JP4504564B2 - スルホン酸またはスルホニルアミノn−(ヘテロアラルキル)−アザヘテロシクリルアミド化合物 - Google Patents
スルホン酸またはスルホニルアミノn−(ヘテロアラルキル)−アザヘテロシクリルアミド化合物 Download PDFInfo
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- JP4504564B2 JP4504564B2 JP2000552115A JP2000552115A JP4504564B2 JP 4504564 B2 JP4504564 B2 JP 4504564B2 JP 2000552115 A JP2000552115 A JP 2000552115A JP 2000552115 A JP2000552115 A JP 2000552115A JP 4504564 B2 JP4504564 B2 JP 4504564B2
- Authority
- JP
- Japan
- Prior art keywords
- chloro
- ylmethyl
- amino
- sulfonic acid
- oxopyrrolidin
- 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.)
- Expired - Fee Related
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 455
- 125000004475 heteroaralkyl group Chemical group 0.000 title description 22
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 title description 2
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 title 1
- -1 {1- [2- (2-amino-3-chloro-pyridin-4-ylamino) -ethyl] -2-oxo- Pyrrolidin-3-yl} -amide ditrifluoroacetate Chemical compound 0.000 claims description 442
- 229910052739 hydrogen Inorganic materials 0.000 claims description 84
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 150000003839 salts Chemical class 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 36
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- ZYDGKFWFDVZKMG-UHFFFAOYSA-N 6-chloro-1-benzothiophene-2-sulfonic acid Chemical compound C1=C(Cl)C=C2SC(S(=O)(=O)O)=CC2=C1 ZYDGKFWFDVZKMG-UHFFFAOYSA-N 0.000 claims description 21
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- WCPZEBOPCZXRBB-NTISSMGPSA-N 6-chloro-n-[(3s)-2-oxo-1-[2-(pyridin-4-ylamino)ethyl]pyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C2=CC3=CC=C(C=C3S2)Cl)CN1CCNC1=CC=NC=C1 WCPZEBOPCZXRBB-NTISSMGPSA-N 0.000 claims description 6
- GWLVVMNKTMZAIA-UHFFFAOYSA-N 2-[3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]-n-pyridin-4-ylacetamide Chemical compound C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)NC(C1=O)CCN1CC(=O)NC1=CC=NC=C1 GWLVVMNKTMZAIA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- MKNKQJJWTRJHOY-UHFFFAOYSA-N 2-(5-chlorothiophen-2-yl)-n-[2-oxo-1-[2-(pyridin-4-ylamino)ethyl]pyrrolidin-3-yl]ethenesulfonamide Chemical compound S1C(Cl)=CC=C1C=CS(=O)(=O)NC1C(=O)N(CCNC=2C=CN=CC=2)CC1 MKNKQJJWTRJHOY-UHFFFAOYSA-N 0.000 claims description 3
- LIJZKQFQDFEZNT-UHFFFAOYSA-N 3-amino-1-[2-(pyridin-4-ylamino)ethyl]pyrrolidin-2-one Chemical compound O=C1C(N)CCN1CCNC1=CC=NC=C1 LIJZKQFQDFEZNT-UHFFFAOYSA-N 0.000 claims description 3
- ORVHHMJJQWRUGQ-UHFFFAOYSA-N 6-chloro-N-[2-oxo-1-[2-(pyridin-4-ylamino)ethyl]pyrrolidin-3-yl]thieno[2,3-b]pyridine-2-sulfonamide 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.S1C2=NC(Cl)=CC=C2C=C1S(=O)(=O)NC(C1=O)CCN1CCNC1=CC=NC=C1 ORVHHMJJQWRUGQ-UHFFFAOYSA-N 0.000 claims description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- SJNOGWCYGAPNTC-UHFFFAOYSA-N n-(3-aminopyridin-4-yl)-2-[3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]acetamide Chemical compound C=1C2=CC(OC)=CC=C2C=CC=1S(=O)(=O)NC(C1=O)CCN1CC(=O)NC1=CC=NC=C1N SJNOGWCYGAPNTC-UHFFFAOYSA-N 0.000 claims description 3
- UDXIIXUCGCZZHQ-UTLKBRERSA-N n-[(3s)-1-[2-[(2-amino-3-chloropyridin-4-yl)amino]ethyl]-2-oxopyrrolidin-3-yl]-6-chloro-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.NC1=NC=CC(NCCN2C([C@@H](NS(=O)(=O)C=3SC4=CC(Cl)=CC=C4C=3)CC2)=O)=C1Cl UDXIIXUCGCZZHQ-UTLKBRERSA-N 0.000 claims description 3
- XJOKKMKDBLSIBJ-LTCKWSDVSA-N n-[(3s)-1-[2-[(2-amino-3-chloropyridin-4-yl)amino]ethyl]-2-oxopyrrolidin-3-yl]thieno[3,2-b]pyridine-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.NC1=NC=CC(NCCN2C([C@@H](NS(=O)(=O)C=3SC4=CC=CN=C4C=3)CC2)=O)=C1Cl XJOKKMKDBLSIBJ-LTCKWSDVSA-N 0.000 claims description 3
- AXFPFBCUDRXGED-UHFFFAOYSA-N n-[2-oxo-1-[2-(pyridin-4-ylamino)ethyl]pyrrolidin-3-yl]thieno[3,2-b]pyridine-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.O=C1C(NS(=O)(=O)C=2SC3=CC=CN=C3C=2)CCN1CCNC1=CC=NC=C1 AXFPFBCUDRXGED-UHFFFAOYSA-N 0.000 claims description 3
