AU714319B2 - Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-((aminoiminomethyl)phenylalkyl)- azaheterocyclylamide compounds - Google Patents
Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-((aminoiminomethyl)phenylalkyl)- azaheterocyclylamide compounds Download PDFInfo
- Publication number
- AU714319B2 AU714319B2 AU61669/96A AU6166996A AU714319B2 AU 714319 B2 AU714319 B2 AU 714319B2 AU 61669/96 A AU61669/96 A AU 61669/96A AU 6166996 A AU6166996 A AU 6166996A AU 714319 B2 AU714319 B2 AU 714319B2
- Authority
- AU
- Australia
- Prior art keywords
- trifluoroacetate
- oxopyrrolidin
- acid
- benzyl
- methoxynaphthalene
- 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.)
- Ceased
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- 150000001875 compounds Chemical class 0.000 title claims description 691
- -1 sulfinylamino Chemical group 0.000 title claims description 151
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 title claims description 16
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 title description 14
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 title description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 364
- 239000002253 acid Substances 0.000 claims description 357
- 229910052739 hydrogen Inorganic materials 0.000 claims description 248
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 216
- 229910052757 nitrogen Inorganic materials 0.000 claims description 189
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 172
- 150000001408 amides Chemical class 0.000 claims description 73
- 239000001257 hydrogen Substances 0.000 claims description 67
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 51
- 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 claims description 47
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 44
- 150000002431 hydrogen Chemical group 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 40
- 230000015572 biosynthetic process Effects 0.000 claims description 34
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 21
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 17
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- QSELGEUCFNFITD-UHFFFAOYSA-N thiophene-2-carboximidamide Chemical compound NC(=N)C1=CC=CS1 QSELGEUCFNFITD-UHFFFAOYSA-N 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 108010074860 Factor Xa Proteins 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 11
- JWOCZCVIXWLBNG-UHFFFAOYSA-N benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)C1=CC=CC=C1 JWOCZCVIXWLBNG-UHFFFAOYSA-N 0.000 claims description 10
- FOIKGWJGRNNGQP-UHFFFAOYSA-N 6-methoxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=CC(OC)=CC=C21 FOIKGWJGRNNGQP-UHFFFAOYSA-N 0.000 claims description 9
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 claims description 9
- KNXKVYCVGXFLES-UHFFFAOYSA-N pyridine-2-carboximidamide Chemical compound NC(=N)C1=CC=CC=N1 KNXKVYCVGXFLES-UHFFFAOYSA-N 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 8
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- IIGVTBXGSGACRA-UHFFFAOYSA-N 4-(3-methoxyphenyl)benzenesulfonic acid Chemical compound COC1=CC=CC(C=2C=CC(=CC=2)S(O)(=O)=O)=C1 IIGVTBXGSGACRA-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- MODKMHXGCGKTLE-UHFFFAOYSA-N N-acetylphenylethylamine Chemical compound CC(=O)NCCC1=CC=CC=C1 MODKMHXGCGKTLE-UHFFFAOYSA-N 0.000 claims description 6
- 239000003146 anticoagulant agent Substances 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- AFCCDDWKHLHPDF-UHFFFAOYSA-M metam-sodium Chemical compound [Na+].CNC([S-])=S AFCCDDWKHLHPDF-UHFFFAOYSA-M 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- IVIIAEVMQHEPAY-UHFFFAOYSA-N tridodecyl phosphite Chemical compound CCCCCCCCCCCCOP(OCCCCCCCCCCCC)OCCCCCCCCCCCC IVIIAEVMQHEPAY-UHFFFAOYSA-N 0.000 claims description 5
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 claims description 4
- AMTXWXZUNMMYFQ-UHFFFAOYSA-N 7-ethylnaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(CC)=CC=C21 AMTXWXZUNMMYFQ-UHFFFAOYSA-N 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 208000007536 Thrombosis Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 4
- 150000001555 benzenes Chemical class 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- 230000002792 vascular Effects 0.000 claims description 4
- 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 3
- DLEXGQNBBCPGTH-UHFFFAOYSA-N 7-ethoxynaphthalene-2-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=CC(OCC)=CC=C21 DLEXGQNBBCPGTH-UHFFFAOYSA-N 0.000 claims description 3
- 208000005189 Embolism Diseases 0.000 claims description 3
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- 208000001435 Thromboembolism Diseases 0.000 claims description 3
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
- 210000001367 artery Anatomy 0.000 claims description 3
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 claims description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
- 125000004494 ethyl ester group Chemical group 0.000 claims description 3
- UGRVUSWSAGRCSJ-UHFFFAOYSA-N ethylammonium trifluoroacetate Chemical compound CC[NH3+].[O-]C(=O)C(F)(F)F UGRVUSWSAGRCSJ-UHFFFAOYSA-N 0.000 claims description 3
- 150000004702 methyl esters Chemical class 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
- 230000002093 peripheral effect Effects 0.000 claims description 3
- 210000005166 vasculature Anatomy 0.000 claims description 3
- RKIVBXUNCCKPJO-UHFFFAOYSA-N 2-methoxyquinoline-7-sulfonic acid Chemical compound C1=CC(S(O)(=O)=O)=CC2=NC(OC)=CC=C21 RKIVBXUNCCKPJO-UHFFFAOYSA-N 0.000 claims description 2
- CTEWUQNEQPLMMJ-UHFFFAOYSA-N 5,6,7,8-tetrahydronaphthalene-2-sulfonic acid Chemical compound C1CCCC2=CC(S(=O)(=O)O)=CC=C21 CTEWUQNEQPLMMJ-UHFFFAOYSA-N 0.000 claims description 2
- ZQPOQWZJSQZACS-UHFFFAOYSA-N 5,6,7,8-tetrahydrophenanthrene-3-sulfonic acid Chemical compound C1CCCC2=C1C=CC1=CC=C(S(=O)(=O)O)C=C12 ZQPOQWZJSQZACS-UHFFFAOYSA-N 0.000 claims description 2
- GXWGRQOMOLFZDN-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene-2-sulfonic acid Chemical compound C1=C(Cl)C=C2C(C)=C(S(O)(=O)=O)SC2=C1 GXWGRQOMOLFZDN-UHFFFAOYSA-N 0.000 claims description 2
- GJJURAXVGOIXKG-UHFFFAOYSA-N 5-chloro-6,7-dimethoxynaphthalene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=C2C(Cl)=C(OC)C(OC)=CC2=C1 GJJURAXVGOIXKG-UHFFFAOYSA-N 0.000 claims description 2
- AAQLVLMRJCRWNU-UHFFFAOYSA-N 6-chloro-6-(2-nitrophenoxy)cyclohexa-2,4-diene-1-sulfonic acid Chemical compound ClC1(C(C=CC=C1)S(=O)(=O)O)OC1=CC=CC=C1[N+](=O)[O-] AAQLVLMRJCRWNU-UHFFFAOYSA-N 0.000 claims description 2
- 206010002388 Angina unstable Diseases 0.000 claims description 2
- 101100063435 Caenorhabditis elegans din-1 gene Proteins 0.000 claims description 2
- 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 claims description 2
- 206010053567 Coagulopathies Diseases 0.000 claims description 2
- 206010022562 Intermittent claudication Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 206010040070 Septic Shock Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 208000032109 Transient ischaemic attack Diseases 0.000 claims description 2
- 208000007814 Unstable Angina Diseases 0.000 claims description 2
- 208000036142 Viral infection Diseases 0.000 claims description 2
- 230000003187 abdominal effect Effects 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- 210000005249 arterial vasculature Anatomy 0.000 claims description 2
- HLMGQSNPAYICCF-UHFFFAOYSA-N benzo[f][1,3]benzodioxole-6-sulfonic acid Chemical compound C1=C2OCOC2=CC2=CC(S(=O)(=O)O)=CC=C21 HLMGQSNPAYICCF-UHFFFAOYSA-N 0.000 claims description 2
- 208000015294 blood coagulation disease Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 238000007887 coronary angioplasty Methods 0.000 claims description 2
- FUVVSNUVSKUJAS-UHFFFAOYSA-N furan-2-carboximidamide Chemical compound NC(=N)C1=CC=CO1 FUVVSNUVSKUJAS-UHFFFAOYSA-N 0.000 claims description 2
- 238000001631 haemodialysis Methods 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
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- 238000012423 maintenance Methods 0.000 claims description 2
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 2
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- 230000036303 septic shock Effects 0.000 claims description 2
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- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 4
- PNQPQIIGGUWDPR-UHFFFAOYSA-N 1-(3-chloropyridin-2-yl)oxycyclohexa-2,4-diene-1-sulfonic acid Chemical compound N=1C=CC=C(Cl)C=1OC1(S(=O)(=O)O)CC=CC=C1 PNQPQIIGGUWDPR-UHFFFAOYSA-N 0.000 claims 1
- LBRJUBLMIYOGNN-FERBBOLQSA-N 3-[[(3s)-2-oxo-3-(2-phenylethenylsulfonylamino)pyrrolidin-1-yl]methyl]benzenecarboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.NC(=N)C1=CC=CC(CN2C([C@@H](NS(=O)(=O)C=CC=3C=CC=CC=3)CC2)=O)=C1 LBRJUBLMIYOGNN-FERBBOLQSA-N 0.000 claims 1
- ITSMLVBLBSCNPN-UHFFFAOYSA-N 4-(2-methoxyphenyl)benzenesulfonic acid Chemical compound COC1=CC=CC=C1C1=CC=C(S(O)(=O)=O)C=C1 ITSMLVBLBSCNPN-UHFFFAOYSA-N 0.000 claims 1
- ADAKMYBJTQFVMB-UHFFFAOYSA-N 4-(3-methylphenyl)benzenesulfonic acid Chemical compound CC1=CC=CC(C=2C=CC(=CC=2)S(O)(=O)=O)=C1 ADAKMYBJTQFVMB-UHFFFAOYSA-N 0.000 claims 1
- VDHZTKHCEVXDOO-FERBBOLQSA-N 4-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CSC(C(N)=N)=C1 VDHZTKHCEVXDOO-FERBBOLQSA-N 0.000 claims 1
- GOSCQCGNFATPPM-FERBBOLQSA-N 5-[[(3s)-3-[(7-methoxynaphthalen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]thiophene-2-carboximidamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=C(C(N)=N)S1 GOSCQCGNFATPPM-FERBBOLQSA-N 0.000 claims 1
- UWDQVEPXORTQFO-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene Chemical compound C1=C(Cl)C=C2C(C)=CSC2=C1 UWDQVEPXORTQFO-UHFFFAOYSA-N 0.000 claims 1
- JLTUANWNGKWRQO-UHFFFAOYSA-N 5-chloro-3-methyl-1-benzothiophene-2-sulfonyl chloride Chemical group C1=C(Cl)C=C2C(C)=C(S(Cl)(=O)=O)SC2=C1 JLTUANWNGKWRQO-UHFFFAOYSA-N 0.000 claims 1
- RRELHGZMPGGKMS-UHFFFAOYSA-N 5-chloro-6-methoxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=CC2=C(Cl)C(OC)=CC=C21 RRELHGZMPGGKMS-UHFFFAOYSA-N 0.000 claims 1
- IMSZMAMIAUKQMV-UHFFFAOYSA-N 6,7-dimethoxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C2C=C(OC)C(OC)=CC2=C1 IMSZMAMIAUKQMV-UHFFFAOYSA-N 0.000 claims 1
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- 239000003937 drug carrier Substances 0.000 claims 1
- TWXDDNPPQUTEOV-UHFFFAOYSA-N hydron;n-methyl-1-phenylpropan-2-amine;chloride Chemical compound Cl.CNC(C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-UHFFFAOYSA-N 0.000 claims 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 34
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- 102100021079 Ornithine decarboxylase Human genes 0.000 description 30
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- NQMUGNMMFTYOHK-UHFFFAOYSA-N 1-methoxynaphthalene Chemical compound C1=CC=C2C(OC)=CC=CC2=C1 NQMUGNMMFTYOHK-UHFFFAOYSA-N 0.000 description 23
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- NVCYUTUFPGPAKI-QHCPKHFHSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-4-(2-methoxyphenyl)benzenesulfonamide Chemical compound COC1=CC=CC=C1C1=CC=C(S(=O)(=O)N[C@@H]2C(N(CC=3C=C(C=CC=3)C#N)CC2)=O)C=C1 NVCYUTUFPGPAKI-QHCPKHFHSA-N 0.000 description 1
- JKJNIUCOTNJIDC-NRFANRHFSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-6,7-dimethoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C2=CC=C3C=C(C(=CC3=C2)OC)OC)CN1CC1=CC=CC(C#N)=C1 JKJNIUCOTNJIDC-NRFANRHFSA-N 0.000 description 1
- ZRCDPNCDMBZSDY-QHCPKHFHSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-7-ethylnaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)CC)CN1CC1=CC=CC(C#N)=C1 ZRCDPNCDMBZSDY-QHCPKHFHSA-N 0.000 description 1
- MYHFINDNIJVRFK-ZDUSSCGKSA-N n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]ethenesulfonamide Chemical compound O=C1[C@@H](NS(=O)(=O)C=C)CCN1CC1=CC=CC(C#N)=C1 MYHFINDNIJVRFK-ZDUSSCGKSA-N 0.000 description 1
- VPVRMYHYFOAKSS-QFIPXVFZSA-N n-[(3s)-1-[(4-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical compound C([C@@H](C1=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)CN1CC1=CC=C(C#N)C=C1 VPVRMYHYFOAKSS-QFIPXVFZSA-N 0.000 description 1
- NIYCWDHSWVJIKD-ZOWNYOTGSA-N n-[(3s)-pyrrolidin-3-yl]naphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=C2C=CC=CC2=CC=1S(=O)(=O)N[C@H]1CCNC1 NIYCWDHSWVJIKD-ZOWNYOTGSA-N 0.000 description 1
- ZZFDGUYWPAUHQW-UHFFFAOYSA-N n-[2-(4-methylphenyl)ethyl]acetamide Chemical compound CC(=O)NCCC1=CC=C(C)C=C1 ZZFDGUYWPAUHQW-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005029 naphthylthio group Chemical group C1(=CC=CC2=CC=CC=C12)S* 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 125000006504 o-cyanobenzyl group Chemical group [H]C1=C([H])C(C#N)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
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- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 108010014806 prothrombinase complex Proteins 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- XELRMPRLCPFTBH-UHFFFAOYSA-N quinazoline-2,4-diamine Chemical compound C1=CC=CC2=NC(N)=NC(N)=C21 XELRMPRLCPFTBH-UHFFFAOYSA-N 0.000 description 1
- ZHNFLHYOFXQIOW-LPYZJUEESA-N quinine sulfate dihydrate Chemical compound [H+].[H+].O.O.[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ZHNFLHYOFXQIOW-LPYZJUEESA-N 0.000 description 1
- AUDKCUOUBLCZQR-UHFFFAOYSA-N quinoline-6-sulfonyl chloride Chemical compound N1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 AUDKCUOUBLCZQR-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- KLVVZEJVDBTUHQ-UHFFFAOYSA-M sodium;5,6,7,8-tetrahydrophenanthrene-3-sulfonate Chemical compound [Na+].C1CCCC2=C1C=CC1=CC=C(S(=O)(=O)[O-])C=C12 KLVVZEJVDBTUHQ-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- QPUVKJBPFFRLRR-ZLTKDMPESA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate;naphthalene-2-sulfonic acid Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1.C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 QPUVKJBPFFRLRR-ZLTKDMPESA-N 0.000 description 1
- DHHKPEUQJIEKOA-UHFFFAOYSA-N tert-butyl 2-[6-(nitromethyl)-6-bicyclo[3.2.0]hept-3-enyl]acetate Chemical class C1C=CC2C(CC(=O)OC(C)(C)C)(C[N+]([O-])=O)CC21 DHHKPEUQJIEKOA-UHFFFAOYSA-N 0.000 description 1
- MQSNSCMXWVADDJ-ZDUSSCGKSA-N tert-butyl n-[(3s)-1-[(3-cyanophenyl)methyl]-2-oxoazetidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CN1CC1=CC=CC(C#N)=C1 MQSNSCMXWVADDJ-ZDUSSCGKSA-N 0.000 description 1
- ZFEBWMJKAXPDNZ-AWEZNQCLSA-N tert-butyl n-[(3s)-1-[(4-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC=C(C#N)C=C1 ZFEBWMJKAXPDNZ-AWEZNQCLSA-N 0.000 description 1
- NJMSEXDHKYVLKY-YFKPBYRVSA-N tert-butyl n-[(3s)-2-oxoazetidin-3-yl]carbamate Chemical group CC(C)(C)OC(=O)N[C@H]1CNC1=O NJMSEXDHKYVLKY-YFKPBYRVSA-N 0.000 description 1
- DVWCHAUBYVZILO-LURJTMIESA-N tert-butyl n-[(3s)-2-oxopyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CCNC1=O DVWCHAUBYVZILO-LURJTMIESA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- ZPHGMBGIFODUMF-UHFFFAOYSA-N thiophen-2-ylmethanol Chemical compound OCC1=CC=CS1 ZPHGMBGIFODUMF-UHFFFAOYSA-N 0.000 description 1
- LAWUZBKFMNSOGG-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=[C]S1 LAWUZBKFMNSOGG-UHFFFAOYSA-N 0.000 description 1
- BSXLLFUSNQCWJP-UHFFFAOYSA-N thiophene-2-sulfonic acid Chemical compound OS(=O)(=O)C1=CC=CS1 BSXLLFUSNQCWJP-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
-
- 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
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
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- 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
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D205/085—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams with a nitrogen atom directly attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
- C07D207/36—Oxygen or sulfur atoms
- C07D207/40—2,5-Pyrrolidine-diones
- C07D207/416—2,5-Pyrrolidine-diones 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 other ring carbon atoms
-
- 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
- C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—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 one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
-
- 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
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D405/02—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 two hetero rings
- C07D405/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/481,024 US5612353A (en) | 1995-06-07 | 1995-06-07 | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
| US08/481024 | 1995-06-07 | ||
| PCT/US1996/009816 WO1996040679A1 (en) | 1995-06-07 | 1996-06-07 | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) n-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU6166996A AU6166996A (en) | 1996-12-30 |
| AU714319B2 true AU714319B2 (en) | 2000-01-06 |
Family
ID=23910281
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU61669/96A Ceased AU714319B2 (en) | 1995-06-07 | 1996-06-07 | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-((aminoiminomethyl)phenylalkyl)- azaheterocyclylamide compounds |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US5612353A (enExample) |
| EP (1) | EP0853618B1 (enExample) |
| JP (1) | JP4312829B2 (enExample) |
| KR (1) | KR100291711B1 (enExample) |
| CN (1) | CN1190395A (enExample) |
| AP (1) | AP799A (enExample) |
| AT (1) | ATE520655T1 (enExample) |
| AU (1) | AU714319B2 (enExample) |
| BG (1) | BG63628B1 (enExample) |
| BR (1) | BR9608405A (enExample) |
| CA (1) | CA2223403C (enExample) |
| CZ (1) | CZ385397A3 (enExample) |
| EA (1) | EA000700B1 (enExample) |
| HU (1) | HUP9801882A3 (enExample) |
| MX (1) | MX9709977A (enExample) |
| NO (1) | NO310457B1 (enExample) |
| OA (1) | OA10752A (enExample) |
| PL (1) | PL323780A1 (enExample) |
| SI (1) | SI9620093A (enExample) |
| SK (1) | SK160697A3 (enExample) |
| WO (1) | WO1996040679A1 (enExample) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5731315A (en) * | 1995-06-07 | 1998-03-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted sulfonic acid n- (aminoiminomethyl)phenylalkyl!-azaheterocyclamide compounds |
| US6034093A (en) * | 1995-06-07 | 2000-03-07 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted sulfonic acid N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
| US5958918A (en) * | 1995-06-07 | 1999-09-28 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N- (aminominomethyl)phenylalkyl!-azaheterocyclylamide compounds |
| US6080767A (en) * | 1996-01-02 | 2000-06-27 | Aventis Pharmaceuticals Products Inc. | Substituted n-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides |
| US6057342A (en) * | 1996-08-16 | 2000-05-02 | Dupont Pharmaceutical Co. | Amidinophenyl-pyrrolidines, -pyrrolines, and -isoxazolidines and derivatives thereof |
| US6602864B1 (en) * | 1996-12-13 | 2003-08-05 | Aventis Pharma Deutschland Gmbh | Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds |
| SK71299A3 (en) * | 1996-12-13 | 2000-12-11 | Rhone Poulenc Rorer Pharma | Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
| WO1998054164A1 (en) | 1997-05-30 | 1998-12-03 | Takeda Chemical Industries, Ltd. | Sulfonamide derivatives, their production and use |
| ZA985247B (en) * | 1997-06-19 | 1999-12-17 | Du Pont Merck Pharma | Guanidine mimics as factor Xa inhibitors. |
| WO1999016747A1 (en) | 1997-09-30 | 1999-04-08 | Daiichi Pharmaceutical Co., Ltd. | Sulfonyl derivatives |
| WO1999032454A1 (en) * | 1997-12-22 | 1999-07-01 | Du Pont Pharmaceuticals Company | Nitrogen containing heteroaromatics with ortho-substituted p1's as factor xa inhibitors |
| US6271237B1 (en) | 1997-12-22 | 2001-08-07 | Dupont Pharmaceuticals Company | Nitrogen containing heteromatics with ortho-substituted P1s as factor Xa inhabitors |
| KR20010034442A (ko) * | 1998-01-27 | 2001-04-25 | 아벤티스 파마슈티칼즈 프로덕츠 인코포레이티드 | 치환된 옥소아자헤테로사이클릴 인자 Xa 억제제 |
| WO1999040075A1 (en) | 1998-02-05 | 1999-08-12 | Takeda Chemical Industries, Ltd. | Sulfonamide derivatives, process for producing the same and utilization thereof |
| US6291514B1 (en) | 1998-02-09 | 2001-09-18 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines, preparation thereof, and use thereof as protease inhibitors |
| EP1054886B1 (en) * | 1998-02-09 | 2002-09-04 | 3-Dimensional Pharmaceuticals, Inc. | Heteroaryl amidines, methylamidines and guanidines as protease inhibitors, in particular as urokinase inhibitors |
| US6747023B1 (en) * | 1998-08-11 | 2004-06-08 | Daiichi Pharmaceutical Co., Ltd. | Sulfonyl derivatives |
| DE19839499A1 (de) * | 1998-08-29 | 2000-03-02 | Merck Patent Gmbh | 2-Oxo-2H-chinolinderivate |
| WO2000032590A1 (en) * | 1998-11-25 | 2000-06-08 | Aventis Pharmaceuticals Products Inc. | SUBSTITUTED OXOAZAHETEROCYCLYL FACTOR Xa INHIBITORS |
| CZ20012858A3 (cs) * | 1999-02-09 | 2002-05-15 | 3-Dimensional Pharmaceuticals, Inc. | Heteroarylamidiny, methylamidininy a guanidiny jako inhibitory proteasy |
| DE19909237A1 (de) * | 1999-03-03 | 2000-09-07 | Merck Patent Gmbh | Pyrazol-3-on-derivate |
| US6794412B1 (en) * | 1999-03-11 | 2004-09-21 | Bristol-Myers Squibb Pharma Company | Treatment of thrombosis by combined use of a factor Xa inhibitor and aspirin |
| JP2001026506A (ja) * | 1999-04-28 | 2001-01-30 | Takeda Chem Ind Ltd | スルホンアミド誘導体 |
| US6586617B1 (en) | 1999-04-28 | 2003-07-01 | Sumitomo Chemical Takeda Agro Company, Limited | Sulfonamide derivatives |
| DE60027718T2 (de) | 1999-06-22 | 2007-05-16 | Takeda Pharmaceutical Co. Ltd. | Acylhydrazinderivate, verfahren zu ihrer herstellung und ihre verwendung |
| KR20020087041A (ko) * | 1999-07-28 | 2002-11-21 | 아벤티스 파마슈티칼스 프로덕츠 인크. | 치환된 옥소아자헤테로사이클릴 화합물 |
| US6544981B2 (en) | 2000-06-09 | 2003-04-08 | Bristol-Myers Squibb Company | Lactam inhibitors of factor Xa and method |
| US6511973B2 (en) | 2000-08-02 | 2003-01-28 | Bristol-Myers Squibb Co. | Lactam inhibitors of FXa and method |
| JP2004509104A (ja) | 2000-09-11 | 2004-03-25 | ジェネンテック・インコーポレーテッド | セリンプロテアーゼのアミジンインヒビター |
| DE60116655T2 (de) * | 2000-11-08 | 2006-11-16 | Takeda Pharmaceutical Co. Ltd. | Carbamatderivate, verfahren zu deren herstellung und deren verwendung |
| US6982251B2 (en) | 2000-12-20 | 2006-01-03 | Schering Corporation | Substituted 2-azetidinones useful as hypocholesterolemic agents |
| AR032230A1 (es) * | 2001-01-16 | 2003-10-29 | Sumitomo Chem Takeda Agro Co | Derivado sulfonamida conteniendo una composicion agricola y horticola |
| IL156422A0 (en) | 2001-01-26 | 2004-01-04 | Schering Corp | The use of substituted azetidinone compounds for the treatment of sitosterolemia |
| US20060287254A1 (en) * | 2001-01-26 | 2006-12-21 | Schering Corporation | Use of substituted azetidinone compounds for the treatment of sitosterolemia |
