OA11068A - Pharmaceutical aminophosphonic acid derivatives - Google Patents

Pharmaceutical aminophosphonic acid derivatives Download PDF

Info

Publication number: OA11068A
Authority: OA; OAPI
Prior art keywords: hydroxy; compound; formula; diethyl; methoxy
Prior art date: 1996-12-20

Application number

OA9900136A

Other languages

English (en)

Inventor

Lan Mong Nguyen

Hieu Trung Phan

Vinh Van Diep

Simon Floret

Raymond Azoulay

Eric Niesor

Rober John Ife

Craig Leigh Bentzen

Original Assignee

Symphar Sa

Smithkline Beecham Plc

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.)

1996-12-20

Filing date

1999-06-18

Publication date

2003-03-10

1999-06-18 Application filed by Symphar Sa, Smithkline Beecham Plc filed Critical Symphar Sa

2003-03-10 Publication of OA11068A publication Critical patent/OA11068A/en

Links

PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical class NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 title abstract description 5
108010033266 Lipoprotein(a) Proteins 0.000 claims abstract description 5
102000057248 Lipoprotein(a) Human genes 0.000 claims abstract 3
150000001875 compounds Chemical class 0.000 claims description 78
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 31
125000000217 alkyl group Chemical group 0.000 claims description 28
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
-1 nitro, hydroxy,hydroxymethyl Chemical group 0.000 claims description 18
ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 claims description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 14
125000004076 pyridyl group Chemical group 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 13
238000000034 method Methods 0.000 claims description 13
239000001257 hydrogen Substances 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
150000002466 imines Chemical class 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 7
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
108090001030 Lipoproteins Proteins 0.000 claims description 5
102000004895 Lipoproteins Human genes 0.000 claims description 5
230000003247 decreasing effect Effects 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 4
229910052796 boron Inorganic materials 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
238000002560 therapeutic procedure Methods 0.000 claims description 4
201000001320 Atherosclerosis Diseases 0.000 claims description 3
241000790917 Dioxys <bee> Species 0.000 claims description 3
208000007536 Thrombosis Diseases 0.000 claims description 3
125000001118 alkylidene group Chemical group 0.000 claims description 3
238000002399 angioplasty Methods 0.000 claims description 3
208000037803 restenosis Diseases 0.000 claims description 3
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 2
125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
229910052801 chlorine Inorganic materials 0.000 claims description 2
125000004663 dialkyl amino group Chemical group 0.000 claims description 2
201000010099 disease Diseases 0.000 claims description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
238000006268 reductive amination reaction Methods 0.000 claims description 2
125000004665 trialkylsilyl group Chemical group 0.000 claims description 2
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 6
YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims 2
125000003282 alkyl amino group Chemical group 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
125000004093 cyano group Chemical group *C#N 0.000 claims 1
OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
230000000694 effects Effects 0.000 abstract description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract 1
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
239000000203 mixture Substances 0.000 description 40
102100040214 Apolipoprotein(a) Human genes 0.000 description 34
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
101710115418 Apolipoprotein(a) Proteins 0.000 description 31
125000003118 aryl group Chemical group 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
239000007787 solid Substances 0.000 description 18
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
239000002904 solvent Substances 0.000 description 17
238000004440 column chromatography Methods 0.000 description 14
239000000243 solution Substances 0.000 description 14
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
NFORZJQPTUSMRL-UHFFFAOYSA-N dipropan-2-yl hydrogen phosphite Chemical compound CC(C)OP(O)OC(C)C NFORZJQPTUSMRL-UHFFFAOYSA-N 0.000 description 7
239000012071 phase Substances 0.000 description 7
150000003839 salts Chemical class 0.000 description 7
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 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
WISXXOGOMDYNSN-UHFFFAOYSA-N 2,6-dimethylpyridin-3-amine Chemical compound CC1=CC=C(N)C(C)=N1 WISXXOGOMDYNSN-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
101150041968 CDC13 gene Proteins 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
NVLTWXMZECWWPC-UHFFFAOYSA-N 3-hydroxy-4,5-dimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(O)=C1OC NVLTWXMZECWWPC-UHFFFAOYSA-N 0.000 description 4
241000282567 Macaca fascicularis Species 0.000 description 4
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
229960004132 diethyl ether Drugs 0.000 description 4
230000003287 optical effect Effects 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000012360 testing method Methods 0.000 description 4
238000001665 trituration Methods 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
235000019502 Orange oil Nutrition 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
208000006011 Stroke Diseases 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000000969 carrier Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
230000003197 catalytic effect Effects 0.000 description 3
229910052681 coesite Inorganic materials 0.000 description 3
208000029078 coronary artery disease Diseases 0.000 description 3
