FI75830B - Foerfarande foer framstaellning av terapeutiskt anvaendbara metylendifosfonsyraderivat. - Google Patents

Foerfarande foer framstaellning av terapeutiskt anvaendbara metylendifosfonsyraderivat. Download PDF

Info

Publication number
FI75830B
FI75830B FI832758A FI832758A FI75830B FI 75830 B FI75830 B FI 75830B FI 832758 A FI832758 A FI 832758A FI 832758 A FI832758 A FI 832758A FI 75830 B FI75830 B FI 75830B
Authority
FI
Finland
Prior art keywords
group
acid
atom
ester
formula
Prior art date
Application number
FI832758A
Other languages
English (en)
Finnish (fi)
Other versions
FI75830C (sv
FI832758A0 (fi
FI832758A (fi
Inventor
Georges Garcia
Xavier Emonds-Alt
Jean-Claude Breliere
Original Assignee
Sanofi Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sanofi Sa filed Critical Sanofi Sa
Publication of FI832758A0 publication Critical patent/FI832758A0/fi
Publication of FI832758A publication Critical patent/FI832758A/fi
Application granted granted Critical
Publication of FI75830B publication Critical patent/FI75830B/fi
Publication of FI75830C publication Critical patent/FI75830C/sv

Links

Classifications

    • 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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
    • 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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
    • C07F9/6539—Five-membered rings
    • C07F9/6541—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
    • 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]
    • 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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
    • C07F9/3804—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se) not used, see subgroups
    • C07F9/3839—Polyphosphonic acids
    • C07F9/3865—Polyphosphonic acids containing sulfur substituents
    • 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 System
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids RP(=O)(OH)2; Thiophosphonic acids, i.e. RP(=X)(XH)2 (X = S, Se)
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4025—Esters of poly(thio)phosphonic acids
    • C07F9/4043—Esters of poly(thio)phosphonic acids containing sulfur substituents
    • 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 System
    • 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
    • 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 System
    • 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
    • C07F9/65068—Five-membered rings having the nitrogen atoms in positions 1 and 3 condensed with carbocyclic rings or carbocyclic ring 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 System
    • 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
    • C07F9/6509—Six-membered rings
    • C07F9/6512—Six-membered rings having the nitrogen atoms in positions 1 and 3
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Claims (6)

1. Förfarande för framställning av terapeutiskt använd-bara metylendifosfonsyror med formeln (I) 5 R0 R, O ^__ O 3 O ^ OR, 1 »i i n — 1 -C -P CT Rl°^^ (CH2)n ^0Rl (I) S
10 R R2 väri R^ är en väteatom eller en rakkedjad eller förgrenad alkyl-grupp med 1-4 kolatomer;
15 R2 är - en väteatom; - en alkylgrupp, vilken kan vara substituerad med en hydr-oxi-, tiol- eller en fenylgrupp eller en eller flera halo- /Zl 20 genatomer, en alkoxikarbonylgrupp eller gruppen Z2 väri Z^ och Z2 oberoende av varandra betecknar en väteatom eller en lägre alkylgrupp; - en fenylgrupp, vilken kan vara substituerad med en eller 25 flera halogenatomer, eller en eller flera nitro-, lägre alkyl-, lägre alkoxi- eller trifluormetylgrupper eller en NH2~, COOH- eller COO-alkylgrupp; X . Z, " / 1 - gruppen -C-N , van X ar en syre- eller svavelatom 30 z2 och Zj och Z2 har ovan angiven betydelse; - en 5 eller 6-ledad heterocyklisk grupp, vilken kan inne-hälla 1 eller 2 kväve- eller svavelatomer och vilken kan vara substituerad med en lägre alkylgrupp; 35. en 5-ledad heterocyklisk grupp, vilken kondenserats med en bensenring och vilken har formeln II 39 7 5 8 3 0 <xr 5 väri X är en syreatom, en NH-grupp eller en svavelatom och är en väte- eller halogenatom, företrädesvis en kloratom; - R^ är en väteatom eller en hydroxigrupp; - n är ett heltal 0-10, under förbehäll att 10. n icke är O dä R3=OH; - R2 icke är en metyl- eller pyridylgrupp da R^=R3=H och n=0; - R_ icke är gruppen
2 OP » 0- Q väri Q är en halogenatom eller en nitro- eller trifluorme-tylengrupp, P är en metyl- eller etylgrupp dä är en metyl- eller etylgrupp, R3=H och n=0;
20. R2 Mr icke en fenylgrupp dä R^ är en etylgrupp, R3=H och n=0; - R2 är icke en alkyl- eller osubstituerad fenylgrupp, dä R^= OH och n=l; 25 samt salter av nämnda derivat, väri R=H, med oorganiska och organiska baser, kännetecknat därav, att a) en lägre alkylester av metylendifosfonsyra omvand-las tili motsvarande natrium- eller kaliumderivat, vilket omsätts med en förening R2-S-S-R2# R2SC1 eller
30 Hai-(CH2>n~S-R2, väri R2 och n har ovan angiven betydelse och Hai är en halogenatom för erhällande av en förening med formeln I, väri är en väteatom, eller b) en lägre alkylester av metylendifosfonsyra omsätts med en allylhalogenid och den sälunda erhällna föreningen 35 omsätts med en tiol med formeln SHR2, väri R2 har ovan angiven betydelse, för erhällande av en förening med formeln I, väri n är 3, eller
FI832758A 1982-07-29 1983-07-29 Förfarande för framställning av terapeutiskt användbara metylendifosfo nsyraderivat FI75830C (sv)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR8213250 1982-07-29
FR8213250A FR2531088B1 (fr) 1982-07-29 1982-07-29 Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation

Publications (4)

Publication Number Publication Date
FI832758A0 FI832758A0 (fi) 1983-07-29
FI832758A FI832758A (fi) 1984-01-30
FI75830B true FI75830B (fi) 1988-04-29
FI75830C FI75830C (sv) 1988-08-08

Family

ID=9276447

Family Applications (1)

Application Number Title Priority Date Filing Date
FI832758A FI75830C (sv) 1982-07-29 1983-07-29 Förfarande för framställning av terapeutiskt användbara metylendifosfo nsyraderivat

Country Status (35)

Country Link
US (2) US4746654A (sv)
EP (1) EP0100718B1 (sv)
JP (1) JPS5942395A (sv)
KR (1) KR910000726B1 (sv)
AR (2) AR242393A1 (sv)
AT (1) ATE30235T1 (sv)
AU (1) AU566880B2 (sv)
CA (1) CA1267650A (sv)
CS (1) CS252463B2 (sv)
CZ (1) CZ419191A3 (sv)
DD (1) DD213670A5 (sv)
DE (1) DE3374062D1 (sv)
DK (1) DK170342B1 (sv)
DZ (1) DZ562A1 (sv)
EG (1) EG15968A (sv)
ES (1) ES8403923A1 (sv)
FI (1) FI75830C (sv)
FR (1) FR2531088B1 (sv)
GR (1) GR79597B (sv)
HU (1) HU190454B (sv)
IE (1) IE56343B1 (sv)
IL (1) IL69347A (sv)
LU (1) LU88723I2 (sv)
MA (1) MA19858A1 (sv)
NL (1) NL960007I2 (sv)
NO (2) NO164712C (sv)
NZ (1) NZ205061A (sv)
OA (1) OA07507A (sv)
PH (1) PH22082A (sv)
PL (2) PL141316B1 (sv)
PT (1) PT77122B (sv)
SG (1) SG18588G (sv)
SU (2) SU1333240A3 (sv)
YU (1) YU45143B (sv)
ZA (1) ZA835578B (sv)

