DK170257B1 - Heterocyclisk biphosphonsyrederivat, fremgangsmåde til fremstilling deraf og farmaceutisk præparat indeholdende et sådant derivat - Google Patents

Heterocyclisk biphosphonsyrederivat, fremgangsmåde til fremstilling deraf og farmaceutisk præparat indeholdende et sådant derivat Download PDF

Info

Publication number: DK170257B1
Authority: DK; Denmark
Prior art keywords: compound; hydrogen atom; hydroxy; salts; pharmaceutically acceptable
Prior art date: 1988-08-12

Application number

DK394789A

Other languages

Danish (da)

English (en)

Other versions

DK394789A (da

DK394789D0 (da

Inventor

Yasuo Isomura

Makoto Takeuchi

Tetsushi Abe

Original Assignee

Yamanouchi Pharma Co 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.)

1988-08-12

Filing date

1989-08-11

Publication date

1995-07-17

1989-08-11 Application filed by Yamanouchi Pharma Co Ltd filed Critical Yamanouchi Pharma Co Ltd

1989-08-11 Publication of DK394789D0 publication Critical patent/DK394789D0/da

1990-02-13 Publication of DK394789A publication Critical patent/DK394789A/da

1995-07-17 Application granted granted Critical

1995-07-17 Publication of DK170257B1 publication Critical patent/DK170257B1/da

Links

239000002253 acid Substances 0.000 title claims abstract description 9
125000000623 heterocyclic group Chemical group 0.000 title claims abstract description 5
238000000034 method Methods 0.000 title claims description 5
238000002360 preparation method Methods 0.000 title claims description 5
239000008194 pharmaceutical composition Substances 0.000 title claims description 3
150000001875 compounds Chemical class 0.000 claims abstract description 51
150000003839 salts Chemical class 0.000 claims abstract description 21
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
125000005843 halogen group Chemical group 0.000 claims abstract description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
239000004480 active ingredient Substances 0.000 claims abstract 2
-1 imidazo [1,2-a] pyridin-3-yl Chemical group 0.000 claims description 11
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
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 claims description 2
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 2
239000011734 sodium Substances 0.000 claims description 2
229910052708 sodium Inorganic materials 0.000 claims description 2
239000012467 final product Substances 0.000 claims 1
150000004820 halides Chemical class 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
125000000217 alkyl group Chemical group 0.000 abstract description 5
229940078581 Bone resorption inhibitor Drugs 0.000 abstract 1
125000004429 atom Chemical group 0.000 abstract 1
239000002617 bone density conservation agent Substances 0.000 abstract 1
239000000203 mixture Substances 0.000 description 14
208000006386 Bone Resorption Diseases 0.000 description 10
230000024279 bone resorption Effects 0.000 description 10
239000011575 calcium Substances 0.000 description 10
239000000243 solution Substances 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
210000002966 serum Anatomy 0.000 description 7
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
229910052791 calcium Inorganic materials 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
208000037147 Hypercalcaemia Diseases 0.000 description 5
108090000445 Parathyroid hormone Proteins 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
230000000148 hypercalcaemia Effects 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
239000002504 physiological saline solution Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
238000001816 cooling Methods 0.000 description 4
230000000694 effects Effects 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
238000001819 mass spectrum Methods 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
102100036893 Parathyroid hormone Human genes 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
229940098773 bovine serum albumin Drugs 0.000 description 3
239000002775 capsule Substances 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
238000000921 elemental analysis Methods 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000008101 lactose Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
102000003982 Parathyroid hormone Human genes 0.000 description 2
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
239000008112 carboxymethyl-cellulose Substances 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
150000005332 diethylamines Chemical class 0.000 description 2
150000004656 dimethylamines Chemical class 0.000 description 2
239000003814 drug Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000008187 granular material Substances 0.000 description 2
239000001863 hydroxypropyl cellulose Substances 0.000 description 2
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
208000030915 hypercalcemia disease Diseases 0.000 description 2
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
239000000199 parathyroid hormone Substances 0.000 description 2
229960001319 parathyroid hormone Drugs 0.000 description 2
239000011574 phosphorus Substances 0.000 description 2
229910052698 phosphorus Inorganic materials 0.000 description 2
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
239000002904 solvent Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
238000011282 treatment Methods 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
WFZSCQPAHBSKLE-UHFFFAOYSA-N 2-imidazo[1,2-a]pyridin-2-ylacetic acid;hydrochloride Chemical compound Cl.C1=CC=CC2=NC(CC(=O)O)=CN21 WFZSCQPAHBSKLE-UHFFFAOYSA-N 0.000 description 1
SGNOGHAGXLAOHG-UHFFFAOYSA-N 2-imidazo[1,2-a]pyridin-3-ylacetic acid;hydrochloride Chemical compound Cl.C1=CC=CN2C(CC(=O)O)=CN=C21 SGNOGHAGXLAOHG-UHFFFAOYSA-N 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
208000010191 Osteitis Deformans Diseases 0.000 description 1
208000001132 Osteoporosis Diseases 0.000 description 1
208000027868 Paget disease Diseases 0.000 description 1
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
210000000683 abdominal cavity Anatomy 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000001760 anti-analgesic effect Effects 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000002585 base Substances 0.000 description 1
210000000988 bone and bone Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000003913 calcium metabolism Effects 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
150000003946 cyclohexylamines Chemical class 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical class OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
150000002169 ethanolamines Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
150000003947 ethylamines Chemical class 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000002723 inhibitory effect on hypercalcemia Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
208000027202 mammary Paget disease Diseases 0.000 description 1
230000001394 metastastic effect Effects 0.000 description 1
206010061289 metastatic neoplasm Diseases 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
150000003956 methylamines Chemical class 0.000 description 1
239000011259 mixed solution Substances 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
201000008968 osteosarcoma Diseases 0.000 description 1
150000003009 phosphonic acids Chemical class 0.000 description 1
239000006187 pill Substances 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000008213 purified water Substances 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
229910000679 solder Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000010998 test method Methods 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
150000005691 triesters Chemical class 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1