229910052906 cristobalite Inorganic materials 0.000 description 3
238000000921 elemental analysis Methods 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
239000010502 orange oil Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
235000012239 silicon dioxide Nutrition 0.000 description 3
229910052682 stishovite Inorganic materials 0.000 description 3
239000003826 tablet Substances 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
229910052905 tridymite Inorganic materials 0.000 description 3
MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 2
JLTXBASHJPWWES-UHFFFAOYSA-N 3,4-dimethoxy-5-methylbenzaldehyde Chemical compound COC1=CC(C=O)=CC(C)=C1OC JLTXBASHJPWWES-UHFFFAOYSA-N 0.000 description 2
MGJSDNCLGHCTIL-UHFFFAOYSA-N 4-hydroxy-3-methoxy-5-methylbenzaldehyde Chemical compound COC1=CC(C=O)=CC(C)=C1O MGJSDNCLGHCTIL-UHFFFAOYSA-N 0.000 description 2
108010012927 Apoprotein(a) Proteins 0.000 description 2
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
238000003556 assay Methods 0.000 description 2
239000002585 base Substances 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
238000009835 boiling Methods 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000003086 colorant Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
238000003821 enantio-separation Methods 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000001963 growth medium Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
208000010125 myocardial infarction Diseases 0.000 description 2
235000001968 nicotinic acid Nutrition 0.000 description 2
229960003512 nicotinic acid Drugs 0.000 description 2
239000011664 nicotinic acid Substances 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
235000011149 sulphuric acid Nutrition 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
238000005303 weighing Methods 0.000 description 2
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
MJVZSRZTBDMYLX-UHFFFAOYSA-N 2,6-dichloropyridin-3-amine Chemical compound NC1=CC=C(Cl)N=C1Cl MJVZSRZTBDMYLX-UHFFFAOYSA-N 0.000 description 1
PTBHRJOTANEONS-UHFFFAOYSA-N 2,6-dimethoxypyridin-3-amine Chemical compound COC1=CC=C(N)C(OC)=N1 PTBHRJOTANEONS-UHFFFAOYSA-N 0.000 description 1
HVHZEKKZMFRULH-UHFFFAOYSA-N 2,6-ditert-butyl-4-methylpyridine Chemical compound CC1=CC(C(C)(C)C)=NC(C(C)(C)C)=C1 HVHZEKKZMFRULH-UHFFFAOYSA-N 0.000 description 1
UQGXJTFCHIBNLQ-UHFFFAOYSA-N 3,4-dihydroxy-5-methylbenzaldehyde Chemical compound CC1=CC(C=O)=CC(O)=C1O UQGXJTFCHIBNLQ-UHFFFAOYSA-N 0.000 description 1
XDOKRVXGCWSNFV-UHFFFAOYSA-N 3-hydroxy-4-methoxy-5-methylbenzaldehyde Chemical compound COC1=C(C)C=C(C=O)C=C1O XDOKRVXGCWSNFV-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
235000003911 Arachis Nutrition 0.000 description 1
244000105624 Arachis hypogaea Species 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
208000014882 Carotid artery disease Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
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 1
102000003886 Glycoproteins Human genes 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 1
206010061216 Infarction Diseases 0.000 description 1
206010022562 Intermittent claudication Diseases 0.000 description 1
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
102000013566 Plasminogen Human genes 0.000 description 1
108010051456 Plasminogen Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
241000288906 Primates Species 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
235000003434 Sesamum indicum Nutrition 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
239000008365 aqueous carrier Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
230000000923 atherogenic effect Effects 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
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 1
229940045348 brown mixture Drugs 0.000 description 1
244000309466 calf Species 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
208000037876 carotid Atherosclerosis Diseases 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
239000000470 constituent Substances 0.000 description 1
238000011161 development Methods 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000009826 distribution Methods 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
239000003925 fat Substances 0.000 description 1
235000019197 fats Nutrition 0.000 description 1
238000001030 gas--liquid chromatography Methods 0.000 description 1
238000003304 gavage Methods 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
230000035876 healing Effects 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
230000007574 infarction Effects 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
208000021156 intermittent vascular claudication Diseases 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
229910052808 lithium carbonate Inorganic materials 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
235000011837 pasties Nutrition 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
208000030613 peripheral artery disease Diseases 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229940093956 potassium carbonate Drugs 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
235000008001 rakum palm Nutrition 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
229960001866 silicon dioxide Drugs 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000010186 staining Methods 0.000 description 1
239000003270 steroid hormone Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
239000003104 tissue culture media Substances 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
230000035899 viability Effects 0.000 description 1
239000001993 wax Substances 0.000 description 1
230000003442 weekly effect Effects 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
- C07F9/547—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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Biochemistry (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

