CA2258753A1 - Piperidine acetic acid derivatives and their use in the treatment of thrombotic disorders - Google Patents
Piperidine acetic acid derivatives and their use in the treatment of thrombotic disorders Download PDFInfo
- Publication number
- CA2258753A1 CA2258753A1 CA002258753A CA2258753A CA2258753A1 CA 2258753 A1 CA2258753 A1 CA 2258753A1 CA 002258753 A CA002258753 A CA 002258753A CA 2258753 A CA2258753 A CA 2258753A CA 2258753 A1 CA2258753 A1 CA 2258753A1
- Authority
- CA
- Canada
- Prior art keywords
- piperidin
- formula
- compound
- indazol
- acetic acid
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 15
- 208000007536 Thrombosis Diseases 0.000 title claims abstract description 9
- RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical class CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 154
- 150000003839 salts Chemical class 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 33
- 239000012453 solvate Substances 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims abstract description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 28
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
- -1 {4-[1-methanesulfonyl4-(2-piperidin4-yl-ethyl)-1H-indazol-3-yl]-piperidin-1-yl}-acetic acid Chemical compound 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 229940124597 therapeutic agent Drugs 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 108090000288 Glycoproteins Proteins 0.000 claims description 5
- 102000003886 Glycoproteins Human genes 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 238000010511 deprotection reaction Methods 0.000 claims description 4
- 108010044426 integrins Proteins 0.000 claims description 4
- 102000006495 integrins Human genes 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- XMFZLJKDRKWLFH-UHFFFAOYSA-N 2-[4-[3-carbamoyl-5-(2-piperidin-4-ylethyl)indazol-1-yl]piperidin-1-yl]acetic acid Chemical compound C12=CC=C(CCC3CCNCC3)C=C2C(C(=O)N)=NN1C1CCN(CC(O)=O)CC1 XMFZLJKDRKWLFH-UHFFFAOYSA-N 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- TXNRMUQNJBBBLI-UHFFFAOYSA-N 2-[4-[1-methylsulfonyl-6-(2-piperidin-4-ylethyl)indazol-3-yl]piperidin-1-yl]acetic acid Chemical compound C12=CC=C(CCC3CCNCC3)C=C2N(S(=O)(=O)C)N=C1C1CCN(CC(O)=O)CC1 TXNRMUQNJBBBLI-UHFFFAOYSA-N 0.000 claims description 2
- HRBXFFUAVXSJLI-UHFFFAOYSA-N 2-[4-[3-methylsulfonyl-5-(2-piperidin-4-ylethyl)indazol-1-yl]piperidin-1-yl]acetic acid Chemical compound C12=CC=C(CCC3CCNCC3)C=C2C(S(=O)(=O)C)=NN1C1CCN(CC(O)=O)CC1 HRBXFFUAVXSJLI-UHFFFAOYSA-N 0.000 claims description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- DKUCIUIGYGXACR-NSCUHMNNSA-N 2-[4-[1-methylsulfonyl-6-[(e)-2-piperidin-4-ylethenyl]indazol-3-yl]piperidin-1-yl]acetic acid Chemical compound C12=CC=C(\C=C\C3CCNCC3)C=C2N(S(=O)(=O)C)N=C1C1CCN(CC(O)=O)CC1 DKUCIUIGYGXACR-NSCUHMNNSA-N 0.000 claims 1
- QDLYADRWMRXFEU-OWOJBTEDSA-N 2-[4-[3-carbamoyl-5-[(e)-2-piperidin-4-ylethenyl]indazol-1-yl]piperidin-1-yl]acetic acid Chemical compound C12=CC=C(\C=C\C3CCNCC3)C=C2C(C(=O)N)=NN1C1CCN(CC(O)=O)CC1 QDLYADRWMRXFEU-OWOJBTEDSA-N 0.000 claims 1
- LKANVFBUWHBRSO-NSCUHMNNSA-N c1c2c(S(=O)(=O)C)nn(C3CCN(CC(O)=O)CC3)c2ccc1\C=C\C1CCNCC1 Chemical compound c1c2c(S(=O)(=O)C)nn(C3CCN(CC(O)=O)CC3)c2ccc1\C=C\C1CCNCC1 LKANVFBUWHBRSO-NSCUHMNNSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
- 239000000203 mixture Substances 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- 239000007787 solid Substances 0.000 description 43
- 239000000243 solution Substances 0.000 description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- 238000001819 mass spectrum Methods 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- 239000000725 suspension Substances 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 229920002554 vinyl polymer Polymers 0.000 description 17
- 239000000284 extract Substances 0.000 description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- 239000003054 catalyst Substances 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 210000001772 blood platelet Anatomy 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 229910052681 coesite Inorganic materials 0.000 description 11