Families Citing this family (104)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2558837B1 (fr) * 1984-01-26 1986-06-27 Sanofi Sa Derives de l'acide methylenediphosphonique, procede d'obtention et medicaments antirhumatismaux les contenant
IL77243A (en) * 1984-12-21 1996-11-14 Procter & Gamble Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds
PH27078A (en) * 1984-12-21 1993-02-01 Procter & Gamble Pharmaceutical compositions containing geminal diphosphonates
US5641762A (en) * 1985-05-02 1997-06-24 Research Corporation Technologies, Inc. Bone targeted inhibitors of carbonic anhydrase
US4761406A (en) * 1985-06-06 1988-08-02 The Procter & Gamble Company Regimen for treating osteoporosis
US4902679A (en) * 1985-12-13 1990-02-20 Norwich Eaton Pharmaceuticals, Inc. Methods of treating diseases with certain geminal diphosphonates
ES2039237T3 (es) * 1986-04-24 1993-09-16 Fujisawa Pharmaceutical Co., Ltd. Procedimiento para preparar nuevos compuestos de acido difosfonico.
IL84731A0 (en) * 1986-12-19 1988-05-31 Norwich Eaton Pharma Heterocycle-substituted diphosphonic acids and salts and esters and pharmaceutical compositions containing them
KR880011136A (ko) * 1987-03-11 1988-10-26 모리오까 시게오 아졸- 아미노메틸렌 비스포스폰산 유도체
IL86951A (en) * 1987-07-06 1996-07-23 Procter & Gamble Pharma Methylene phosphonoalkylphosphinates and pharmaceutical preparations containing them
DE3805663A1 (de) * 1988-02-24 1989-09-07 Henkel Kgaa Oxaalkanpolyphosphonsaeuren, ihre verwendung als thresholder sowie diese verbindungen enthaltende, komplexierend wirkende zusammensetzungen
CH675422A5 (sv) * 1988-03-31 1990-09-28 Symphar Sa
FR2629716B1 (fr) * 1988-04-07 1991-07-19 Sanofi Sa Composition pharmaceutique pour administration orale a base d'un derive d'acide diphosphonique
DE3822650A1 (de) * 1988-07-05 1990-02-01 Boehringer Mannheim Gmbh Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel
EP0449942B1 (en) * 1988-11-01 1996-04-17 Arch Development Corporation Method for separating metal ions using phosphonic acids as complexants
US5154843A (en) * 1989-02-08 1992-10-13 The Lubrizol Corporation Hydroxyalkane phosphonic acids and derivatives thereof and lubricants containing the same
PH26923A (en) * 1989-03-08 1992-12-03 Ciba Geigy N-substituted amino alkanediphosphonic acids
US5220021A (en) * 1989-04-03 1993-06-15 The Upjohn Company Geminal bisphosphonic acids and derivatives as anti-arthritic agents
JPH0377894A (ja) * 1989-08-18 1991-04-03 Toray Ind Inc メチレンジホスホン酸化合物
EP0416689B1 (en) * 1989-09-06 1995-11-29 Merck & Co. Inc. Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors
DE59107135D1 (de) * 1990-01-18 1996-02-08 Ciba Geigy Ag Phoshponsäure- und Thionophosphonsäure-Derivate
IE912115A1 (en) * 1990-06-25 1992-01-01 Takeda Chemical Industries Ltd Bisphosphonic acid derivatives, their production and use
AU8495091A (en) * 1990-08-21 1992-03-17 Upjohn Company, The Bisphosphonic acid derivatives as anti-arthritic agents
EP0561948B1 (en) * 1990-12-07 1995-04-05 The Upjohn Company Phosphonic acid derivatives useful as antiinflammatory agents
ATE133677T1 (de) * 1990-12-19 1996-02-15 Takeda Chemical Industries Ltd Bisphosphonsäurederivate, ihre produktion und ihre verwendung
IT1244698B (it) * 1991-02-01 1994-08-08 Gentili Ist Spa Acidi aril-o arilalchil-acil ammino-alchil-idrossidifosfonici, procedimento per la loro preparazione e loro uso in terapia osteo-articolare e dei tessuti connettori in generale
EP0590009B1 (en) * 1991-06-19 1998-03-18 PHARMACIA &amp; UPJOHN COMPANY Dialkyl (dialkoxyphosphinyl)methyl phosphates as anti-inflammatory agents
EP0521622B1 (en) * 1991-07-03 1997-08-13 PHARMACIA &amp; UPJOHN COMPANY Pyrazolopyrimidine and pyrimidinyl bisphosphonic esters as anti-inflammatories
WO1993005052A1 (fr) * 1991-09-05 1993-03-18 Toray Industries, Inc. Derive d'acide methanediphosphonique, sa production et son utilisation comme remede
JPH06172372A (ja) * 1991-11-06 1994-06-21 Takeda Chem Ind Ltd スクアレン合成酵素阻害剤およびその用途
EP0541037A3 (en) * 1991-11-06 1997-02-26 Takeda Chemical Industries Ltd Squalene synthetase inhibitory composition and use thereof
US5763611A (en) * 1992-05-29 1998-06-09 The Procter & Gamble Company Thio-substituted cyclic phosphonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism
CA2188066C (en) * 1992-05-29 2000-12-05 Susan Mary Kaas Thio-substituted phosphonate compounds
RU2126414C1 (ru) * 1992-05-29 1999-02-20 Дзе Проктер энд Гэмбл Фармасьютикалз, Инк. Содержащие четвертичный азот фосфонаты для лечения анормального кальциевого и фосфатного метаболизма, а также профилактики и лечения зубных налетов и зубных камней, фармацевтические композиции и способ лечения