- GUPNEBAUHJRGMD-UHFFFAOYSA-N 6-chloro-n-methyl-n-[2-oxo-1-[2-(pyridin-4-ylamino)ethyl]pyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound C=1C2=CC=C(Cl)C=C2SC=1S(=O)(=O)N(C)C(C1=O)CCN1CCNC1=CC=NC=C1 GUPNEBAUHJRGMD-UHFFFAOYSA-N 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- KHMVACAHGFJHFQ-ZOWNYOTGSA-N n-[(3s)-1-[2-[(2-amino-3-chloropyridin-4-yl)amino]ethyl]-2-oxopyrrolidin-3-yl]-2-(5-chlorothiophen-2-yl)ethenesulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC1=NC=CC(NCCN2C([C@@H](NS(=O)(=O)C=CC=3SC(Cl)=CC=3)CC2)=O)=C1Cl KHMVACAHGFJHFQ-ZOWNYOTGSA-N 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 239000000203 mixture Substances 0.000 abstract description 109
- 108010074860 Factor Xa Proteins 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 8
- 239000003112 inhibitor Substances 0.000 abstract description 5
- 230000001668 ameliorated effect Effects 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 230000004962 physiological condition Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 383
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 377
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 297
- 239000000243 solution Substances 0.000 description 296
- 238000005160 1H NMR spectroscopy Methods 0.000 description 281
- 239000007787 solid Substances 0.000 description 234
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 227
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 182
- 235000019439 ethyl acetate Nutrition 0.000 description 176
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 165
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 151
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 149
- 239000012043 crude product Substances 0.000 description 134
- 239000000460 chlorine Substances 0.000 description 133
- 239000000047 product Substances 0.000 description 131
- 238000004440 column chromatography Methods 0.000 description 114
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 104
- 238000010828 elution Methods 0.000 description 104
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 95
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 81
- 239000012141 concentrate Substances 0.000 description 77
- 235000008504 concentrate Nutrition 0.000 description 77
- 239000011541 reaction mixture Substances 0.000 description 77
- 239000012044 organic layer Substances 0.000 description 76
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
- 238000004007 reversed phase HPLC Methods 0.000 description 68
- 229910052757 nitrogen Inorganic materials 0.000 description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 49
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 45
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
- 239000002253 acid Substances 0.000 description 42
- 238000000034 method Methods 0.000 description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 42
- 239000007858 starting material Substances 0.000 description 42
- 125000001072 heteroaryl group Chemical group 0.000 description 38
- 229920006395 saturated elastomer Polymers 0.000 description 38
- 238000000746 purification Methods 0.000 description 34
- 150000002500 ions Chemical class 0.000 description 33
- 239000007921 spray Substances 0.000 description 33
- 239000012267 brine Substances 0.000 description 32
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 32
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 31
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 30
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 30
- 239000010410 layer Substances 0.000 description 29
- CKARHIGQRRNVFD-UHFFFAOYSA-N 7-methoxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(OC)=CC=C21 CKARHIGQRRNVFD-UHFFFAOYSA-N 0.000 description 28
- 125000003710 aryl alkyl group Chemical group 0.000 description 28
