IL77243A - Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds - Google Patents
Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compoundsInfo
- Publication number
- IL77243A IL77243A IL7724385A IL7724385A IL77243A IL 77243 A IL77243 A IL 77243A IL 7724385 A IL7724385 A IL 7724385A IL 7724385 A IL7724385 A IL 7724385A IL 77243 A IL77243 A IL 77243A
- Authority
- IL
- Israel
- Prior art keywords
- diphosphonic acid
- substituted
- hydrogen
- unsubstituted
- amino
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 36
- XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical group OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 title claims description 15
- 150000001875 compounds Chemical class 0.000 title description 31
- 239000011575 calcium Substances 0.000 claims abstract description 38
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 38
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 19
- 239000010452 phosphate Substances 0.000 claims abstract description 19
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract description 18
- 230000002159 abnormal effect Effects 0.000 claims abstract description 13
- 230000004060 metabolic process Effects 0.000 claims abstract description 12
- 201000010099 disease Diseases 0.000 claims abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
- -1 diphosphonic acid compound Chemical group 0.000 claims description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 239000001257 hydrogen Substances 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 33
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 150000002148 esters Chemical class 0.000 claims description 31
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 239000003937 drug carrier Substances 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 16
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 15
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000003368 amide group Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 150000007942 carboxylates Chemical class 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- SEEGPWYJEBDACP-UHFFFAOYSA-N P(=O)(O)OP(=O)O.N1=C(N=CC=C1)NC Chemical compound P(=O)(O)OP(=O)O.N1=C(N=CC=C1)NC SEEGPWYJEBDACP-UHFFFAOYSA-N 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 25
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 11
- NURQLCJSMXZBPC-UHFFFAOYSA-N 3,4-dimethylpyridine Chemical compound CC1=CC=NC=C1C NURQLCJSMXZBPC-UHFFFAOYSA-N 0.000 claims 2
- ZCNSXYZTSSTVER-UHFFFAOYSA-N (1-phosphono-1-pyridin-2-ylethyl)phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(C)C1=CC=CC=N1 ZCNSXYZTSSTVER-UHFFFAOYSA-N 0.000 claims 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 9
- 229960005069 calcium Drugs 0.000 description 35
- 235000001465 calcium Nutrition 0.000 description 35
- DCCMANRPEHXGDK-UHFFFAOYSA-L azane;hydroxy-[[[hydroxy(oxido)phosphoryl]methyl-(phosphonomethyl)amino]methyl]phosphinate;platinum(2+) Chemical compound N.N.[Pt+2].OP(O)(=O)CN(CP(O)(O)=O)CP([O-])([O-])=O DCCMANRPEHXGDK-UHFFFAOYSA-L 0.000 description 33
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 22
- 241001465754 Metazoa Species 0.000 description 18
- 150000002430 hydrocarbons Chemical group 0.000 description 18
- 235000021317 phosphate Nutrition 0.000 description 15
- 230000005764 inhibitory process Effects 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 208000001132 Osteoporosis Diseases 0.000 description 12
- 241000700159 Rattus Species 0.000 description 12
- 230000037396 body weight Effects 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 12
- 208000006386 Bone Resorption Diseases 0.000 description 11
- 210000000988 bone and bone Anatomy 0.000 description 11
- 230000024279 bone resorption Effects 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 229910052799 carbon Inorganic materials 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 102000003982 Parathyroid hormone Human genes 0.000 description 8
- 108090000445 Parathyroid hormone Proteins 0.000 description 8
- 230000033558 biomineral tissue development Effects 0.000 description 8
- 125000001624 naphthyl group Chemical group 0.000 description 8
- 239000000199 parathyroid hormone Substances 0.000 description 8
- 229960001319 parathyroid hormone Drugs 0.000 description 8
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-Lutidine Substances CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- XQRLCLUYWUNEEH-UHFFFAOYSA-L diphosphonate(2-) Chemical class [O-]P(=O)OP([O-])=O XQRLCLUYWUNEEH-UHFFFAOYSA-L 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 206010020584 Hypercalcaemia of malignancy Diseases 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 230000008021 deposition Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 208000008750 humoral hypercalcemia of malignancy Diseases 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- NGMZSXZBZNXBGX-UHFFFAOYSA-N (1-phosphono-2-pyridin-2-ylethyl)phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)CC1=CC=CC=N1 NGMZSXZBZNXBGX-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 208000010191 Osteitis Deformans Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 210000004349 growth plate Anatomy 0.000 description 5
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 208000004434 Calcinosis Diseases 0.000 description 4
- 208000027868 Paget disease Diseases 0.000 description 4
- 150000001412 amines Chemical group 0.000 description 4
- 230000002547 anomalous effect Effects 0.000 description 4
- 230000000123 anti-resoprtive effect Effects 0.000 description 4
- 239000001506 calcium phosphate Substances 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 208000027202 mammary Paget disease Diseases 0.000 description 4
- 210000002303 tibia Anatomy 0.000 description 4
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical group [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 4
- MXYOPVWZZKEAGX-UHFFFAOYSA-N 1-phosphonoethylphosphonic acid Chemical compound OP(=O)(O)C(C)P(O)(O)=O MXYOPVWZZKEAGX-UHFFFAOYSA-N 0.000 description 3
- 206010065687 Bone loss Diseases 0.000 description 3
- 206010006811 Bursitis Diseases 0.000 description 3
- 201000002980 Hyperparathyroidism Diseases 0.000 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 description 3
- 206010027452 Metastases to bone Diseases 0.000 description 3
- 208000010358 Myositis Ossificans Diseases 0.000 description 3
- 206010029240 Neuritis Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 208000000491 Tendinopathy Diseases 0.000 description 3
- 206010043255 Tendonitis Diseases 0.000 description 3
- FRCICXIVPRNPLM-UHFFFAOYSA-N [amino(phosphono)methyl]phosphonic acid Chemical compound OP(=O)(O)C(N)P(O)(O)=O FRCICXIVPRNPLM-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000004097 bone metabolism Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 230000004968 inflammatory condition Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 201000004415 tendinitis Diseases 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- KZMOFWIRXNQJET-UHFFFAOYSA-N (1-phosphono-2-pyridin-3-ylethyl)phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)CC1=CC=CN=C1 KZMOFWIRXNQJET-UHFFFAOYSA-N 0.000 description 2
- RGDQRXPEZUNWHX-UHFFFAOYSA-N 3-methylpyridin-2-amine Chemical compound CC1=CC=CN=C1N RGDQRXPEZUNWHX-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- MHRRTVVGLQIJHH-UHFFFAOYSA-N C(=C)P(=O)(O)OP(=O)O Chemical compound C(=C)P(=O)(O)OP(=O)O MHRRTVVGLQIJHH-UHFFFAOYSA-N 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical group CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- AZZAXZGZBUSIEE-UHFFFAOYSA-N OP(=O)OP(O)=O.CNC1=CC=CC=N1 Chemical class OP(=O)OP(O)=O.CNC1=CC=CC=N1 AZZAXZGZBUSIEE-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 229930003316 Vitamin D Natural products 0.000 description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 2
- BHVCADPDEFLLGM-UHFFFAOYSA-N [1-phosphono-2-(pyridin-2-ylamino)ethyl]phosphonic acid Chemical compound OP(O)(=O)C(P(O)(O)=O)CNC1=CC=CC=N1 BHVCADPDEFLLGM-UHFFFAOYSA-N 0.000 description 2
- 206010000059 abdominal discomfort Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000011149 active material Substances 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
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- 230000018678 bone mineralization Effects 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 150000001721 carbon Chemical class 0.000 description 2
- ACSIXWWBWUQEHA-UHFFFAOYSA-N clodronic acid Chemical compound OP(O)(=O)C(Cl)(Cl)P(O)(O)=O ACSIXWWBWUQEHA-UHFFFAOYSA-N 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
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- 235000019166 vitamin D Nutrition 0.000 description 2
- 239000011710 vitamin D Substances 0.000 description 2
- 150000003710 vitamin D derivatives Chemical class 0.000 description 2
- 229940046008 vitamin d Drugs 0.000 description 2
- OXESJJSYVCTOKO-UHFFFAOYSA-N (1-amino-1-phosphono-2-pyridin-2-ylethyl)phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(N)CC1=CC=CC=N1 OXESJJSYVCTOKO-UHFFFAOYSA-N 0.000 description 1