| US7071181B2 (en) | 2001-01-26 | 2006-07-04 | Schering Corporation | Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors |
| SI1413331T1 (sl) * | 2001-01-26 | 2008-02-29 | Schering Corp | Kombinacije fenofibrata peroksisomskega proliferator aktivirajocega receptorja (PPAR) z ezetimib zaviralcem absorpcije sterola za vaskularne indikacije |
| HUP0304058A2 (hu) | 2001-01-30 | 2004-04-28 | Bristol-Myers Squibb Company | Xa faktor szulfonamid-laktám inhibitorok és alkalmazásuk és ezeket tartalmazó gyógyszerkészítmények |
| US6538017B2 (en) | 2001-03-09 | 2003-03-25 | Ortho-Mcneil Pharmaceutical, Inc. | Aminopyrrolidine sulfonamides as serine protease inhibitors |
| US6710061B2 (en) | 2001-03-09 | 2004-03-23 | Ortho-Mcneil Pharamceutical, Inc. | Aminopyrrolidine sulfonamides as serine protease inhibitors |
| DE10112768A1 (de) * | 2001-03-16 | 2002-09-19 | Merck Patent Gmbh | Phenylderivate 3 |
| DE10139060A1 (de) | 2001-08-08 | 2003-02-20 | Merck Patent Gmbh | Phenylderivate |
| JP2005504091A (ja) * | 2001-09-21 | 2005-02-10 | シェーリング コーポレイション | ステロール吸収阻害剤としてアゼチジノンを用いる黄色腫の処置 |
| US7053080B2 (en) * | 2001-09-21 | 2006-05-30 | Schering Corporation | Methods and therapeutic combinations for the treatment of obesity using sterol absorption inhibitors |
| DE10239821A1 (de) | 2002-08-29 | 2004-03-11 | Roche Diagnostics Gmbh | Verbesserung der Spezifität bei der Bestimmung von Antithrombin |
| EP1562582A1 (en) | 2002-11-06 | 2005-08-17 | Schering Corporation | Cholesterol absorption inhibitors for the treatment of demyelination |
| AU2003284596A1 (en) | 2002-11-22 | 2004-06-18 | Takeda Pharmaceutical Company Limited | Imidazole derivative, process for producing the same, and use |
| SI1569912T1 (sl) | 2002-12-03 | 2015-09-30 | Pharmacyclics Llc | Derivati 2-(2-hidroksibifenil-3-il)-1h-benzoimidazol-5-karboksamidina kot inhibitorji faktorja viia |
| DE10302500A1 (de) | 2003-01-23 | 2004-07-29 | Merck Patent Gmbh | Carbonsäureamidderivate |
| CN1756756A (zh) * | 2003-03-07 | 2006-04-05 | 先灵公司 | 取代的2-吖丁啶酮化合物、其制剂及其治疗高胆甾醇血症的用途 |
| WO2004081002A1 (en) | 2003-03-07 | 2004-09-23 | Schering Corporation | Substituted azetidinone compounds, formulations and uses thereof for the treatment of hypercholesterolemia |
| JP2006519869A (ja) | 2003-03-07 | 2006-08-31 | シェーリング コーポレイション | 置換アゼチジノン化合物、置換アゼチジノン化合物を調製するためのプロセス、それらの処方物および使用 |
| US7459442B2 (en) * | 2003-03-07 | 2008-12-02 | Schering Corporation | Substituted azetidinone compounds, processes for preparing the same, formulations and uses thereof |
| EP1628954A2 (en) | 2003-05-20 | 2006-03-01 | Genentech, Inc. | Acylsulfamide inhibitors of factor viia |
| EP1626966A1 (en) | 2003-05-20 | 2006-02-22 | Genentech, Inc. | Benzofuran inhibitors of factor viia |
| NZ547528A (en) * | 2003-10-29 | 2008-11-28 | Elan Pharm Inc | N-substituted benzene sulfonamides |
| EP1533298A1 (en) | 2003-11-21 | 2005-05-25 | Newron Pharmaceuticals S.p.A. | 3-aminopyrrolidone derivatives |
| TWI396686B (zh) | 2004-05-21 | 2013-05-21 | Takeda Pharmaceutical | 環狀醯胺衍生物、以及其製品和用法 |
| ATE517085T1 (de) * | 2004-11-23 | 2011-08-15 | Astrazeneca Ab | Zur behandlung von atemwegserkrankungen geeignete phenoxyessigsäurederivate |
| EP1891063B1 (en) * | 2005-05-10 | 2012-07-25 | Vertex Pharmaceuticals, Inc. | Bicyclic derivatives as modulators of ion channels |
| AU2019387370A1 (en) | 2018-11-30 | 2021-06-10 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4121947A1 (de) * | 1991-07-03 | 1993-01-07 | Basf Ag | 2-(3-(4-amidino-phenyl))-propionsaeurederivate, ihre herstellung und verwendung |
| WO1993007141A1 (en) * | 1991-10-11 | 1993-04-15 | Smithkline Beecham Corporation | Heterocyclic 3-phenylpyrrolidin-2-ones, their preparation and use for the manufacture of a medicament for inhibiting tumor necrosis factor production |