- 238000010992 reflux Methods 0.000 description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 125000003118 aryl group Chemical group 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 20
- 239000000843 powder Substances 0.000 description 20
- 239000007864 aqueous solution Substances 0.000 description 19
- 239000002585 base Substances 0.000 description 19
- 125000005843 halogen group Chemical group 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- ZEXCZHWVXMIOFB-UHFFFAOYSA-N 7-methoxynaphthalene-2-sulfonyl chloride Chemical compound C1=CC(S(Cl)(=O)=O)=CC2=CC(OC)=CC=C21 ZEXCZHWVXMIOFB-UHFFFAOYSA-N 0.000 description 18
- 125000001309 chloro group Chemical group Cl* 0.000 description 18
- 238000000921 elemental analysis Methods 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 18
- 239000000463 material Substances 0.000 description 17
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- 229910000104 sodium hydride Inorganic materials 0.000 description 17
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
- 239000012312 sodium hydride Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 150000001408 amides Chemical class 0.000 description 15
- 125000000623 heterocyclic group Chemical group 0.000 description 15
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 15
- 125000000547 substituted alkyl group Chemical group 0.000 description 15
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 14
- 239000005695 Ammonium acetate Substances 0.000 description 14
- 235000019257 ammonium acetate Nutrition 0.000 description 14
- 229940043376 ammonium acetate Drugs 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- PHPBFBHVSTXJOL-UHFFFAOYSA-N 6-chloro-1-benzothiophene-2-sulfonyl chloride Chemical compound ClC1=CC=C2C=C(S(Cl)(=O)=O)SC2=C1 PHPBFBHVSTXJOL-UHFFFAOYSA-N 0.000 description 13
- DKSJHPRSSYLKRE-UHFFFAOYSA-N 7-(bromomethyl)-1-chloroisoquinoline Chemical compound C1=C(CBr)C=C2C(Cl)=NC=CC2=C1 DKSJHPRSSYLKRE-UHFFFAOYSA-N 0.000 description 13
- 239000000543 intermediate Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 125000004104 aryloxy group Chemical group 0.000 description 12
- 125000001246 bromo group Chemical group Br* 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 229910052801 chlorine Inorganic materials 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 239000000377 silicon dioxide Substances 0.000 description 11
- UVLKAUNUFWQFID-UHFFFAOYSA-N thieno[3,2-b]pyridine-2-sulfonic acid Chemical compound C1=CC=C2SC(S(=O)(=O)O)=CC2=N1 UVLKAUNUFWQFID-UHFFFAOYSA-N 0.000 description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 10
- 125000003545 alkoxy group Chemical group 0.000 description 10
- 239000012458 free base Substances 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 125000003107 substituted aryl group Chemical group 0.000 description 10
- 229910052717 sulfur Inorganic materials 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- 238000010626 work up procedure Methods 0.000 description 10
- FBQJSTRRHBTMMQ-UHFFFAOYSA-N 1-chloro-7-methylisoquinoline Chemical compound C1=CN=C(Cl)C2=CC(C)=CC=C21 FBQJSTRRHBTMMQ-UHFFFAOYSA-N 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 9
- 125000002252 acyl group Chemical group 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000003960 organic solvent Substances 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- 238000010791 quenching Methods 0.000 description 9
- KTVOMLQUDMNZLK-UHFFFAOYSA-N 1-benzothiophene-2-sulfonic acid Chemical compound C1=CC=C2SC(S(=O)(=O)O)=CC2=C1 KTVOMLQUDMNZLK-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 239000006260 foam Substances 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000002002 slurry Substances 0.000 description 8
- ZMOKFOPJBQAHGO-LBPRGKRZSA-N (3S)-3-amino-1-[(1-aminoisoquinolin-7-yl)methyl]pyrrolidin-2-one Chemical compound O=C1[C@@H](N)CCN1CC1=CC=C(C=CN=C2N)C2=C1 ZMOKFOPJBQAHGO-LBPRGKRZSA-N 0.000 description 7
