AP778A - Aminophosphonates and pharmaceutical compositions containing them. - Google Patents
Aminophosphonates and pharmaceutical compositions containing them. Download PDFInfo
- Publication number
- AP778A AP778A APAP/P/1997/001160A AP9701160A AP778A AP 778 A AP778 A AP 778A AP 9701160 A AP9701160 A AP 9701160A AP 778 A AP778 A AP 778A
- Authority
- AP
- ARIPO
- Prior art keywords
- diethyl
- compound
- pyridyl
- formula
- aminomethylphosphonate
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- PTMHPRAIXMAOOB-UHFFFAOYSA-N phosphoramidic acid Chemical class NP(O)(O)=O PTMHPRAIXMAOOB-UHFFFAOYSA-N 0.000 title abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 23
- 102000004895 Lipoproteins Human genes 0.000 claims abstract description 6
- 108090001030 Lipoproteins Proteins 0.000 claims abstract description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 84
- 150000001875 compounds Chemical class 0.000 claims description 82
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 53
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 50
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 39
- -1 methoxy, methoxy Chemical group 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 150000002466 imines Chemical class 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 108010033266 Lipoprotein(a) Proteins 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 208000037803 restenosis Diseases 0.000 claims description 11
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 claims description 10
- 230000003247 decreasing effect Effects 0.000 claims description 10
- 201000001320 Atherosclerosis Diseases 0.000 claims description 9
- 208000007536 Thrombosis Diseases 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 238000002399 angioplasty Methods 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 5
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 5
- 208000030613 peripheral artery disease Diseases 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 238000006268 reductive amination reaction Methods 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 3
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 241000790917 Dioxys <bee> Species 0.000 claims description 2
- 125000001118 alkylidene group Chemical group 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 229910052751 metal Chemical class 0.000 claims description 2
- 239000002184 metal Chemical class 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000004665 trialkylsilyl group Chemical class 0.000 claims description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 102000057248 Lipoprotein(a) Human genes 0.000 claims 1
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 claims 1
- 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 66
- 102100040214 Apolipoprotein(a) Human genes 0.000 description 62
- 101710115418 Apolipoprotein(a) Proteins 0.000 description 49
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 125000003118 aryl group Chemical group 0.000 description 36
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 24
- 239000000243 solution Substances 0.000 description 20
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 20
- 239000007787 solid Substances 0.000 description 19
- 238000004440 column chromatography Methods 0.000 description 16
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 14
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 239000003208 petroleum Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 238000003556 assay Methods 0.000 description 9
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- 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 7
- 150000001299 aldehydes Chemical class 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 6
- 241000282567 Macaca fascicularis Species 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 6
- 208000006011 Stroke Diseases 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 210000003494 hepatocyte Anatomy 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 6