| JPH05201971A (ja) * | 1992-01-28 | 1993-08-10 | Hokuriku Seiyaku Co Ltd | 環状アミン含有ベンゼンスルホンアミド誘導体 |
| US5665754A (en) * | 1993-09-20 | 1997-09-09 | Glaxo Wellcome Inc. | Substituted pyrrolidines |
| AU7665694A (en) * | 1993-09-21 | 1995-04-10 | Yamanouchi Pharmaceutical Co., Ltd. | N-(3-pyrrolidinyl)benzamide derivative |
| FR2714378B1 (fr) * | 1993-12-24 | 1996-03-15 | Sanofi Sa | Dérivés de l'indol-2-one substitués en 3 par un groupe azoté, leur préparation, les compositions pharmaceutiques en contenant. |
-
1995
- 1995-06-07 US US08/481,024 patent/US5612353A/en not_active Expired - Lifetime
-
1996
- 1996-06-07 CA CA002223403A patent/CA2223403C/en not_active Expired - Fee Related
- 1996-06-07 AP APAP/P/1997/001144A patent/AP799A/en active
- 1996-06-07 SK SK1606-97A patent/SK160697A3/sk unknown
- 1996-06-07 PL PL96323780A patent/PL323780A1/xx unknown
- 1996-06-07 CZ CZ973853A patent/CZ385397A3/cs unknown
- 1996-06-07 EA EA199800043A patent/EA000700B1/ru not_active IP Right Cessation
- 1996-06-07 WO PCT/US1996/009816 patent/WO1996040679A1/en not_active Ceased
- 1996-06-07 AU AU61669/96A patent/AU714319B2/en not_active Ceased
- 1996-06-07 KR KR1019970708866A patent/KR100291711B1/ko not_active Expired - Fee Related
- 1996-06-07 JP JP50202997A patent/JP4312829B2/ja not_active Expired - Fee Related
- 1996-06-07 AT AT96919298T patent/ATE520655T1/de not_active IP Right Cessation
- 1996-06-07 BR BR9608405A patent/BR9608405A/pt not_active Application Discontinuation
- 1996-06-07 EP EP96919298A patent/EP0853618B1/en not_active Expired - Lifetime
- 1996-06-07 HU HU9801882A patent/HUP9801882A3/hu unknown
- 1996-06-07 CN CN96194489A patent/CN1190395A/zh active Pending
- 1996-06-07 SI SI9620093A patent/SI9620093A/sl unknown
-
1997
- 1997-12-03 OA OA70149A patent/OA10752A/en unknown
- 1997-12-08 MX MX9709977A patent/MX9709977A/es not_active IP Right Cessation
- 1997-12-08 NO NO19975762A patent/NO310457B1/no unknown
-
1998
- 1998-01-06 BG BG102162A patent/BG63628B1/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPH11507368A (ja) | 1999-06-29 |
| EP0853618A1 (en) | 1998-07-22 |
| OA10752A (en) | 2001-07-04 |
| CZ385397A3 (cs) | 1999-05-12 |
| EA199800043A1 (ru) | 1998-08-27 |
| HUP9801882A3 (en) | 1999-01-28 |
| EA000700B1 (ru) | 2000-02-28 |
| AP799A (en) | 2000-01-19 |
| CA2223403A1 (en) | 1996-12-19 |
| CN1190395A (zh) | 1998-08-12 |
| MX9709977A (es) | 1998-07-31 |
| NO975762L (no) | 1998-02-06 |
| ATE520655T1 (de) | 2011-09-15 |
| AP9701144A0 (en) | 1998-01-31 |
| KR100291711B1 (ko) | 2001-09-17 |
| NO310457B1 (no) | 2001-07-09 |
| BG102162A (en) | 1998-09-30 |
| PL323780A1 (en) | 1998-04-27 |
| WO1996040679A1 (en) | 1996-12-19 |
| BR9608405A (pt) | 1999-08-24 |
| EP0853618A4 (en) | 2000-03-15 |
| SI9620093A (sl) | 1999-02-28 |
| KR19990022386A (ko) | 1999-03-25 |
| AU6166996A (en) | 1996-12-30 |
| BG63628B1 (bg) | 2002-07-31 |
| NO975762D0 (no) | 1997-12-08 |
| CA2223403C (en) | 2002-04-23 |
| US5612353A (en) | 1997-03-18 |
| EP0853618B1 (en) | 2011-08-17 |
| JP4312829B2 (ja) | 2009-08-12 |
| HUP9801882A2 (hu) | 1998-12-28 |
| SK160697A3 (en) | 1998-11-04 |
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Legal Events
| Date | Code | Title | Description |
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| FGA | Letters patent sealed or granted (standard patent) | ||
| HB | Alteration of name in register |
Owner name: AVENTIS PHARMACEUTICALS PRODUCTS INC. Free format text: FORMER NAME WAS: RHONE-POULENC RORER PHARMACEUTICALS INC. |
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| HB | Alteration of name in register |
Owner name: AVENTIS PHARMACEUTICALS INC. Free format text: FORMER NAME WAS: AVENTIS PHARMACEUTICALS PRODUCTS INC. |