KR920008055A - 벤조헤테로사이클릴알킬아미노알칸디포스폰산 - Google Patents
벤조헤테로사이클릴알킬아미노알칸디포스폰산 Download PDFInfo
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- KR920008055A KR920008055A KR1019910018380A KR910018380A KR920008055A KR 920008055 A KR920008055 A KR 920008055A KR 1019910018380 A KR1019910018380 A KR 1019910018380A KR 910018380 A KR910018380 A KR 910018380A KR 920008055 A KR920008055 A KR 920008055A
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- 239000002253 acid Substances 0.000 title claims abstract 4
- 150000003839 salts Chemical class 0.000 claims abstract 26
- 150000001875 compounds Chemical class 0.000 claims abstract 21
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 17
- 239000001257 hydrogen Substances 0.000 claims abstract 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract 12
- 150000002431 hydrogen Chemical class 0.000 claims abstract 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract 8
- 150000002367 halogens Chemical class 0.000 claims abstract 8
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims abstract 8
- 238000000034 method Methods 0.000 claims abstract 6
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract 5
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims abstract 3
- 230000003913 calcium metabolism Effects 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims abstract 2
- -1 2,3-dihydrobenzofuranyl Chemical group 0.000 claims 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 7
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 claims 5
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims 5
- 239000004480 active ingredient Substances 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 208000037147 Hypercalcaemia Diseases 0.000 claims 1
- 206010027476 Metastases Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims 1
- 208000010191 Osteitis Deformans Diseases 0.000 claims 1
- 208000001132 Osteoporosis Diseases 0.000 claims 1
- 208000027868 Paget disease Diseases 0.000 claims 1
- QVHDQYPWHWQEAD-UHFFFAOYSA-N [1-hydroxy-3-[(5-methoxy-2,3-dihydro-1-benzofuran-2-yl)methylamino]-1-phosphonopropyl]phosphonic acid Chemical compound COC1=CC=C2OC(CNCCC(O)(P(O)(O)=O)P(O)(O)=O)CC2=C1 QVHDQYPWHWQEAD-UHFFFAOYSA-N 0.000 claims 1
- FYARYEHYPNBVDZ-UHFFFAOYSA-N [1-hydroxy-3-[(6-methoxy-2,3-dihydro-1,4-benzodioxin-2-yl)methyl-methylamino]-1-phosphonopropyl]phosphonic acid Chemical compound O1C(CN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O)COC2=CC(OC)=CC=C21 FYARYEHYPNBVDZ-UHFFFAOYSA-N 0.000 claims 1
- NZFLJJWJSYLLPQ-UHFFFAOYSA-N [1-hydroxy-3-[(6-methyl-2,3-dihydro-1,4-benzodioxin-2-yl)methylamino]-1-phosphonopropyl]phosphonic acid Chemical compound O1C(CNCCC(O)(P(O)(O)=O)P(O)(O)=O)COC2=CC(C)=CC=C21 NZFLJJWJSYLLPQ-UHFFFAOYSA-N 0.000 claims 1
- RZXDZJMWWDSATQ-UHFFFAOYSA-N [1-hydroxy-3-[methyl-[(6-methyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl]amino]-1-phosphonopropyl]phosphonic acid Chemical compound CC1=CC=C2OC(CN(CCC(O)(P(O)(O)=O)P(O)(O)=O)C)COC2=C1 RZXDZJMWWDSATQ-UHFFFAOYSA-N 0.000 claims 1
- ISOLAHJVCZRFNY-UHFFFAOYSA-N [3-[(6-chloro-2,3-dihydro-1,4-benzodioxin-2-yl)methyl-methylamino]-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound ClC1=CC=C2OC(CN(CCC(O)(P(O)(O)=O)P(O)(O)=O)C)COC2=C1 ISOLAHJVCZRFNY-UHFFFAOYSA-N 0.000 claims 1
- GEMHTXLLSWDLGC-UHFFFAOYSA-N [3-[(6-chloro-2,3-dihydro-1,4-benzodioxin-3-yl)methyl-methylamino]-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound C1=C(Cl)C=C2OC(CN(CCC(O)(P(O)(O)=O)P(O)(O)=O)C)COC2=C1 GEMHTXLLSWDLGC-UHFFFAOYSA-N 0.000 claims 1
