DK167808B1 - Methylen-bisphosphonsyrederivat, fremgangsmaade til fremstilling heraf samt farmaceutisk sammensaetning indeholdende disse derivater - Google Patents

Methylen-bisphosphonsyrederivat, fremgangsmaade til fremstilling heraf samt farmaceutisk sammensaetning indeholdende disse derivater Download PDF

Info

Publication number: DK167808B1
Authority: DK; Denmark
Prior art keywords: methyl; formula; compound; alkyl; carbon atoms
Prior art date: 1984-07-31

Application number

DK147386A

Other languages

Danish (da)

English (en)

Other versions

DK147386D0 (da

DK147386A (da

Inventor

Ernst Torndal Binderup

Original Assignee

Leo Pharm Prod Ltd

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.)

1984-07-31

Filing date

1986-04-01

Publication date

1993-12-20

1986-04-01 Application filed by Leo Pharm Prod Ltd filed Critical Leo Pharm Prod Ltd

1986-04-01 Publication of DK147386D0 publication Critical patent/DK147386D0/da

1986-04-01 Publication of DK147386A publication Critical patent/DK147386A/da

1993-12-20 Application granted granted Critical

1993-12-20 Publication of DK167808B1 publication Critical patent/DK167808B1/da

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MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical class OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 title claims description 5
238000004519 manufacturing process Methods 0.000 title claims 2
239000008194 pharmaceutical composition Substances 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims description 67
-1 3 -phthalidyl Chemical group 0.000 claims description 56
239000000203 mixture Substances 0.000 claims description 34
239000002253 acid Substances 0.000 claims description 20
238000000034 method Methods 0.000 claims description 20
125000004432 carbon atom Chemical group C* 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 15
150000002148 esters Chemical class 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 10
239000007788 liquid Substances 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
239000001257 hydrogen Substances 0.000 claims description 7
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 6
238000007257 deesterification reaction Methods 0.000 claims description 6
239000012312 sodium hydride Substances 0.000 claims description 6
229910000104 sodium hydride Inorganic materials 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
239000007787 solid Substances 0.000 claims description 5
125000005848 1-(alkoxycarbonyloxy)ethyl group Chemical group 0.000 claims description 4
239000002841 Lewis acid Substances 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 4
150000007517 lewis acids Chemical class 0.000 claims description 4
231100000252 nontoxic Toxicity 0.000 claims description 4
230000003000 nontoxic effect Effects 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 claims description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 3
241001460678 Napo <wasp> Species 0.000 claims description 3
PJRBPPUAKJRQAP-UHFFFAOYSA-N [phenoxy(phosphono)methyl]phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)OC1=CC=CC=C1 PJRBPPUAKJRQAP-UHFFFAOYSA-N 0.000 claims description 3
125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 3
125000005042 acyloxymethyl group Chemical group 0.000 claims description 3
125000005206 alkoxycarbonyloxymethyl group Chemical group 0.000 claims description 3
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 3
125000005846 1-(alkanoyloxy)ethyl group Chemical group 0.000 claims description 2
102000055006 Calcitonin Human genes 0.000 claims description 2
108060001064 Calcitonin Proteins 0.000 claims description 2
FCBNUTOTWPYDNT-UHFFFAOYSA-N [(4-hydroxyphenoxy)-phosphonomethyl]phosphonic acid Chemical group OC1=CC=C(OC(P(O)(O)=O)P(O)(O)=O)C=C1 FCBNUTOTWPYDNT-UHFFFAOYSA-N 0.000 claims description 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
229910052783 alkali metal Inorganic materials 0.000 claims description 2
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
150000003973 alkyl amines Chemical class 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
150000003939 benzylamines Chemical class 0.000 claims description 2
BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 claims description 2
229960004015 calcitonin Drugs 0.000 claims description 2
239000000262 estrogen Substances 0.000 claims description 2