US5391743A (en) * 1992-05-29 1995-02-21 Procter & Gamble Pharmaceuticals, Inc. Quaternary nitrogen-containing phosphonate compounds, pharmaceutical compositions, and methods of treating abnormal calcium and phosphate metabolism and methods of treating and preventing dental calculus and plaque
PL175046B1 (pl) * 1992-05-29 1998-10-30 Procter & Gamble Pharma Nowe tio-podstawione, zawierające azot heterocykliczne związki fosfonianowe
US5753634A (en) * 1992-05-29 1998-05-19 The Procter & Gamble Company Quaternary nitrogen containing phosphonate compounds, pharmaceutical compostions, and methods for treating abnormal calcium and phosphate metabolism
HUT72437A (en) * 1992-06-30 1996-04-29 Procter & Gamble Pharma Compositions for the treatment of arthritis containing phosphonates and nsaids
ES2155446T3 (es) * 1992-07-10 2001-05-16 Toray Industries Derivado de metanodifosfonato, su produccion y su uso farmaceutico.
GB9215433D0 (en) * 1992-07-21 1992-09-02 Cmb Foodcan Plc Apparatus for stripping a drawn article from a punch
FR2694558B1 (fr) * 1992-08-05 1994-10-28 Sanofi Elf Monohydrate du sel disodique de l'acide 4-chlorophénylthiométhylène bisphosphonique, sa préparation, les compositions pharmaceutiques en contenant.
JPH07509712A (ja) * 1992-08-07 1995-10-26 ジ・アップジョン・カンパニー 抗炎症剤としてのホスホノ酢酸エステルおよびホスホノ酢酸
WO1994009017A1 (en) * 1992-10-09 1994-04-28 The Upjohn Company Pyrimidine bisphosphonate esters and (alkoxymethylphosphinyl)alkyl phosphonic acids as anti-inflammatories
JPH06135976A (ja) * 1992-10-30 1994-05-17 Toray Ind Inc メタンジホスホン酸誘導体、その製造方法およびその医薬用途
US5332728A (en) * 1992-11-23 1994-07-26 Bristol-Myers Squibb Company Method for treating a fungal infection
AU670337B2 (en) 1992-11-30 1996-07-11 Novartis Ag Use of certain methanebisphosphonic acid derivatives in fracture healing
US6399592B1 (en) 1992-12-23 2002-06-04 Merck & Co., Inc. Bishphosphonate/estrogen synergistic therapy for treating and preventing bone loss
AU674059B2 (en) * 1993-02-25 1996-12-05 Toray Industries, Inc. Process for producing methanediphosphonate compound
FR2703590B1 (fr) * 1993-04-05 1995-06-30 Sanofi Elf Utilisation de derives d'acide bisphosphonique pour la preparation de medicaments destines a favoriser la reparation osseuse .
US5854227A (en) * 1994-03-04 1998-12-29 Hartmann; John F. Therapeutic derivatives of diphosphonates
US20010007863A1 (en) * 1998-06-18 2001-07-12 Merck & Co., Inc. Wet granulation formulation for bisphosphonic acids
AU699641B2 (en) * 1994-08-24 1998-12-10 Toray Industries, Inc. Process for production of methanediphosphonic acid compound
AU5973496A (en) 1995-06-06 1996-12-24 Merck & Co., Inc. Bisphosphonate cement composition to prevent aseptic loosening of orthopedic implant devices
US5880111A (en) * 1995-06-07 1999-03-09 Farcasiu; Dan Therapeutic derivations of diphosphonates
DE69634487T2 (de) * 1995-09-29 2006-01-05 Novartis Ag Verfahren zur behandlung navikularer krankheiten bei pferden
US6333424B1 (en) * 1996-10-09 2001-12-25 Eliza Nor Biopharmaceuticals, Inc. Therapeutic derivatives of diphosphonates
US8586781B2 (en) 1998-04-02 2013-11-19 Mbc Pharma, Inc. Bone targeted therapeutics and methods of making and using the same
NZ510308A (en) 1998-09-09 2003-06-30 Metabasis Therapeutics Inc Heteroaromatic alkylene substituted phosphonate derivatives useful as inhibitors of Fructose 1,6-bisphosphatase
FR2784031B1 (fr) * 1998-10-02 2002-02-01 Sanofi Elf Utilisation de derives de l'acide bisphosphonique pour la preparation d'un medicament destine au traitement des boiteries
EP1057488A4 (en) * 1998-12-25 2003-10-22 Toray Industries INTERLEUKIN-6 PRODUCTION INHIBITORS
DE60041876D1 (de) * 1999-07-23 2009-05-07 Philadelphia Children Hospital Polyurethanderivatzusammensetzungen und Verfahren zu ihrer Herstellung
AR021347A1 (es) 1999-10-20 2002-07-17 Cipla Ltd Una composicion farmaceutica que contiene acido(s) bisfosfoncio o sal(es) del mismo y un proceso de preparacion de la misma
EP1248790A1 (en) 1999-12-17 2002-10-16 Ariad Pharmaceuticals, Inc. Proton pump inhibitors
BR0017048A (pt) * 1999-12-22 2002-11-05 Metabasis Therapeutics Inc Pró-drogas de bisamidato fosfonato
US6677320B2 (en) 2000-01-20 2004-01-13 Hoffmann-La Roches Inc. Parenteral bisphosphonate composition with improved local tolerance
US7563774B2 (en) * 2000-06-29 2009-07-21 Metabasis Therapeutics, Inc. Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes
WO2002083150A1 (en) * 2001-04-10 2002-10-24 Mbc Research, Inc. Bisphosphonate conjugates and methods of making and using the same
US6558702B2 (en) * 2001-04-13 2003-05-06 Alkermes Controlled Therapeutics, Inc. Method of modifying the release profile of sustained release compositions
