UA65631C2 - Bispiperidines as antithrombotic agents, a method for the preparation thereof and intermediate products - Google Patents
Bispiperidines as antithrombotic agents, a method for the preparation thereof and intermediate products Download PDFInfo
- Publication number
- UA65631C2 UA65631C2 UA2001021081A UA2001021081A UA65631C2 UA 65631 C2 UA65631 C2 UA 65631C2 UA 2001021081 A UA2001021081 A UA 2001021081A UA 2001021081 A UA2001021081 A UA 2001021081A UA 65631 C2 UA65631 C2 UA 65631C2
- Authority
- UA
- Ukraine
- Prior art keywords
- piperidyl
- groups
- amino
- formula
- alkyl
- Prior art date
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- 239000003146 anticoagulant agent Substances 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 title claims description 21
- 238000002360 preparation method Methods 0.000 title claims description 10
- 229960004676 antithrombotic agent Drugs 0.000 title abstract description 3
- 239000013067 intermediate product Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- 102000008946 Fibrinogen Human genes 0.000 claims abstract description 9
- 108010049003 Fibrinogen Proteins 0.000 claims abstract description 9
- 229940012952 fibrinogen Drugs 0.000 claims abstract description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 175
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 106
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 95
- 235000019260 propionic acid Nutrition 0.000 claims description 94
- -1 benzodioxanyl Chemical group 0.000 claims description 74
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 33
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 28
- 210000001772 blood platelet Anatomy 0.000 claims description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000001624 naphthyl group Chemical group 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 208000007536 Thrombosis Diseases 0.000 claims description 9
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 150000007513 acids Chemical class 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000005493 quinolyl group Chemical group 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 230000002776 aggregation Effects 0.000 claims description 6
- 238000004220 aggregation Methods 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 125000003367 polycyclic group Chemical group 0.000 claims description 5
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 239000004305 biphenyl Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000001294 propane Substances 0.000 claims description 3
- 230000001732 thrombotic effect Effects 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000006267 biphenyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
- 229940127217 antithrombotic drug Drugs 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 239000007858 starting material Substances 0.000 description 160
- 238000005481 NMR spectroscopy Methods 0.000 description 148
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 16
- 239000007787 solid Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 11
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 241000700198 Cavia Species 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 210000004623 platelet-rich plasma Anatomy 0.000 description 7
- 238000001356 surgical procedure Methods 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 238000003818 flash chromatography Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 4
- SFWWGMKXCYLZEG-UHFFFAOYSA-N 3-methylmorpholine Chemical compound CC1COCCN1 SFWWGMKXCYLZEG-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 4
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 3
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 3
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- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 3
- AJNWGKMIJZNIBI-UHFFFAOYSA-N butanoic acid;dihydrochloride Chemical compound Cl.Cl.CCCC(O)=O AJNWGKMIJZNIBI-UHFFFAOYSA-N 0.000 description 3
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- XJLSEXAGTJCILF-UHFFFAOYSA-N nipecotic acid Chemical compound OC(=O)C1CCCNC1 XJLSEXAGTJCILF-UHFFFAOYSA-N 0.000 description 3
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- YYFIGOPUHPDIBO-UHFFFAOYSA-N propanoic acid;hydrochloride Chemical compound Cl.CCC(O)=O YYFIGOPUHPDIBO-UHFFFAOYSA-N 0.000 description 3
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- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 2
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- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
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- ATSZQDTVNRNXKB-UHFFFAOYSA-N ethyl 3-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(N)C1=CC=CC=C1 ATSZQDTVNRNXKB-UHFFFAOYSA-N 0.000 description 1
- GGANVLPLTUQZIF-UHFFFAOYSA-N ethyl 3-amino-3-pyridin-3-ylpropanoate;dihydrochloride Chemical compound Cl.Cl.CCOC(=O)CC(N)C1=CC=CN=C1 GGANVLPLTUQZIF-UHFFFAOYSA-N 0.000 description 1
- NMUSXIMXVQNKBA-UHFFFAOYSA-N ethyl 3-amino-5-phenylpentanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(N)CCC1=CC=CC=C1 NMUSXIMXVQNKBA-UHFFFAOYSA-N 0.000 description 1
- HHIOOBJZIASBFF-UHFFFAOYSA-N ethyl 3-aminobutanoate Chemical compound CCOC(=O)CC(C)N HHIOOBJZIASBFF-UHFFFAOYSA-N 0.000 description 1
- ISVBSAIYXBEVSI-UHFFFAOYSA-N ethyl 3-aminobutanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC(C)N ISVBSAIYXBEVSI-UHFFFAOYSA-N 0.000 description 1
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- 239000011737 fluorine Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
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- 239000008273 gelatin Substances 0.000 description 1