229940011871 estrogen Drugs 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical group 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims description 2
CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 claims description 2
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
229960003171 plicamycin Drugs 0.000 claims description 2
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 2
229960004919 procaine Drugs 0.000 claims description 2
239000011775 sodium fluoride Substances 0.000 claims description 2
235000013024 sodium fluoride Nutrition 0.000 claims description 2
229960000414 sodium fluoride Drugs 0.000 claims description 2
125000003944 tolyl group Chemical group 0.000 claims description 2
125000005847 1-methyl-1-(alkanoyloxy)-ethyl group Chemical group 0.000 claims 1
MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 claims 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
229940122361 Bisphosphonate Drugs 0.000 description 9
208000006386 Bone Resorption Diseases 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
238000009835 boiling Methods 0.000 description 9
230000024279 bone resorption Effects 0.000 description 9
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 8
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 7
239000011575 calcium Substances 0.000 description 7
229910052791 calcium Inorganic materials 0.000 description 7
238000009472 formulation Methods 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
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238000001704 evaporation Methods 0.000 description 6
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239000000725 suspension Substances 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
239000012230 colorless oil Substances 0.000 description 5
230000008021 deposition Effects 0.000 description 5
HKYGSMOFSFOEIP-UHFFFAOYSA-N dichloro(dichloromethoxy)methane Chemical class ClC(Cl)OC(Cl)Cl HKYGSMOFSFOEIP-UHFFFAOYSA-N 0.000 description 5
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229910052708 sodium Inorganic materials 0.000 description 5
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
230000037396 body weight Effects 0.000 description 4
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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XQMDCFILHWVIPX-UHFFFAOYSA-N bis(diethoxyphosphoryl)methoxybenzene Chemical compound CCOP(=O)(OCC)C(P(=O)(OCC)OCC)OC1=CC=CC=C1 XQMDCFILHWVIPX-UHFFFAOYSA-N 0.000 description 3
150000004663 bisphosphonates Chemical class 0.000 description 3
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CVLVBAUTUFWUGL-UHFFFAOYSA-N 1,1-bis(diethoxyphosphoryl)propoxybenzene Chemical compound CCOP(=O)(OCC)C(CC)(P(=O)(OCC)OCC)OC1=CC=CC=C1 CVLVBAUTUFWUGL-UHFFFAOYSA-N 0.000 description 2
IMSWEHIZVIKMQK-UHFFFAOYSA-N 1-(dichloromethoxy)-2-methoxyethane Chemical compound COCCOC(Cl)Cl IMSWEHIZVIKMQK-UHFFFAOYSA-N 0.000 description 2
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FCUKQLCAKJXJCH-UHFFFAOYSA-N 1-[bis(diethoxyphosphoryl)methoxy]butane Chemical compound CCCCOC(P(=O)(OCC)OCC)P(=O)(OCC)OCC FCUKQLCAKJXJCH-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
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ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 2
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KZJPVUDYAMEDRM-UHFFFAOYSA-M silver;2,2,2-trifluoroacetate Chemical compound [Ag+].[O-]C(=O)C(F)(F)F KZJPVUDYAMEDRM-UHFFFAOYSA-M 0.000 description 1
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FXJYEWSZMRTNSO-UHFFFAOYSA-J tetrasilver;dioxido-oxo-[phenoxy(phosphonato)methyl]-$l^{5}-phosphane Chemical compound [Ag+].[Ag+].[Ag+].[Ag+].[O-]P([O-])(=O)C(P([O-])([O-])=O)OC1=CC=CC=C1 FXJYEWSZMRTNSO-UHFFFAOYSA-J 0.000 description 1
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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 Table
- 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 ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or 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 Table
- 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 ; [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
- C07F9/3839—Polyphosphonic acids
- C07F9/386—Polyphosphonic acids containing hydroxy substituents in the hydrocarbon radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Nutrition Science (AREA)
Endocrinology (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

