SK178397A3 - Aminophosphonate compounds and pharmaceutical compositions containing them - Google Patents

Aminophosphonate compounds and pharmaceutical compositions containing them Download PDF

Info

Publication number: SK178397A3
Authority: SK; Slovakia
Prior art keywords: formula; pyridyl; aminomethylphosphonate; compound; diethyl
Prior art date: 1995-06-30

Application number

SK1783-97A

Other languages

English (en)

Slovak (sk)

Inventor

Lan Mong Nguyen

Eric Niesor

Craig L Bentzen

Hieu Trung Phan

Vinh Van Diep

Simon Floret

Raymond Azoulay

Alexandre Bulla

Yves Guyon-Gellin

Robert J Ife

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.)

1995-06-30

Filing date

1996-06-26

Publication date

1998-06-03

1996-06-26 Application filed by Symphar Sa, Smithkline Beecham Plc filed Critical Symphar Sa

1998-06-03 Publication of SK178397A3 publication Critical patent/SK178397A3/sk

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 16
-1 Aminophosphonate compound Chemical class 0.000 claims description 110
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 81
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 81
150000001875 compounds Chemical class 0.000 claims description 75
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 52
229910052739 hydrogen Inorganic materials 0.000 claims description 37
239000001257 hydrogen Substances 0.000 claims description 31
150000002466 imines Chemical class 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 26
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
238000000034 method Methods 0.000 claims description 19
239000002904 solvent Substances 0.000 claims description 18
150000002431 hydrogen Chemical class 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 16
238000006243 chemical reaction Methods 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 12
229910052799 carbon Inorganic materials 0.000 claims description 12
201000001320 Atherosclerosis Diseases 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
208000037803 restenosis Diseases 0.000 claims description 11
208000007536 Thrombosis Diseases 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
238000002399 angioplasty Methods 0.000 claims description 7
239000003054 catalyst Substances 0.000 claims description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
230000008569 process Effects 0.000 claims description 7
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
102000004895 Lipoproteins Human genes 0.000 claims description 5
108090001030 Lipoproteins Proteins 0.000 claims description 5
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 5
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
238000009833 condensation Methods 0.000 claims description 4
230000005494 condensation Effects 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
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
230000001476 alcoholic effect Effects 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
208000030613 peripheral artery disease Diseases 0.000 claims description 3
125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 2
239000011734 sodium Substances 0.000 claims description 2
125000004665 trialkylsilyl group Chemical group 0.000 claims description 2
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 claims 1
239000000546 pharmaceutical excipient Substances 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
229910052708 sodium Inorganic materials 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
108010033266 Lipoprotein(a) Proteins 0.000 abstract description 15
230000000694 effects Effects 0.000 abstract description 4
102000057248 Lipoprotein(a) Human genes 0.000 abstract description 2
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 63
239000000203 mixture Substances 0.000 description 47
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 40
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
125000003118 aryl group Chemical group 0.000 description 36
238000001819 mass spectrum Methods 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
238000005481 NMR spectroscopy Methods 0.000 description 29
238000010992 reflux Methods 0.000 description 25
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 23
102100040214 Apolipoprotein(a) Human genes 0.000 description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 19
239000007787 solid Substances 0.000 description 19
239000000243 solution Substances 0.000 description 19
238000004440 column chromatography Methods 0.000 description 16
238000012360 testing method Methods 0.000 description 15
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
238000002844 melting Methods 0.000 description 13
230000008018 melting Effects 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
239000003208 petroleum Substances 0.000 description 12
125000004432 carbon atom Chemical group C* 0.000 description 11
239000003921 oil Substances 0.000 description 11
235000019198 oils Nutrition 0.000 description 11
239000000047 product Substances 0.000 description 11
239000000725 suspension Substances 0.000 description 10
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 9
210000001519 tissue Anatomy 0.000 description 9
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 8
150000001299 aldehydes Chemical class 0.000 description 8
230000003197 catalytic effect Effects 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
