NO313671B1 - Forbindelse med anti-hypertensive, kardiobeskyttende, anti- iskemiske og antilipolytiske egenskaper - Google Patents
Forbindelse med anti-hypertensive, kardiobeskyttende, anti- iskemiske og antilipolytiske egenskaper Download PDFInfo
- Publication number
- NO313671B1 NO313671B1 NO19990063A NO990063A NO313671B1 NO 313671 B1 NO313671 B1 NO 313671B1 NO 19990063 A NO19990063 A NO 19990063A NO 990063 A NO990063 A NO 990063A NO 313671 B1 NO313671 B1 NO 313671B1
- Authority
- NO
- Norway
- Prior art keywords
- purin
- ylamino
- diol
- pyrrolidin
- hydroxymethyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims description 96
- 230000003243 anti-lipolytic effect Effects 0.000 title claims description 23
- 230000003276 anti-hypertensive effect Effects 0.000 title description 17
- 230000003293 cardioprotective effect Effects 0.000 title description 12
- 230000002253 anti-ischaemic effect Effects 0.000 title description 5
- -1 monosubstituted phenyl Chemical group 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 25
- 208000031225 myocardial ischemia Diseases 0.000 claims description 22
- 206010020772 Hypertension Diseases 0.000 claims description 20
- VCVOSERVUCJNPR-UHFFFAOYSA-N cyclopentane-1,2-diol Chemical compound OC1CCCC1O VCVOSERVUCJNPR-UHFFFAOYSA-N 0.000 claims description 19
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 17
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 16
- SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- MVKIXHIOACTLHW-ZKFGIXCSSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(6-chloropyrimidin-4-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CN=C(Cl)C=3)=C2N=C1 MVKIXHIOACTLHW-ZKFGIXCSSA-N 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- GBLRQXKSCRCLBZ-YVQAASCFSA-N (1R,2S,1'R,2'S)-doxacurium Chemical compound COC1=C(OC)C(OC)=CC(C[C@H]2[N@+](CCC3=C2C(=C(OC)C(OC)=C3)OC)(C)CCCOC(=O)CCC(=O)OCCC[N@@+]2(C)[C@@H](C3=C(OC)C(OC)=C(OC)C=C3CC2)CC=2C=C(OC)C(OC)=C(OC)C=2)=C1 GBLRQXKSCRCLBZ-YVQAASCFSA-N 0.000 claims description 6
- YZCZVEDEWQCCAK-OUYBGJKKSA-N (1s,2r,3r,5r)-3-(methoxymethyl)-5-[6-[[(3s)-1-[5-(trifluoromethyl)pyridin-2-yl]pyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC(=CC=3)C(F)(F)F)=C2N=C1 YZCZVEDEWQCCAK-OUYBGJKKSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- SRKHPJZKIAVOAS-QODLLSGVSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(4-chlorophenyl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C=CC(Cl)=CC=3)=C2N=C1 SRKHPJZKIAVOAS-QODLLSGVSA-N 0.000 claims description 5
- GBLCPEBPIFRFMJ-KHEYOILXSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(5-bromopyridin-2-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC(Br)=CC=3)=C2N=C1 GBLCPEBPIFRFMJ-KHEYOILXSA-N 0.000 claims description 5
- QXGPJFRSGVXUBB-OUYBGJKKSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(5-bromopyridin-2-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(methoxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC(Br)=CC=3)=C2N=C1 QXGPJFRSGVXUBB-OUYBGJKKSA-N 0.000 claims description 5