- WIIXGYAVEZWIQF-YDALLXLXSA-N (3s)-3-amino-1-[(1-chloroisoquinolin-7-yl)methyl]pyrrolidin-2-one;hydrochloride Chemical compound Cl.O=C1[C@@H](N)CCN1CC1=CC=C(C=CN=C2Cl)C2=C1 WIIXGYAVEZWIQF-YDALLXLXSA-N 0.000 description 7
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- PFXMDSGRKNVHAA-UHFFFAOYSA-N 7-methoxynaphthalene-2-sulfonic acid 2,2,2-trifluoroacetic acid Chemical compound COC1=CC=C2C=CC(=CC2=C1)S(=O)(=O)O.FC(C(=O)O)(F)F PFXMDSGRKNVHAA-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 239000006185 dispersion Substances 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 229910052740 iodine Inorganic materials 0.000 description 7
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 7
- 239000002480 mineral oil Substances 0.000 description 7
- 235000010446 mineral oil Nutrition 0.000 description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
- 239000012047 saturated solution Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- JGKXLERCKLMGTP-LBPRGKRZSA-N (3s)-3-amino-1-[(1-chloroisoquinolin-7-yl)methyl]pyrrolidin-2-one Chemical compound O=C1[C@@H](N)CCN1CC1=CC=C(C=CN=C2Cl)C2=C1 JGKXLERCKLMGTP-LBPRGKRZSA-N 0.000 description 6
- FKIIVBOPAHICHQ-UHFFFAOYSA-N 1-benzothiophene-2-sulfonyl chloride Chemical compound C1=CC=C2SC(S(=O)(=O)Cl)=CC2=C1 FKIIVBOPAHICHQ-UHFFFAOYSA-N 0.000 description 6
- ZMULFNPBBJBUSJ-UHFFFAOYSA-N 2-(5-chlorothiophen-2-yl)ethenesulfonic acid Chemical compound OS(=O)(=O)C=CC1=CC=C(Cl)S1 ZMULFNPBBJBUSJ-UHFFFAOYSA-N 0.000 description 6
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
Classifications
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- 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
-
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- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/090,492 | 1998-06-03 | ||
| US09/090,492 US6602864B1 (en) | 1996-12-13 | 1998-06-03 | Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds |
| PCT/US1999/012312 WO1999062904A1 (en) | 1998-06-03 | 1999-06-03 | Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002517393A JP2002517393A (ja) | 2002-06-18 |
| JP2002517393A5 JP2002517393A5 (https=) | 2006-07-13 |
| JP4504564B2 true JP4504564B2 (ja) | 2010-07-14 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000552115A Expired - Fee Related JP4504564B2 (ja) | 1998-06-03 | 1999-06-03 | スルホン酸またはスルホニルアミノn−(ヘテロアラルキル)−アザヘテロシクリルアミド化合物 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6602864B1 (https=) |
| EP (1) | EP1086099B1 (https=) |
| JP (1) | JP4504564B2 (https=) |
| KR (1) | KR20010052501A (https=) |
| AT (1) | ATE305469T1 (https=) |
| AU (1) | AU758642B2 (https=) |
| BR (1) | BR9910899A (https=) |
| CA (1) | CA2333994A1 (https=) |
| DE (1) | DE69927497T2 (https=) |
| ES (1) | ES2246582T3 (https=) |
| NO (1) | NO20005912L (https=) |
| WO (1) | WO1999062904A1 (https=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6281227B1 (en) * | 1996-12-13 | 2001-08-28 | Aventis Pharma Deutschland Gmbh | Sulfonic acid sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
| AU753675B2 (en) | 1998-03-19 | 2002-10-24 | Ajinomoto Co., Inc. | Aminoisoquinoline derivatives |
| JP2001294572A (ja) * | 2000-02-09 | 2001-10-23 | Dai Ichi Seiyaku Co Ltd | 新規スルホニル誘導体 |
| US6506754B1 (en) * | 2000-04-14 | 2003-01-14 | Corvas International, Inc. | Non-covalent thrombin inhibitors |
| US7229986B2 (en) | 2000-05-16 | 2007-06-12 | Takeda Pharmaceutical Company Ltd. | Melanin-concentrating hormone antagonist |
| WO2002080853A2 (en) | 2001-04-09 | 2002-10-17 | Bristol-Myers Squibb Company | Fused heterocyclic inhibitors of factor xa |
| GB0114005D0 (en) | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
| GB0114004D0 (en) | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
| GB0127568D0 (en) * | 2001-11-16 | 2002-01-09 | Glaxo Group Ltd | Chemical compounds |
| AU2003302238A1 (en) | 2002-12-03 | 2004-06-23 | Axys Pharmaceuticals, Inc. | 2-(2-hydroxybiphenyl-3-yl)-1h-benzoimidazole-5-carboxamidine derivatives as factor viia inhibitors |