230000000875 corresponding effect Effects 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
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
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 6
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 6
229910004298 SiO 2 Inorganic materials 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
ODFJOVXVLFUVNQ-UHFFFAOYSA-N acetarsol Chemical group CC(=O)NC1=CC([As](O)(O)=O)=CC=C1O ODFJOVXVLFUVNQ-UHFFFAOYSA-N 0.000 description 6
201000010099 disease Diseases 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
238000002360 preparation method Methods 0.000 description 6
238000000926 separation method Methods 0.000 description 6
239000007858 starting material Substances 0.000 description 6
101710115418 Apolipoprotein(a) Proteins 0.000 description 5
102000007330 LDL Lipoproteins Human genes 0.000 description 5
108010007622 LDL Lipoproteins Proteins 0.000 description 5
241000282567 Macaca fascicularis Species 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
229940079593 drug Drugs 0.000 description 5
238000000921 elemental analysis Methods 0.000 description 5
210000003494 hepatocyte Anatomy 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
KCDXJAYRVLXPFO-UHFFFAOYSA-N syringaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1O KCDXJAYRVLXPFO-UHFFFAOYSA-N 0.000 description 5
COBXDAOIDYGHGK-UHFFFAOYSA-N syringaldehyde Natural products COC1=CC=C(C=O)C(OC)=C1O COBXDAOIDYGHGK-UHFFFAOYSA-N 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
241000282412 Homo Species 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
230000004913 activation Effects 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 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
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 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
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
239000003826 tablet Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-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
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
102000013566 Plasminogen Human genes 0.000 description 3
108010051456 Plasminogen Proteins 0.000 description 3
239000002775 capsule Substances 0.000 description 3
208000029078 coronary artery disease Diseases 0.000 description 3
238000007327 hydrogenolysis reaction Methods 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
230000000144 pharmacologic effect Effects 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
229960003912 probucol Drugs 0.000 description 3
230000035755 proliferation Effects 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
238000003307 slaughter Methods 0.000 description 3
210000000329 smooth muscle myocyte Anatomy 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
239000003270 steroid hormone Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
238000001665 trituration Methods 0.000 description 3
RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 2
ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 2
OPHQOIGEOHXOGX-UHFFFAOYSA-N 3,4,5-trimethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(OC)=C1OC OPHQOIGEOHXOGX-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
206010003210 Arteriosclerosis Diseases 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
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
238000002965 ELISA Methods 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
241001465754 Metazoa Species 0.000 description 2
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208000005764 Peripheral Arterial Disease Diseases 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
241000288906 Primates Species 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
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238000004458 analytical method Methods 0.000 description 2
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CBOQJANXLMLOSS-UHFFFAOYSA-N ethyl vanillin Chemical compound CCOC1=CC(C=O)=CC=C1O CBOQJANXLMLOSS-UHFFFAOYSA-N 0.000 description 2
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JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 2
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239000007937 lozenge Substances 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
230000014759 maintenance of location Effects 0.000 description 2
MCSAQVGDZLPTBS-UHFFFAOYSA-N n-methyl-1-pyridin-3-ylmethanamine Chemical compound CNCC1=CC=CN=C1 MCSAQVGDZLPTBS-UHFFFAOYSA-N 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
238000007911 parenteral administration Methods 0.000 description 2
150000002978 peroxides Chemical class 0.000 description 2
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 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
QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 2
BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 2
230000002829 reductive effect Effects 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
238000004611 spectroscopical analysis Methods 0.000 description 2
239000008107 starch Substances 0.000 description 2
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- 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

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

SK1783-97A 1995-06-30 1996-06-26 Aminophosphonate compounds and pharmaceutical compositions containing them SK178397A3 (en)

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 (1)