- JSTANQWEEKECAR-UHFFFAOYSA-N (1-chloro-1-phosphono-2-pyridin-2-ylethyl)phosphonic acid Chemical compound OP(O)(=O)C(Cl)(P(O)(O)=O)CC1=CC=CC=N1 JSTANQWEEKECAR-UHFFFAOYSA-N 0.000 description 1
- DBZOQWQSJXNJCJ-UHFFFAOYSA-N (1-hydroxy-1-phosphono-2-pyrimidin-2-ylethyl)phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=NC=CC=N1 DBZOQWQSJXNJCJ-UHFFFAOYSA-N 0.000 description 1
- YUEFGDDCJLELFH-UHFFFAOYSA-N (2-amino-1-phosphonoethyl)phosphonic acid Chemical compound NCC(P(O)(O)=O)P(O)(O)=O YUEFGDDCJLELFH-UHFFFAOYSA-N 0.000 description 1
- PAHDQAFSLSSCTG-UHFFFAOYSA-N (2-phosphono-1-pyridin-2-ylpropan-2-yl)phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(C)CC1=CC=CC=N1 PAHDQAFSLSSCTG-UHFFFAOYSA-N 0.000 description 1
- DYBRVYFKIDRHSZ-UHFFFAOYSA-N (hydroxy-phosphono-pyridin-2-yloxymethyl)phosphonic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)OC1=CC=CC=N1 DYBRVYFKIDRHSZ-UHFFFAOYSA-N 0.000 description 1
- NRGGMCIBEHEAIL-UHFFFAOYSA-N 2-ethylpyridine Chemical compound CCC1=CC=CC=N1 NRGGMCIBEHEAIL-UHFFFAOYSA-N 0.000 description 1
- ROPQINLWRARCTM-UHFFFAOYSA-N 2-phosphonopropan-2-ylphosphonic acid Chemical compound OP(=O)(O)C(C)(C)P(O)(O)=O ROPQINLWRARCTM-UHFFFAOYSA-N 0.000 description 1
- XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 description 1
- UPXRTVAIJMUAQR-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)OC(C)(C)C)CC1NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 UPXRTVAIJMUAQR-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101001135732 Bos taurus Parathyroid hormone Proteins 0.000 description 1
- JLUKGOAGTLRMIN-UHFFFAOYSA-N CC1=CC=CC=N1.OP(=O)OP(O)=O Chemical compound CC1=CC=CC=N1.OP(=O)OP(O)=O JLUKGOAGTLRMIN-UHFFFAOYSA-N 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)]
- 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
- C07F9/3873—Polyphosphonic acids containing nitrogen substituent, e.g. N.....H or N-hydrocarbon group which can be substituted by halogen or nitro(so), N.....O, N.....S, N.....C(=X)- (X =O, S), N.....N, N...C(=X)...N (X =O, S)
-
- 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
- C07F9/58—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 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
- C07F9/6509—Six-membered rings
- C07F9/650905—Six-membered rings having the nitrogen atoms in the positions 1 and 2
-
- 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
- C07F9/645—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
- C07F9/650952—Six-membered rings having the nitrogen atoms in the positions 1 and 4
-
- 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
- C07F9/645—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
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)
- Output Control And Ontrol Of Special Type Engine (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US68454384A | 1984-12-21 | 1984-12-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL77243A true IL77243A (en) | 1996-11-14 |
Family
ID=24748488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL7724385A IL77243A (en) | 1984-12-21 | 1985-12-05 | Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US5583122A (fr) |
| EP (1) | EP0186405B1 (fr) |
| AT (1) | ATE61370T1 (fr) |
| DE (2) | DE10075030I2 (fr) |
| DK (1) | DK168754B1 (fr) |
| ES (4) | ES8707543B9 (fr) |
| IE (1) | IE58749B1 (fr) |
| IL (1) | IL77243A (fr) |
| LU (1) | LU90669I2 (fr) |
| NL (1) | NL300031I2 (fr) |
| ZA (1) | ZA859694B (fr) |
Families Citing this family (127)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4902679A (en) * | 1985-12-13 | 1990-02-20 | Norwich Eaton Pharmaceuticals, Inc. | Methods of treating diseases with certain geminal diphosphonates |
| IL84494A (en) * | 1986-11-21 | 1992-08-18 | Ciba Geigy Ag | Heteroaryl substituted aminomethane-diphosphonic acids,their preparation and pharmaceutical compositions containing them |
| DE3770787D1 (en) * | 1986-11-21 | 1991-07-18 | Ciba Geigy Ag | Aromatisch substituierte azacyclo-alkylalkandiphosphonsaeuren. |
| EP0275821B1 (fr) * | 1986-11-21 | 1992-02-26 | Ciba-Geigy Ag | Acides alcanediphosphoniques substitués |
| US5057505A (en) * | 1986-11-21 | 1991-10-15 | Ciba-Geigy Corporation | Substituted aminomethanediphosphonic acids and use in medicaments |
| DE3640938A1 (de) * | 1986-11-29 | 1988-06-01 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindung enthaltende arzneimittel |
| IL84731A0 (en) * | 1986-12-19 | 1988-05-31 | Norwich Eaton Pharma | Heterocycle-substituted diphosphonic acids and salts and esters and pharmaceutical compositions containing them |
