FI108034B - Menetelmä terapeuttisesti tai profylaktisesti käyttökelpoisten guanidiinialkyyli-1,1-bisfosfonihappojohdannaisten valmistamiseksi - Google Patents

Menetelmä terapeuttisesti tai profylaktisesti käyttökelpoisten guanidiinialkyyli-1,1-bisfosfonihappojohdannaisten valmistamiseksi Download PDF

Info

Publication number: FI108034B
Authority: FI; Finland
Prior art keywords: formula; atom; alkyl; compound; zero
Prior art date: 1992-12-02

Application number

FI935360A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI935360A0 (fi

FI935360L (fi

Inventor

Hans-Jochen Lang

Christoph Naumann

Anne-Marie Moura

Juergen Sandow

Original Assignee

Hoechst Ag

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.)

1992-12-02

Filing date

1993-11-30

Publication date

2001-11-15

1993-05-13 Priority claimed from DE19934316019 external-priority patent/DE4316019A1/de

1993-11-30 Application filed by Hoechst Ag filed Critical Hoechst Ag

1993-11-30 Publication of FI935360A0 publication Critical patent/FI935360A0/fi

1994-06-03 Publication of FI935360L publication Critical patent/FI935360L/fi

2001-11-15 Application granted granted Critical

2001-11-15 Publication of FI108034B publication Critical patent/FI108034B/fi

Links

239000002253 acid Substances 0.000 title claims description 31
238000000034 method Methods 0.000 title claims description 23
238000002360 preparation method Methods 0.000 title claims description 22
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 title claims description 17
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 title claims description 10
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 title claims description 10
150000001875 compounds Chemical class 0.000 claims abstract description 71
-1 (aminoiminomethyl) amino Chemical group 0.000 claims description 67
229910052801 chlorine Inorganic materials 0.000 claims description 31
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 31
229910052731 fluorine Inorganic materials 0.000 claims description 26
239000000460 chlorine Substances 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
150000002148 esters Chemical class 0.000 claims description 19
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
239000011737 fluorine Substances 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
229910052794 bromium Inorganic materials 0.000 claims description 13
125000001309 chloro group Chemical group Cl* 0.000 claims description 13
125000005843 halogen group Chemical group 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 13
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 11
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
229910052740 iodine Inorganic materials 0.000 claims description 11
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 11
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
125000001153 fluoro group Chemical group F* 0.000 claims description 10
239000012442 inert solvent Substances 0.000 claims description 10
GLBYWZQBFIWDCZ-UHFFFAOYSA-N 1,1-bis(diethoxyphosphoryl)ethane Chemical compound CCOP(=O)(OCC)C(C)P(=O)(OCC)OCC GLBYWZQBFIWDCZ-UHFFFAOYSA-N 0.000 claims description 9
MXYOPVWZZKEAGX-UHFFFAOYSA-N 1-phosphonoethylphosphonic acid Chemical compound OP(=O)(O)C(C)P(O)(O)=O MXYOPVWZZKEAGX-UHFFFAOYSA-N 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
239000001257 hydrogen Substances 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
229910052717 sulfur Inorganic materials 0.000 claims description 8
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
125000005956 isoquinolyl group Chemical group 0.000 claims description 7
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 7
125000004430 oxygen atom Chemical group O* 0.000 claims description 7
125000003342 alkenyl group Chemical group 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
125000005493 quinolyl group Chemical group 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
125000004434 sulfur atom Chemical group 0.000 claims description 5
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
125000004122 cyclic group Chemical group 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 3
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 3
125000002947 alkylene group Chemical group 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 2
LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical compound C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 0.000 claims description 2
239000011630 iodine Substances 0.000 claims description 2
239000011591 potassium Substances 0.000 claims description 2
229910052700 potassium Inorganic materials 0.000 claims description 2
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 11
239000003814 drug Substances 0.000 abstract description 9
208000020084 Bone disease Diseases 0.000 abstract description 3
230000003412 degenerative effect Effects 0.000 abstract 1
238000011321 prophylaxis Methods 0.000 abstract 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
239000002904 solvent Substances 0.000 description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Natural products CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
239000011734 sodium Substances 0.000 description 12
230000007062 hydrolysis Effects 0.000 description 11
238000006460 hydrolysis reaction Methods 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
238000004679 31P NMR spectroscopy Methods 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
235000019441 ethanol Nutrition 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000000546 pharmaceutical excipient Substances 0.000 description 9
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
229960004198 guanidine Drugs 0.000 description 8
238000002844 melting Methods 0.000 description 8
230000008018 melting Effects 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
239000000243 solution Substances 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
208000001132 Osteoporosis Diseases 0.000 description 7
239000002585 base Substances 0.000 description 7
238000001816 cooling Methods 0.000 description 7
239000003480 eluent Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
210000000988 bone and bone Anatomy 0.000 description 6
239000000969 carrier Substances 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
238000010992 reflux Methods 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
238000005160 1H NMR spectroscopy Methods 0.000 description 5
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 5
238000009835 boiling Methods 0.000 description 5
239000000463 material Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
238000000967 suction filtration Methods 0.000 description 5
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
208000006386 Bone Resorption Diseases 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
150000001558 benzoic acid derivatives Chemical class 0.000 description 4
230000024279 bone resorption Effects 0.000 description 4
229910052736 halogen Inorganic materials 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 3
150000001735 carboxylic acids Chemical class 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
201000010099 disease Diseases 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
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239000003995 emulsifying agent Substances 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
230000001605 fetal effect Effects 0.000 description 3
239000007789 gas Substances 0.000 description 3
239000001963 growth medium Substances 0.000 description 3
150000002367 halogens Chemical class 0.000 description 3
230000002265 prevention Effects 0.000 description 3
239000000047 product Substances 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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
102000003982 Parathyroid hormone Human genes 0.000 description 2
108090000445 Parathyroid hormone Proteins 0.000 description 2
241000700159 Rattus Species 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
229910052786 argon Inorganic materials 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000000470 constituent Substances 0.000 description 2
239000002178 crystalline material Substances 0.000 description 2
229940042400 direct acting antivirals phosphonic acid derivative Drugs 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000001727 glucose Nutrition 0.000 description 2
239000008187 granular material Substances 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
239000002609 medium Substances 0.000 description 2
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
239000000199 parathyroid hormone Substances 0.000 description 2
229960001319 parathyroid hormone Drugs 0.000 description 2
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150000003007 phosphonic acid derivatives Chemical class 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
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239000007787 solid Substances 0.000 description 2
238000004611 spectroscopical analysis Methods 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000725 suspension Substances 0.000 description 2
239000003826 tablet Substances 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
206010005949 Bone cancer Diseases 0.000 description 1
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FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
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238000005727 Friedel-Crafts reaction Methods 0.000 description 1
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241000124008 Mammalia Species 0.000 description 1
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238000005481 NMR spectroscopy Methods 0.000 description 1
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FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 1
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150000008064 anhydrides Chemical class 0.000 description 1
239000010775 animal oil Substances 0.000 description 1
239000002518 antifoaming agent Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
235000006708 antioxidants Nutrition 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
150000001559 benzoic acids Chemical class 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000003026 cod liver oil Substances 0.000 description 1
235000012716 cod liver oil Nutrition 0.000 description 1
239000003086 colorant Substances 0.000 description 1
229940125890 compound Ia Drugs 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000013583 drug formulation Substances 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
210000003754 fetus Anatomy 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000003349 gelling agent Substances 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
230000000148 hypercalcaemia Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
231100000518 lethal Toxicity 0.000 description 1
230000001665 lethal effect Effects 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000014380 magnesium carbonate Nutrition 0.000 description 1
239000000395 magnesium oxide Substances 0.000 description 1
CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
235000012245 magnesium oxide Nutrition 0.000 description 1
AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
208000027202 mammary Paget disease Diseases 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
230000001394 metastastic effect Effects 0.000 description 1
206010061289 metastatic neoplasm Diseases 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
QUDIHMKRNFWABQ-UHFFFAOYSA-N n-(n'-methylcarbamimidoyl)-1h-indole-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2NC(C(=O)NC(N)=NC)=CC2=C1 QUDIHMKRNFWABQ-UHFFFAOYSA-N 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
239000012434 nucleophilic reagent Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
230000011164 ossification Effects 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
238000000527 sonication Methods 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000005406 washing 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)]
- 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)
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4025—Esters of poly(thio)phosphonic acids
- C07F9/405—Esters of poly(thio)phosphonic 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
- C07F9/5532—Seven-(or more) membered rings
- C07F9/5535—Seven-(or more) membered rings condensed with carbocyclic rings or ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic 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
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic 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
- C07F9/60—Quinoline or hydrogenated quinoline ring systems

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Rheumatology (AREA)
Hematology (AREA)
Obesity (AREA)
Vascular Medicine (AREA)
Diabetes (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

FI935360A 1992-12-02 1993-11-30 Menetelmä terapeuttisesti tai profylaktisesti käyttökelpoisten guanidiinialkyyli-1,1-bisfosfonihappojohdannaisten valmistamiseksi FI108034B (fi)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
DE4240422		1992-12-02
DE4240422		1992-12-02
DE19934316019 DE4316019A1 (de)	1993-05-13	1993-05-13	Benzoylguanidinalkyl-1,1-bisphosphonsäuren, Verfahren zu ihrer Herstellung und ihre Verwendung
DE4316019		1993-05-13
DE4332362		1993-09-23
DE4332362		1993-09-23

Publications (3)

Publication Number	Publication Date
FI935360A0 FI935360A0 (fi)	1993-11-30
FI935360L FI935360L (fi)	1994-06-03
FI108034B true FI108034B (fi)	2001-11-15

Family

ID=27204511

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI935360A FI108034B (fi)	1992-12-02	1993-11-30	Menetelmä terapeuttisesti tai profylaktisesti käyttökelpoisten guanidiinialkyyli-1,1-bisfosfonihappojohdannaisten valmistamiseksi

Country Status (15)

Country	Link
US (3)	US5395826A (pt)
EP (1)	EP0600371B1 (pt)
JP (1)	JP3499905B2 (pt)
KR (1)	KR100347423B1 (pt)
AT (1)	ATE176476T1 (pt)
AU (1)	AU663983B2 (pt)
BR (1)	BR9304910A (pt)
CA (1)	CA2110443C (pt)
DE (1)	DE59309360D1 (pt)
DK (1)	DK0600371T3 (pt)
ES (1)	ES2129485T3 (pt)
FI (1)	FI108034B (pt)
GR (1)	GR3030020T3 (pt)
NZ (1)	NZ250322A (pt)
RU (1)	RU2114855C1 (pt)

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DE4223940A1 (de) *	1992-07-21	1994-01-27	Boehringer Mannheim Gmbh	Neue acyclische Amidingruppen-haltige Diphosphonsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
EP0600371B1 (de) *	1992-12-02	1999-02-03	Hoechst Aktiengesellschaft	Guanidinalkyl-1, 1-bisphosphonsäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung
US6169107B1 (en)	1993-04-28	2001-01-02	Sumitomo Pharmaceutical Co., Ltd.	Indoloylguanidine derivatives
DE4404183A1 (de) *	1994-02-10	1995-08-17	Merck Patent Gmbh	4-Amino-1-piperidylbenzoylguanidine
DE4421495A1 (de) *	1994-06-20	1995-12-21	Merck Patent Gmbh	Heterocyclyloxy-benzoylguanidine
CA2160600A1 (en) *	1994-10-18	1996-04-19	Masahumi Kitano	Indoloylguanidine derivatives
DE19540995A1 (de) *	1995-11-03	1997-05-07	Hoechst Ag	Substituierte Sulfonimidamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
DE19542306A1 (de) *	1995-11-14	1997-05-15	Hoechst Ag	Sulfonylamino-substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
PL316439A1 (en) *	1995-11-20	1997-05-26	Hoechst Ag	Novel substituted derivatives of benzoyloguanidine, method of obtaining them, their application in production of pharmaceutic and diagnostic agents and pharmaceutic agent as such
DE19601303A1 (de) *	1996-01-16	1997-07-17	Boehringer Ingelheim Kg	Neuartige Benzoylguanidin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung bei der Herstellung von Arzneimitteln
ZA981936B (en) *	1997-03-07	1999-09-06	Metabasis Therapeutics Inc	Novel benzimidazole 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
AU6452098A (en) *	1997-03-07	1998-09-22	Metabasis Therapeutics, Inc.	Novel purine inhibitors of fructose-1,6-bisphosphatase
US6558784B1 (en)	1999-03-02	2003-05-06	Adc Composites, Llc	Composite footwear upper and method of manufacturing a composite footwear upper
WO2001049295A1 (en) *	2000-01-04	2001-07-12	The Regents Of The University Of California	Use of low dosage bisphosphonates to inhibit cardiac and arterial calcification
CA2444718A1 (en) *	2001-05-02	2002-11-14	Novartis Ag	Method of administration of bisphosphonates by inhalation in the treatment or prevention of bone resorption and osteoporosis
KR100620672B1 (ko) *	2002-12-14	2006-09-13	주식회사 하이닉스반도체	포토레지스트 조성물
WO2005090370A1 (en) *	2004-02-05	2005-09-29	The Regents Of The University Of California	Pharmacologically active agents containing esterified phosphonates and methods for use thereof
US8642577B2 (en)	2005-04-08	2014-02-04	Chimerix, Inc.	Compounds, compositions and methods for the treatment of poxvirus infections
US20070003608A1 (en) *	2005-04-08	2007-01-04	Almond Merrick R	Compounds, compositions and methods for the treatment of viral infections and other medical disorders
CA2658834A1 (en) *	2006-11-21	2008-05-29	Teikoku Pharma Usa, Inc.	Bisphosphonate inhalant formulations and methods for using the same
JP5562255B2 (ja) *	2008-01-25	2014-07-30	キメリクス，インコーポレイテッド	ウイルス感染を治療する方法
US20100034752A1 (en) *	2008-08-11	2010-02-11	Toru Hibi	Inhalant formulations comprising a bisphosphonate and a pyrazolone derivative and methods for using the same
US8614200B2 (en)	2009-07-21	2013-12-24	Chimerix, Inc.	Compounds, compositions and methods for treating ocular conditions
EP2462152A4 (en)	2009-08-03	2013-02-13	Chimerix Inc	COMPOSITION AND METHOD FOR THE TREATMENT OF VIRUS INFECTIONS AND TEMPORED VIRUSES
ES2629165T3 (es)	2010-02-12	2017-08-07	Chimerix, Inc.	Métodos de tratamiento de una infección vírica
WO2011139709A2 (en)	2010-04-26	2011-11-10	Chimerix, Inc.	Methods of treating retroviral infections and related dosage regimes

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IL77243A (en) *	1984-12-21	1996-11-14	Procter & Gamble	Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds
DE3623397A1 (de) *	1986-07-11	1988-01-14	Boehringer Mannheim Gmbh	Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel
KR880011136A (ko) *	1987-03-11	1988-10-26	모리오까 시게오	아졸- 아미노메틸렌 비스포스폰산 유도체
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US4990503A (en) *	1988-08-12	1991-02-05	Yamanouchi Pharmaceutical Co., Ltd.	Heterocyclic bisphosphonic acid derivatives
DE3929582A1 (de) *	1989-09-06	1991-03-07	Hoechst Ag	Benzoylguanidine, verfahren zu ihrer herstellung, ihre verwendung als medikament sowie sie enthaltendes medikament
TW222637B (pt) *	1991-12-12	1994-04-21	Hoechst Ag
EP0600371B1 (de) *	1992-12-02	1999-02-03	Hoechst Aktiengesellschaft	Guanidinalkyl-1, 1-bisphosphonsäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung

1993
- 1993-11-25 EP EP93118992A patent/EP0600371B1/de not_active Expired - Lifetime
- 1993-11-25 ES ES93118992T patent/ES2129485T3/es not_active Expired - Lifetime
- 1993-11-25 DK DK93118992T patent/DK0600371T3/da active
- 1993-11-25 DE DE59309360T patent/DE59309360D1/de not_active Expired - Fee Related
- 1993-11-25 AT AT93118992T patent/ATE176476T1/de not_active IP Right Cessation
- 1993-11-30 US US08/159,119 patent/US5395826A/en not_active Expired - Fee Related
- 1993-11-30 FI FI935360A patent/FI108034B/fi not_active IP Right Cessation
- 1993-11-30 AU AU52040/93A patent/AU663983B2/en not_active Ceased
- 1993-11-30 NZ NZ250322A patent/NZ250322A/en unknown
- 1993-12-01 JP JP30142893A patent/JP3499905B2/ja not_active Expired - Fee Related
- 1993-12-01 RU RU93054537A patent/RU2114855C1/ru not_active IP Right Cessation
- 1993-12-01 CA CA002110443A patent/CA2110443C/en not_active Expired - Fee Related
- 1993-12-01 BR BR9304910A patent/BR9304910A/pt not_active Application Discontinuation
- 1993-12-02 KR KR1019930026202A patent/KR100347423B1/ko not_active Expired - Fee Related
1994
- 1994-11-23 US US08/346,239 patent/US5498617A/en not_active Expired - Fee Related
1996
- 1996-03-01 US US08/609,473 patent/US5661174A/en not_active Expired - Fee Related
1999
- 1999-04-21 GR GR990401101T patent/GR3030020T3/el unknown

Also Published As

Publication number	Publication date
EP0600371B1 (de)	1999-02-03
US5661174A (en)	1997-08-26
JP3499905B2 (ja)	2004-02-23
NZ250322A (en)	1995-12-21
US5395826A (en)	1995-03-07
DK0600371T3 (da)	1999-09-20
BR9304910A (pt)	1994-08-16
KR940014421A (ko)	1994-07-18
CA2110443A1 (en)	1994-06-03
JPH06279470A (ja)	1994-10-04
EP0600371A1 (de)	1994-06-08
AU663983B2 (en)	1995-10-26
FI935360A0 (fi)	1993-11-30
AU5204093A (en)	1994-06-16
US5498617A (en)	1996-03-12
KR100347423B1 (ko)	2002-10-30
DE59309360D1 (de)	1999-03-18
GR3030020T3 (en)	1999-07-30
ES2129485T3 (es)	1999-06-16
CA2110443C (en)	2006-02-21
FI935360L (fi)	1994-06-03
ATE176476T1 (de)	1999-02-15
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