| GB0228552D0 (en) * | 2002-12-06 | 2003-01-15 | Glaxo Group Ltd | Chemical compounds |
| GB0228533D0 (en) * | 2002-12-06 | 2003-01-15 | Glaxo Group Ltd | Crystalline form |
| US7338975B2 (en) | 2003-02-12 | 2008-03-04 | Bristol-Myers Squibb Co. | Lactams as modulators of chemokine receptor activity |
| JP2008509222A (ja) * | 2004-08-09 | 2008-03-27 | グラクソ グループ リミテッド | 抗菌剤 |
| US7511035B2 (en) | 2005-01-25 | 2009-03-31 | Glaxo Group Limited | Antibacterial agents |
| EP1932839A4 (en) * | 2005-09-06 | 2014-09-10 | Shionogi & Co | INDOLECARBOXYLATE ACID DERIVATIVE HAVING ANTAGONIST EFFECT OF THE PGD2 RECEPTOR |
| US20100260751A1 (en) | 2007-09-28 | 2010-10-14 | Raju T Shantha | Methods and Structural Conformations of Antibody Preparations with Increased Resistance to Proteases |
| ES2622102T3 (es) | 2009-10-29 | 2017-07-05 | Janssen Biotech, Inc. | Variantes de anticuerpo de glicosilación |
| EP2606893A1 (en) | 2011-12-21 | 2013-06-26 | Sanofi | Sulphonylaminopyrrolidinone derivatives, their preparation and their therapeutic application |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5130323A (en) * | 1988-10-31 | 1992-07-14 | Fujisawa Pharmaceutical Co., Ltd. | Pyrrolidine derivatives |
| DE4121947A1 (de) * | 1991-07-03 | 1993-01-07 | Basf Ag | 2-(3-(4-amidino-phenyl))-propionsaeurederivate, ihre herstellung und verwendung |
| US5731315A (en) * | 1995-06-07 | 1998-03-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted sulfonic acid n- (aminoiminomethyl)phenylalkyl!-azaheterocyclamide compounds |
| US5612353A (en) * | 1995-06-07 | 1997-03-18 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
| CN1079396C (zh) * | 1996-05-31 | 2002-02-20 | C&C新药研究所 | 用作选择性凝血酶抑制剂的芳族脒衍生物 |
| DE69718194T2 (de) * | 1996-08-16 | 2003-10-16 | Bristol-Myers Squibb Pharma Co., Wilmington | Amidinophenyl-pyrrolidine, -pyrroline und -isoxazolidine und ihre derivate |
| IL130152A0 (en) * | 1996-12-13 | 2000-06-01 | Rhone Poulenc Rorer Pharma | Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclyamide compounds |
| US6281227B1 (en) * | 1996-12-13 | 2001-08-28 | Aventis Pharma Deutschland Gmbh | Sulfonic acid sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
| IL123986A (en) * | 1997-04-24 | 2011-10-31 | Organon Nv | Medicinal compounds |
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1998
- 1998-06-03 US US09/090,492 patent/US6602864B1/en not_active Expired - Fee Related
-
1999
- 1999-06-03 WO PCT/US1999/012312 patent/WO1999062904A1/en not_active Ceased
- 1999-06-03 DE DE69927497T patent/DE69927497T2/de not_active Expired - Lifetime
- 1999-06-03 EP EP99955266A patent/EP1086099B1/en not_active Expired - Lifetime
- 1999-06-03 KR KR1020007013635A patent/KR20010052501A/ko not_active Withdrawn
- 1999-06-03 JP JP2000552115A patent/JP4504564B2/ja not_active Expired - Fee Related
- 1999-06-03 AT AT99955266T patent/ATE305469T1/de not_active IP Right Cessation
- 1999-06-03 CA CA002333994A patent/CA2333994A1/en not_active Abandoned
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- 1999-06-03 AU AU43298/99A patent/AU758642B2/en not_active Ceased
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2000
- 2000-11-22 NO NO20005912A patent/NO20005912L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AU4329899A (en) | 1999-12-20 |
| ES2246582T3 (es) | 2006-02-16 |
| NO20005912L (no) | 2001-01-31 |
| CA2333994A1 (en) | 1999-12-09 |
| BR9910899A (pt) | 2001-10-09 |
| KR20010052501A (ko) | 2001-06-25 |
| ATE305469T1 (de) | 2005-10-15 |
| DE69927497D1 (de) | 2006-02-09 |
| NO20005912D0 (no) | 2000-11-22 |
| US6602864B1 (en) | 2003-08-05 |
| EP1086099B1 (en) | 2005-09-28 |
| WO1999062904A1 (en) | 1999-12-09 |
| JP2002517393A (ja) | 2002-06-18 |
| AU758642B2 (en) | 2003-03-27 |
| EP1086099A1 (en) | 2001-03-28 |
| EP1086099A4 (en) | 2002-01-02 |
| DE69927497T2 (de) | 2006-06-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
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