OA9900136A 1996-12-20 1999-06-18 Pharmaceutical aminophosphonic acid derivatives OA11068A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GBGB9626615.0A GB9626615D0 (en)	1996-12-20	1996-12-20	Novel compounds

Publications (1)

Publication Number	Publication Date
OA11068A true OA11068A (en)	2003-03-10

Family

ID=10804837

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9900136A OA11068A (en)	1996-12-20	1999-06-18	Pharmaceutical aminophosphonic acid derivatives

Country Status (31)

Country	Link
US (2)	US6303784B1 (id)
EP (1)	EP0946572B1 (id)
JP (1)	JP2001506667A (id)
KR (1)	KR20000069609A (id)
CN (1)	CN1105117C (id)
AP (1)	AP9901546A0 (id)
AR (1)	AR008541A1 (id)
AT (1)	ATE255117T1 (id)
AU (1)	AU5858898A (id)
BG (1)	BG103574A (id)
BR (1)	BR9714650A (id)
CA (1)	CA2275696A1 (id)
CO (1)	CO4930276A1 (id)
DE (1)	DE69726449T2 (id)
DZ (1)	DZ2377A1 (id)
EA (1)	EA199900580A1 (id)
GB (1)	GB9626615D0 (id)
HU (1)	HUP0002171A3 (id)
ID (1)	ID22053A (id)
IL (1)	IL130334A0 (id)
MA (1)	MA24427A1 (id)
NO (1)	NO993001D0 (id)
NZ (1)	NZ335884A (id)
OA (1)	OA11068A (id)
PE (1)	PE46799A1 (id)
PL (1)	PL334189A1 (id)
SK (1)	SK81099A3 (id)
TR (1)	TR199901423T2 (id)
TW (1)	TW434221B (id)
WO (1)	WO1998028310A1 (id)
ZA (1)	ZA9711431B (id)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ520752A (en)	2000-02-16	2004-03-26	Smithkline Beecham P	Pyrimidine-4-one derivatives as LDL-PLA2 inhibitors
US7442689B2 (en)	2000-02-29	2008-10-28	Medicure International Inc.	Cardioprotective phosphonates and malonates
EP1531157B1 (en) *	2000-02-29	2008-03-19	Medicure International Inc.	Cardioprotective phosphonates
WO2001064692A1 (en) *	2000-02-29	2001-09-07	Medicure International Inc.	Cardioprotective phosphonates and malonates
US6897228B2 (en)	2000-07-07	2005-05-24	Medicure International Inc.	Pyridoxine and pyridoxal analogues: new uses
US20030114421A1 (en) *	2000-09-27	2003-06-19	Phan Hieu Trung	Alpha-substituted beta-aminoethyl phosphonate derivatives
EP1320536A1 (en) *	2000-09-27	2003-06-25	Ilex Oncology Research S.A.	$g(a)-SUBSTITUTED $g(b)-AMINOETHYL PHOSPHONATES
GB0024808D0 (en)	2000-10-10	2000-11-22	Smithkline Beecham Plc	Novel compounds
GB0025849D0 (en) *	2000-10-23	2000-12-06	Smithkline Beecham Plc	Novel compounds
MXPA04007797A (es) *	2002-02-11	2005-09-08	Ilex Products Inc	Derivados de fosfonato heteroarilalquilo a-sustituidos.
US7208481B2 (en) *	2002-02-19	2007-04-24	Ilex Products, Inc.	Aminodiphosphonate apolipoprotein E modulators
US7459468B2 (en)	2004-10-28	2008-12-02	Medicure International, Inc.	Aryl sulfonic pyridoxines as antiplatelet agents
JP4824968B2 (ja) *	2005-08-18	2011-11-30	株式会社クレハ	ホスホン酸誘導体及びその酸付加塩、並びにそれを用いた農園芸用病害防除剤
KR101861883B1 (ko)	2010-12-06	2018-05-28	글락소 그룹 리미티드	Lp-PLA₂에 의해 매개되는 질환 또는 상태의 치료에 사용하기 위한 피리미디논 화합물
EP2739627A4 (en)	2011-07-27	2015-01-21	Glaxo Group Ltd	2,3-DIHYDROIMIDAZO [1,2-C] PYRIMIDIN-5 (1H) -ONE COMPOUNDS AND USE AS INHIBITORS OF LP-PLA2
EP2736908A1 (en)	2011-07-27	2014-06-04	Glaxo Group Limited	Bicyclic pyrimidone compounds
SI2751094T1 (sl)	2011-09-01	2018-10-30	Glaxo Group Limited	Nova kristalinična oblika
CA2899124A1 (en)	2013-01-25	2014-07-31	Glaxosmithkline Intellectual Property Development Limited	Compounds
UY35276A (es)	2013-01-25	2014-08-29	Glaxosmithkline Ip Dev Ltd	Nuevos compuestos que inhiben la actividad de Lp-PLA2
BR112015017397A2 (pt)	2013-01-25	2017-07-11	Glaxosmithkline Ip Dev Ltd	compostos pirimidona bicíclica como inibidores de lp-pla2
WO2016012917A1 (en)	2014-07-22	2016-01-28	Glaxosmithkline Intellectual Property Development Limited	1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2
WO2016012916A1 (en)	2014-07-22	2016-01-28	Glaxosmithkline Intellectual Property Development Limited	1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2
CN114805389B (zh)	2019-11-09	2023-08-29	上海赛默罗生物科技有限公司	三环二氢咪唑并嘧啶酮衍生物、其制备方法、药物组合物和用途
CN115304620A (zh)	2021-05-07	2022-11-08	上海赛默罗生物科技有限公司	嘧啶酮衍生物、其制备方法、药物组合物和用途

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CH683996A5 (fr)	1992-03-05	1994-06-30	Symphar Sa	Dérivés aminophosphonates substitués, leur procédé de préparation et compositions pharmaceutiques les contenant.
DE4433244A1 (de)	1994-09-19	1996-03-28	Hoechst Ag	Aminomethylphosphon- und Aminomethylphosphinsäure-Derivate und deren Verwendung zur Behandlung von degenerativen Gelenkserkrankungen
CH690264A5 (fr)	1995-06-30	2000-06-30	Symphar Sa	Dérivés aminophosphonates substitués, leur procédé de préparation et leur utilisation pour la préparation de compositions pharmaceutiques.
GB9626536D0 (en)	1996-12-20	1997-02-05	Symphar Sa	Novel compounds

1996
- 1996-12-20 GB GBGB9626615.0A patent/GB9626615D0/en active Pending
1997
- 1997-12-17 HU HU0002171A patent/HUP0002171A3/hu unknown
- 1997-12-17 IL IL13033497A patent/IL130334A0/xx unknown
- 1997-12-17 DZ DZ970227A patent/DZ2377A1/xx active
- 1997-12-17 BR BR9714650-1A patent/BR9714650A/pt not_active Application Discontinuation
- 1997-12-17 AT AT97954436T patent/ATE255117T1/de not_active IP Right Cessation
- 1997-12-17 AP APAP/P/1999/001546A patent/AP9901546A0/en unknown
- 1997-12-17 US US09/331,385 patent/US6303784B1/en not_active Expired - Fee Related
- 1997-12-17 ID IDW990550A patent/ID22053A/id unknown
- 1997-12-17 JP JP52836498A patent/JP2001506667A/ja active Pending
- 1997-12-17 KR KR1019997005605A patent/KR20000069609A/ko not_active Ceased
- 1997-12-17 CA CA002275696A patent/CA2275696A1/en not_active Abandoned
- 1997-12-17 EP EP97954436A patent/EP0946572B1/en not_active Expired - Lifetime
- 1997-12-17 AU AU58588/98A patent/AU5858898A/en not_active Abandoned
- 1997-12-17 NZ NZ335884A patent/NZ335884A/xx unknown
- 1997-12-17 CN CN97180724A patent/CN1105117C/zh not_active Expired - Fee Related
- 1997-12-17 EA EA199900580A patent/EA199900580A1/ru unknown
- 1997-12-17 DE DE69726449T patent/DE69726449T2/de not_active Expired - Fee Related
- 1997-12-17 SK SK810-99A patent/SK81099A3/sk unknown
- 1997-12-17 TR TR1999/01423T patent/TR199901423T2/xx unknown
- 1997-12-17 PL PL97334189A patent/PL334189A1/xx unknown
- 1997-12-17 WO PCT/EP1997/007161 patent/WO1998028310A1/en not_active Ceased
- 1997-12-18 MA MA24903A patent/MA24427A1/fr unknown
- 1997-12-18 AR ARP970105997A patent/AR008541A1/es unknown
- 1997-12-18 CO CO97073902A patent/CO4930276A1/es unknown