- GRUCXHJHQXYAMF-UHFFFAOYSA-N [3-[2,3-dihydro-1,4-benzodioxin-3-ylmethyl(methyl)amino]-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound C1=CC=C2OC(CN(CCC(O)(P(O)(O)=O)P(O)(O)=O)C)COC2=C1 GRUCXHJHQXYAMF-UHFFFAOYSA-N 0.000 claims 1
- RDBPDDSKMLPQCE-UHFFFAOYSA-N [3-[2,3-dihydro-1-benzothiophen-2-ylmethyl(methyl)amino]-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound C1=CC=C2SC(CN(CCC(O)(P(O)(O)=O)P(O)(O)=O)C)CC2=C1 RDBPDDSKMLPQCE-UHFFFAOYSA-N 0.000 claims 1
- KXOVBGSDANUSCB-UHFFFAOYSA-N [3-[2-(3,4-dihydro-2h-chromen-2-yl)ethyl-methylamino]-1-hydroxy-1-phosphonopropyl]phosphonic acid Chemical compound C1=CC=C2OC(CCN(C)CCC(O)(P(O)(O)=O)P(O)(O)=O)CCC2=C1 KXOVBGSDANUSCB-UHFFFAOYSA-N 0.000 claims 1
- 230000005856 abnormality Effects 0.000 claims 1
- 125000005087 alkynylcarbonyl group Chemical group 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 206010003246 arthritis Diseases 0.000 claims 1
- 210000001188 articular cartilage Anatomy 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 claims 1
- 229910052791 calcium Inorganic materials 0.000 claims 1
- 239000011575 calcium Substances 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000003412 degenerative effect Effects 0.000 claims 1
- 230000008021 deposition Effects 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 230000000148 hypercalcaemia Effects 0.000 claims 1
- 208000030915 hypercalcemia disease Diseases 0.000 claims 1
- 206010020718 hyperplasia Diseases 0.000 claims 1
- 239000007943 implant Substances 0.000 claims 1
- 208000018937 joint inflammation Diseases 0.000 claims 1
- 208000027202 mammary Paget disease Diseases 0.000 claims 1
- 230000009401 metastasis Effects 0.000 claims 1
- 229910017604 nitric acid Inorganic materials 0.000 claims 1
- 201000001245 periodontitis Diseases 0.000 claims 1
- 230000000865 phosphorylative effect Effects 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- GPTFURBXHJWNHR-UHFFFAOYSA-N protopine Chemical compound C1=C2C(=O)CC3=CC=C4OCOC4=C3CN(C)CCC2=CC2=C1OCO2 GPTFURBXHJWNHR-UHFFFAOYSA-N 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 abstract 2
- 241001465754 Metazoa Species 0.000 abstract 1
- 150000007513 acids Chemical class 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
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- 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)]
-
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
- C07F9/65522—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- A—HUMAN NECESSITIES
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
- C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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- C07F9/655354—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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Abstract
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Claims (20)
- 일반식(I)의 벤조헤테로사이클릴알킬아미노알칸디포스폰산 또는 이의 염.상기식에서, R1및 R2는 서로 독립적으로 수소, 저급 알킬, 저급 알콕시, 할로겐 또는 트리플루오로메틸이고, R3는 수소 또는 저급알킬이며, X 및 Y는 서로 독립적으로 옥시 또는 티오이고, alk1및 alk2는 동일하거나 또는 상이한 저급 알킬렌 라디칼이고, n은 0 또는 1이며, m과 m′은 서로 독립적으로 0,1 또는 2이고, n,m 및 m′의 합은 1,2 또는 3이다.
- 제1항에서, R1및 R2는 서로 독립적으로 수소, 저급 알킬, 저급 알콕시, 할로겐 또는 트리플루오로메틸이고, R3가 수소 또는 저급알킬이며, 일반식(Ia)의 벤조헤테로사이클릴 라디칼이 2,3-디하이드로벤조 푸라닐, 2,3-디하이드로벤조티에닐, 크로마닐, 티오 크로미닐, 1,4-벤조디옥사닐, 1,4-벤즈옥시티아닐, 1,4-벤조디티아닐, 2,3,4,5-테트라하이드로벤즈옥세피닐, 2,3,4,5-테트라하이드로벤조티에피닐, 2,3,4,5-테트라하이드로벤조디옥세피닐, 2,3,4,5-테트라하이드로벤즈옥사티에피닐 또는 2,3,4,5-테트라하이드로벤조 디티에피닐이고, alk1및 alk2는 동일하거나 또는 상이한 저급 알킬렌 라디칼인 일반식(I)의 화합물 또는 이의 염.
