NO300546B1 - Nye fosfonoravsyrederivater samt legemiddel inneholdende derivatene - Google Patents

Nye fosfonoravsyrederivater samt legemiddel inneholdende derivatene Download PDF

Info

Publication number: NO300546B1
Authority: NO; Norway
Prior art keywords: general formula; acid; compound; compounds; denotes
Prior art date: 1991-12-19

Application number

NO942304A

Other languages

English (en)

Norwegian (no)

Other versions

NO942304L (es

NO942304D0 (no

Inventor

Christos Tsaklakidis

Elmar Bosies

Angelika Esswein

Frieder Bauss

Original Assignee

Boehringer Mannheim Gmbh

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.)

1991-12-19

Filing date

1994-06-17

Publication date

1997-06-16

1994-06-17 Application filed by Boehringer Mannheim Gmbh filed Critical Boehringer Mannheim Gmbh

1994-06-17 Publication of NO942304D0 publication Critical patent/NO942304D0/no

1994-08-16 Publication of NO942304L publication Critical patent/NO942304L/no

1997-06-16 Publication of NO300546B1 publication Critical patent/NO300546B1/no

Links

239000003814 drug Substances 0.000 title claims abstract 3
229940079593 drug Drugs 0.000 title claims 2
239000002253 acid Substances 0.000 title description 8
150000001875 compounds Chemical class 0.000 claims abstract description 88
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
239000001257 hydrogen Substances 0.000 claims abstract description 11
150000003839 salts Chemical class 0.000 claims abstract description 8
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
125000002947 alkylene group Chemical group 0.000 claims abstract description 4
229910052736 halogen Inorganic materials 0.000 claims abstract description 4
150000002367 halogens Chemical class 0.000 claims abstract description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 3
125000003277 amino group Chemical group 0.000 claims abstract description 3
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims abstract description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 4
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
239000000463 material Substances 0.000 claims description 4
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
KMDMOMDSEVTJTI-UHFFFAOYSA-N 2-phosphonobutanedioic acid Chemical class OC(=O)CC(C(O)=O)P(O)(O)=O KMDMOMDSEVTJTI-UHFFFAOYSA-N 0.000 claims description 3
125000000623 heterocyclic group Chemical group 0.000 claims description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 2
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 2
MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 2
238000000034 method Methods 0.000 abstract description 17
125000000217 alkyl group Chemical group 0.000 abstract 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract 1
125000003342 alkenyl group Chemical group 0.000 abstract 1
125000006193 alkinyl group Chemical group 0.000 abstract 1
125000006615 aromatic heterocyclic group Chemical group 0.000 abstract 1
229910052791 calcium Inorganic materials 0.000 abstract 1
239000011575 calcium Substances 0.000 abstract 1
230000002503 metabolic effect Effects 0.000 abstract 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 1
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 49
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 20
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
-1 hexa-2,4-dienyl Chemical group 0.000 description 14
239000000243 solution Substances 0.000 description 14
239000002904 solvent Substances 0.000 description 14
229910000104 sodium hydride Inorganic materials 0.000 description 12
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 11
239000012312 sodium hydride Substances 0.000 description 11
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
239000003921 oil Substances 0.000 description 9
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
238000007792 addition Methods 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
150000002148 esters Chemical class 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
239000003480 eluent Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
GETQZCLCWQTVFV-UHFFFAOYSA-N anhydrous trimethylamine Natural products CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
150000002431 hydrogen Chemical class 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 4
229910000105 potassium hydride Inorganic materials 0.000 description 4
239000000843 powder Substances 0.000 description 4
235000011121 sodium hydroxide Nutrition 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
150000001733 carboxylic acid esters Chemical class 0.000 description 3
XUYJLQHKOGNDPB-UHFFFAOYSA-N carboxymethyl phosphonic acid Natural products OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 description 3
229920001429 chelating resin Polymers 0.000 description 3