DK147386A 1984-07-31 1986-04-01 Methylen-bisphosphonsyrederivat, fremgangsmaade til fremstilling heraf samt farmaceutisk sammensaetning indeholdende disse derivater DK167808B1 (da)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB8419489		1984-07-31
GB848419489A GB8419489D0 (en)	1984-07-31	1984-07-31	Chemical compounds
DK8500071		1985-07-25
PCT/DK1985/000071 WO1986000902A1 (en)	1984-07-31	1985-07-25	Derivatives of methylene-bisphosphonic acid, process for their preparation and a pharmaceutical composition

Publications (3)

Publication Number	Publication Date
DK147386D0 DK147386D0 (da)	1986-04-01
DK147386A DK147386A (da)	1986-04-01
DK167808B1 true DK167808B1 (da)	1993-12-20

Family

ID=10564711

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK147386A DK167808B1 (da)	1984-07-31	1986-04-01	Methylen-bisphosphonsyrederivat, fremgangsmaade til fremstilling heraf samt farmaceutisk sammensaetning indeholdende disse derivater

Country Status (15)

Country	Link
US (1)	US4732998A (pt)
EP (1)	EP0191044B1 (pt)
JP (1)	JPH068303B2 (pt)
KR (1)	KR860700254A (pt)
AU (1)	AU583848B2 (pt)
DE (1)	DE3575929D1 (pt)
DK (1)	DK167808B1 (pt)
ES (1)	ES8707964A1 (pt)
FI (1)	FI861357A0 (pt)
GB (1)	GB8419489D0 (pt)
GR (1)	GR851865B (pt)
IE (1)	IE58614B1 (pt)
PT (1)	PT80886B (pt)
WO (1)	WO1986000902A1 (pt)
ZA (1)	ZA855264B (pt)

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DE3805663A1 (de) *	1988-02-24	1989-09-07	Henkel Kgaa	Oxaalkanpolyphosphonsaeuren, ihre verwendung als thresholder sowie diese verbindungen enthaltende, komplexierend wirkende zusammensetzungen
DE3822650A1 (de) *	1988-07-05	1990-02-01	Boehringer Mannheim Gmbh	Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel
US5266722A (en) *	1988-11-09	1993-11-30	W. R. Grace & Co.-Conn.	Polyether bis-phosphonic acid compounds
PH26923A (en) *	1989-03-08	1992-12-03	Ciba Geigy	N-substituted amino alkanediphosphonic acids
FI83421C (fi) *	1989-06-21	1991-07-10	Huhtamaeki Oy	Foerfarande foer framstaellning av farmakologiskt anvaendbara metylenbisfosfonsyraderivat.
US5227506A (en) *	1989-09-06	1993-07-13	Merck & Co., Inc.	Acyloxymethyl esters of bisphosphonic acids as bone resorption inhibitors
DE69023844T2 (de) *	1989-09-06	1996-06-20	Merck & Co Inc	Acyloxymethylester der Bisphonsäuren als Knochenresorptions-Inhibitoren.
GB9024345D0 (en) *	1990-11-08	1990-12-19	Merck Sharp & Dohme	Therapeutic agents
JP3141053B2 (ja) *	1991-12-26	2001-03-05	アベンティスファーマ株式会社	ビスホスホン酸誘導体
US5200554A (en) *	1992-01-21	1993-04-06	Nasman Jan Anders H	Bisphosphonic acid derivatives and their use
EP0603401B1 (en) *	1992-07-10	2001-04-11	Toray Industries, Inc.	Methanediphosphonate derivative, production thereof, and pharmaceutical use thereof
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 .
US20010007863A1 (en) *	1998-06-18	2001-07-12	Merck & Co., Inc.	Wet granulation formulation for bisphosphonic acids
US6143919A (en) *	1999-05-18	2000-11-07	3M Innovative Properties Company	Polymerizable acidic compounds and methods of preparation
US6315566B1 (en)	1999-05-18	2001-11-13	3M Innovative Properties Company	Dental materials
WO2003032909A2 (en) *	2001-10-18	2003-04-24	Ilex Products, Inc.	Methods of treating skin with diphosphonate derivatives
DE102004032781A1 (de) *	2004-01-23	2005-08-11	Mcs Micro Carrier Systems Gmbh	Bisphosphonsäurederivate
JP2006028024A (ja) *	2004-07-12	2006-02-02	Toray Ind Inc	リン含有有機化合物の製造方法。
EP2289900A1 (en) *	2009-08-26	2011-03-02	Humboldt Universität zu Berlin	Bisphosphonates as inhibitors of acid sphingomyelinase
JP6226974B2 (ja) *	2012-07-05	2017-11-08	ユニバーシティーオブアイオワリサーチファウンデーション	治療用ビスホスホネート
US10557039B2 (en) *	2016-02-22	2020-02-11	Surfactis Technologies	Compositions comprising bisphosphonic compounds dissolved in a fluorinated solvent, and use thereof for covering the surface of a part

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CA777769A (en) *	1963-03-18	1968-02-06	H. Roy Clarence	Substituted methylene diphosphonic acid compounds and detergent compositions
US3400131A (en) *	1964-03-05	1968-09-03	Hoffmann La Roche	1, 3-di (4-pyridyl)-2-propanol derivatives
GB1115044A (en) *	1964-08-06	1968-05-22	Albright & Wilson Mfg Ltd	Derivatives of hydroxy diphosphonic acids
AT279051B (de) *	1966-12-29	1970-02-25	Procter & Gamble	Mundpflegemittel
US3400151A (en) *	1967-12-28	1968-09-03	Procter & Gamble	Bicyclic dimer of ethane-1-hydroxy-1, 1-diphosphonic acid and salts thereof
US4014959A (en) *	1975-04-24	1977-03-29	Monsanto Company	Phosphonoether carboxylates
SU772152A1 (ru) *	1977-07-20	1983-02-15	Центральный научно-исследовательский институт оловянной промышленности	1-Алкоксиалкилиден-1,1-дифосфоновые кислоты или их калиевые,натриевые или аммониевые соли в качестве собирателей дл флотации касситерита и способ их получени
IT1201087B (it) *	1982-04-15	1989-01-27	Gentili Ist Spa	Bifosfonati farmacologicamente attivi,procedimento per la loro preparazione e relative composizioni farmaceutiche

1984
- 1984-07-31 GB GB848419489A patent/GB8419489D0/en active Pending
1985
- 1985-07-08 IE IE171785A patent/IE58614B1/en not_active IP Right Cessation
- 1985-07-12 ZA ZA855264A patent/ZA855264B/xx unknown
- 1985-07-25 KR KR1019860700180A patent/KR860700254A/ko not_active Application Discontinuation
- 1985-07-25 US US06/852,248 patent/US4732998A/en not_active Expired - Fee Related
- 1985-07-25 DE DE8585903807T patent/DE3575929D1/de not_active Expired - Fee Related
- 1985-07-25 WO PCT/DK1985/000071 patent/WO1986000902A1/en active IP Right Grant
- 1985-07-25 AU AU46736/85A patent/AU583848B2/en not_active Ceased
- 1985-07-25 EP EP85903807A patent/EP0191044B1/en not_active Expired - Lifetime
- 1985-07-25 JP JP60503564A patent/JPH068303B2/ja not_active Expired - Lifetime
- 1985-07-29 GR GR851865A patent/GR851865B/el unknown
- 1985-07-30 PT PT80886A patent/PT80886B/pt not_active IP Right Cessation
- 1985-07-31 ES ES545783A patent/ES8707964A1/es not_active Expired
1986
- 1986-03-27 FI FI861357A patent/FI861357A0/fi not_active Application Discontinuation
- 1986-04-01 DK DK147386A patent/DK167808B1/da not_active IP Right Cessation