- 제1항에서, R1및 R2는 서로 독립적으로 수소, 저급 알킬, 저급 알콕시, 할로겐 또는 트리플루오로메틸이고, R3는 수소 또는 저급알킬이며, 일반시(Ia)의 벤조헤테로사이클릴 라디칼이 2,3-디하이드로벤조 푸라닐, 크로마닐 또는 1,4-벤조디옥사닐이고, alk1및 alk2는 동일하거나 또는 상이한 저급 알킬렌 라디칼인 일반식(I)의 화합물 또는 이의 염.
- 제2항에서, R1및 R2는 서로 독립적으로 수소, C1-C4알킬, C1-C4알콕시 또는 원자번호 35이하의 할로겐이고, R3가 수소 또는 C1-C7알킬이며, 일반식(Ia)의 벤조헤테로사이클릴 라디칼이 2,3-디하이드로벤조 푸라닐, 2,3-디하이드로벤조티에닐, 크로마닐, 티오 크로미닐, 1,4-벤조디옥사닐, 1,4-벤즈옥시티아닐, 1,4-벤조디티아닐, 2,3,4,5-테트라하이드로벤즈옥세피닐, 2,3,4,5-테트라하이드로벤조티에피닐, 2,3,4,5-테트라하이드로벤조디옥세피닐, 2,3,4,5-테트라하이드로벤즈옥사티에피닐 또는 2,3,4,5-테트라하이드로벤조 디티에피닐이고, alk1및 alk2는 동일하거나 또는 상이한 C1-C4알킬렌 라디칼인 일반식(I)의 화합물 또는 이의 염.
- 제2항에서, R1및 R2는 서로 독립적으로 수소, C1-C4알킬, C1-C4알콕시 또는 원자번호 35이하의 할로겐이고, R3가 수소 또는 C1-C4알킬이며, 일반식(Ia)의 벤조헤테로사이클릴 라디칼이 2,3-디하이드로벤조 푸라닐, 크로마닐 또는 1,4-벤조디옥사닐이고, alk1이 C1-C4알킬렌이며 alk2가 C2-C3알킬렌인 일반식(I)의 화합물 또는 이의 염.
- 제2항에서, R1이 수소, C1-C4알킬, C1-C4알콕시 또는 원자번호 35이하의 할로겐이고, R2가 수소이며, R3가 수소 또는 C1-C7알킬이고, 일반식(Ia)의 벤조헤테로사이클릴 라디칼이 2,3-디하이드로벤조 푸라닐, 크로마닐 또는 1,4-벤조디옥사닐이며, alk1이 C1-C3알킬렌이고 alk2가 에틸렌인 일반식(I)의 화합물 또는 이의 염.
- 3-{N-2[2-(크로만-3-일)에틸]아미노}-1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-{N-2[2-(크로만-3-일)에틸]-N-메틸아미노}-1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-[N-(6-메틸-1,4-벤조디옥산-2-일)메틸-N-메틸아미노]-1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-[N-(6-메톡시-1,4-벤조디옥산-2-일)메틸-N-메틸아미노]-1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-[N-(7-클로로-1,4-벤조디옥산-2-일)메틸-N-메틸아미노]-1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-[N-(2,3-디하이드로벤조티엔-2-일)메틸-N-메틸아미노]-1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-[N-[2-(크로만-2-일)에틸]-N-메틸아미노]-1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-[N-(6-메틸벤조-1,4-디옥산-2-일메틸)아미노]1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-[N-(벤조-1,4-디옥산-2-일메틸)메틸아미노]1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-[N-(5-메톡시-2,3-디하이드로벤조푸란-2-일)메틸아미노]1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 3-[N-(6-클로로벤조-1,4-디옥산-2-일메틸)-N-메틸아미노]1-하이드록시프로판-1,1-디포스폰산 또는 이의 염.
- 약학적으로 활성성분으로서 유리형태 또는 약학적으로 허용가능한 염 형태의 제1항 내지 제17항 중 어느 한 항에 따른 화합물을 통상적인 약학적 부형제와 함께 함유하는 약학적 조성물.
