing the same
WO1996000730A1 (en) * 1994-06-29 1996-01-11 Smithkline Beecham Corporation Vitronectin receptor antagonists
DK0882718T3 (en) * 1995-12-28 2005-12-12 Astellas Pharma Inc benzimidazole
TW453999B (en) 1997-06-27 2001-09-11 Fujisawa Pharmaceutical Co Benzimidazole derivatives
SE9903028D0 (en) 1999-08-27 1999-08-27 Astra Ab New use
DE10314702A1 (en) * 2003-03-31 2004-10-21 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for the preparation of telmisartan
CA2542499A1 (en) * 2003-10-16 2005-04-28 Teva Pharmaceutical Industries Ltd. Preparation of candesartan cilexetil
JP2008503595A (en) * 2004-10-15 2008-02-07 テバ ファーマシューティカル インダストリーズ リミティド Preparation of telmisartan
US8969514B2 (en) 2007-06-04 2015-03-03 Synergy Pharmaceuticals, Inc. Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
MX354786B (en) 2007-06-04 2018-03-21 Synergy Pharmaceuticals Inc AGONISTS OF GUANYLATE CYCLASE USEFUL FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS, INFLAMMATION, CANCER and OTHER DISORDERS.
CA2726917C (en) 2008-06-04 2018-06-26 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
WO2010009319A2 (en) 2008-07-16 2010-01-21 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
US8829035B2 (en) 2009-05-29 2014-09-09 Sumitomo Chemical Company, Limited Agent for treatment or prevention of diseases associated with activity of neurotrophic factors
US9616097B2 (en) 2010-09-15 2017-04-11 Synergy Pharmaceuticals, Inc. Formulations of guanylate cyclase C agonists and methods of use
WO2014151200A2 (en) 2013-03-15 2014-09-25 Synergy Pharmaceuticals Inc. Compositions useful for the treatment of gastrointestinal disorders
EP2970384A1 (en) 2013-03-15 2016-01-20 Synergy Pharmaceuticals Inc. Agonists of guanylate cyclase and their uses
JP6606491B2 (en) 2013-06-05 2019-11-13 シナジー ファーマシューティカルズ インコーポレイテッド Ultra high purity agonist of guanylate cyclase C, method for producing and using the same
JP6461118B2 (en) 2013-06-21 2019-01-30 ゼニス・エピジェネティクス・リミテッドZenith Epigenetics Ltd. Novel substituted bicyclic compounds as bromodomain inhibitors
NZ714669A (en) 2013-06-21 2021-07-30 Zenith Epigenetics Ltd Novel bicyclic bromodomain inhibitors
EA201690087A1 (en) 2013-07-31 2016-08-31 Зенит Эпидженетикс Корп. NEW QUINAZOLINONS AS BROMOMODENIAL INHIBITORS
JP2017523214A (en) * 2014-08-05 2017-08-17 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company Heterocyclic kinase inhibitor
WO2016087936A1 (en) 2014-12-01 2016-06-09 Zenith Epigenetics Corp. Substituted pyridinones as bromodomain inhibitors
CA2966449A1 (en) 2014-12-11 2016-06-16 Zenith Epigenetics Ltd. Substituted heterocycles as bromodomain inhibitors
CN107406438B (en) 2014-12-17 2021-05-14 恒翼生物医药科技(上海)有限公司 Inhibitors of bromodomains

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4820843A (en) * 1987-05-22 1989-04-11 E. I. Du Pont De Nemours And Company Tetrazole intermediates to antihypertensive compounds
US4880804A (en) * 1988-01-07 1989-11-14 E. I. Du Pont De Nemours And Company Angiotensin II receptor blocking benzimidazoles
EP0400835A1 (en) * 1989-05-15 1990-12-05 Merck & Co. Inc. Substituted benzimidazoles as angiotensin II antagonists
AU645022B2 (en) * 1989-06-30 1994-01-06 E.I. Du Pont De Nemours And Company Fused-ring aryl substituted imidazoles
IE70593B1 (en) * 1989-09-29 1996-12-11 Eisai Co Ltd Biphenylmethane derivative the use of it and pharmacological compositions containing same
IL95975A (en) * 1989-10-24 1997-06-10 Takeda Chemical Industries Ltd N-benzyl- 2-alkylbenzimidazole derivatives, their production and pharmaceutical compositions containing them
IL96019A0 (en) * 1989-10-31 1991-07-18 Fujisawa Pharmaceutical Co Imidazole derivatives,processes for the preparation thereof and pharmaceutical compositions containing the same