US20060269602A1 (en) * 2001-04-13 2006-11-30 Dasch James R Method of modifying the release profile of sustained release compositions
TWI315982B (en) * 2001-07-19 2009-10-21 Novartis Ag Combinations comprising epothilones and pharmaceutical uses thereof
PL371264A1 (en) * 2001-12-21 2005-06-13 The Procter & Gamble Company Method for the treatment of bone disorders
US20050070504A1 (en) * 2001-12-21 2005-03-31 The Procter & Gamble Co. Risedronate compositions and their methods of use
CA2472578A1 (en) * 2002-01-24 2003-07-31 Yissum Research Development Company Of The Hebrew University Of Jerusalem Anti-cancer combination and use thereof
US20030195171A1 (en) * 2002-04-05 2003-10-16 Daifotis Anastasia G. Method for inhibiting bone resorption with an alendronate and vitamin D formulation
NZ535705A (en) 2002-05-10 2007-08-31 Hoffmann La Roche Ibandronic acid for the treatment and prevention of osteoporosis
CA2487977A1 (en) * 2002-06-06 2003-12-18 Merck Frosst Canada & Co./Merck Frosst Canada & Cie 1,5-disubstituted imidazolidin-2-one derivatives for use as ep4 receptor agonists in the treatment of eye and bone diseases
AU2003276990A1 (en) * 2002-09-26 2004-04-19 The Children's Hospital Of Philadelphia Derivatized polyurethane compositions which exhibit enhanced stability in biological systems and methods of making the same
US20040138180A1 (en) * 2002-10-03 2004-07-15 Barr Laboratories, Inc. Bisphosphonate composition and process for the preparation thereof
DK1790347T3 (en) * 2002-12-20 2015-01-19 Hoffmann La Roche Ibandronate high-dose-formulation
US7408014B2 (en) * 2003-07-08 2008-08-05 The Children's Hospital Of Philadelphia Steroid lipid-modified polyurethane as an implantable biomaterial, the preparation and uses thereof
JP4553899B2 (ja) 2003-08-21 2010-09-29 メルク フロスト カナダ リミテツド カテプシンシステインプロテアーゼ阻害剤
JP2007505886A (ja) * 2003-09-19 2007-03-15 ファイザー・プロダクツ・インク ２−メチレン−１９−ノル−ビタミンｄ誘導体及びビスホスフォネートの組み合わせを含む医薬組成物及び方法
US20050261250A1 (en) * 2004-05-19 2005-11-24 Merck & Co., Inc., Compositions and methods for inhibiting bone resorption
ATE475412T1 (de) 2004-05-24 2010-08-15 Warner Chilcott Co Llc Enterische feste orale dosierform eines bisphosphonats mit einem chelate
UA87854C2 (en) 2004-06-07 2009-08-25 Мерк Энд Ко., Инк. N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
AU2005277479A1 (en) * 2004-08-18 2006-03-02 Metabasis Therapeutics, Inc. Novel thiazole inhibitors of fructose 1,6-bisphosphatase
US8697139B2 (en) 2004-09-21 2014-04-15 Frank M. Phillips Method of intervertebral disc treatment using articular chondrocyte cells
WO2007046842A2 (en) 2005-03-02 2007-04-26 Merck & Co., Inc. Composition for inhibition of cathepsin k
NZ561666A (en) * 2005-03-17 2010-05-28 Elan Pharma Int Ltd Nanoparticulate biphosphonate compositions
US7538163B2 (en) * 2005-03-24 2009-05-26 Medtronic, Inc. Modification of thermoplastic polymers
CN101945853B (zh) 2007-12-21 2014-08-20 配体药物公司 选择性雄激素受体调节剂(sarm)及其应用
EP2324041A4 (en) 2008-08-13 2012-06-13 Targanta Therapeutics Corp PHOSPHONIZED RIFAMYCINS AND ITS APPLICATION FOR THE PREVENTION AND TREATMENT OF BONE AND JOINT INFECTIONS
EP2440250A1 (en) 2009-06-11 2012-04-18 Yissum Research Development Company of the Hebrew University of Jerusalem, Ltd. Targeted liposomes comprising n-containing bisphosphonates and uses thereof
FR2954320B1 (fr) 2009-12-17 2012-06-15 Cll Pharma Composition pharmaceutique orale suprabiodisponible contenant un acide biphosphonique ou un de ses sels
EP2675440B1 (en) 2011-02-14 2020-03-25 Merck Sharp & Dohme Corp. Cathepsin cysteine protease inhibitors
RS61235B1 (sr) 2011-07-13 2021-01-29 Yissum Res Dev Co Of Hebrew Univ Jerusalem Ltd Lipozomi koji ko-inkapsuliraju bisfosfonat i amfipatički agens
AU2012290089B2 (en) 2011-08-01 2016-09-29 Mbc Pharma, Inc. Vitamin B6 derivatives of nucleotides, acyclonucleotides and acyclonucleoside phosphonates
GB201200868D0 (en) 2012-01-19 2012-02-29 Depuy Int Ltd Bone filler composition
WO2015054089A1 (en) 2013-10-08 2015-04-16 Merck Sharp & Dohme Corp. Cathepsin cysteine protease inhibitors
WO2015051479A1 (en) 2013-10-08 2015-04-16 Merck Sharp & Dohme Corp. Cathepsin cysteine protease inhibitors
WO2015120580A1 (en) 2014-02-11 2015-08-20 Merck Sharp & Dohme Corp. Cathepsin cysteine protease inhibitors
PL407922A1 (pl) 2014-04-16 2015-10-26 Wrocławskie Centrum Badań Eit + Spółka Z Ograniczoną Odpowiedzialnością Nowe bisfosfoniany i ich zastosowanie
CA2950390C (en) 2014-05-30 2020-09-22 Pfizer Inc. Carbonitrile derivatives as selective androgen receptor modulators
WO2023275715A1 (en) 2021-06-30 2023-01-05 Pfizer Inc. Metabolites of selective androgen receptor modulators

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1302557B (sv) * 1963-04-09 1971-08-26
US3654151A (en) * 1970-04-13 1972-04-04 Monsanto Co Deflocculation of solid materials in aqueous medium
US3705191A (en) * 1970-04-13 1972-12-05 Monsanto Co Substituted ethane diphosphonic acids and salts and esters thereof
US3957858A (en) * 1970-04-13 1976-05-18 Monsanto Company Substituted ethane diphosphonic acids and salts and esters thereof
US3683080A (en) * 1970-08-28 1972-08-08 Procter & Gamble Compositions for inhibiting anomalous deposition and mobilization of calcium phosphate in animal tissue
US4171373A (en) * 1974-01-07 1979-10-16 William H. Rorer, Inc. Ethynylbenzene compounds and derivatives thereof to treat pain, fever and inflammation
US4071584A (en) * 1977-01-03 1978-01-31 Monsanto Company Hydroxyphenylthiophosphoranylidene organophosphorus compounds
US4264582A (en) * 1978-07-31 1981-04-28 The Procter & Gamble Company Isobutylphenylacetate anti-inflammatory composition
JPS5598193A (en) * 1979-01-22 1980-07-25 Nissan Chem Ind Ltd Methylenediphosphonic acid derivative and herbicide comprising it as active constituent
GB2043072B (en) * 1979-02-13 1983-11-23 Symphar Sa Diphosphonate compounds
US4330530A (en) * 1980-12-22 1982-05-18 The Procter & Gamble Company Anti-arthritic compositions and method using gold salts and organophosphonates
EP0085321B1 (de) * 1982-01-27 1986-08-27 Schering Aktiengesellschaft Diphosphonsäure-Derivate und diese enthaltende pharmazeutische Präparate