- 약학적으로 활성성분으로서 유리형태 또는 약학적으로 허용가능한 염 형태의 제1항 내지 제17항 중 어느 한 항에 따른 일반식 화합물을 통상적인 약학적 부형제와 함께 포함함을 특징으로 하여, 칼슘대사 이상으로 기인되는 질환, 관절의 염증진행, 관절연골의 퇴행성 진행 및 혈관내 또는 인공기간 이식체내의 칼슘침적 치료, 특히 종양-유발된 과칼슘증, 골전이 및 파젯씨 질환(Paget′s disease), 골다공증, 치근막지주염, 및 상피소체기능항진증을 치료하기 위한 약학적 조성물.
- a)일반식(Ⅱ) 화합물에서, 관능적으로 변형된 포스포노 Z1및 필요할 경우, Z2를 포스포노 그룹으로 전환시키거나, b)일반식(Ⅲa) 및 (Ⅳa)의 또는 이의 염을 서로 반응 시키거나, 환원조건하에서, 일반식(Ⅲb) 및 (Ⅳb)의 화합물을 서로 반응시키거나, c)일반식(V)의 화합물을 인산화제와 반응시키고 Z5가 시아노 또는 카바모일인 일반식(V)의 화합물로부터 출발하여 수득한 일반식(Va)의 중간체 또는 이의 염에서, 이의 1차 생성물을 가수분해하며 질산으로 처리하여 아미노 그룹을 하이드록시로 대체하며, 각각의 경우 아미노-보호그룹 R0을 제거하고, 존재하거나 필요할 경우, 생성된 화합물을 일반식(I)의 상이한 화합물로 전환시키고, 이 방법에 따라 수득가능한 이성체 혼합물을 각 성분으로 분리하며, 바람직한 이성체를 분리하고/하거나 본 방법에 따라 수득가능한 유리 화합물을 염으로 전환시키고/시키거나 본 방법에 따라 수득가능한 염을 상응하는 유리 화합물로 전환시킴을 특징으로 하여, 일반식(I)의 벤조헤테로사이클린알킬아미노알칼디포스폰산을 제조하는 방법.상기식에서, R1및 R2는 서로 독립적으로 수소, 저급 알킬, 저급 알콕시, 할로겐 또는 트리플루오로메틸이고, R3는 수소 또는 저급알킬이며, X 및 Y는 서로 독립적으로 옥시 또는 티오이고, alk1및 alk2는 동일하거나 또는 상이한 저급 알킬렌 라디칼이며, n은 0 또는 1이고, m과 m′은 서로 독립적으로 0,1 또는 2이고, n,m 및 m′의 합은 1,2 또는 3이며, R′3은 상기 정의한 R3그룹 중의 하나이거나 또는 아미노 보호그룹 Ro이고, Z1은 관능적으로 변형된 포스포노 그룹이고, Z2는 유리 또는 관능적으로 변형된 포스포노 그룹이며, 라디칼 Z3및 Z4중 하나는 반응적으로 에스테르화된 하이드록시 그룹이고 다른 하나는 -N(R′3)-H(여기에서, R′3는 상기 정의한 바와 같다)그룹이고, alk3는 라디칼 alk1에 상응하는 이중결합된 라디칼, 즉 저급 알카닐릴리덴 라디칼이며, Z5는 카복시, 카바모일 또는 시아노이다.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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CH3332/90-3 | 1990-10-18 | ||
CH333290 | 1990-10-18 |
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US (1) | US5204334A (ko) |
EP (1) | EP0481920B1 (ko) |
JP (1) | JPH04264091A (ko) |
KR (1) | KR920008055A (ko) |
AT (1) | ATE125262T1 (ko) |
AU (1) | AU652384B2 (ko) |
CA (1) | CA2053599A1 (ko) |
DE (1) | DE59106021D1 (ko) |
DK (1) | DK0481920T3 (ko) |
ES (1) | ES2074690T3 (ko) |
FI (1) | FI914854A (ko) |
HU (1) | HU213206B (ko) |
IE (1) | IE66985B1 (ko) |
IL (1) | IL99723A (ko) |
MX (1) | MX9101616A (ko) |
NO (1) | NO178340C (ko) |
NZ (1) | NZ240254A (ko) |
PT (1) | PT99241B (ko) |
ZA (1) | ZA918274B (ko) |
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JPH06135976A (ja) * | 1992-10-30 | 1994-05-17 | Toray Ind Inc | メタンジホスホン酸誘導体、その製造方法およびその医薬用途 |
DE4301072B4 (de) * | 1993-01-16 | 2006-08-24 | Crystal Growing Systems Gmbh | Verfahren zum Ziehen von Einkristallen aus einer Schmelze |
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DE3203308A1 (de) * | 1982-01-27 | 1983-07-28 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Diphosphonsaeure-derivate und diese enthaltende pharmazeutische praeparate |
EP0084822B1 (de) * | 1982-01-27 | 1986-01-08 | Schering Aktiengesellschaft | Diphosphonsäure-Derivate und diese enthaltende pharmazeutische Präparate |
DE3365492D1 (en) * | 1982-01-27 | 1986-10-02 | Schering Ag | Diphosphonic acid derivatives and pharmaceutical preparations containing them |
DE3428524A1 (de) * | 1984-08-02 | 1986-02-13 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