- 1997-12-18 PE PE1997001130A patent/PE46799A1/es not_active Application Discontinuation
- 1997-12-19 ZA ZA9711431A patent/ZA9711431B/xx unknown
- 1997-12-20 TW TW086119555A patent/TW434221B/zh active
1999
- 1999-06-18 NO NO993001A patent/NO993001D0/no not_active Application Discontinuation
- 1999-06-18 OA OA9900136A patent/OA11068A/en unknown
- 1999-07-13 BG BG103574A patent/BG103574A/bg unknown
2001
- 2001-09-04 US US09/946,737 patent/US20020082423A1/en not_active Abandoned

Also Published As

Publication number	Publication date
TR199901423T2 (xx)	1999-10-21
AU5858898A (en)	1998-07-17
BG103574A (bg)	2000-11-30
IL130334A0 (en)	2000-06-01
WO1998028310A1 (en)	1998-07-02
EA199900580A1 (ru)	1999-12-29
CA2275696A1 (en)	1998-07-02
GB9626615D0 (en)	1997-02-05
SK81099A3 (en)	1999-11-08
JP2001506667A (ja)	2001-05-22
NZ335884A (en)	2000-11-24
CN1240451A (zh)	2000-01-05
US20020082423A1 (en)	2002-06-27
KR20000069609A (ko)	2000-11-25
AR008541A1 (es)	2000-01-19
EP0946572A1 (en)	1999-10-06
TW434221B (en)	2001-05-16
PL334189A1 (en)	2000-02-14
ATE255117T1 (de)	2003-12-15
CN1105117C (zh)	2003-04-09
EP0946572B1 (en)	2003-11-26
ID22053A (id)	1999-08-26
AP9901546A0 (en)	1999-06-30
DZ2377A1 (fr)	2002-12-28
NO993001L (no)	1999-06-18
HUP0002171A2 (hu)	2001-05-28
NO993001D0 (no)	1999-06-18
ZA9711431B (en)	1999-06-21
DE69726449T2 (de)	2004-08-26
MA24427A1 (fr)	1998-07-01
BR9714650A (pt)	2000-10-03
CO4930276A1 (es)	2000-06-27
PE46799A1 (es)	1999-06-24
DE69726449D1 (en)	2004-01-08
HUP0002171A3 (en)	2002-12-28
US6303784B1 (en)	2001-10-16

Publication	Publication Date	Title
OA11068A (en)	2003-03-10	Pharmaceutical aminophosphonic acid derivatives
US6660724B1 (en)	2003-12-09	Compounds and pharmaceutical compositions containing them
MXPA98000189A (en)	1998-04-01	Compounds and pharmaceutical compositions that contains them
WO1998028312A1 (en)	1998-07-02	Pharmaceutical aminophosphonic acid derivatives
WO1998028311A1 (en)	1998-07-02	Pharmaceutical aminophosphonic acid derivatives
KR100722586B1 (ko)	2007-05-28	α-치환된 β-아미노에틸 포스포네이트
CZ219699A3 (cs)	2000-02-16	Farmaceutické deriváty kyseliny aminofosfonové
US6872711B2 (en)	2005-03-29	β-substituted β-aminoethyl phosphonate derivatives
US20030114421A1 (en)	2003-06-19	Alpha-substituted beta-aminoethyl phosphonate derivatives
MXPA04007797A (es)	2005-09-08	Derivados de fosfonato heteroarilalquilo a-sustituidos.