Also Published As

Publication number Publication date
EG15968A (en) 1989-01-30
JPS5942395A (ja) 1984-03-08
IE831716L (en) 1984-01-29
FI75830C (sv) 1988-08-08
ZA835578B (en) 1984-04-25
DD213670A5 (de) 1984-09-19
DK336783A (da) 1984-01-30
GR79597B (sv) 1984-10-31
ATE30235T1 (de) 1987-10-15
SU1367859A3 (ru) 1988-01-15
FR2531088B1 (fr) 1987-08-28
PL142022B1 (en) 1987-09-30
KR840005459A (ko) 1984-11-12
PT77122A (fr) 1983-08-01
JPH0429676B2 (sv) 1992-05-19
NZ205061A (en) 1987-08-31
NO832701L (no) 1984-01-30
SU1333240A3 (ru) 1987-08-23
PL141316B1 (en) 1987-07-31
CA1267650A (en) 1990-04-10
CZ419191A3 (en) 1993-10-13
MA19858A1 (fr) 1984-04-01
KR910000726B1 (ko) 1991-01-31
CS568883A2 (en) 1987-01-15
NO164712C (no) 1990-11-07
IL69347A (en) 1987-02-27
PH22082A (en) 1988-05-20
CS252463B2 (en) 1987-09-17
HU190454B (en) 1986-09-29
DK336783D0 (da) 1983-07-22
FI832758A0 (fi) 1983-07-29
OA07507A (fr) 1985-03-31
FR2531088A1 (fr) 1984-02-03
NO1998011I1 (no) 1998-03-06
AR242394A1 (es) 1993-03-31
EP0100718A1 (fr) 1984-02-15
US4876248A (en) 1989-10-24
IE56343B1 (en) 1991-07-03
ES524495A0 (es) 1984-04-16
DE3374062D1 (en) 1987-11-19
DK170342B1 (da) 1995-08-07
AU566880B2 (en) 1987-11-05
EP0100718B1 (fr) 1987-10-14
ES8403923A1 (es) 1984-04-16
YU160083A (en) 1986-08-31
SG18588G (en) 1988-09-30
AR242393A1 (es) 1993-03-31
NO164712B (no) 1990-07-30
NL960007I1 (nl) 1996-09-02
IL69347A0 (en) 1983-11-30
PT77122B (fr) 1986-01-24
FI832758A (fi) 1984-01-30
US4746654A (en) 1988-05-24
YU45143B (en) 1992-03-10
AU1732483A (en) 1984-02-02
LU88723I2 (fr) 1996-08-23
DZ562A1 (fr) 2004-09-13
PL243229A1 (en) 1984-07-16
NL960007I2 (nl) 1997-03-03