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
- C07F9/547—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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Biochemistry (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Detergent Compositions (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Adhesives Or Adhesive Processes (AREA)

DK394789A 1988-08-12 1989-08-11 Heterocyclisk biphosphonsyrederivat, fremgangsmåde til fremstilling deraf og farmaceutisk præparat indeholdende et sådant derivat DK170257B1 (da)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
JP20153688		1988-08-12
JP20153688		1988-08-12
JP20153588		1988-08-12
JP20153588		1988-08-12

Publications (3)

Publication Number	Publication Date
DK394789D0 DK394789D0 (da)	1989-08-11
DK394789A DK394789A (da)	1990-02-13
DK170257B1 true DK170257B1 (da)	1995-07-17

Family

ID=26512843

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK394789A DK170257B1 (da)	1988-08-12	1989-08-11	Heterocyclisk biphosphonsyrederivat, fremgangsmåde til fremstilling deraf og farmaceutisk præparat indeholdende et sådant derivat

Country Status (14)

Country	Link
US (2)	US4990503A (de)
EP (1)	EP0354806B1 (de)
KR (1)	KR0156239B1 (de)
CN (1)	CN1027167C (de)
AT (1)	ATE129714T1 (de)
AU (1)	AU624405B2 (de)
CA (1)	CA1332058C (de)
DE (1)	DE68924681T2 (de)
DK (1)	DK170257B1 (de)
ES (1)	ES2082780T3 (de)
GR (1)	GR3018086T3 (de)
HU (2)	HU205766B (de)
IE (1)	IE71185B1 (de)
PH (1)	PH26376A (de)

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* Cited by examiner, † Cited by third party
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EP0521622B1 (de) *	1991-07-03	1997-08-13	PHARMACIA & UPJOHN COMPANY	Pyrazolopyrimiden- und Pyrimidinylbisphosphonsäureester als entzündungshemmende Mittel
TW222637B (de) *	1991-12-12	1994-04-21	Hoechst Ag
US5270365A (en) *	1991-12-17	1993-12-14	Merck & Co., Inc.	Prevention and treatment of periodontal disease with alendronate
JPH05345791A (ja) *	1992-03-18	1993-12-27	Hoechst Japan Ltd	環状アミノメチレンビスホスホン酸誘導体
AU4356693A (en) *	1992-06-23	1994-01-24	Yamanouchi Pharmaceutical Co., Ltd.	Novel crystal of monohydrate of heterocyclic bis(phosphonic acid) derivative
US5635495A (en) *	1992-10-09	1997-06-03	The Upjohn Company	Pyrimidine bisphosphonate esters and (alkoxymethylphosphinyl)alkyl phosphonic acids as anti-inflammatories
DE59309360D1 (de) *	1992-12-02	1999-03-18	Hoechst Ag	Guanidinalkyl-1, 1-bisphosphonsäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung
JPH06298779A (ja) *	1993-04-15	1994-10-25	Hoechst Japan Ltd	ヘテロ環イミノビスメチレンビスホスホン酸誘導体
US5728650A (en) *	1993-10-07	1998-03-17	Zeneca Limited	Herbicidal aza bisphosphonic acids and compositions containing the same
US5854227A (en) *	1994-03-04	1998-12-29	Hartmann; John F.	Therapeutic derivatives of diphosphonates
US5880111A (en) *	1995-06-07	1999-03-09	Farcasiu; Dan	Therapeutic derivations of diphosphonates
WO1998039344A1 (en)	1997-03-07	1998-09-11	Metabasis Therapeutics, Inc.	Novel purine inhibitors of fructose-1,6-bisphosphatase
WO1998039342A1 (en)	1997-03-07	1998-09-11	Metabasis Therapeutics, Inc.	Novel indole and azaindole inhibitors of fructose-1,6-bisphosphatase
US7008645B2 (en) *	1998-07-14	2006-03-07	Yissum Research Development Company Of The Hebrew University Of Jerusalem	Method of inhibiting restenosis using bisphosphonates
AU1798700A (en) *	1998-12-25	2000-07-31	Yamanouchi Pharmaceutical Co., Ltd.	Medicinal compositions for treating osseous lesion in multiple myeloma
US20030036537A1 (en) *	2001-07-16	2003-02-20	Marc Lecouvey	Bisphosphonate derivatives, their preparations and uses
NZ536273A (en)	2002-12-20	2007-08-31	Hoffmann La Roche	High dose ibandronate formulation
HUP0300227A2 (hu) *	2003-01-28	2004-09-28	Richter Gedeon Vegyészeti Gyár Rt.	Eljárás nagy tisztaságú 2-szubsztituált -1-(hidroxi-etilidén)-1,1-biszfoszfonsavak és sóik előállítására
US20060051407A1 (en) *	2003-06-27	2006-03-09	Yoram Richter	Method of treating ischemia-reperfusion injury
US10517883B2 (en)	2003-06-27	2019-12-31	Zuli Holdings Ltd.	Method of treating acute myocardial infarction
JPWO2005072746A1 (ja) *	2004-01-30	2007-10-11	アステラス製薬株式会社	Ｐ２ｘ受容体阻害剤
CN101531681B (zh) *	2008-03-10	2013-06-05	北京德众万全医药科技有限公司	一种高纯度的米诺膦酸及其制备方法
WO2010033980A2 (en) *	2008-09-22	2010-03-25	Isis Innovation Ltd.	4-azaindole bisphosphonates
WO2010033978A2 (en) *	2008-09-22	2010-03-25	Isis Innovation Ltd.	IMIDAZO[1,2-α ]PYRIDINYL BISPHOSPHONATES
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1989
- 1989-08-07 US US07/390,090 patent/US4990503A/en not_active Expired - Lifetime
- 1989-08-08 AU AU39419/89A patent/AU624405B2/en not_active Ceased
- 1989-08-09 CA CA000607874A patent/CA1332058C/en not_active Expired - Fee Related
- 1989-08-11 ES ES89308180T patent/ES2082780T3/es not_active Expired - Lifetime
- 1989-08-11 DE DE68924681T patent/DE68924681T2/de not_active Expired - Fee Related
- 1989-08-11 HU HU894150A patent/HU205766B/hu unknown
- 1989-08-11 KR KR1019890011432A patent/KR0156239B1/ko not_active Expired - Fee Related
- 1989-08-11 IE IE260189A patent/IE71185B1/en not_active IP Right Cessation
- 1989-08-11 EP EP89308180A patent/EP0354806B1/de not_active Expired - Lifetime
- 1989-08-11 DK DK394789A patent/DK170257B1/da not_active IP Right Cessation
- 1989-08-11 PH PH39086A patent/PH26376A/en unknown
- 1989-08-11 AT AT89308180T patent/ATE129714T1/de not_active IP Right Cessation
- 1989-08-12 CN CN89106373A patent/CN1027167C/zh not_active Expired - Fee Related
1990
- 1990-08-10 US US07/566,145 patent/US5039669A/en not_active Expired - Fee Related
1995
- 1995-06-30 HU HU95P/P00618P patent/HU211949A9/hu unknown
- 1995-11-15 GR GR950403204T patent/GR3018086T3/el unknown

Also Published As

Publication number	Publication date
ATE129714T1 (de)	1995-11-15
CN1027167C (zh)	1994-12-28
HUT51637A (en)	1990-05-28
US5039669A (en)	1991-08-13
HU205766B (en)	1992-06-29
DE68924681T2 (de)	1996-04-04
US4990503A (en)	1991-02-05
KR0156239B1 (ko)	1998-12-01
CA1332058C (en)	1994-09-20
AU3941989A (en)	1990-02-15
KR900003186A (ko)	1990-03-26
EP0354806A3 (de)	1991-05-02
HU211949A9 (en)	1996-01-29
DK394789A (da)	1990-02-13
IE892601L (en)	1990-02-12
GR3018086T3 (en)	1996-02-29
AU624405B2 (en)	1992-06-11
EP0354806B1 (de)	1995-11-02
ES2082780T3 (es)	1996-04-01
PH26376A (en)	1992-06-01
EP0354806A2 (de)	1990-02-14
DE68924681D1 (de)	1995-12-07
CN1040590A (zh)	1990-03-21
DK394789D0 (da)	1989-08-11
IE71185B1 (en)	1997-01-29

Legal Events

Date	Code	Title	Description
1995-07-17	B1	Patent granted (law 1993)
2009-03-30	PBP	Patent lapsed	Country of ref document: DK

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