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 3
SCILSIRRNFEWQZ-UHFFFAOYSA-N dimethyl 2-diethoxyphosphoryl-3-methylidenebutanedioate Chemical compound CCOP(=O)(OCC)C(C(=O)OC)C(=C)C(=O)OC SCILSIRRNFEWQZ-UHFFFAOYSA-N 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000203 mixture Substances 0.000 description 3
210000002997 osteoclast Anatomy 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
229960003975 potassium Drugs 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
238000006845 Michael addition reaction Methods 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
239000000654 additive Substances 0.000 description 2
239000003513 alkali Substances 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
125000000746 allylic group Chemical group 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
230000031709 bromination Effects 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
239000000872 buffer Substances 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 2
239000012876 carrier material Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
239000013078 crystal Substances 0.000 description 2
OQODIDDHELVXTM-ACCUITESSA-N diethyl (e)-2-(4-imidazol-1-ylbutyl)but-2-enedioate Chemical compound CCOC(=O)\C=C(C(=O)OCC)/CCCCN1C=CN=C1 OQODIDDHELVXTM-ACCUITESSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
238000005342 ion exchange Methods 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
201000008482 osteoarthritis Diseases 0.000 description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
125000001918 phosphonic acid ester group Chemical group 0.000 description 2
ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
239000011574 phosphorus Substances 0.000 description 2
229910052698 phosphorus Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
125000004825 2,2-dimethylpropylene group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[*:1])C([H])([H])[*:2] 0.000 description 1
DWIKYFWVCREMNE-UHFFFAOYSA-N 2-(2-aminoethyl)-3-phosphonobutanedioic acid Chemical compound NCCC(C(O)=O)C(C(O)=O)P(O)(O)=O DWIKYFWVCREMNE-UHFFFAOYSA-N 0.000 description 1
LUTJXFXLXOLPFN-UHFFFAOYSA-N 2-(3-aminopropyl)-3-phosphonobutanedioic acid Chemical compound NCCCC(C(O)=O)C(C(O)=O)P(O)(O)=O LUTJXFXLXOLPFN-UHFFFAOYSA-N 0.000 description 1
XPJXLFOSZUIVMM-UHFFFAOYSA-N 2-(4-aminobutyl)-3-phosphonobutanedioic acid Chemical compound NCCCCC(C(O)=O)C(C(O)=O)P(O)(O)=O XPJXLFOSZUIVMM-UHFFFAOYSA-N 0.000 description 1
LJDRKIGZOZXKOV-UHFFFAOYSA-N 2-(aminomethyl)-3-phosphonobutanedioic acid Chemical compound NCC(C(O)=O)C(C(O)=O)P(O)(O)=O LJDRKIGZOZXKOV-UHFFFAOYSA-N 0.000 description 1
SXFGJATXHINJKW-UHFFFAOYSA-N 2-(imidazol-1-ylmethyl)-3-phosphonobutanedioic acid Chemical compound OC(=O)C(P(O)(O)=O)C(C(=O)O)CN1C=CN=C1 SXFGJATXHINJKW-UHFFFAOYSA-N 0.000 description 1
XHFXYNCFTROUOP-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-3-phosphonobutanedioic acid Chemical compound CN(C)CC(C(O)=O)C(C(O)=O)P(O)(O)=O XHFXYNCFTROUOP-UHFFFAOYSA-N 0.000 description 1
AQVDGWSWFLGAHQ-UHFFFAOYSA-N 2-amino-3-phosphonobutanedioic acid Chemical compound OC(=O)C(N)C(C(O)=O)P(O)(O)=O AQVDGWSWFLGAHQ-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
XQFHZWGVCRSZDF-UHFFFAOYSA-N 2-phosphono-3-(pyrrolidin-1-ylmethyl)butanedioic acid Chemical compound OC(=O)C(P(O)(O)=O)C(C(=O)O)CN1CCCC1 XQFHZWGVCRSZDF-UHFFFAOYSA-N 0.000 description 1
125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
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150000007530 organic bases Chemical class 0.000 description 1
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238000007254 oxidation reaction Methods 0.000 description 1
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125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
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239000011736 potassium bicarbonate Substances 0.000 description 1
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TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
230000002265 prevention Effects 0.000 description 1
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229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
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QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
208000008281 urolithiasis Diseases 0.000 description 1
235000019871 vegetable fat Nutrition 0.000 description 1
239000008096 xylene Substances 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)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
- 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
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
- 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
- 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
- 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
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3