| FR2611203B1 (fr) * | 1987-02-20 | 1989-06-09 | Sturtz Georges | Analogues gem-diphosphoniques d'amethopterine (methotrexate) et de derives deaza-n-10 amethopterine. leur preparation et les compositions pharmaceutiques qui les contiennent |
| US4973576A (en) * | 1987-03-10 | 1990-11-27 | Yamanouchi Pharmaceutical Co., Ltd. | Bisphophonic acid derivatives and pharmaceutical compositions containing the same |
| 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 |
| EP0317505A1 (fr) * | 1987-11-13 | 1989-05-24 | Ciba-Geigy Ag | Acides azacycloalkylalcanediphosphoniques |
| EP0320455B1 (fr) * | 1987-12-11 | 1993-06-09 | Ciba-Geigy Ag | Acides aminoalcanediphosphoniques araliphatiques |
| US5110807A (en) * | 1988-12-01 | 1992-05-05 | Ciba-Geigy Corporation | Araliphatylaminoalkanediphosphonic acids |
| US5190930A (en) * | 1987-12-11 | 1993-03-02 | Ciba-Geigy Corporation | Araliphatylaminoalkanediphosphonic acids |
| US4933472A (en) * | 1988-04-08 | 1990-06-12 | Yamanouchi Pharmaceutical Co., Ltd. | Substituted aminomethylenebis(phosphonic acid) derivatives |
| DE3822650A1 (de) * | 1988-07-05 | 1990-02-01 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| TW198039B (fr) * | 1988-11-28 | 1993-01-11 | Ciba Geigy Ag | |
| DE68910288T2 (de) * | 1988-12-14 | 1994-02-17 | Pfizer | Derivate von 5-Hydroxy- und 5-Methoxy-2-amino-pyrimidin als Inhibitoren der Interleukin-1-Produktion. |
| 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. |
| MX21452A (es) * | 1989-07-07 | 1994-01-31 | Ciba Geigy Ag | Preparaciones farmaceuticas que se administran en forma topica. |
| US5139786A (en) * | 1989-07-07 | 1992-08-18 | Ciba-Geigy Corporation | Topical formulations |
| FI89366C (fi) * | 1990-12-20 | 1993-09-27 | Leiras Oy | Foerfarande foer framstaellning av nya farmakologiskt anvaendbara metylenbisfosfonsyraderivat |
| CA2102303A1 (fr) * | 1991-06-19 | 1992-12-20 | Roy Allen Johnson | Utilisation de dialkyl(dialcoxyphosphinyl)methylphosphates comme anti-inflammatoires |
| EP0522576A3 (en) * | 1991-07-12 | 1993-07-14 | Hoechst Aktiengesellschaft | Aminoethane-1,1-bisphosphonic acids and aminoethane-1,1-alkylphospinic/phosphonic acids, process of their preparation and their use |
| US6096342A (en) * | 1997-03-12 | 2000-08-01 | The Procter & Gamble Company | Dosage forms of risedronate |
| KR100274734B1 (ko) * | 1991-11-22 | 2000-12-15 | 제이코버스 코넬리스 레이서 | 리제드로네이트 지연-방출성 조성물 |
| TW222637B (fr) * | 1991-12-12 | 1994-04-21 | Hoechst Ag | |
| DE4141928A1 (de) * | 1991-12-19 | 1993-06-24 | Boehringer Mannheim Gmbh | Neue phosphonobernsteinsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| US5283057A (en) * | 1992-04-24 | 1994-02-01 | The Procter & Gamble Company | Risedronate in oral compositions |
| US5731299A (en) * | 1992-05-29 | 1998-03-24 | The Procter & Gamble Company | Phosphonosulfonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
| 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 |
| JPH07507315A (ja) * | 1992-05-29 | 1995-08-10 | プロクター、エンド、ギャンブル、ファーマスーティカルズ、インコーポレーテッド | カルシウムおよびホスフェート代謝異常治療用含硫ホスホネート化合物 |
| 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 |
| SG47603A1 (en) * | 1992-05-29 | 1998-04-17 | Procter & Gamble Pharma | Thio-substitute nitrogen containing heterocyclic phosphonate compounds for treating abnormal calcium and phosphate metabolism |
| DK0642518T3 (da) * | 1992-05-29 | 1998-12-14 | Procter & Gamble Pharma | Phosphonosulfonat-forbindelser til behandling af abnormt calcium- og phosphatstofskifte |
| IL105838A (en) * | 1992-05-29 | 1998-03-10 | Procter & Gamble Pharma | Pharmaceutical compositions containing phosphonocarboxylates and some novel compounds of this type |
| US5760021A (en) * | 1992-05-29 | 1998-06-02 | The Procter & Gamble Company | Phosphonocarboxylate compounds pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
| CZ297094A3 (en) * | 1992-05-29 | 1995-12-13 | Procter & Gamble Pharma | Phosphate compounds containing quaternary nitrogen, their use and pharmaceutical compositions containing thereof |
| 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 |
| JP4481368B2 (ja) * | 1992-06-30 | 2010-06-16 | 味の素株式会社 | 骨粗鬆症の治療用のためのホスホネート類の用途 |
| CA2138366C (fr) * | 1992-06-30 | 1998-09-22 | Kristine Hovancik | Methodes pour le traitement de l'arthrite au moyen de phosphonates et d'ains |
| EP0663919A1 (fr) * | 1992-10-09 | 1995-07-26 | PHARMACIA & UPJOHN COMPANY | Esters de biphosphonate de pyrimidine utilises comme anti-inflammatoires |