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- 210000003709 heart valve Anatomy 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- WVKIFIROCHIWAY-UHFFFAOYSA-N hydron;2-(methylamino)acetic acid;chloride Chemical compound Cl.CNCC(O)=O WVKIFIROCHIWAY-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
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- OSDPSOBLGQUCQX-UHFFFAOYSA-N methyl 2,2,3,3,4,4,5,5,5-nonafluoropentanoate Chemical compound COC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F OSDPSOBLGQUCQX-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
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- 208000031225 myocardial ischemia Diseases 0.000 description 1
- PJHVZZODQMXUDU-UHFFFAOYSA-N naphthalen-2-ylmethanesulfonyl chloride Chemical compound C1=CC=CC2=CC(CS(=O)(=O)Cl)=CC=C21 PJHVZZODQMXUDU-UHFFFAOYSA-N 0.000 description 1
- DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000012071 phase Substances 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
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- KGMXPXPXPAAUMD-UHFFFAOYSA-N propane;dihydrochloride Chemical class Cl.Cl.CCC KGMXPXPXPAAUMD-UHFFFAOYSA-N 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- JUYUYCIJACTHMK-UHFFFAOYSA-N quinoline-8-sulfonyl chloride Chemical compound C1=CN=C2C(S(=O)(=O)Cl)=CC=CC2=C1 JUYUYCIJACTHMK-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Materials For Medical Uses (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9809166A FR2781223B1 (fr) | 1998-07-17 | 1998-07-17 | Bispiperidines et leurs applications therapeutiques |
| PCT/FR1999/001745 WO2000003986A1 (fr) | 1998-07-17 | 1999-07-16 | Bispiperidines comme agents antithrombotiques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA65631C2 true UA65631C2 (en) | 2004-04-15 |
Family
ID=9528732
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA2001021081A UA65631C2 (en) | 1998-07-17 | 1999-07-16 | Bispiperidines as antithrombotic agents, a method for the preparation thereof and intermediate products |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US6333338B1 (xx) |
| EP (1) | EP1098878B1 (xx) |
| JP (1) | JP2002520393A (xx) |
| KR (1) | KR100584032B1 (xx) |
| CN (1) | CN1286812C (xx) |
| AT (1) | ATE256661T1 (xx) |
| AU (1) | AU761655B2 (xx) |
| BR (1) | BR9912835A (xx) |
| CA (1) | CA2337776A1 (xx) |
| DE (1) | DE69913701T2 (xx) |
| DK (1) | DK1098878T3 (xx) |
| EA (1) | EA003674B1 (xx) |
| ES (1) | ES2212576T3 (xx) |
| FR (1) | FR2781223B1 (xx) |
| HU (1) | HUP0103623A3 (xx) |
| IL (2) | IL140581A0 (xx) |
| NO (1) | NO318963B1 (xx) |
| NZ (1) | NZ509170A (xx) |
| PL (1) | PL193804B1 (xx) |
| PT (1) | PT1098878E (xx) |
| SK (1) | SK152001A3 (xx) |
| TR (1) | TR200100159T2 (xx) |
| UA (1) | UA65631C2 (xx) |
| WO (1) | WO2000003986A1 (xx) |
| ZA (1) | ZA200100238B (xx) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2207001A (en) * | 1999-12-24 | 2001-07-09 | Smithkline Beecham Plc | Novel compounds and process |
| CA2529486A1 (en) * | 2003-06-18 | 2004-12-23 | Nst Neurosurvival Technologies Ltd. | Method for selective targeting of apoptotic cells and small molecule ligands used thereof |
| CA3145453A1 (en) | 2019-07-01 | 2021-01-07 | Tonix Pharma Limited | Anti-cd154 antibodies and uses thereof |
| AU2022205313A1 (en) | 2021-01-06 | 2023-07-20 | Tonix Pharma Limited | Methods of inducing immune tolerance with modified anti-cd154 antibodies |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ239876A (en) * | 1990-09-27 | 1993-12-23 | Merck & Co Inc | Glycyl-b-alanine derivatives and pharmaceutical compositions thereof. |
-
1998
- 1998-07-17 FR FR9809166A patent/FR2781223B1/fr not_active Expired - Fee Related
-
1999
- 1999-07-16 DK DK99929495T patent/DK1098878T3/da active
- 1999-07-16 AU AU46290/99A patent/AU761655B2/en not_active Ceased
- 1999-07-16 PL PL99345418A patent/PL193804B1/pl not_active IP Right Cessation
- 1999-07-16 IL IL14058199A patent/IL140581A0/xx active IP Right Grant
- 1999-07-16 US US09/743,910 patent/US6333338B1/en not_active Expired - Fee Related
- 1999-07-16 AT AT99929495T patent/ATE256661T1/de not_active IP Right Cessation
- 1999-07-16 EP EP99929495A patent/EP1098878B1/fr not_active Expired - Lifetime
- 1999-07-16 SK SK15-2001A patent/SK152001A3/sk unknown
- 1999-07-16 KR KR1020017000665A patent/KR100584032B1/ko not_active IP Right Cessation
- 1999-07-16 NZ NZ509170A patent/NZ509170A/en unknown
- 1999-07-16 JP JP2000560094A patent/JP2002520393A/ja active Pending
- 1999-07-16 PT PT99929495T patent/PT1098878E/pt unknown
- 1999-07-16 WO PCT/FR1999/001745 patent/WO2000003986A1/fr active IP Right Grant
- 1999-07-16 ES ES99929495T patent/ES2212576T3/es not_active Expired - Lifetime
- 1999-07-16 DE DE69913701T patent/DE69913701T2/de not_active Expired - Fee Related
- 1999-07-16 HU HU0103623A patent/HUP0103623A3/hu unknown
- 1999-07-16 UA UA2001021081A patent/UA65631C2/uk unknown
- 1999-07-16 TR TR2001/00159T patent/TR200100159T2/xx unknown
- 1999-07-16 BR BR9912835-7A patent/BR9912835A/pt not_active Application Discontinuation
- 1999-07-16 EA EA200100150A patent/EA003674B1/ru not_active IP Right Cessation
- 1999-07-16 CN CNB998097772A patent/CN1286812C/zh not_active Expired - Fee Related
- 1999-07-16 CA CA002337776A patent/CA2337776A1/en not_active Abandoned
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2000
- 2000-12-26 IL IL140581A patent/IL140581A/en not_active IP Right Cessation
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2001
- 2001-01-09 ZA ZA200100238A patent/ZA200100238B/en unknown
- 2001-01-15 NO NO20010252A patent/NO318963B1/no unknown
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