Also Published As

Publication number Publication date
AU8122791A (en) 1992-01-30
IE912563A1 (en) 1992-01-29
JP2539113B2 (en) 1996-10-02
GR3024027T3 (en) 1997-10-31
NO912859L (en) 1992-01-24
PT98414A (en) 1992-05-29
IL98933A (en) 1995-12-31
IL98933A0 (en) 1992-07-15
HUT58298A (en) 1992-02-28
FI913503A0 (en) 1991-07-22
CA2047496C (en) 2001-10-23
DE59108658D1 (en) 1997-05-22
JPH04253966A (en) 1992-09-09
RU1836357C (en) 1993-08-23
CA2047496A1 (en) 1992-01-24
PT98414B (en) 1999-01-29
CS230491A3 (en) 1992-02-19
EP0468470A1 (en) 1992-01-29
NO912859D0 (en) 1991-07-22
NZ239089A (en) 1994-07-26
ATE151766T1 (en) 1997-05-15
EP0468470B1 (en) 1997-04-16
DK0468470T3 (en) 1997-09-22
NO178927C (en) 1996-07-03
ES2100907T3 (en) 1997-07-01
HU912456D0 (en) 1991-12-30
FI105811B (en) 2000-10-13
AU640505B2 (en) 1993-08-26
NO178927B (en) 1996-03-25

Similar Documents

Publication Publication Date Title
FI913503A (en) BENSIMIDAZOLER, DESSA FOERENINGAR INNEHAOLLANDE CEILING MODEL OCH FOERFARANDE FOER DERAS FRAMSTAELLNING.
FI901739A0 (en) BENSIMIDAZOLER, DESSA FOERENINGAR INNEHAOLLANDE CEILING MODEL OCH FOERFARANDE FOER DERAS FRAMSTAELLNING.
DK0546583T3 (en) Piperidinyl and piperazinylcyclohexanols
BG92804A (en) 4-BENZOYLISOXAZOLE DERIVATIVES
FI915282A0 (en) MONO-N-SUBSTITUERADE 1,4,7,10-TETRA -AZACYKLODODEKANDERIVAT, FOERFARANDE FOER DERAS FRAMSTAELLNING OCH DESSA INNEHAOLLANDE PHARMACEUTICAL AEMNEN.
DK0530505T3 (en) hydantoin derivatives
FI930236A0 (en) BENSIMIDAZOLER, DESSA FOERENINGAR INNEHAOLLANDE CEILING MODEL OCH FOERFARANDEFOER DERAS FRAMSTAELLNING
FI834730A0 (en) 1-CARBOXYKANOYLPERHYDRO-INDOL-2-CARBOXYLSYROR OR DERIVATIVES
FI881609A (en) DIHYDROPYRIDINAMIDER, FOERFARANDE FOER DERAS FRAMSTAELLNING OCH DERAS ANVAENDNING I LAEKEMEDEL.
IT1246275B (en) AMMELINIC COMPOUNDS AND THEIR USE IN SELF-EXTINGUISHING POLYMER COMPOSITIONS
DE69013330D1 (en) Triazine compounds.
FI870067A0 (en) METHIONIC SUBSTITUTES 1,4-DIHYDROPYRIDINER, FOERFARANDE FOER DERAS FRAMSTAELLNING OCH DERAS ANVAENDNING.
CY1110467T1 (en) 2- (OTHER-) ARYLI SUBSTITUTED SUBSTITUTES OF tetrahydroquinoline

Legal Events

Date Code Title Description
MA Patent expired