Also Published As

Publication number	Publication date
WO1986000902A1 (en)	1986-02-13
ES545783A0 (es)	1987-09-01
US4732998A (en)	1988-03-22
PT80886A (en)	1985-08-01
AU4673685A (en)	1986-02-25
IE58614B1 (en)	1993-10-20
PT80886B (pt)	1987-11-30
EP0191044A1 (en)	1986-08-20
GB8419489D0 (en)	1984-09-05
AU583848B2 (en)	1989-05-11
GR851865B (pt)	1985-12-02
IE851717L (en)	1986-01-31
ZA855264B (en)	1986-03-26
DK147386D0 (da)	1986-04-01
JPH068303B2 (ja)	1994-02-02
FI861357A (fi)	1986-03-27
DK147386A (da)	1986-04-01
KR860700254A (ko)	1986-08-01
JPS61503034A (ja)	1986-12-25
EP0191044B1 (en)	1990-02-07
ES8707964A1 (es)	1987-09-01
FI861357A0 (fi)	1986-03-27
DE3575929D1 (de)	1990-03-15

Legal Events

Date	Code	Title
1992-10-26	PBP	Patent lapsed
1993-12-20	B1	Patent granted (law 1993)
1996-03-25	PBP	Patent lapsed

Publication	Publication Date	Title
DK167808B1 (da)	1993-12-20	Methylen-bisphosphonsyrederivat, fremgangsmaade til fremstilling heraf samt farmaceutisk sammensaetning indeholdende disse derivater
US3988443A (en)	1976-10-26	Azacycloalkane-2,2-diphosphonic acids
KR0171570B1 (ko)	1999-05-01	N-헤테로사이클릭프로필리덴-1,1-비스포스폰산,이의제조방법및약제학적조성물
JPS5942395A (ja)	1984-03-08	メチレン−ジホスホン酸から誘導された炎症抑制性生成物およびその製造方法
JP3347324B2 (ja)	2002-11-20	新規なメチレンビスホスホン酸誘導体
RU2124519C1 (ru)	1999-01-10	Производные гуанидиналкил-1,1-бис-фосфоновой кислоты, способ их получения, лекарственное средство и способ его получения
JPS63501956A (ja)	1988-08-04	新規ビスホスホン酸誘導体、その製造および用途
EP0016310B1 (en)	1982-09-22	Monophosphonate compounds, process for their preparation and pharmaceutical compositions containing them
JPH10500977A (ja)	1998-01-27	ピリジルビスホスホン酸エステルよりなる治療用活性薬剤
US6172050B1 (en)	2001-01-09	Phospholipid derivatives
CA2511753C (en)	2007-09-25	Phospholipid derivatives
CA2138127C (en)	2006-01-24	New acyclic amidine group-containing diphosphonic acid derivatives, processes for their preparation and medicaments containing these compounds
SK144794A3 (en)	1995-08-09	Quaternary nitrogen containing phosphonate compounds for treating abnormal calcium and phosphate metabolism
US20080139845A1 (en)	2008-06-12	Ibandronate sodium propylene glycol solvate and processes for the preparation thereof
US3341409A (en)	1967-09-12	Acylsulfamoylphenyl phosphate warmblooded animal systemic insecticides
IE48334B1 (en)	1984-12-12	Arylalkyl and aryloxyalkyl phosphonates and preparation thereof
DK169677B1 (da)	1995-01-09	N-heterocykliske propyliden-1,1-bisphosphonsyrer og salte deraf, deres fremstilling, farmaceutisk præparat indeholdende disse, og deres anvendelse
DK200200115U3 (da)	2002-06-28	Hidtil ukendte salte af 4-amino-1-hydroxybutyliden-1, 1-bisphosphonsyre, deres fremstilling og anvendelse
WO2001030788A1 (en)	2001-05-03	Novel salts of 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid, their preparation and use