Publication Number	Publication Date
SK178397A3 true SK178397A3 (en)	1998-06-03

Family

ID=4221681

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1783-97A SK178397A3 (en)	1995-06-30	1996-06-26	Aminophosphonate compounds 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)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6548084B2 (en)	1995-07-20	2003-04-15	Smithkline Beecham Plc	Controlled release compositions
GB9626536D0 (en) *	1996-12-20	1997-02-05	Symphar Sa	Novel compounds
GB9626616D0 (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
JP2003512426A (ja)	1999-10-27	2003-04-02	テバファーマシューティカルインダストリーズリミティド	双極性気分障害における躁病の治療のための１−アミノインダンの使用。
DE60139429D1 (de)	2000-02-16	2009-09-10	Smithkline Beecham Plc	Pyrimidin-5-Onderivate als LDL-PLA2 Inhibitoren
CN1489596A (zh) *	2000-09-27	2004-04-14	�Ʒ�	α-取代的β-氨基乙基膦酸酯类化合物
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
CA2475882A1 (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
EP1534679A4 (fr) *	2002-08-30	2007-06-06	Biostratum Inc	Inhibiteurs de produits terminaux avances de glycation post-amadori
US8637536B2 (en)	2010-12-06	2014-01-28	Glaxo Group Limited	Pyrimidinone compounds for use in the treatment of diseases or conditions mediated by Lp-PLA2
US9273054B2 (en)	2011-07-27	2016-03-01	Glaxo Group Limited	Substituted pyrimido[1,6-a]pyrimidines as Lp-PLA2 inhibitors
EP2739627A4 (fr)	2011-07-27	2015-01-21	Glaxo Group Ltd	Composés 2,3-dihydroimidazo[1,2-c]pyrimidin-5(1h)-one et utilisation en tant qu'inhibiteurs de lp-pla2
US9227953B2 (en)	2011-09-01	2016-01-05	Glaxo Group Limited	Crystal form
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ＧｌａｘｏｓｍｉｔｈｋｌｉｎｅＩｎｔｅｌｌｅｃｔｕａｌＰｒｏｐｅｒｔｙＤｅｖｅｌｏｐｍｅｎｔＬｉｍｉｔｅｄ	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
WO2014114694A1 (fr)	2013-01-25	2014-07-31	Glaxosmithkline Intellectual Property Development Limited	Inhibiteurs de la phospholipase associée aux lipoprotéines a2 (lp-pla2) à base de 2,3-dihydro-imidazol[1,2-c]pyrimidin-5(1 h)-one
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
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 (2)

* 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

1995
- 1995-06-30 CH CH01920/95A patent/CH690264A5/fr not_active IP Right Cessation
1996
- 1996-06-26 KR KR1019970709860A patent/KR19990028542A/ko not_active Withdrawn
- 1996-06-26 MX MX9800189A patent/MX9800189A/es unknown
- 1996-06-26 TR TR97/01700T patent/TR199701700T1/xx unknown
- 1996-06-26 IL IL12271796A patent/IL122717A0/xx unknown
- 1996-06-26 PL PL96324341A patent/PL187024B1/pl unknown
- 1996-06-26 CA CA002225391A patent/CA2225391A1/fr not_active Abandoned
- 1996-06-26 NZ NZ312696A patent/NZ312696A/en unknown
- 1996-06-26 HU HU9901684A patent/HUP9901684A3/hu unknown
- 1996-06-26 SK SK1783-97A patent/SK178397A3/sk unknown
- 1996-06-26 US US08/973,669 patent/US6060464A/en not_active Expired - Fee Related
- 1996-06-26 AU AU64185/96A patent/AU705206B2/en not_active Ceased
- 1996-06-26 CZ CZ974220A patent/CZ422097A3/cs unknown
- 1996-06-26 AP APAP/P/1997/001160A patent/AP778A/en active
- 1996-06-26 CN CN96196395A patent/CN1113654C/zh not_active Expired - Fee Related
- 1996-06-26 WO PCT/EP1996/002842 patent/WO1997002037A1/fr not_active Ceased
- 1996-06-26 BR BR9609653-5A patent/BR9609653A/pt not_active Application Discontinuation
- 1996-06-26 EP EP96923971A patent/EP0835116A1/fr not_active Withdrawn
- 1996-06-26 JP JP9504801A patent/JPH11508576A/ja not_active Withdrawn
- 1996-06-26 EA EA199800106A patent/EA199800106A1/ru unknown
- 1996-06-28 AR ARP960103399A patent/AR004498A1/es unknown
- 1996-06-28 ZA ZA9605505A patent/ZA965505B/xx unknown
- 1996-06-28 MA MA24297A patent/MA24340A1/fr 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