US4761406A (en) * | 1985-06-06 | 1988-08-02 | The Procter & Gamble Company | Regimen for treating osteoporosis |
DE3626058A1 (de) * | 1986-08-01 | 1988-02-11 | Boehringer Mannheim Gmbh | Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel |
ATE64397T1 (de) * | 1986-11-21 | 1991-06-15 | Ciba Geigy Ag | Aromatisch substituierte azacycloalkylalkandiphosphons|uren. |
US5110807A (en) * | 1988-12-01 | 1992-05-05 | Ciba-Geigy Corporation | Araliphatylaminoalkanediphosphonic acids |
US4933472A (en) * | 1988-04-08 | 1990-06-12 | Yamanouchi Pharmaceutical Co., Ltd. | Substituted aminomethylenebis(phosphonic acid) derivatives |
-
1991
- 1991-09-25 US US07/765,360 patent/US5204334A/en not_active Expired - Fee Related
- 1991-10-02 AU AU85541/91A patent/AU652384B2/en not_active Ceased
- 1991-10-09 DE DE59106021T patent/DE59106021D1/de not_active Expired - Fee Related
- 1991-10-09 DK DK91810786.3T patent/DK0481920T3/da active
- 1991-10-09 ES ES91810786T patent/ES2074690T3/es not_active Expired - Lifetime
- 1991-10-09 AT AT91810786T patent/ATE125262T1/de not_active IP Right Cessation
- 1991-10-09 EP EP91810786A patent/EP0481920B1/de not_active Expired - Lifetime
- 1991-10-11 IL IL9972391A patent/IL99723A/en not_active IP Right Cessation
- 1991-10-15 FI FI914854A patent/FI914854A/fi not_active Application Discontinuation
- 1991-10-16 CA CA002053599A patent/CA2053599A1/en not_active Abandoned
- 1991-10-16 PT PT99241A patent/PT99241B/pt not_active IP Right Cessation
- 1991-10-16 MX MX9101616A patent/MX9101616A/es not_active IP Right Cessation
- 1991-10-16 NZ NZ240254A patent/NZ240254A/en unknown
- 1991-10-17 IE IE365191A patent/IE66985B1/en not_active IP Right Cessation
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- 1991-10-17 HU HU913281A patent/HU213206B/hu not_active IP Right Cessation
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Also Published As
Publication number | Publication date |
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AU652384B2 (en) | 1994-08-25 |
JPH04264091A (ja) | 1992-09-18 |
IL99723A (en) | 1996-01-19 |
PT99241B (pt) | 1999-04-30 |
HU913281D0 (en) | 1992-01-28 |
EP0481920B1 (de) | 1995-07-19 |
DE59106021D1 (de) | 1995-08-24 |
IL99723A0 (en) | 1992-08-18 |
DK0481920T3 (da) | 1995-09-11 |
US5204334A (en) | 1993-04-20 |
NO178340C (no) | 1996-03-06 |
NZ240254A (en) | 1993-12-23 |
CA2053599A1 (en) | 1992-04-19 |
PT99241A (pt) | 1992-09-30 |
EP0481920A1 (de) | 1992-04-22 |
FI914854A0 (fi) | 1991-10-15 |
MX9101616A (es) | 1992-06-05 |
NO914078D0 (no) | 1991-10-17 |
AU8554191A (en) | 1992-04-30 |
NO178340B (no) | 1995-11-27 |
FI914854A (fi) | 1992-04-19 |
NO914078L (no) | 1992-04-21 |
IE66985B1 (en) | 1996-02-21 |
HUT59415A (en) | 1992-05-28 |
IE913651A1 (en) | 1992-04-22 |
ES2074690T3 (es) | 1995-09-16 |
HU213206B (en) | 1997-03-28 |
ZA918274B (en) | 1992-06-24 |
ATE125262T1 (de) | 1995-08-15 |
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