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

NO942304A 1991-12-19 1994-06-17 Nye fosfonoravsyrederivater samt legemiddel inneholdende derivatene NO300546B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE4141928A DE4141928A1 (de)	1991-12-19	1991-12-19	Neue phosphonobernsteinsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel
PCT/EP1992/002890 WO1993012122A1 (de)	1991-12-19	1992-12-14	Neue phosphonobernsteinsäurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel

Publications (3)

Publication Number	Publication Date
NO942304D0 NO942304D0 (no)	1994-06-17
NO942304L NO942304L (es)	1994-08-16
NO300546B1 true NO300546B1 (no)	1997-06-16

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ID=6447460

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Application Number	Title	Priority Date	Filing Date
NO942304A NO300546B1 (no)	1991-12-19	1994-06-17	Nye fosfonoravsyrederivater samt legemiddel inneholdende derivatene

Country Status (22)

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US (2)	US5538957A (es)
EP (1)	EP0618920B1 (es)
JP (1)	JPH07507046A (es)
AT (1)	ATE141277T1 (es)
AU (1)	AU662790B2 (es)
CA (1)	CA2125867A1 (es)
CZ (1)	CZ151894A3 (es)
DE (2)	DE4141928A1 (es)
DK (1)	DK0618920T3 (es)
ES (1)	ES2093399T3 (es)
FI (1)	FI942910A0 (es)
GR (1)	GR3021110T3 (es)
HU (1)	HUT66771A (es)
IL (1)	IL104090A (es)
MX (1)	MX9207335A (es)
NO (1)	NO300546B1 (es)
NZ (1)	NZ246152A (es)
RU (1)	RU2115656C1 (es)
SK (1)	SK74694A3 (es)
TW (1)	TW222636B (es)
WO (1)	WO1993012122A1 (es)
ZA (1)	ZA929815B (es)

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DE4410601A1 (de) *	1994-03-26	1995-09-28	Boehringer Mannheim Gmbh	Neue 2.4-Diphosphonoglutarsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
US6011021A (en) *	1996-06-17	2000-01-04	Guilford Pharmaceuticals Inc.	Methods of cancer treatment using naaladase inhibitors
GB2313126A (en) *	1996-05-14	1997-11-19	Albright & Wilson Uk Ltd	Polymer compositions containing phosphorus
US5795877A (en) *	1996-12-31	1998-08-18	Guilford Pharmaceuticals Inc.	Inhibitors of NAALADase enzyme activity
US6071965A (en) *	1996-06-17	2000-06-06	Guilford Pharmaceuticals Inc.	Phosphinic alkanoic acid derivatives
TR199802638T2 (xx)	1996-06-17	1999-03-22	Guilford Pharmaceuticals, Inc.	Kanser tedavisinde naaladase inhibit�rleri kullan�m�.
US6384022B1 (en)	1996-06-17	2002-05-07	Guilford Pharmaceuticals Inc.	Prodrugs of NAALAdase inhibitors
US5902817A (en) *	1997-04-09	1999-05-11	Guilford Pharmaceuticals Inc.	Certain sulfoxide and sulfone derivatives
US6054444A (en) *	1997-04-24	2000-04-25	Guilford Pharmaceuticals Inc.	Phosphonic acid derivatives
US5977090A (en) *	1996-09-27	1999-11-02	Guilford Pharmaceuticals Inc.	Pharmaceutical compositions and methods of treating compulsive disorders using NAALADase inhibitors
US6025344A (en) *	1996-06-17	2000-02-15	Guilford Pharmaceuticals Inc.	Certain dioic acid derivatives useful as NAALADase inhibitors
US6046180A (en) *	1996-06-17	2000-04-04	Guilford Pharmaceuticals Inc.	NAALADase inhibitors
US5672592A (en) *	1996-06-17	1997-09-30	Guilford Pharmaceuticals Inc.	Certain phosphonomethyl-pentanedioic acid derivatives thereof
US6025345A (en) *	1996-06-17	2000-02-15	Guilford Pharmaceuticals Inc.	Inhibitors of NAALADase enzyme activity
US5863536A (en) *	1996-12-31	1999-01-26	Guilford Pharmaceuticals Inc.	Phosphoramidate derivatives
US5962521A (en) *	1997-04-04	1999-10-05	Guilford Pharmaceuticals Inc.	Hydroxamic acid derivatives
US5981209A (en) *	1997-12-04	1999-11-09	Guilford Pharmaceuticals Inc.	Use of NAALADase activity to identify prostate cancer and benign prostatic hyperplasia
US6028216A (en) *	1997-12-31	2000-02-22	Guilford Pharmaceuticals Inc.	Asymmetric syntheses and intermediates for preparing enantiomer-enriched hydroxyphosphinyl derivatives
US6121252A (en) *	1998-03-30	2000-09-19	Guilford Pharmaceuticals Inc.	Phosphinic acid derivatives
US6395718B1 (en)	1998-07-06	2002-05-28	Guilford Pharmaceuticals Inc.	Pharmaceutical compositions and methods of inhibiting angiogenesis using naaladase inhibitors
HUP0103382A3 (en)	1998-07-06	2002-12-28	Guilford Pharmaceuticals Inc B	Naaladase inhibitors useful as pharmaceutical compounds and compositions
US6265609B1 (en)	1998-07-06	2001-07-24	Guilford Pharmaceuticals Inc.	Thio-substituted pentanedioic acid derivatives
IT1303672B1 (it)	1998-07-28	2001-02-23	Nicox Sa	Sali nitrati di farmaci attivi nei disordini ossei
US6313159B1 (en)	1999-08-20	2001-11-06	Guilford Pharmaceuticals Inc.	Metabotropic glutamate receptor ligand derivatives as naaladase inhibitors
ATE343390T1 (de) *	2000-10-25	2006-11-15	Smithkline Beecham Corp	Kalzilytische verbindungen