Also Published As

Publication number	Publication date
AU6418596A (en)	1997-02-05
US6060464A (en)	2000-05-09
PL324341A1 (en)	1998-05-25
AP9701160A0 (en)	1998-01-31
MX9800189A (es)	1998-04-30
NO976128L (no)	1998-02-10
CZ422097A3 (cs)	1998-10-14
MA24340A1 (fr)	1998-07-01
CN1193913A (zh)	1998-09-23
EP0835116A1 (fr)	1998-04-15
CN1113654C (zh)	2003-07-09
WO1997002037A1 (fr)	1997-01-23
IL122717A0 (en)	1998-08-16
BR9609653A (pt)	1999-12-21
OA10554A (en)	2002-05-29
NZ312696A (en)	1999-10-28
NO976128D0 (no)	1997-12-29
TW413681B (en)	2000-12-01
AR004498A1 (es)	1998-12-16
TR199701700T1 (xx)	1998-03-21
CH690264A5 (fr)	2000-06-30
US6660724B1 (en)	2003-12-09
KR19990028542A (ko)	1999-04-15
AU705206B2 (en)	1999-05-20
BG102215A (en)	1998-09-30
AP778A (en)	1999-10-29
PL187024B1 (pl)	2004-04-30
EA199800106A1 (ru)	1998-08-27
HUP9901684A2 (hu)	1999-09-28
JPH11508576A (ja)	1999-07-27
HUP9901684A3 (en)	2000-04-28
CA2225391A1 (fr)	1997-01-23
ZA965505B (en)	1998-03-30

Publication	Publication Date	Title
US6060464A (en)	2000-05-09	Compounds and pharmaceutical compositions containing them
US6303784B1 (en)	2001-10-16	Pharmaceutical aminophosphonic acid derivatives
MXPA98000189A (en)	1998-04-01	Compounds and pharmaceutical compositions that contains them
US5424303A (en)	1995-06-13	Substituted aminophosphonate derivatives, process for their preparation and pharmaceutical compositions containing them
WO1998028311A1 (fr)	1998-07-02	Derives pharmaceutiques d'acide aminophosphonique
WO1998028312A1 (fr)	1998-07-02	Derives pharmaceutiques de l'acide aminophosphonique
AU2001294792B2 (en)	2006-12-14	Alpha-substituted beta-aminoethyl phosphonates
IL116873A (en)	2002-05-23	History of phosphonoacetate acid, pharmaceutical preparations containing them and their use in the treatment of joint degenerative diseases
US5641762A (en)	1997-06-24	Bone targeted inhibitors of carbonic anhydrase
US6872711B2 (en)	2005-03-29	β-substituted β-aminoethyl phosphonate derivatives
US20030114421A1 (en)	2003-06-19	Alpha-substituted beta-aminoethyl phosphonate derivatives
CZ219699A3 (cs)	2000-02-16	Farmaceutické deriváty kyseliny aminofosfonové
JP2005529071A (ja)	2005-09-29	α−置換ヘテロアリールアルキルホスホン酸エステル誘導体
JP2005517711A (ja)	2005-06-16	α−置換アリールアルキルホスホン酸エステル誘導体
JPH05221983A (ja)	1993-08-31	新規なジヒドロピリジン誘導体