SK144494A3 - Sulfur-containing phosphate compounds and their using in pharmaceutical compound for treating abnormal calcium and phosphate metabolism - Google Patents
Sulfur-containing phosphate compounds and their using in pharmaceutical compound for treating abnormal calcium and phosphate metabolism Download PDFInfo
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- SK144494A3 SK144494A3 SK1444-94A SK144494A SK144494A3 SK 144494 A3 SK144494 A3 SK 144494A3 SK 144494 A SK144494 A SK 144494A SK 144494 A3 SK144494 A3 SK 144494A3
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- substituted
- unsubstituted
- alkyl
- hydrogen
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 85
- 229910052717 sulfur Inorganic materials 0.000 title claims abstract description 53
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 title claims abstract description 42
- 239000011575 calcium Substances 0.000 title claims abstract description 42
- 229910052791 calcium Inorganic materials 0.000 title claims abstract description 42
- 229910019142 PO4 Inorganic materials 0.000 title claims abstract description 40
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 title claims abstract description 37
- 239000010452 phosphate Substances 0.000 title claims abstract description 37
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title claims description 37
- 239000011593 sulfur Substances 0.000 title claims description 37
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- 238000011282 treatment Methods 0.000 claims abstract description 58
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
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Classifications
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- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
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- C—CHEMISTRY; METALLURGY
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- 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
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- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
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- 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
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- 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
- C07F9/5532—Seven-(or more) membered rings
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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- 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
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- C07F9/576—Six-membered rings
- C07F9/5765—Six-membered rings condensed with carbocyclic rings or carbocyclic ring systems
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- 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
- C07F9/58—Pyridine rings
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- 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
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- C—CHEMISTRY; METALLURGY
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07F9/02—Phosphorus compounds
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- C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
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- Veterinary Medicine (AREA)
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- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Orthopedic Medicine & Surgery (AREA)
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- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Removal Of Specific Substances (AREA)
- Processing Of Solid Wastes (AREA)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US89130992A | 1992-05-29 | 1992-05-29 | |
PCT/US1993/004977 WO1993024496A1 (en) | 1992-05-29 | 1993-05-26 | Sulfur-containing phosponate compounds for treating abnormal calcium and phosphate metabolism |
Publications (1)
Publication Number | Publication Date |
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SK144494A3 true SK144494A3 (en) | 1995-05-10 |