| ATE176476T1 (de) * | 1992-12-02 | 1999-02-15 | Hoechst Ag | Guanidinalkyl-1, 1-bisphosphonsäurederivate, verfahren zu ihrer herstellung und ihre verwendung |
| CN1043423C (zh) * | 1993-01-02 | 1999-05-19 | 曼海姆泊灵格股份公司 | 新膦酰基琥珀酸衍生物及其制备方法和含这些化合物的药物组合物 |
| 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 . |
| 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 |
| US5451401A (en) * | 1993-09-29 | 1995-09-19 | The Procter & Gamble Company | Diphosphonic acid esters as tartar control agents |
| US5728650A (en) * | 1993-10-07 | 1998-03-17 | Zeneca Limited | Herbicidal aza bisphosphonic acids and compositions containing the same |
| US20010007863A1 (en) * | 1998-06-18 | 2001-07-12 | Merck & Co., Inc. | Wet granulation formulation for bisphosphonic acids |
| SE9402001D0 (sv) * | 1994-06-09 | 1994-06-09 | Leiras Oy | Pyridylbisphosphonates for use as a therapeutical agent |
| US5880111A (en) * | 1995-06-07 | 1999-03-09 | Farcasiu; Dan | Therapeutic derivations of diphosphonates |
| US20010031244A1 (en) * | 1997-06-13 | 2001-10-18 | Chiesi Farmaceutici S.P.A. | Pharmaceutical aerosol composition |
| US6432932B1 (en) | 1997-07-22 | 2002-08-13 | Merck & Co., Inc. | Method for inhibiting bone resorption |
| US5994329A (en) | 1997-07-22 | 1999-11-30 | Merck & Co., Inc. | Method for inhibiting bone resorption |
| IT1303672B1 (it) * | 1998-07-28 | 2001-02-23 | Nicox Sa | Sali nitrati di farmaci attivi nei disordini ossei |
| AU761267C (en) | 1998-09-09 | 2007-08-09 | Metabasis Therapeutics, Inc. | Novel heteroaromatic inhibitors of fructose 1,6-bisphosphatase |
| US7205404B1 (en) | 1999-03-05 | 2007-04-17 | Metabasis Therapeutics, Inc. | Phosphorus-containing prodrugs |
| JP2003531111A (ja) | 1999-12-17 | 2003-10-21 | アライアッド・ファーマシューティカルズ・インコーポレーテッド | プロトンポンプインヒビター |
| IL150059A0 (en) * | 1999-12-17 | 2002-12-01 | Ariad Pharma Inc | Novel heterocycles |
| US6420384B2 (en) * | 1999-12-17 | 2002-07-16 | Ariad Pharmaceuticals, Inc. | Proton pump inhibitors |
| US6410520B2 (en) * | 2000-02-01 | 2002-06-25 | The Procter & Gamble Company | Selective crystallization of 3-pyridyl-1-hydroxyethylidene-1, 1-bisphosphonic acid sodium as the hemipentahydrate or monohydrate |
| US6562974B2 (en) | 2000-02-01 | 2003-05-13 | The Procter & Gamble Company | Process for making geminal bisphosphonates |
| US7563774B2 (en) | 2000-06-29 | 2009-07-21 | Metabasis Therapeutics, Inc. | Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes |
| PL194770B1 (pl) * | 2001-03-19 | 2007-07-31 | Adamed Sp Z Oo | Sposób wytwarzania kwasu rizedronowego |
| 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 |
| WO2003055496A1 (fr) * | 2001-12-21 | 2003-07-10 | The Procter & Gamble Company | Methode de traitement d'affections osseuses |
| US20050070504A1 (en) * | 2001-12-21 | 2005-03-31 | The Procter & Gamble Co. | Risedronate compositions and their methods of use |
| WO2003086415A1 (fr) * | 2002-04-05 | 2003-10-23 | Merck & Co., Inc. | Procede d'inhibition de resorption osseuse a l'aide d'une formulation a base d'alendronate et de vitamine d |
| KR100937184B1 (ko) * | 2002-04-11 | 2010-01-19 | 테바 파마슈티컬 인더스트리즈 리미티드 | 리세드로네이트 나트륨의 신규한 동질이상체 및 유사동질이상체 |
| TW200413381A (en) | 2002-11-04 | 2004-08-01 | Hoffmann La Roche | Novel amino-substituted dihydropyrimido [4,5-d]pyrimidinone derivatives, their manufacture and use as pharmaceutical agents |
| US7358331B2 (en) * | 2003-05-19 | 2008-04-15 | Elan Pharmaceuticals, Inc. | Truncated fragments of alpha-synuclein in Lewy body disease |
| US20050065171A1 (en) * | 2003-06-25 | 2005-03-24 | Shakespeare William C. | Substituted purine derivatives |
| US20040265565A1 (en) * | 2003-06-30 | 2004-12-30 | Fischer Patrick J. | Microporous article containing flame retardant |
| BRPI0413067A (pt) * | 2003-07-30 | 2006-10-17 | Procter & Gamble | processo para controlar a estrututra cristalina do risedronato |
| CA2539359A1 (fr) * | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Compositions pharmaceutiques et methodes de traitement consistant en des associations d'un derive de la 2-alkylidene-19-nor-vitamine d et d'un bisphosphonate |
| DE602004032577D1 (de) * | 2003-12-23 | 2011-06-16 | Alchymars S P A | Amorphe Form das Natriumsalzes der Ibandronsäure |
| WO2005090370A1 (fr) | 2004-02-05 | 2005-09-29 | The Regents Of The University Of California | Agents pharmacologiquement actifs contenant des phosphonates esterifies, et leurs procedes d'utilisation |
| DE602005001873T2 (de) * | 2004-03-03 | 2008-04-24 | Chemi S.P.A., Cinisello Balsamo | Amorphe 3-Pyridyl-1-Hydroxyethyliden-1,1-Bisphosphonsäure Mononatriumsalz und Verfahren zu deren Herstellung |
| WO2005107714A2 (fr) * | 2004-05-05 | 2005-11-17 | Alkermes Controlled Therapeutics, Inc. | Procede de formation de microparticules comportant un bisphosphonate et un polymere |
| US20050261250A1 (en) * | 2004-05-19 | 2005-11-24 | Merck & Co., Inc., | Compositions and methods for inhibiting bone resorption |
| KR20080083068A (ko) | 2004-05-24 | 2008-09-12 | 더 프록터 앤드 갬블 캄파니 | 킬레이팅제를 함유하는 비스포스포네이트의 고형의 장용 경구 투여 형태 |
| ES2517840T3 (es) * | 2004-08-25 | 2014-11-04 | University Of Iowa Research Foundation | Inhibidores de la geranilgeranil pirofosfato sintasa |
| US7358361B2 (en) * | 2004-10-08 | 2008-04-15 | The Board Of Trustees Of The University Of Illinois | Biophosphonate compounds and methods for bone resorption diseases, cancer, bone pain, immune disorders, and infectious diseases |
| US8012949B2 (en) * | 2004-10-08 | 2011-09-06 | The Board Of Trustees Of The University Of Illinois | Bisphosphonate compounds and methods with enhanced potency for multiple targets including FPPS, GGPPS, and DPPS |
| CA2590046A1 (fr) * | 2004-11-09 | 2006-05-18 | Jubilant Organosys Limited | Procede de synthese d'une forme polymorphique pure du 3-pyridyl-1-hydroxyethylidine-1,1-bisphosphonate de sodium |
| PL199215B1 (pl) | 2004-12-28 | 2008-08-29 | Politechnika Gdanska | Sposób wytwarzania kwasu [1-hydroksy-2-(3-pirydylo)etylidenobisfosfonowego] oraz jego soli monosodowej dwu i pół wodnej |
| WO2006110656A2 (fr) | 2005-04-08 | 2006-10-19 | Chimerix, Inc. | Composes, compositions et methodes de traitement d'infections virales et autres troubles medicaux |
| US8642577B2 (en) | 2005-04-08 | 2014-02-04 | Chimerix, Inc. | Compounds, compositions and methods for the treatment of poxvirus infections |
| WO2006116057A2 (fr) * | 2005-04-21 | 2006-11-02 | Duke University | Transport facilite de biphosphonates par la vitamine c |
| CA2606879A1 (fr) * | 2005-05-06 | 2007-03-01 | Medichem, S.A. | Processus de fabrication d'acides bisphosphoniques gemines et de sels et/ou d'hydrates de ceux-ci repondant aux normes pharmaceutiques |
| WO2007026379A2 (fr) * | 2005-08-30 | 2007-03-08 | Natco Pharma Limited | Formes cristallines de risedronate |
| EP1775302A1 (fr) | 2005-10-11 | 2007-04-18 | Sandoz A/S | Méthode pour la préparation de risedronate de sodium cristallin |
| CA2646334A1 (fr) * | 2006-03-17 | 2007-09-27 | The Board Of Trustees Of The University Of Illinois | Composes de biphosphonates et procedes |
| JP5354858B2 (ja) * | 2006-05-09 | 2013-11-27 | 株式会社Ａｄｅｋａ | スルホンアミド化合物の金属塩を含有するポリエステル樹脂組成物 |
| KR20090005206A (ko) | 2006-05-11 | 2009-01-12 | 인드-스위프트 래버러토리즈 리미티드 | 순수한 리세드론산 또는 염의 제조 방법 |
| PT103600B (pt) | 2006-11-06 | 2009-01-30 | Hovione Farmaciencia Sa | Processo para a preparação de ácidos biosfónicos e seus sais farmaceuticamente aceitáveis |
| US7781418B2 (en) | 2006-12-14 | 2010-08-24 | Isis Innovation Ltd. | Composition for treating bone disorders |
| US20110039804A1 (en) | 2006-12-20 | 2011-02-17 | Landsteiner Scientific, S.A. De C.V. | Composition of Risedronate and Vitamin D3 |
| WO2009050731A2 (fr) * | 2007-06-20 | 2009-04-23 | Alkem Laboratories Ltd | Procédé inédit de préparation de l'acide risédronique |
| DE102007030370A1 (de) | 2007-06-29 | 2009-01-02 | Ratiopharm Gmbh | Essigsäure-Solvate von Risedronat, Polymorph hiervon, deren Herstellung und Verwendung sowie pharmazeutische Zusammensetzung, enthaltend diese |
| US20090075940A1 (en) * | 2007-09-19 | 2009-03-19 | Protia, Llc | Deuterium-enriched risedronate |
| ITPA20070034A1 (it) * | 2007-10-30 | 2009-04-30 | Tetrapharm S R L | Bifosfonati geminali, loro preparazione e loro impiego in campo oncologico. |
| WO2009105140A2 (fr) | 2007-12-11 | 2009-08-27 | Viamet Pharmaceuticals, Inc. | Inhibiteurs de métalloenzymes utilisant des fractions de liaison à un métal en combinaison avec des fractions de ciblage |
| EP2254582B1 (fr) | 2008-01-25 | 2016-01-20 | Chimerix, Inc. | Méthodes de traitement d'infections virales |
| TR200900878A2 (tr) | 2009-02-05 | 2010-08-23 | Bi̇lgi̇ç Mahmut | Tek bir dozaj formunda kombine edilen farmasötik formülasyonlar |
| WO2011011519A1 (fr) | 2009-07-21 | 2011-01-27 | Chimerix, Inc. | Composés, compositions et procédés pour traiter des troubles oculaires |
| BR112012002551A2 (pt) | 2009-08-03 | 2017-06-13 | Chimerix Inc | composição e métodos de tratamento de infecções virais e tumores induzidos por vírus |
| FR2954320B1 (fr) | 2009-12-17 | 2012-06-15 | Cll Pharma | Composition pharmaceutique orale suprabiodisponible contenant un acide biphosphonique ou un de ses sels |
| WO2011100698A2 (fr) | 2010-02-12 | 2011-08-18 | Chimerix, Inc. | Méthodes de traitement d'une infection virale |
| EP2563367A4 (fr) | 2010-04-26 | 2013-12-04 | Chimerix Inc | Méthodes de traitement d'infections rétrovirales et régimes posologiques associés |
| TR201100149A2 (tr) | 2011-01-06 | 2012-07-23 | Bi̇lgi̇ç Mahmut | Geliştirilmiş risedronat formülasyonu. |
| WO2012093974A1 (fr) | 2011-01-06 | 2012-07-12 | Mahmut Bilgic | Formulations améliorées de bisphosphonates |
| CN102286024B (zh) * | 2011-08-30 | 2013-12-04 | 江苏正大清江制药有限公司 | 利塞膦酸钠的合成方法 |
| GB201200868D0 (en) | 2012-01-19 | 2012-02-29 | Depuy Int Ltd | Bone filler composition |
| AU2013286683B2 (en) | 2012-07-05 | 2017-07-13 | University Of Iowa Research Foundation | Therapeutic bisphosphonates |
| EP3105238A4 (fr) | 2014-02-13 | 2017-11-08 | Ligand Pharmaceuticals, Inc. | Composés de promédicaments et leurs utilisations |
| WO2016003812A1 (fr) | 2014-07-02 | 2016-01-07 | Ligand Pharmaceuticals, Inc. | Composés de promédicaments et leurs utilisations |
| WO2017011686A1 (fr) | 2015-07-14 | 2017-01-19 | University Of Iowa Research Foundation | Promédicaments fluorescents |
| KR102116528B1 (ko) * | 2015-09-09 | 2020-05-28 | 칭화 유니버시티 | 고-효율 백신 아쥬반트로서 메발로네이트 경로 억제제 |
| CA3102210C (fr) | 2015-11-02 | 2022-06-14 | Pura Scents, Inc. | Distribution de parfum |
| USD816506S1 (en) | 2015-11-02 | 2018-05-01 | Pura Scents, Inc. | Vial for a scent dispenser |
| USD809116S1 (en) | 2015-11-02 | 2018-01-30 | Pura Scents | Dispenser |
| CN111788196A (zh) | 2018-01-09 | 2020-10-16 | 配体药物公司 | 缩醛化合物及其治疗用途 |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3553314A (en) * | 1968-12-23 | 1971-01-05 | Procter & Gamble | Oral compositions for calculus retardation |
| US3979385A (en) * | 1969-11-19 | 1976-09-07 | Henkel & Cie G.M.B.H. | 1-Aminoalkane-1,1-diphosphonic acids and their salts |
| DE1958123C3 (de) * | 1969-11-19 | 1978-09-28 | Henkel Kgaa, 4000 Duesseldorf | Verfahren zur Herstellung von 1 -Aminoalkan-1,1 -diphosphonsäuren oder deren Salzen |
| US3683080A (en) * | 1970-08-28 | 1972-08-08 | Procter & Gamble | Compositions for inhibiting anomalous deposition and mobilization of calcium phosphate in animal tissue |
| DE2104476C2 (de) * | 1971-02-01 | 1983-12-01 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur Verhinderung von Ausfällungen in Wasser oder wäßrigen Lösungen |
| CA1011820A (en) * | 1972-09-14 | 1977-06-07 | Richard H. Rein | Shielding gas for laser welding |
| DE2343147C2 (de) * | 1973-08-27 | 1982-06-09 | Henkel KGaA, 4000 Düsseldorf | Pyrrolidon-5,5-diphosphonsäuren, deren wasserlösliche Salze, und Verfahren zu ihrer Herstellung |
| US4034086A (en) * | 1973-08-27 | 1977-07-05 | Henkel & Cie G.M.B.H. | Pyrrolidone-5,5-diphosphonic acids |
| DE2343196C3 (de) * | 1973-08-27 | 1980-01-10 | Henkel Kgaa, 4000 Duesseldorf | Aiacycloalkan-2^-diphosphonsäuren oder deren wasserlösliche Salze |
| US3988443A (en) * | 1973-08-27 | 1976-10-26 | Henkel & Cie G.M.B.H. | Azacycloalkane-2,2-diphosphonic acids |
| US4134969A (en) * | 1974-02-04 | 1979-01-16 | Henkel Kommanditgesellschaft Auf Aktien (Henkel Kgaa) | Method of treatment of calcium disorders using aminoalkane-diphosphonic acids |
| DE2456666A1 (de) * | 1974-11-30 | 1976-08-12 | Henkel & Cie Gmbh | Verfahren zum stabilisieren von calcium-hydrogenphosphat-dihydrat gegen hydrolyse |
| DE2513966C2 (de) * | 1975-03-29 | 1983-06-23 | Henkel KGaA, 4000 Düsseldorf | Piperidon-6,6-diphosphonsäure und Verfahren zu deren Herstellung |
| DE2541981A1 (de) * | 1975-09-20 | 1977-03-24 | Bayer Ag | Verfahren zur herstellung von azacycloalkandiphosphonsaeuren |
| JPS5359674A (en) * | 1976-10-25 | 1978-05-29 | Nissan Chem Ind Ltd | 1-piperidinoalkane-1,1-diphosphonic acid derivatives and herbicidescontaining the same as active agent |
| US4239695A (en) * | 1977-03-24 | 1980-12-16 | Magna Corporation | Method of preparing phosphonates from nitriles |
| US4100167A (en) * | 1977-05-09 | 1978-07-11 | Nalco Chemical Company | Production of 1-aminoalkane-1, 1-diphosphonic acids using phosphorous acid and nitriles in a non-aqueous system |
| US4447256A (en) * | 1977-07-20 | 1984-05-08 | Nissan Chemical Industries, Ltd. | N-(Unsubstituted or substituted pyridyl)aminomethylene-diphosphonic acids, herbicidal compositions containing same, their use for herbicides, and process for preparing same |
| BR7804629A (pt) * | 1977-07-20 | 1979-04-03 | Nissan Chemical Ind Ltd | Compostos de acido n-piridil-amino-metileno-difosfonico,herbicidas que contem os mesmos e processo para sua producao |