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DE2360797C2 (de) *	1973-12-06	1985-05-23	Henkel KGaA, 4000 Düsseldorf	Pharmazeutische Präparate
IL77243A (en) *	1984-12-21	1996-11-14	Procter & Gamble	Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds
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1991
- 1991-12-19 DE DE4141928A patent/DE4141928A1/de not_active Withdrawn
1992
- 1992-12-01 TW TW081109635A patent/TW222636B/zh active
- 1992-12-14 DK DK93900042.8T patent/DK0618920T3/da active
- 1992-12-14 WO PCT/EP1992/002890 patent/WO1993012122A1/de not_active Application Discontinuation
- 1992-12-14 SK SK746-94A patent/SK74694A3/sk unknown
- 1992-12-14 HU HU9401834A patent/HUT66771A/hu unknown
- 1992-12-14 NZ NZ246152A patent/NZ246152A/en unknown
- 1992-12-14 DE DE59206925T patent/DE59206925D1/de not_active Expired - Fee Related
- 1992-12-14 CZ CZ941518A patent/CZ151894A3/cs unknown
- 1992-12-14 ES ES93900042T patent/ES2093399T3/es not_active Expired - Lifetime
- 1992-12-14 CA CA002125867A patent/CA2125867A1/en not_active Abandoned
- 1992-12-14 AT AT93900042T patent/ATE141277T1/de active
- 1992-12-14 EP EP93900042A patent/EP0618920B1/de not_active Expired - Lifetime
- 1992-12-14 RU RU94030812A patent/RU2115656C1/ru active
- 1992-12-14 AU AU31580/93A patent/AU662790B2/en not_active Ceased
- 1992-12-14 IL IL104090A patent/IL104090A/xx not_active IP Right Cessation
- 1992-12-14 US US08/244,245 patent/US5538957A/en not_active Expired - Fee Related
- 1992-12-14 JP JP5510624A patent/JPH07507046A/ja active Pending
- 1992-12-16 MX MX9207335A patent/MX9207335A/es not_active IP Right Cessation
- 1992-12-18 ZA ZA929815A patent/ZA929815B/xx unknown
1994
- 1994-06-17 FI FI942910A patent/FI942910A0/fi unknown
- 1994-06-17 NO NO942304A patent/NO300546B1/no not_active IP Right Cessation
1995
- 1995-06-05 US US08/465,360 patent/US5627170A/en not_active Expired - Fee Related
1996
- 1996-09-19 GR GR960402474T patent/GR3021110T3/el unknown