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Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1444-94A SK144494A3 (en) | 1992-05-29 | 1993-05-26 | Sulfur-containing phosphate compounds and their using in pharmaceutical compound for treating abnormal calcium and phosphate metabolism |
Country Status (25)
Country | Link |
---|---|
US (1) | US5824661A (zh) |
EP (1) | EP0642519B1 (zh) |
JP (1) | JPH07507315A (zh) |
KR (1) | KR950701929A (zh) |
CN (2) | CN1061049C (zh) |
AT (1) | ATE195317T1 (zh) |
AU (1) | AU669372B2 (zh) |
CA (2) | CA2136818C (zh) |
CZ (1) | CZ296794A3 (zh) |
DE (1) | DE69329199D1 (zh) |
DK (1) | DK0642519T3 (zh) |
FI (1) | FI945593A (zh) |
HK (1) | HK1014002A1 (zh) |
HU (1) | HUT69699A (zh) |
IL (2) | IL105834A (zh) |
MX (1) | MX9303251A (zh) |
MY (1) | MY109736A (zh) |
NO (1) | NO305960B1 (zh) |
NZ (1) | NZ253524A (zh) |
PL (1) | PL175475B1 (zh) |
RU (1) | RU2136691C1 (zh) |
SG (1) | SG50518A1 (zh) |
SK (1) | SK144494A3 (zh) |
WO (1) | WO1993024496A1 (zh) |
ZA (1) | ZA933759B (zh) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE168379T1 (de) * | 1992-05-29 | 1998-08-15 | Procter & Gamble Pharma | Quaternare stickstoff-enthaltende phosphonat- verbindungen zur behandlung abnormalen calzium und phosphat-metabolismus sowie zahnsteinbildung |
PL175046B1 (pl) * | 1992-05-29 | 1998-10-30 | Procter & Gamble Pharma | Nowe tio-podstawione, zawierające azot heterocykliczne związki fosfonianowe |
TW401276B (en) * | 1993-10-07 | 2000-08-11 | Zeneca Ltd | Novel compounds and a method of controlling growth of plants |
US5728650A (en) * | 1993-10-07 | 1998-03-17 | Zeneca Limited | Herbicidal aza bisphosphonic acids and compositions containing the same |
US5646134A (en) * | 1994-04-21 | 1997-07-08 | Merck & Co., Inc. | Alendronate therapy to prevent loosening of, or pain associated with, orthopedic implant devices |
US6333424B1 (en) * | 1996-10-09 | 2001-12-25 | Eliza Nor Biopharmaceuticals, Inc. | Therapeutic derivatives of diphosphonates |
US6121253A (en) * | 1998-11-20 | 2000-09-19 | Merck Frosst Canada & Co. | Prostaglandin conjugates for treating or preventing bone disease |
FR2947266B1 (fr) * | 2009-06-26 | 2011-06-17 | Servier Lab | Nouveaux derives d'acide 2-mercaptocyclopentanecarboxylique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
TWI730039B (zh) * | 2016-01-29 | 2021-06-11 | 日商富士藥品股份有限公司 | 新穎雙膦酸化合物 |
US11793452B2 (en) | 2019-10-03 | 2023-10-24 | Johnson & Johnson Consumer Inc. | Method of visualizing and quantifying remineralization |
Family Cites Families (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3957858A (en) * | 1970-04-13 | 1976-05-18 | Monsanto Company | Substituted ethane diphosphonic acids and salts and esters thereof |
US4208401A (en) * | 1977-08-19 | 1980-06-17 | Colgate-Palmolive Company | Quaternary ammonium alkylene diphosphonate anti-calculus agents |
DE2745083C2 (de) * | 1977-10-07 | 1985-05-02 | Henkel KGaA, 4000 Düsseldorf | Hydroxydiphosphonsäuren und Verfahren zu deren Herstellung |
DE3016289A1 (de) * | 1980-04-28 | 1981-10-29 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur herstellung von omega -amino-1-hydroxyalkyliden-1,1-bis-phosphonsaeuren |
FR2531088B1 (fr) * | 1982-07-29 | 1987-08-28 | Sanofi Sa | Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation |
AU566610B2 (en) * | 1983-09-15 | 1987-10-22 | University Of Bath | Disinfection of contact lenses |
FR2558837B1 (fr) * | 1984-01-26 | 1986-06-27 | Sanofi Sa | Derives de l'acide methylenediphosphonique, procede d'obtention et medicaments antirhumatismaux les contenant |
DE3428524A1 (de) * | 1984-08-02 | 1986-02-13 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
US4687768A (en) * | 1984-12-21 | 1987-08-18 | The Procter & Gamble Company | Certain hexahydroindan-2,2-diphosphonic acids useful in treating diseases associated with abnormal calcium and phosphate metabolism |
US5104863A (en) * | 1984-12-21 | 1992-04-14 | The Procter & Gamble Company | Certain bicycloalkane and azabicycloalkane-1,1-diphosphonic acid derivatives useful for treating diseases associated with abnormal calcium and phosphate metabolism |
IL77243A (en) * | 1984-12-21 | 1996-11-14 | Procter & Gamble | Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds |
US4902679A (en) * | 1985-12-13 | 1990-02-20 | Norwich Eaton Pharmaceuticals, Inc. | Methods of treating diseases with certain geminal diphosphonates |
DE3776880D1 (de) * | 1986-11-21 | 1992-04-02 | Ciba Geigy Ag | Neue substituierte alkandiphosphonsaeuren. |
DE3640938A1 (de) * | 1986-11-29 | 1988-06-01 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindung enthaltende arzneimittel |
US4868164A (en) * | 1986-12-19 | 1989-09-19 | Norwich Eaton Pharmaceuticals, Inc. | Octahydro-pyridine diphosphonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
US5071840A (en) * | 1986-12-19 | 1991-12-10 | Norwich Eaton Pharmaceuticals, Inc. | Certain heterocyclic substituted diphosphonate compounds pharmaceutical compositions, and methods of treating abnormal calcium and phosphate metabolism |
IL86951A (en) * | 1987-07-06 | 1996-07-23 | Procter & Gamble Pharma | Methylene phosphonoalkylphosphinates and pharmaceutical preparations containing them |
ATE90353T1 (de) * | 1987-12-11 | 1993-06-15 | Ciba Geigy Ag | Araliphatylaminoalkandiphosphonsaeuren. |
US4933472A (en) * | 1988-04-08 | 1990-06-12 | Yamanouchi Pharmaceutical Co., Ltd. | Substituted aminomethylenebis(phosphonic acid) derivatives |
TW198039B (zh) * | 1988-11-28 | 1993-01-11 | Ciba Geigy Ag | |
AU628158B2 (en) * | 1989-04-03 | 1992-09-10 | Upjohn Company, The | Geminal bisphosphonic acids and derivatives as anti-arthritic agents |
DE4011777A1 (de) * | 1989-04-14 | 1990-10-18 | Ciba Geigy Ag | N-trisubstituierte aminoalkandiphosphonsaeuren |
US4922007A (en) * | 1989-06-09 | 1990-05-01 | Merck & Co., Inc. | Process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid or salts thereof |
EP0416689B1 (en) * | 1989-09-06 | 1995-11-29 | Merck & Co. Inc. | Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors |
AU7165791A (en) * | 1990-01-12 | 1991-08-05 | Rhone-Poulenc Rorer International (Holdings) Inc. | 1-azetidyl and 1-hexamethylenimine alkyl or aryl bisphosphonic acids and their use as pharmacological agents |
ATE165603T1 (de) * | 1991-09-05 | 1998-05-15 | Toray Industries | Methandiphosphonsäurederivat, herstellung davon und verwendung davon als arzneimittel |
-
1993
- 1993-05-26 PL PL93306139A patent/PL175475B1/pl unknown
- 1993-05-26 EP EP93914151A patent/EP0642519B1/en not_active Expired - Lifetime
- 1993-05-26 HU HU9403408A patent/HUT69699A/hu unknown
- 1993-05-26 CA CA002136818A patent/CA2136818C/en not_active Expired - Fee Related
- 1993-05-26 CA CA002188066A patent/CA2188066C/en not_active Expired - Fee Related
- 1993-05-26 WO PCT/US1993/004977 patent/WO1993024496A1/en not_active Application Discontinuation
- 1993-05-26 RU RU94046117A patent/RU2136691C1/ru active
- 1993-05-26 JP JP6500722A patent/JPH07507315A/ja active Pending
- 1993-05-26 DK DK93914151T patent/DK0642519T3/da active
- 1993-05-26 KR KR1019940704307A patent/KR950701929A/ko active IP Right Grant
- 1993-05-26 SK SK1444-94A patent/SK144494A3/sk unknown
- 1993-05-26 CZ CZ942967A patent/CZ296794A3/cs unknown
- 1993-05-26 SG SG1996003361A patent/SG50518A1/en unknown
- 1993-05-26 DE DE69329199T patent/DE69329199D1/de not_active Expired - Lifetime
- 1993-05-26 NZ NZ253524A patent/NZ253524A/en unknown
- 1993-05-26 AT AT93914151T patent/ATE195317T1/de not_active IP Right Cessation
- 1993-05-26 AU AU43917/93A patent/AU669372B2/en not_active Ceased
- 1993-05-28 IL IL10583493A patent/IL105834A/en not_active IP Right Cessation
- 1993-05-28 MY MYPI93001056A patent/MY109736A/en unknown
- 1993-05-28 ZA ZA933759A patent/ZA933759B/xx unknown
- 1993-05-29 CN CN93108419A patent/CN1061049C/zh not_active Expired - Fee Related
- 1993-05-31 MX MX9303251A patent/MX9303251A/es not_active IP Right Cessation
-
1994
- 1994-09-07 US US08/301,514 patent/US5824661A/en not_active Expired - Fee Related
- 1994-11-24 NO NO944499A patent/NO305960B1/no not_active IP Right Cessation
- 1994-11-28 FI FI945593A patent/FI945593A/fi unknown
-
1996
- 1996-11-19 IL IL11964896A patent/IL119648A0/xx unknown
-
1998
- 1998-12-21 HK HK98114257A patent/HK1014002A1/xx not_active IP Right Cessation
-
1999
- 1999-12-23 CN CN99127416A patent/CN1288008A/zh active Pending
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