| DE2745083C2 (de) * | 1977-10-07 | 1985-05-02 | Henkel KGaA, 4000 Düsseldorf | Hydroxydiphosphonsäuren und Verfahren zu deren Herstellung |
| DE2755940C2 (de) * | 1977-12-15 | 1986-01-02 | Basf Ag, 6700 Ludwigshafen | Mittel zur Regulierung des Pflanzenwachstums |
| JPS54135724A (en) * | 1978-04-11 | 1979-10-22 | Nissan Chem Ind Ltd | Preparation of amino-methylenedisulfonic acid derivative |
| JPS5598193A (en) * | 1979-01-22 | 1980-07-25 | Nissan Chem Ind Ltd | Methylenediphosphonic acid derivative and herbicide comprising it as active constituent |
| DE3016289A1 (de) * | 1980-04-28 | 1981-10-29 | Henkel KGaA, 4000 Düsseldorf | Verfahren zur herstellung von omega -amino-1-hydroxyalkyliden-1,1-bis-phosphonsaeuren |
| US4304734A (en) * | 1980-10-16 | 1981-12-08 | Vysoka Skola Chemicko-Technologicka | 6-Amino-1-hydroxyhexylidene diphosphonic acid, salts and a process for production thereof |
| DE3203308A1 (de) * | 1982-01-27 | 1983-07-28 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Diphosphonsaeure-derivate und diese enthaltende pharmazeutische praeparate |
| EP0085321B1 (fr) * | 1982-01-27 | 1986-08-27 | Schering Aktiengesellschaft | Dérivés d'acides diphosphoniques et préparations pharmaceutiques les contenant |
| DE3208600A1 (de) * | 1982-03-10 | 1983-09-22 | Henkel KGaA, 4000 Düsseldorf | Amidinodiphosphonsaeuren |
| IT1201087B (it) * | 1982-04-15 | 1989-01-27 | Gentili Ist Spa | Bifosfonati farmacologicamente attivi,procedimento per la loro preparazione e relative composizioni farmaceutiche |
| FR2531088B1 (fr) * | 1982-07-29 | 1987-08-28 | Sanofi Sa | Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation |
| DE3425812A1 (de) * | 1984-07-13 | 1986-01-16 | Deutsches Krebsforschungszentrum, 6900 Heidelberg | Neue 1-hydroxy-1,1-diphosphonsaeureverbindungen, verfahren zu ihrer herstellung und pharmakologische zubereitungen, insbesondere zur behandlung von knochentumoren |
| CH664158A5 (fr) * | 1984-07-18 | 1988-02-15 | Symphar Sa | Derives propylidenediphosphonates-1,3 substitues en position 2, leur procede de preparation et compositions pharmaceutiques 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 |
| DE3540150A1 (de) * | 1985-11-13 | 1987-05-14 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
| DE3626058A1 (de) * | 1986-08-01 | 1988-02-11 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
-
1985
- 1985-12-05 IL IL7724385A patent/IL77243A/en not_active IP Right Cessation
- 1985-12-06 US US06/806,155 patent/US5583122A/en not_active Expired - Lifetime
- 1985-12-16 EP EP85309140A patent/EP0186405B1/fr not_active Expired - Lifetime
- 1985-12-16 AT AT85309140T patent/ATE61370T1/de active
- 1985-12-16 DE DE2000175030 patent/DE10075030I2/de active Active
- 1985-12-16 DE DE8585309140T patent/DE3582033D1/de not_active Expired - Lifetime
- 1985-12-19 ZA ZA859694A patent/ZA859694B/xx unknown
- 1985-12-20 ES ES000550302D patent/ES8707543B9/es not_active Expired - Lifetime
- 1985-12-20 ES ES550302A patent/ES8707543A1/es not_active Expired
- 1985-12-20 DK DK599685A patent/DK168754B1/da not_active IP Right Cessation
- 1985-12-21 IE IE328685A patent/IE58749B1/en not_active IP Right Cessation
-
1987
- 1987-01-16 ES ES557322A patent/ES8802428A1/es not_active Expired
- 1987-01-16 ES ES557322D patent/ES8802428B9/es not_active Expired - Lifetime
-
2000
- 2000-11-10 LU LU90669C patent/LU90669I2/fr unknown
- 2000-12-01 NL NL300031C patent/NL300031I2/nl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES8802428A1 (es) | 1988-06-01 |
| ES550302A0 (es) | 1987-08-01 |
| ES8707543B9 (es) | 2013-05-08 |
| DK168754B1 (da) | 1994-06-06 |
| ATE61370T1 (de) | 1991-03-15 |
| ZA859694B (en) | 1986-08-27 |
| NL300031I2 (nl) | 2001-03-01 |
| ES557322A0 (es) | 1988-06-01 |
| IE58749B1 (en) | 1993-11-03 |
| DK599685A (da) | 1986-06-22 |
| EP0186405B1 (fr) | 1991-03-06 |
| EP0186405A3 (en) | 1987-10-28 |
| DK599685D0 (da) | 1985-12-20 |
| LU90669I2 (fr) | 2001-01-10 |
| NL300031I1 (nl) | 2001-02-01 |
| EP0186405A2 (fr) | 1986-07-02 |
| DE10075030I1 (de) | 2000-12-21 |
| IE853286L (en) | 1986-06-21 |
| ES8707543A1 (es) | 1987-08-01 |
| ES8802428B9 (en) | 2011-08-25 |
| DE3582033D1 (de) | 1991-04-11 |
| DE10075030I2 (de) | 2004-01-29 |
| US5583122A (en) | 1996-12-10 |
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| PEL | Intention of commissioner to extend period of protection | ||
| EXTG | Extension of patent term granted | ||
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| EXP | Patent expired |