Also Published As

Publication number	Publication date
FI942910A (fi)	1994-06-17
RU2115656C1 (ru)	1998-07-20
EP0618920B1 (de)	1996-08-14
NO942304L (es)	1994-08-16
DK0618920T3 (da)	1996-12-30
CA2125867A1 (en)	1993-06-24
IL104090A0 (en)	1993-05-13
ZA929815B (en)	1994-06-20
WO1993012122A1 (de)	1993-06-24
DE59206925D1 (de)	1996-09-19
ES2093399T3 (es)	1996-12-16
TW222636B (es)	1994-04-21
JPH07507046A (ja)	1995-08-03
GR3021110T3 (en)	1996-12-31
CZ151894A3 (en)	1995-01-18
IL104090A (en)	1997-03-18
ATE141277T1 (de)	1996-08-15
MX9207335A (es)	1993-06-01
AU662790B2 (en)	1995-09-14
US5627170A (en)	1997-05-06
SK74694A3 (en)	1995-02-08
AU3158093A (en)	1993-07-19
NZ246152A (en)	1995-12-21
DE4141928A1 (de)	1993-06-24
HUT66771A (en)	1994-12-28
EP0618920A1 (de)	1994-10-12
US5538957A (en)	1996-07-23
NO942304D0 (no)	1994-06-17
FI942910A0 (fi)	1994-06-17
HU9401834D0 (en)	1994-09-28

Publication	Publication Date	Title
NO300546B1 (no)	1997-06-16	Nye fosfonoravsyrederivater samt legemiddel inneholdende derivatene
FI87223B (fi)	1992-08-31	Foerfarande foer framstaellning av nya farmakologiskt aktiva alkyldifosfonsyraderivat.
RU1823875C (ru)	1993-06-23	Способ получени производных дифосфоновой кислоты
DK168629B1 (da)	1994-05-09	1-hydroxy-omega-aminoalkan-1,1-diphosphonsyrederivater og fremgangsmåde til fremstilling deraf samt lægemidler indeholdende disse forbindelser
US4687767A (en)	1987-08-18	Certain 1-hydroxyethane, 1,1-di-phosphonic acid derivatives useful in treating calcium metabolism disturbances
US4719203A (en)	1988-01-12	Diphosphonic acid derivatives, processes for the preparation thereof and pharmaceutical compositions containing them
US5393748A (en)	1995-02-28	Methylenebisphosphonic acid derivatives
NO170939B (no)	1992-09-21	Fremgangsmaate for fremstilling av aromatisk-substituerte azacykloalkylalkandifosfonsyrer
NO157504B (no)	1987-12-21	Analogifremgangsmaate til fremstilling av hydroksyamino-alkan- eller -alken-fosfonsyrederivater med antimikrobiell virkning.
US4211786A (en)	1980-07-08	Mercaptoacyldihydropyrazole carboxylic acid derivatives
NO178030B (no)	1995-10-02	Analogifremgangsmåte ved fremstilling av terapeutisk aktive metylenbisfosfonsyrederivater
NO176663B (no)	1995-01-30	Analogifremgangsmåte for fremstilling av terapeutisk anvendbare, aromatisk substituerte alkylaminoalkandifosfonsyrer
US5206253A (en)	1993-04-27	Disphosphonic acid derivatives, processes for their production and pharmaceutical preparations containing these compounds
KR100246809B1 (ko)	2000-04-01	비고리형 아미딘기 함유 디포스폰산유도체, 이들의 제조방법 및 이들을 포함하는 의약조성물
US2849454A (en)	1958-08-26	Gamma (3-indolyl)-gamma-keto-propyl phosphonic acids
US4221804A (en)	1980-09-09	Mercaptoacyldihydropyrazole carboxylic acid derivatives
US4322541A (en)	1982-03-30	Dihydropyrazole-5-carboxylic acid and analogs
US5698541A (en)	1997-12-16	2,4-diphosphonoglutaric acid derivatives, processes for their production and pharmaceutical agents containing these compounds
RUP et al.	1968	Preparation of Esters of 4-Hydroxypyrazole-3, 5-dicarboxylic
CS244815B2 (en)	1986-08-14	Production method of 2-alkylthio-1-aminoalkyl-5-oxo-2-pycarbonitrilles

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