- 229910052906 cristobalite Inorganic materials 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 235000012239 silicon dioxide Nutrition 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 229910052682 stishovite Inorganic materials 0.000 description 11
- 229910052905 tridymite Inorganic materials 0.000 description 11
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
- 239000007832 Na2SO4 Substances 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000012065 filter cake Substances 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 8
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 8
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 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 5
- 239000006071 cream Substances 0.000 description 5
- 229960004132 diethyl ether Drugs 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
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- 238000010992 reflux Methods 0.000 description 5
- 239000012258 stirred mixture Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- 102000008946 Fibrinogen Human genes 0.000 description 4
- 108010049003 Fibrinogen Proteins 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 229940012952 fibrinogen Drugs 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
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- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 4
- ILGTYHMEQSSHFG-UHFFFAOYSA-N 5-bromo-2h-indazole-3-carbaldehyde Chemical compound C1=C(Br)C=CC2=NNC(C=O)=C21 ILGTYHMEQSSHFG-UHFFFAOYSA-N 0.000 description 3
- QIHKDXICUWGQBR-UHFFFAOYSA-N 5-bromo-3-methylsulfonyl-2h-indazole Chemical compound C1=CC(Br)=CC2=C(S(=O)(=O)C)NN=C21 QIHKDXICUWGQBR-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
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- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
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- 150000007524 organic acids Chemical class 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
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- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 229910052723 transition metal Inorganic materials 0.000 description 3
- 150000003624 transition metals Chemical class 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
- BXMFVOCLHLCPJP-UHFFFAOYSA-N (2,4-dibromophenyl)-piperidin-4-ylmethanone;hydrochloride Chemical compound Cl.BrC1=CC(Br)=CC=C1C(=O)C1CCNCC1 BXMFVOCLHLCPJP-UHFFFAOYSA-N 0.000 description 2
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- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 2
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- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003900 succinic acid esters Chemical class 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- WLTVUVZRHZKUJI-UHFFFAOYSA-N tert-butyl 2-[4-(5-bromo-3-methylsulfonylindazol-1-yl)piperidin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCC1N1C2=CC=C(Br)C=C2C(S(C)(=O)=O)=N1 WLTVUVZRHZKUJI-UHFFFAOYSA-N 0.000 description 1
- BJLMWZCUYIQUBV-UHFFFAOYSA-N tert-butyl 2-[4-(6-bromo-2h-indazol-3-yl)piperidin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCC1C1=NNC2=CC(Br)=CC=C12 BJLMWZCUYIQUBV-UHFFFAOYSA-N 0.000 description 1
- LKUCYFONIRHGSQ-UHFFFAOYSA-N tert-butyl 4-ethenylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C=C)CC1 LKUCYFONIRHGSQ-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 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
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000029663 wound healing Effects 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9613018.2 | 1996-06-21 | ||
| GBGB9613018.2A GB9613018D0 (en) | 1996-06-21 | 1996-06-21 | Therapeutic indazoles |
| GB9613095.0 | 1996-06-21 | ||
| GBGB9613017.4A GB9613017D0 (en) | 1996-06-21 | 1996-06-21 | Therapeutic compounds |
| GBGB9613095.0A GB9613095D0 (en) | 1996-06-21 | 1996-06-21 | Therapeutic piperidines |