- KCDXJAYRVLXPFO-UHFFFAOYSA-N syringaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1O KCDXJAYRVLXPFO-UHFFFAOYSA-N 0.000 description 6
- COBXDAOIDYGHGK-UHFFFAOYSA-N syringaldehyde Natural products COC1=CC=C(C=O)C(OC)=C1O COBXDAOIDYGHGK-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 102000007330 LDL Lipoproteins Human genes 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 238000000921 elemental analysis Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- YGCZTXZTJXYWCO-UHFFFAOYSA-N 3-phenylpropanal Chemical compound O=CCCC1=CC=CC=C1 YGCZTXZTJXYWCO-UHFFFAOYSA-N 0.000 description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 208000029078 coronary artery disease Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000004452 microanalysis Methods 0.000 description 4
- 229960003512 nicotinic acid Drugs 0.000 description 4
- 235000001968 nicotinic acid Nutrition 0.000 description 4
- 239000011664 nicotinic acid Substances 0.000 description 4
- 230000036470 plasma concentration Effects 0.000 description 4
- 150000003335 secondary amines Chemical class 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000002617 apheresis Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 229960002965 pravastatin Drugs 0.000 description 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 description 3
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- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 238000004611 spectroscopical analysis Methods 0.000 description 3
- 239000003270 steroid hormone Substances 0.000 description 3
- DOZRDZLFLOODMB-UHFFFAOYSA-N 3,5-di-tert-Butyl-4-hydroxybenzaldehyde Chemical compound CC(C)(C)C1=CC(C=O)=CC(C(C)(C)C)=C1O DOZRDZLFLOODMB-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
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 208000014882 Carotid artery disease Diseases 0.000 description 2
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- 238000002965 ELISA Methods 0.000 description 2
- 239000004150 EU approved colour Substances 0.000 description 2
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- 241001465754 Metazoa Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
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- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 2
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- 238000012216 screening Methods 0.000 description 2
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- 230000002885 thrombogenetic effect Effects 0.000 description 2
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- 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
- C07F9/4056—Esters of arylalkanephosphonic acids
-
- 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
- C07F9/553—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
- C07F9/59—Hydrogenated 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
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH01920/95A CH690264A5 (fr) | 1995-06-30 | 1995-06-30 | Dérivés aminophosphonates substitués, leur procédé de préparation et leur utilisation pour la préparation de compositions pharmaceutiques. |
| PCT/EP1996/002842 WO1997002037A1 (fr) | 1995-06-30 | 1996-06-26 | Composes et compositions pharmaceutiques les contenant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9701160A0 AP9701160A0 (en) | 1998-01-31 |
| AP778A true AP778A (en) | 1999-10-29 |
Family
ID=4221681
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1997/001160A AP778A (en) | 1995-06-30 | 1996-06-26 | Aminophosphonates and pharmaceutical compositions containing them. |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US6060464A (fr) |
| EP (1) | EP0835116A1 (fr) |
| JP (1) | JPH11508576A (fr) |
| KR (1) | KR19990028542A (fr) |
| CN (1) | CN1113654C (fr) |
| AP (1) | AP778A (fr) |
| AR (1) | AR004498A1 (fr) |
| AU (1) | AU705206B2 (fr) |
| BG (1) | BG102215A (fr) |
| BR (1) | BR9609653A (fr) |
| CA (1) | CA2225391A1 (fr) |
| CH (1) | CH690264A5 (fr) |
| CZ (1) | CZ422097A3 (fr) |
| EA (1) | EA199800106A1 (fr) |
| HU (1) | HUP9901684A3 (fr) |
| IL (1) | IL122717A0 (fr) |
| MA (1) | MA24340A1 (fr) |
| MX (1) | MX9800189A (fr) |
| NO (1) | NO976128L (fr) |
| NZ (1) | NZ312696A (fr) |
| OA (1) | OA10554A (fr) |
| PL (1) | PL187024B1 (fr) |
| SK (1) | SK178397A3 (fr) |
| TR (1) | TR199701700T1 (fr) |
| TW (1) | TW413681B (fr) |
| WO (1) | WO1997002037A1 (fr) |
| ZA (1) | ZA965505B (fr) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6548084B2 (en) | 1995-07-20 | 2003-04-15 | Smithkline Beecham Plc | Controlled release compositions |
| GB9626616D0 (en) * | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
| GB9626536D0 (en) * | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
| GB9626615D0 (en) * | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
| DE19748659A1 (de) * | 1997-11-04 | 1999-05-06 | Hoechst Ag | Aminophosphoniumgruppen enthaltende vernetzte Copolymere für medizinische Verwendungen |
| US6017918A (en) * | 1998-08-06 | 2000-01-25 | Warner-Lambert Company | Phenyl glycine compounds and methods of treating atherosclerosis and restenosis |
| US6284795B1 (en) | 1998-09-04 | 2001-09-04 | Warner-Lambert Company | Sulfonamide compounds and methods of treating atherosclerosis and restenosis |
| CA2387394C (fr) | 1999-10-27 | 2009-08-18 | Teva Pharmaceutical Industries, Ltd. | Utilisation de derives de 1-aminoindan pour le traitement de la manie liee a la psychose maniacodepressive |
| WO2001060805A1 (fr) | 2000-02-16 | 2001-08-23 | Smithkline Beecham P.L.C. | Derives de pyrimidine-4-one utilises comme inhibiteurs de ldl-pla¿2? |
| JP2004513891A (ja) * | 2000-09-27 | 2004-05-13 | アイレックス オンコロジー リサーチ エス．エイ． | α−置換β−アミノエチルホスホネート |
| US20030114421A1 (en) * | 2000-09-27 | 2003-06-19 | Phan Hieu Trung | Alpha-substituted beta-aminoethyl phosphonate derivatives |
| 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 |
| WO2003068240A1 (fr) * | 2002-02-11 | 2003-08-21 | Ilex Products, Inc. | Derives alpha-substitues d'heteroarylalkyl phosphonate |
| WO2003094852A2 (fr) * | 2002-05-11 | 2003-11-20 | Ilex Products, Inc. | Utilisation d'hydroxyphosphonates et phosphonophosphates comme modulateurs de l'apolipoproteine e |
| CA2496452A1 (fr) * | 2002-08-30 | 2004-03-11 | Biostratum, Inc. | Inhibiteurs de produits terminaux avances de glycation post-amadori |
| MX2013006342A (es) | 2010-12-06 | 2013-08-26 | Glaxo Group Ltd | Compuestos de pirimidinona para usarse en el tratamiento de enfermedades o afecciones mediadas por fosfolipasa asociada con lipoproteinas a2 (lp-pla2). |
| KR20140059203A (ko) | 2011-07-27 | 2014-05-15 | 글락소 그룹 리미티드 | 2,3-디히드로이미다조[1,2-c]피리미딘-5(1h)-온 화합물의 lp-pla2 억제제로서의 용도 |
| AU2012288865B2 (en) | 2011-07-27 | 2015-10-01 | Glaxo Group Limited | Bicyclic pyrimidone compounds |
| JP6199291B2 (ja) | 2011-09-01 | 2017-09-20 | グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ | 新規な結晶形態 |
| JP2016505053A (ja) | 2013-01-25 | 2016-02-18 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | Ｌｐ‐ＰＬＡ２の阻害剤としての二環式ピリミドン化合物 |
| CA2899124A1 (fr) | 2013-01-25 | 2014-07-31 | Glaxosmithkline Intellectual Property Development Limited | Composes |
| AU2014209949B2 (en) | 2013-01-25 | 2016-09-08 | Glaxosmithkline Intellectual Property Development Limited | 2,3-dihydroimidazol(1,2-c)pyrimidin-5(1h)-one based lipoprotein-associated phospholipase a2 (Lp-PLA2) inhibitors |
| WO2016012917A1 (fr) | 2014-07-22 | 2016-01-28 | Glaxosmithkline Intellectual Property Development Limited | Dérivés 1,2,3,5-tétrahydro-imidazo [1,2-c]pyrimidine utiles pour le traitement de maladies et de troubles médiés par la lp-pla2 |
| WO2016012916A1 (fr) | 2014-07-22 | 2016-01-28 | Glaxosmithkline Intellectual Property Development Limited | Dérivés 1,2,3,5-tétrahydro-imidazo [1,2-c]pyrimidine utiles pour le traitement de maladies et de troubles médiés par la lp-pla2 |
| BR112022008786A2 (pt) | 2019-11-09 | 2022-07-26 | Shanghai Simr Biotechnology Co Ltd | Composto, composição, uso do composto ou da composição, e, método para tratar ou prevenir uma complicação diabética, doença relacionada à neuroinflamação ou aterosclerose |
| 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0559079A1 (fr) * | 1992-03-05 | 1993-09-08 | Symphar S.A. | Dérivés substitués à d'aminophosphonates, leur procédé de préparation et compositions pharmaceutiques les contenant |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4433244A1 (de) * | 1994-09-19 | 1996-03-28 | Hoechst Ag | Aminomethylphosphon- und Aminomethylphosphinsäure-Derivate und deren Verwendung zur Behandlung von degenerativen Gelenkserkrankungen |
-
1995
- 1995-06-30 CH CH01920/95A patent/CH690264A5/fr not_active IP Right Cessation
-
1996
- 1996-06-26 EA EA199800106A patent/EA199800106A1/ru unknown
- 1996-06-26 US US08/973,669 patent/US6060464A/en not_active Expired - Fee Related
- 1996-06-26 HU HU9901684A patent/HUP9901684A3/hu unknown
- 1996-06-26 CA CA002225391A patent/CA2225391A1/fr not_active Abandoned
- 1996-06-26 EP EP96923971A patent/EP0835116A1/fr not_active Withdrawn
- 1996-06-26 CN CN96196395A patent/CN1113654C/zh not_active Expired - Fee Related
- 1996-06-26 JP JP9504801A patent/JPH11508576A/ja not_active Withdrawn
- 1996-06-26 CZ CZ974220A patent/CZ422097A3/cs unknown
- 1996-06-26 NZ NZ312696A patent/NZ312696A/en unknown
- 1996-06-26 IL IL12271796A patent/IL122717A0/xx unknown
- 1996-06-26 MX MX9800189A patent/MX9800189A/es unknown
- 1996-06-26 BR BR9609653-5A patent/BR9609653A/pt not_active Application Discontinuation
- 1996-06-26 TR TR97/01700T patent/TR199701700T1/xx unknown
- 1996-06-26 AP APAP/P/1997/001160A patent/AP778A/en active
- 1996-06-26 WO PCT/EP1996/002842 patent/WO1997002037A1/fr not_active Ceased
- 1996-06-26 KR KR1019970709860A patent/KR19990028542A/ko not_active Withdrawn
- 1996-06-26 PL PL96324341A patent/PL187024B1/pl unknown
- 1996-06-26 AU AU64185/96A patent/AU705206B2/en not_active Ceased
- 1996-06-26 SK SK1783-97A patent/SK178397A3/sk unknown
- 1996-06-28 MA MA24297A patent/MA24340A1/fr unknown
- 1996-06-28 ZA ZA9605505A patent/ZA965505B/xx unknown
- 1996-06-28 AR ARP960103399A patent/AR004498A1/es unknown
- 1996-07-01 TW TW085107922A patent/TW413681B/zh not_active IP Right Cessation
-
1997
- 1997-12-29 NO NO976128A patent/NO976128L/no not_active Application Discontinuation
- 1997-12-30 OA OA70171A patent/OA10554A/en unknown
-
1998
- 1998-01-28 BG BG102215A patent/BG102215A/xx unknown
-
2000
- 2000-04-03 US US09/541,217 patent/US6660724B1/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0559079A1 (fr) * | 1992-03-05 | 1993-09-08 | Symphar S.A. | Dérivés substitués à d'aminophosphonates, leur procédé de préparation et compositions pharmaceutiques les contenant |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1113654C (zh) | 2003-07-09 |
| US6060464A (en) | 2000-05-09 |
| NO976128D0 (no) | 1997-12-29 |
| HUP9901684A2 (hu) | 1999-09-28 |
| SK178397A3 (en) | 1998-06-03 |
| AP9701160A0 (en) | 1998-01-31 |
| NZ312696A (en) | 1999-10-28 |
| AU705206B2 (en) | 1999-05-20 |
| OA10554A (en) | 2002-05-29 |
| KR19990028542A (ko) | 1999-04-15 |
| EP0835116A1 (fr) | 1998-04-15 |
| IL122717A0 (en) | 1998-08-16 |
| US6660724B1 (en) | 2003-12-09 |
| TR199701700T1 (xx) | 1998-03-21 |
| NO976128L (no) | 1998-02-10 |
| HUP9901684A3 (en) | 2000-04-28 |
| AR004498A1 (es) | 1998-12-16 |
| MA24340A1 (fr) | 1998-07-01 |
| PL324341A1 (en) | 1998-05-25 |
| PL187024B1 (pl) | 2004-04-30 |
| CN1193913A (zh) | 1998-09-23 |
| CH690264A5 (fr) | 2000-06-30 |
| EA199800106A1 (ru) | 1998-08-27 |
| ZA965505B (en) | 1998-03-30 |
| CZ422097A3 (cs) | 1998-10-14 |
| WO1997002037A1 (fr) | 1997-01-23 |
| TW413681B (en) | 2000-12-01 |
| AU6418596A (en) | 1997-02-05 |
| JPH11508576A (ja) | 1999-07-27 |
| BR9609653A (pt) | 1999-12-21 |
| BG102215A (en) | 1998-09-30 |
| MX9800189A (es) | 1998-04-30 |
| CA2225391A1 (fr) | 1997-01-23 |
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