- XVVAOGXQOMCSRM-KHEYOILXSA-N (1s,2r,3r,5r)-3-(hydroxymethyl)-5-[6-[[(3s)-1-[4-(trifluoromethyl)pyridin-2-yl]pyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC=C(C=3)C(F)(F)F)=C2N=C1 XVVAOGXQOMCSRM-KHEYOILXSA-N 0.000 claims description 5
- NBLZJQKTZOTPME-KHEYOILXSA-N (1s,2r,3r,5r)-3-(hydroxymethyl)-5-[6-[[(3s)-1-[5-(trifluoromethyl)pyridin-2-yl]pyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC(=CC=3)C(F)(F)F)=C2N=C1 NBLZJQKTZOTPME-KHEYOILXSA-N 0.000 claims description 5
- PSCXRPMJGSTRSP-OICWHWRFSA-N (1s,2r,3r,5r)-3-(hydroxymethyl)-5-[6-[[1-(4-nitrophenyl)pyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(NC3CN(CC3)C=3C=CC(=CC=3)[N+]([O-])=O)=C2N=C1 PSCXRPMJGSTRSP-OICWHWRFSA-N 0.000 claims description 5
- QNYHBWYTPFIGNW-RLPAKPQBSA-N (1s,2r,3r,5r)-3-(methoxymethyl)-5-[6-[[(3s)-1-(6-methoxypyrimidin-4-yl)pyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CN=C(OC)C=3)=C2N=C1 QNYHBWYTPFIGNW-RLPAKPQBSA-N 0.000 claims description 5
- IYUDSWGLLNDIHY-FLOLCQIYSA-N (1s,2r,3r,5r)-3-(methoxymethyl)-5-[6-[[(3s)-1-[4-(trifluoromethyl)phenyl]pyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C=CC(=CC=3)C(F)(F)F)=C2N=C1 IYUDSWGLLNDIHY-FLOLCQIYSA-N 0.000 claims description 5
- ITJHDXWKUVQYAF-NSDPQSHHSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-[[(3s)-1-[5-(trifluoromethyl)pyridin-2-yl]pyrrolidin-3-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC(=CC=3)C(F)(F)F)=C2N=C1 ITJHDXWKUVQYAF-NSDPQSHHSA-N 0.000 claims description 5
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- JMRWUIZMVZSNAC-FLOLCQIYSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(3-chlorophenyl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(methoxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C=C(Cl)C=CC=3)=C2N=C1 JMRWUIZMVZSNAC-FLOLCQIYSA-N 0.000 claims description 4
- MZFIBAWHWOOTHP-FLOLCQIYSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(4-chlorophenyl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(methoxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C=CC(Cl)=CC=3)=C2N=C1 MZFIBAWHWOOTHP-FLOLCQIYSA-N 0.000 claims description 4
- JMABQOHJXYLYAX-PQDLHQDHSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(6-bromoquinolin-2-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=C4C=CC(Br)=CC4=CC=3)=C2N=C1 JMABQOHJXYLYAX-PQDLHQDHSA-N 0.000 claims description 4
- DQDNOPQPWJPPOZ-YXCOWNBQSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(6-chloropyrimidin-4-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(methoxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CN=C(Cl)C=3)=C2N=C1 DQDNOPQPWJPPOZ-YXCOWNBQSA-N 0.000 claims description 4
- RBUXQIAYRXCHRW-NPNZPCOPSA-N (1s,2r,3r,5r)-3-(hydroxymethyl)-5-[6-[[(3r)-pyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@H]3CNCC3)=C2N=C1 RBUXQIAYRXCHRW-NPNZPCOPSA-N 0.000 claims description 4
- PSCXRPMJGSTRSP-KDCHQZPBSA-N (1s,2r,3r,5r)-3-(hydroxymethyl)-5-[6-[[(3s)-1-(4-nitrophenyl)pyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C=CC(=CC=3)[N+]([O-])=O)=C2N=C1 PSCXRPMJGSTRSP-KDCHQZPBSA-N 0.000 claims description 4
- ZHBGXRQURBJVPT-QODLLSGVSA-N (1s,2r,3r,5r)-3-(hydroxymethyl)-5-[6-[[(3s)-1-[4-(trifluoromethyl)phenyl]pyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C=CC(=CC=3)C(F)(F)F)=C2N=C1 ZHBGXRQURBJVPT-QODLLSGVSA-N 0.000 claims description 4
- XIADLLYGDJUBDF-VFNKJPDQSA-N (1s,2r,3r,5r)-3-(hydroxymethyl)-5-[6-[[(3s)-1-isoquinolin-1-ylpyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C4=CC=CC=C4C=CN=3)=C2N=C1 XIADLLYGDJUBDF-VFNKJPDQSA-N 0.000 claims description 4
- CUBTWLOKJOIFBT-FOOXYVKASA-N (1s,2r,3r,5r)-3-(hydroxymethyl)-5-[6-[[(3s)-1-pyridin-2-ylpyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC=CC=3)=C2N=C1 CUBTWLOKJOIFBT-FOOXYVKASA-N 0.000 claims description 4
- QUKINMXQTXVAOG-NSDPQSHHSA-N (2r,3r,4s,5r)-2-[6-[[(3s)-1-(5-chloropyridin-2-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC(Cl)=CC=3)=C2N=C1 QUKINMXQTXVAOG-NSDPQSHHSA-N 0.000 claims description 4
- PXEUJFAFTWSGEL-INHIHJJZSA-N (2r,3r,4s,5r)-2-[6-[[(3s)-1-(6-chloropyrimidin-4-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CN=C(Cl)C=3)=C2N=C1 PXEUJFAFTWSGEL-INHIHJJZSA-N 0.000 claims description 4
- 230000005961 cardioprotection Effects 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims description 4
- FFOYIIYEZKXYIF-KHEYOILXSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(5-chloropyridin-2-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC(Cl)=CC=3)=C2N=C1 FFOYIIYEZKXYIF-KHEYOILXSA-N 0.000 claims description 3
- UMSLWARVIJCHNM-ZKFGIXCSSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=NC(Cl)=CC=3)=C2N=C1 UMSLWARVIJCHNM-ZKFGIXCSSA-N 0.000 claims description 3
- NBYXBRSRTLRLPW-YXCOWNBQSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(methoxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=NC(Cl)=CC=3)=C2N=C1 NBYXBRSRTLRLPW-YXCOWNBQSA-N 0.000 claims description 3
- YUISLCNLOGSCDC-DSJDWBEOSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-benzylpyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC=4C=CC=CC=4)CC3)=C2N=C1 YUISLCNLOGSCDC-DSJDWBEOSA-N 0.000 claims description 3
- LSUIUWWWVVJZNX-SQIXAUHQSA-N (2r,3r,4s,5r)-2-[6-[[(3s)-1-(4-chlorophenyl)pyrrolidin-3-yl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C=CC(Cl)=CC=3)=C2N=C1 LSUIUWWWVVJZNX-SQIXAUHQSA-N 0.000 claims description 3
- UDYVUXIUICWYHE-ZUFLSNEXSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-[[(3s)-1-(4-nitrophenyl)pyrrolidin-3-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C=CC(=CC=3)[N+]([O-])=O)=C2N=C1 UDYVUXIUICWYHE-ZUFLSNEXSA-N 0.000 claims description 3
- ZVGRGHPRKLQEGJ-NXDBGETFSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-[[(3s)-1-(5-methylsulfanylpyridin-2-yl)pyrrolidin-3-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound N1=CC(SC)=CC=C1N1C[C@@H](NC=2C=3N=CN(C=3N=CN=2)[C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)CC1 ZVGRGHPRKLQEGJ-NXDBGETFSA-N 0.000 claims description 3
- OUATYIHMXKXFJA-NSDPQSHHSA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-[[(3s)-1-[4-(trifluoromethyl)pyridin-2-yl]pyrrolidin-3-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC=C(C=3)C(F)(F)F)=C2N=C1 OUATYIHMXKXFJA-NSDPQSHHSA-N 0.000 claims description 3
- CJQLANWPFCSREL-JDLZUTDUSA-N (2r,3s,4r,5r)-2-(methoxymethyl)-5-[6-[[(3s)-1-[5-(trifluoromethyl)pyridin-2-yl]pyrrolidin-3-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)O[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3N=CC(=CC=3)C(F)(F)F)=C2N=C1 CJQLANWPFCSREL-JDLZUTDUSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- CXHFMDYPMORWSB-SDEUGZKCSA-N (1r,2s,3r,5r)-3-[6-[[(3s)-1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]pyrrolidin-3-yl]amino]purin-9-yl]-5-(methoxymethyl)cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](COC)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C(=CC(=CN=3)C(F)(F)F)Cl)=C2N=C1 CXHFMDYPMORWSB-SDEUGZKCSA-N 0.000 claims description 2
- WCJGAOSDNXPPKP-GSFSLZFCSA-N (1s,2r,3r,5r)-3-(hydroxymethyl)-5-[6-[[(3s)-1-quinolin-3-ylpyrrolidin-3-yl]amino]purin-9-yl]cyclopentane-1,2-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)C[C@H]1N1C2=NC=NC(N[C@@H]3CN(CC3)C=3C=C4C=CC=CC4=NC=3)=C2N=C1 WCJGAOSDNXPPKP-GSFSLZFCSA-N 0.000 claims description 2
- WYQOBDBJBUEDJS-FVZMKOMISA-N (2r,3s,4r,5r)-2-(hydroxymethyl)-5-[6-[[(3s)-1-(6-methoxypyrimidin-4-yl)pyrrolidin-3-yl]amino]purin-9-yl]oxolane-3,4-diol Chemical compound C1=NC(OC)=CC(N2C[C@H](CC2)NC=2C=3N=CN(C=3N=CN=2)[C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=N1 WYQOBDBJBUEDJS-FVZMKOMISA-N 0.000 claims description 2
- YSMPURKYECKBKX-QMMMGPOBSA-N (3s)-1-[5-(trifluoromethyl)pyridin-2-yl]pyrrolidin-3-amine Chemical compound C1[C@@H](N)CCN1C1=CC=C(C(F)(F)F)C=N1 YSMPURKYECKBKX-QMMMGPOBSA-N 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- NEPUNMOZAQLFSU-UHFFFAOYSA-M sodium;bromide;hydrate Chemical compound O.[Na+].[Br-] NEPUNMOZAQLFSU-UHFFFAOYSA-M 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 210000002820 sympathetic nervous system Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- AGQSXQUMNKZASE-ZETCQYMHSA-N tert-butyl (3s)-3-[(2,2,2-trifluoroacetyl)amino]pyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](NC(=O)C(F)(F)F)C1 AGQSXQUMNKZASE-ZETCQYMHSA-N 0.000 description 1
- CMIBWIAICVBURI-ZETCQYMHSA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1 CMIBWIAICVBURI-ZETCQYMHSA-N 0.000 description 1
- BFRSOEPNARQSRV-UEWDXFNNSA-N tert-butyl (3s)-4-amino-1-benzyl-5-oxopyrrolidine-3-carboxylate Chemical compound O=C1C(N)[C@@H](C(=O)OC(C)(C)C)CN1CC1=CC=CC=C1 BFRSOEPNARQSRV-UEWDXFNNSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 229940124591 thiazide-type diuretic Drugs 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- CUGZEDSDRBMZMY-UHFFFAOYSA-N trihydrate;hydrochloride Chemical compound O.O.O.Cl CUGZEDSDRBMZMY-UHFFFAOYSA-N 0.000 description 1
- XREXPQGDOPQPAH-QKUPJAQQSA-K trisodium;[(z)-18-[1,3-bis[[(z)-12-sulfonatooxyoctadec-9-enoyl]oxy]propan-2-yloxy]-18-oxooctadec-9-en-7-yl] sulfate Chemical compound [Na+].[Na+].[Na+].CCCCCCC(OS([O-])(=O)=O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(CCCCCC)OS([O-])(=O)=O)COC(=O)CCCCCCC\C=C/CC(CCCCCC)OS([O-])(=O)=O XREXPQGDOPQPAH-QKUPJAQQSA-K 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000003966 vascular damage Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- QYEFBJRXKKSABU-UHFFFAOYSA-N xylazine hydrochloride Chemical compound Cl.CC1=CC=CC(C)=C1NC1=NCCCS1 QYEFBJRXKKSABU-UHFFFAOYSA-N 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Genetics & Genomics (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Diabetes (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2136696P | 1996-07-08 | 1996-07-08 | |
PCT/US1997/011320 WO1998001426A1 (en) | 1996-07-08 | 1997-07-01 | Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties |
Publications (3)
Publication Number | Publication Date |
---|---|
NO990063D0 NO990063D0 (no) | 1999-01-07 |
NO990063L NO990063L (no) | 1999-03-08 |
NO313671B1 true NO313671B1 (no) | 2002-11-11 |
Family
ID=21803790
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19990063A NO313671B1 (no) | 1996-07-08 | 1999-01-07 | Forbindelse med anti-hypertensive, kardiobeskyttende, anti- iskemiske og antilipolytiske egenskaper |
Country Status (22)
Country | Link |
---|---|
EP (1) | EP0912520B1 (cs) |
JP (1) | JP4202421B2 (cs) |
KR (1) | KR20000023635A (cs) |
CN (1) | CN1228770A (cs) |
AP (1) | AP903A (cs) |
AT (1) | ATE239725T1 (cs) |
AU (1) | AU746590B2 (cs) |
BG (1) | BG103135A (cs) |
BR (1) | BR9710156A (cs) |
CA (1) | CA2259538C (cs) |
CZ (1) | CZ291785B6 (cs) |
DE (1) | DE69721776T2 (cs) |
EA (1) | EA001801B1 (cs) |
ES (1) | ES2199365T3 (cs) |
HU (1) | HUP9903815A3 (cs) |
IL (1) | IL127890A0 (cs) |
NO (1) | NO313671B1 (cs) |
OA (1) | OA10953A (cs) |
PL (1) | PL331036A1 (cs) |
SK (1) | SK2299A3 (cs) |
UA (1) | UA51716C2 (cs) |
WO (1) | WO1998001426A1 (cs) |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6376472B1 (en) * | 1996-07-08 | 2002-04-23 | Aventis Pharmaceuticals, Inc. | Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties |
GB9723590D0 (en) | 1997-11-08 | 1998-01-07 | Glaxo Group Ltd | Chemical compounds |
YU44900A (sh) | 1998-01-31 | 2003-01-31 | Glaxo Group Limited | Derivati 2-(purin-9-il)tetrahidrofuran-3,4-diola |
KR20010071591A (ko) | 1998-06-23 | 2001-07-28 | 그레이엄 브레레톤, 레슬리 에드워즈 | 2-(퓨린-9-일)-테트라히드로푸란-3,4-디올 유도체 |
GB9813554D0 (en) * | 1998-06-23 | 1998-08-19 | Glaxo Group Ltd | Chemical compounds |
WO2000030638A1 (fr) * | 1998-11-25 | 2000-06-02 | Daiichi Radioisotope Laboratories, Ltd. | Medicaments ou reactifs contenant des composes cycloalkyl n-acyloxyles |
EP1140933B1 (en) | 1998-12-31 | 2004-09-08 | Aventis Pharmaceuticals Inc. | Process for preparing n6-substituted deaza-adenosine derivatives |
GB0106867D0 (en) * | 2001-03-20 | 2001-05-09 | Glaxo Group Ltd | Process |
MXPA03009946A (es) * | 2001-05-10 | 2005-03-07 | Aventis Pharma Gmbh | Nuevos procedimientos para la preparacion de compuestos de adenosina e intermedios para los mismos. |
EP1258247A1 (en) * | 2001-05-14 | 2002-11-20 | Aventis Pharma Deutschland GmbH | Adenosine analogues for the treatment of insulin resistance syndrome and diabetes |
FR2835186B1 (fr) | 2002-01-28 | 2006-10-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, actifs comme inhibiteurs de beta-lactamases |
HUP0200849A2 (hu) * | 2002-03-06 | 2004-08-30 | Sanofi-Synthelabo | N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra |
EP1375508A1 (en) * | 2002-06-27 | 2004-01-02 | Aventis Pharma Deutschland GmbH | N6-substituted adenosine analogues and their use as pharmaceutical agents |
US7163937B2 (en) | 2003-08-21 | 2007-01-16 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
FR2862969A1 (fr) * | 2003-11-28 | 2005-06-03 | Oreal | Procede de preparation de derives paraphenylenediamine a groupement pyrrolidinyle, substitue par un radical azote, et composes intermediaires |
EP1574508A1 (de) | 2004-01-30 | 2005-09-14 | Lonza AG | Verfahren zur Herstellung von Acetalen und Ketalen von 3-Amino-5-(hydroxymethyl)-cyclopentan-1,2-diolen, sowie deren Derivaten und Salzen |
AR049384A1 (es) | 2004-05-24 | 2006-07-26 | Glaxo Group Ltd | Derivados de purina |
JP2006022045A (ja) * | 2004-07-08 | 2006-01-26 | Kaneka Corp | 光学活性1−t−ブトキシカルボニル−3−アミノピロリジン塩の単離精製方法 |
GB0514809D0 (en) | 2005-07-19 | 2005-08-24 | Glaxo Group Ltd | Compounds |
US7629351B2 (en) | 2006-07-28 | 2009-12-08 | Bristol-Myers Squibb Company | N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-2-oxo-3-(6-(trifluoromethyl)quinazolin-4-ylamino) pyrrolidin-1-yl)cyclohexyl)acetamide and other modulators of chemokine receptor activity, crystalline forms and process |
US7687508B2 (en) | 2006-07-28 | 2010-03-30 | Bristol-Myers Squibb Company | Cyclic derivatives as modulators of chemokine receptor activity |
US7671062B2 (en) | 2006-07-28 | 2010-03-02 | Bristol-Myers Squibb Company | Modulators of chemokine receptor activity, crystalline forms and process |
DE102007002260A1 (de) | 2007-01-16 | 2008-07-31 | Sanofi-Aventis | Verwendung von substituierten Pyranonsäurederivaten zur Herstellung von Medikamenten zur Behandlung des Metabolischen Syndroms |
US8383812B2 (en) | 2009-10-13 | 2013-02-26 | Bristol-Myers Squibb Company | N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-A][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide, a dual modulator of chemokine receptor activity, crystalline forms and processes |
CN108463463A (zh) * | 2016-01-14 | 2018-08-28 | 韩德株式会社 | 拮抗a3腺苷受体的化合物、其制备方法、及其医学用途 |
CN110627765B (zh) * | 2019-10-14 | 2021-08-20 | 浙江乐普药业股份有限公司 | 一种替卡格雷关键中间体的制备方法 |
CN112047919B (zh) * | 2020-09-16 | 2021-06-18 | 常州制药厂有限公司 | 一种替卡格雷中间体及其制备方法 |
KR102308854B1 (ko) * | 2021-02-26 | 2021-10-05 | 퓨쳐메디신 주식회사 | 카보사이클릭 뉴클레오사이드 유도체를 포함하는 코로나바이러스감염증-19 예방 및 치료용 약학적 조성물 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ATE147074T1 (de) * | 1990-09-25 | 1997-01-15 | Rhone Poulenc Rorer Int | Verbindungen welche antihypertensive und antiischemische eigenschaften besitzen |
US5561134A (en) * | 1990-09-25 | 1996-10-01 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Compounds having antihypertensive, cardioprotective, anti-ischemic and antilipolytic properties |
WO1995018817A1 (fr) * | 1994-01-07 | 1995-07-13 | Laboratoires Upsa | Nouveaux derives de l'adenosine, leurs procedes de preparation, compositions pharmaceutiques les contenant |
US5554746A (en) * | 1994-05-16 | 1996-09-10 | Isis Pharmaceuticals, Inc. | Lactam nucleic acids |
-
1997
- 1997-01-07 UA UA99020643A patent/UA51716C2/uk unknown
- 1997-07-01 ES ES97933212T patent/ES2199365T3/es not_active Expired - Lifetime
- 1997-07-01 CA CA002259538A patent/CA2259538C/en not_active Expired - Fee Related
- 1997-07-01 IL IL12789097A patent/IL127890A0/xx unknown
- 1997-07-01 DE DE69721776T patent/DE69721776T2/de not_active Expired - Lifetime
- 1997-07-01 BR BR9710156A patent/BR9710156A/pt not_active IP Right Cessation
- 1997-07-01 PL PL97331036A patent/PL331036A1/xx unknown
- 1997-07-01 EP EP97933212A patent/EP0912520B1/en not_active Expired - Lifetime
- 1997-07-01 JP JP50524798A patent/JP4202421B2/ja not_active Expired - Fee Related
- 1997-07-01 AU AU36454/97A patent/AU746590B2/en not_active Ceased
- 1997-07-01 HU HU9903815A patent/HUP9903815A3/hu unknown
- 1997-07-01 AT AT97933212T patent/ATE239725T1/de not_active IP Right Cessation
- 1997-07-01 CZ CZ199924A patent/CZ291785B6/cs not_active IP Right Cessation
- 1997-07-01 SK SK22-99A patent/SK2299A3/sk unknown
- 1997-07-01 EA EA199900092A patent/EA001801B1/ru not_active IP Right Cessation
- 1997-07-01 WO PCT/US1997/011320 patent/WO1998001426A1/en not_active Application Discontinuation
- 1997-07-01 AP APAP/P/1998/001426A patent/AP903A/en active
- 1997-07-01 CN CN97197444A patent/CN1228770A/zh active Pending
-
1999
- 1999-01-06 OA OA9900003A patent/OA10953A/en unknown
- 1999-01-07 NO NO19990063A patent/NO313671B1/no not_active IP Right Cessation
- 1999-01-08 KR KR1019997000085A patent/KR20000023635A/ko not_active Application Discontinuation
- 1999-02-01 BG BG103135A patent/BG103135A/bg unknown
Also Published As
Publication number | Publication date |
---|---|
BG103135A (bg) | 1999-11-30 |
IL127890A0 (en) | 1999-10-28 |
EP0912520B1 (en) | 2003-05-07 |
CZ2499A3 (cs) | 1999-05-12 |
PL331036A1 (en) | 1999-06-21 |
JP2000514801A (ja) | 2000-11-07 |
AU3645497A (en) | 1998-02-02 |
CA2259538C (en) | 2006-12-19 |
CZ291785B6 (cs) | 2003-05-14 |
EA199900092A1 (ru) | 1999-08-26 |
EP0912520A4 (en) | 1999-10-06 |
DE69721776T2 (de) | 2004-03-25 |
CA2259538A1 (en) | 1998-01-15 |
AP903A (en) | 2000-11-24 |
CN1228770A (zh) | 1999-09-15 |
KR20000023635A (ko) | 2000-04-25 |
ES2199365T3 (es) | 2004-02-16 |
SK2299A3 (en) | 2000-10-09 |
EA001801B1 (ru) | 2001-08-27 |
OA10953A (en) | 2001-10-26 |
UA51716C2 (uk) | 2002-12-16 |
EP0912520A1 (en) | 1999-05-06 |
DE69721776D1 (de) | 2003-06-12 |
ATE239725T1 (de) | 2003-05-15 |
BR9710156A (pt) | 1999-08-10 |
NO990063L (no) | 1999-03-08 |
WO1998001426A1 (en) | 1998-01-15 |
AP9801426A0 (en) | 1998-12-31 |
NO990063D0 (no) | 1999-01-07 |
HUP9903815A3 (en) | 2002-04-29 |
HUP9903815A1 (hu) | 2001-04-28 |
JP4202421B2 (ja) | 2008-12-24 |
AU746590B2 (en) | 2002-05-02 |
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Legal Events
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MM1K | Lapsed by not paying the annual fees |