Similar Documents

Publication Publication Date Title
FI75830B (fi) Foerfarande foer framstaellning av terapeutiskt anvaendbara metylendifosfonsyraderivat.
EP0033195B1 (en) Pyrimidine-2-sulphides and their s-oxides for use in medicine, pharmaceutical compositions containing them, processes for their preparation and such compounds when novel per se
CH661437A5 (it) Bifosfonati farmacologicamente attivi, procedimento per la loro preparazione e relative composizioni farmaceutiche.
AU653428B2 (en) Pyrazolopyrimidine and pyrimidinyl bisphosphonic esters as anti-inflammatories
SK279601B6 (sk) Deriváty kyseliny metylénbisfosfónovej, spôsob ich
AU657018B2 (en) Guanidinoalkyl-1, 1-bisphosphonic acid derivatives, process for their preparation and their use
HUT56376A (en) Process for producing methylenediphosphonic acid derivatives and inflammation inhibitiors comprising same as active ingredient
US4876247A (en) Methlenediphosphonic acid derivatives, and antirheumatic pharmaceutical composition in which they are present and methods of using same
HU199151B (en) Process for producing bis-phosphonic acid derivatives
FI66369C (fi) Foerfarande foer framstaellning av terapeutiskt anvaendbara p-2-tenoyl)fenylalkansyror och derivat av dessa
US4006204A (en) Phosphoric acid diesters
FI75560B (fi) Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 4-(hydroxialkyltiometyl)pyridiner.
US4521619A (en) Therapeutically useful sulphur-containing benzylidene derivatives
FI56966B (fi) Foerfarande foer framstaellning av 2-(2-pyridyl)-omega-fenylalkylaminer med antisekretorisk aktivitet
US4489069A (en) Substituted thiazolidinyl esters of mineral acids
NO169441B (no) Fremgangsmaate til fremstilling av 7-oksomitosanderivater
CA2058012A1 (en) Bisphosphonic acid derivatives, their production and use
PL158165B1 (pl) Sposób wytwarzania acylowych pochodnych hydroksypirymidyn PL PL PL PL
NO841486L (no) Fremgangsmaate for fremstilling av hydroksylerte difenylazometin-derivater
CZ282524B6 (cs) Deriváty kyseliny methylendifosfonové, způsob jejich přípravy a protizánětový a protirevmatický farmaceutický prostředek
JPS59205382A (ja) アミノ２硫化物
JPS6050191B2 (ja) ５↓−フルオロウラシル誘導体
CS247198B2 (cs) Způsob výroby derivátů kyseliny methylendifosfonové
MXPA06007401A (es) Proceso para la preparacion de derivados de piridina
JPH0469373A (ja) アルカンスルホンアニリド誘導体およびそれらを含有する医薬組成物

Legal Events

Date Code Title Description
SPCG Supplementary protection certificate granted

Spc suppl protection certif: L65

Extension date: 20080729

ND Supplementary protection certificate (spc) granted
MA Patent expired

Owner name: SANOFI-SYNTHELABO

PC Transfer of assignment of patent

Owner name: SANOFI-AVENTIS