| GB9613017.4 | 1996-06-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2258753A1 true CA2258753A1 (en) | 1997-12-31 |
Family
ID=27268341
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002258753A Abandoned CA2258753A1 (en) | 1996-06-21 | 1997-06-19 | Piperidine acetic acid derivatives and their use in the treatment of thrombotic disorders |
Country Status (17)
| Country | Link |
|---|---|
| EP (1) | EP0912555A1 (cs) |
| JP (1) | JP2000512648A (cs) |
| KR (1) | KR20000022041A (cs) |
| AP (1) | AP9801417A0 (cs) |
| AR (1) | AR008245A1 (cs) |
| AU (1) | AU3261197A (cs) |
| BR (1) | BR9709930A (cs) |
| CA (1) | CA2258753A1 (cs) |
| CZ (1) | CZ424698A3 (cs) |
| EA (1) | EA199801015A1 (cs) |
| ID (1) | ID17052A (cs) |
| IL (1) | IL127464A0 (cs) |
| IS (1) | IS4924A (cs) |
| NO (1) | NO985974L (cs) |
| PL (1) | PL330797A1 (cs) |
| TR (1) | TR199802665T2 (cs) |
| WO (1) | WO1997049699A1 (cs) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7642278B2 (en) | 2001-07-03 | 2010-01-05 | Novartis Vaccines And Diagnostics, Inc. | Indazole benzimidazole compounds |
| WO2003004488A1 (en) | 2001-07-03 | 2003-01-16 | Chiron Corporation | Indazole benzimidazole compounds as tyrosine and serine/threonine kinase inhibitors |
| TW200401641A (en) | 2002-07-18 | 2004-02-01 | Wyeth Corp | 1-Heterocyclylalkyl-3-sulfonylindole or-indazole derivatives as 5-hydroxytryptamine-6 ligands |
| TW200505904A (en) * | 2003-02-14 | 2005-02-16 | Wyeth Corp | Heterocyclyl-3-sulfonylindazoles as 5-hydroxytryptamine-6 ligands |
| CA2648055A1 (en) | 2006-04-05 | 2007-10-18 | Wyeth | Sulfonyl-3-heterocyclylindazole derivatives as 5-hydroxytryptamine-6 ligands |
| AU2008204583A1 (en) | 2007-01-10 | 2008-07-17 | F. Hoffmann-La Roche Ag | Sulfonamide derivatives as chymase inhibitors |
| CN113655155A (zh) * | 2021-07-28 | 2021-11-16 | 任贤金 | 一种测定sph3127有关物质的方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4124942A1 (de) * | 1991-07-27 | 1993-01-28 | Thomae Gmbh Dr K | 5-gliedrige heterocyclen, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| EP0612313A1 (en) * | 1991-11-14 | 1994-08-31 | Glaxo Group Limited | Piperidine acetic acid derivatives as inhibitors of fibrinogen-dependent blood platelet aggregation |
| GB9208740D0 (en) * | 1992-04-23 | 1992-06-10 | Glaxo Group Ltd | Chemical compounds |
-
1997
- 1997-06-18 AR ARP970102676A patent/AR008245A1/es unknown
- 1997-06-19 KR KR1019980710439A patent/KR20000022041A/ko not_active Withdrawn
- 1997-06-19 WO PCT/EP1997/003196 patent/WO1997049699A1/en not_active Application Discontinuation
- 1997-06-19 PL PL97330797A patent/PL330797A1/xx unknown
- 1997-06-19 BR BR9709930A patent/BR9709930A/pt not_active Application Discontinuation
- 1997-06-19 CA CA002258753A patent/CA2258753A1/en not_active Abandoned
- 1997-06-19 EA EA199801015A patent/EA199801015A1/ru unknown
- 1997-06-19 JP JP10502284A patent/JP2000512648A/ja active Pending
- 1997-06-19 EP EP97928243A patent/EP0912555A1/en not_active Withdrawn
- 1997-06-19 CZ CZ984246A patent/CZ424698A3/cs unknown
- 1997-06-19 ID IDP972092A patent/ID17052A/id unknown
- 1997-06-19 AP APAP/P/1998/001417A patent/AP9801417A0/en unknown
- 1997-06-19 AU AU32611/97A patent/AU3261197A/en not_active Abandoned
- 1997-06-19 IL IL12746497A patent/IL127464A0/xx unknown
- 1997-06-19 TR TR1998/02665T patent/TR199802665T2/xx unknown
-
1998
- 1998-12-15 IS IS4924A patent/IS4924A/is unknown
- 1998-12-18 NO NO985974A patent/NO985974L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IS4924A (is) | 1998-12-15 |
| JP2000512648A (ja) | 2000-09-26 |
| AU3261197A (en) | 1998-01-14 |
| AR008245A1 (es) | 1999-12-29 |
| AP9801417A0 (en) | 1998-12-31 |
| NO985974D0 (no) | 1998-12-18 |
| EP0912555A1 (en) | 1999-05-06 |
| NO985974L (no) | 1999-02-17 |
| IL127464A0 (en) | 1999-10-28 |
| EA199801015A1 (ru) | 1999-08-26 |
| BR9709930A (pt) | 1999-08-10 |
| WO1997049699A1 (en) | 1997-12-31 |
| KR20000022041A (ko) | 2000-04-25 |
| TR199802665T2 (xx) | 1999-03-22 |
| CZ424698A3 (cs) | 1999-05-12 |
| ID17052A (id) | 1997-12-04 |
| PL330797A1 (en) | 1999-06-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |