SK12342000A3 - Deriváty n-[(substituovaný päťčlenný di-alebo triáza-di- -nenasýtený kruh)karbonyl] guanidínu pre liečenie ischémie - Google Patents

Deriváty n-[(substituovaný päťčlenný di-alebo triáza-di- -nenasýtený kruh)karbonyl] guanidínu pre liečenie ischémie Download PDF

Info

Publication number: SK12342000A3
Authority: SK; Slovakia
Prior art keywords: mono; alkyl; carbon atoms; compound; pharmaceutically acceptable
Prior art date: 1998-02-27

Application number

SK1234-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Ernest S. Hamanaka

Angel Guzman-Perez

Roger B. Ruggeri

Ronald T. Wester

Christian J. Mularski

Original Assignee

Pfizer Products Inc.

Priority date (The priority date 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 date listed.)

1998-02-27

Filing date

1999-02-05

Publication date

2001-03-12

1999-02-05 Application filed by Pfizer Products Inc. filed Critical Pfizer Products Inc.

2001-03-12 Publication of SK12342000A3 publication Critical patent/SK12342000A3/sk

Links

208000028867 ischemia Diseases 0.000 title claims abstract description 33
150000002357 guanidines Chemical class 0.000 title description 6
229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 title description 3
238000000034 method Methods 0.000 claims abstract description 114
230000000451 tissue damage Effects 0.000 claims abstract description 31
231100000827 tissue damage Toxicity 0.000 claims abstract description 31
239000003112 inhibitor Substances 0.000 claims abstract description 23
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
150000001875 compounds Chemical class 0.000 claims description 522
125000000217 alkyl group Chemical group 0.000 claims description 490
229910052757 nitrogen Inorganic materials 0.000 claims description 486
125000004432 carbon atom Chemical group C* 0.000 claims description 467
-1 cyano, thio Chemical group 0.000 claims description 410
150000003839 salts Chemical class 0.000 claims description 268
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 195
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 142
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 119
229920006395 saturated elastomer Polymers 0.000 claims description 115
229910052799 carbon Inorganic materials 0.000 claims description 114
125000000753 cycloalkyl group Chemical group 0.000 claims description 110
125000003545 alkoxy group Chemical group 0.000 claims description 100
229910052760 oxygen Inorganic materials 0.000 claims description 97
229940002612 prodrug Drugs 0.000 claims description 96
239000000651 prodrug Substances 0.000 claims description 96
125000001153 fluoro group Chemical group F* 0.000 claims description 92
125000005842 heteroatom Chemical group 0.000 claims description 91
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 90
229910052717 sulfur Inorganic materials 0.000 claims description 90
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 89
239000001301 oxygen Substances 0.000 claims description 89
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 84
239000011593 sulfur Chemical group 0.000 claims description 84
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 78
125000002619 bicyclic group Chemical group 0.000 claims description 77
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 76
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 73
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 67
125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 66
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 65
125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 64
229910052736 halogen Inorganic materials 0.000 claims description 64
125000004414 alkyl thio group Chemical group 0.000 claims description 63
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 61
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 61
150000002367 halogens Chemical class 0.000 claims description 57
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 55
210000001519 tissue Anatomy 0.000 claims description 55
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
125000001424 substituent group Chemical group 0.000 claims description 49
241000124008 Mammalia Species 0.000 claims description 44
229910052739 hydrogen Inorganic materials 0.000 claims description 44
239000001257 hydrogen Substances 0.000 claims description 44
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 43
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 41
239000000203 mixture Substances 0.000 claims description 41
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 40
FUQOTYRCMBZFOL-UHFFFAOYSA-N 5-chloro-1H-indole-2-carboxylic acid Chemical compound ClC1=CC=C2NC(C(=O)O)=CC2=C1 FUQOTYRCMBZFOL-UHFFFAOYSA-N 0.000 claims description 40
230000000302 ischemic effect Effects 0.000 claims description 39
125000002252 acyl group Chemical group 0.000 claims description 37
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 37
125000003282 alkyl amino group Chemical group 0.000 claims description 36
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 35
210000002216 heart Anatomy 0.000 claims description 35
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 29
239000003937 drug carrier Substances 0.000 claims description 28
239000002552 dosage form Substances 0.000 claims description 27
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
150000001721 carbon Chemical group 0.000 claims description 26
125000004093 cyano group Chemical group *C#N 0.000 claims description 26
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 26
125000004423 acyloxy group Chemical group 0.000 claims description 24
125000005236 alkanoylamino group Chemical group 0.000 claims description 24
239000003085 diluting agent Substances 0.000 claims description 24
239000003288 aldose reductase inhibitor Substances 0.000 claims description 23
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 23
125000004076 pyridyl group Chemical group 0.000 claims description 23
230000001225 therapeutic effect Effects 0.000 claims description 23
239000011230 binding agent Substances 0.000 claims description 22
239000003795 chemical substances by application Substances 0.000 claims description 22
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 21
125000005843 halogen group Chemical group 0.000 claims description 20
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 20
125000000714 pyrimidinyl group Chemical group 0.000 claims description 20
125000004429 atom Chemical group 0.000 claims description 19
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 19
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 19
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 19
238000001356 surgical procedure Methods 0.000 claims description 19
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 18
229940118148 Aldose reductase inhibitor Drugs 0.000 claims description 18
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 18
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 18
125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 17
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 17
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 17
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 16
125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 claims description 16
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 16
ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 claims description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 14
239000002327 cardiovascular agent Substances 0.000 claims description 14
229940125692 cardiovascular agent Drugs 0.000 claims description 14
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 13
210000000056 organ Anatomy 0.000 claims description 13
125000003884 phenylalkyl group Chemical group 0.000 claims description 13
230000006378 damage Effects 0.000 claims description 12
125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
125000001041 indolyl group Chemical class 0.000 claims description 11
125000001624 naphthyl group Chemical group 0.000 claims description 11
125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 10
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 10
125000000623 heterocyclic group Chemical group 0.000 claims description 10
125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 claims description 10
125000002950 monocyclic group Chemical group 0.000 claims description 10
125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 9
125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 claims description 9
230000000747 cardiac effect Effects 0.000 claims description 9
238000007675 cardiac surgery Methods 0.000 claims description 9
MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 claims description 9
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 8
125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 8
210000004556 brain Anatomy 0.000 claims description 8
150000002148 esters Chemical class 0.000 claims description 8
229910052731 fluorine Inorganic materials 0.000 claims description 8
235000019000 fluorine Nutrition 0.000 claims description 8
239000001103 potassium chloride Substances 0.000 claims description 8
235000011164 potassium chloride Nutrition 0.000 claims description 8
239000003379 purinergic P1 receptor agonist Substances 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 7
230000000968 intestinal effect Effects 0.000 claims description 7
238000002054 transplantation Methods 0.000 claims description 7
WSLKLYKPUZWAQW-UHFFFAOYSA-N 5-cyclopropyl-1-quinolin-5-ylpyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NN(C=2C3=CC=CN=C3C=CC=2)C=1C1CC1 WSLKLYKPUZWAQW-UHFFFAOYSA-N 0.000 claims description 6
ZEDQLIICZORELY-UHFFFAOYSA-N 5-methyl-1-quinolin-6-ylpyrazole-4-carboxylic acid Chemical compound CC1=C(C(O)=O)C=NN1C1=CC=C(N=CC=C2)C2=C1 ZEDQLIICZORELY-UHFFFAOYSA-N 0.000 claims description 6
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 6
239000002126 C01EB10 - Adenosine Substances 0.000 claims description 6
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 claims description 6
229960001138 acetylsalicylic acid Drugs 0.000 claims description 6
229960005305 adenosine Drugs 0.000 claims description 6
125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
210000005003 heart tissue Anatomy 0.000 claims description 6
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 5
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 5
125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 claims description 5
CNAUCBNUTUGRDC-UHFFFAOYSA-N 5-cyclopropyl-1-[2-(trifluoromethyl)phenyl]pyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NN(C=2C(=CC=CC=2)C(F)(F)F)C=1C1CC1 CNAUCBNUTUGRDC-UHFFFAOYSA-N 0.000 claims description 5
NWYHYJVRSBVTGC-UHFFFAOYSA-N 5-ethyl-1-quinolin-5-ylpyrazole-4-carboxylic acid Chemical compound CCC1=C(C(O)=O)C=NN1C1=CC=CC2=NC=CC=C12 NWYHYJVRSBVTGC-UHFFFAOYSA-N 0.000 claims description 5
239000005541 ACE inhibitor Substances 0.000 claims description 5
229940127291 Calcium channel antagonist Drugs 0.000 claims description 5
GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
125000000304 alkynyl group Chemical group 0.000 claims description 5
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 5
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
239000000480 calcium channel blocker Substances 0.000 claims description 5
229960002896 clonidine Drugs 0.000 claims description 5
IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 claims description 5
229960002768 dipyridamole Drugs 0.000 claims description 5
239000002934 diuretic Substances 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
229930182470 glycoside Natural products 0.000 claims description 5
150000002338 glycosides Chemical class 0.000 claims description 5
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
208000037891 myocardial injury Diseases 0.000 claims description 5
GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 5
229960002816 potassium chloride Drugs 0.000 claims description 5
HYNXFOPOJQHNAI-UHFFFAOYSA-N 1-isoquinolin-5-yl-3-methylpyrazole-4-carboxylic acid Chemical compound C1=C(C(O)=O)C(C)=NN1C1=CC=CC2=CN=CC=C12 HYNXFOPOJQHNAI-UHFFFAOYSA-N 0.000 claims description 4
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 4
GZILZCCGDNKAAV-UHFFFAOYSA-N 5-chloro-1h-indole-2-carboxamide Chemical compound ClC1=CC=C2NC(C(=O)N)=CC2=C1 GZILZCCGDNKAAV-UHFFFAOYSA-N 0.000 claims description 4
GOZINTPHLXUATQ-UHFFFAOYSA-N 5-cyclopropyl-1-quinolin-8-ylpyrazole-4-carboxylic acid Chemical compound OC(=O)C=1C=NN(C=2C3=NC=CC=C3C=CC=2)C=1C1CC1 GOZINTPHLXUATQ-UHFFFAOYSA-N 0.000 claims description 4
LFXTUZDNFLZCNR-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-[2-(trifluoromethyl)phenyl]pyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C(=CC=CC=2)C(F)(F)F)C=1C1CC1 LFXTUZDNFLZCNR-UHFFFAOYSA-N 0.000 claims description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 4
125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 4
210000004185 liver Anatomy 0.000 claims description 4
210000004072 lung Anatomy 0.000 claims description 4
IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 claims description 4
230000002207 retinal effect Effects 0.000 claims description 4
210000002027 skeletal muscle Anatomy 0.000 claims description 4
210000000952 spleen Anatomy 0.000 claims description 4
230000002537 thrombolytic effect Effects 0.000 claims description 4
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
IWLPHHUXVUATBQ-UHFFFAOYSA-N 2-isoquinolin-5-yl-5-methyltriazole-4-carboxylic acid Chemical compound N1=C(C(O)=O)C(C)=NN1C1=CC=CC2=CN=CC=C12 IWLPHHUXVUATBQ-UHFFFAOYSA-N 0.000 claims description 3
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 3
HDPFDIUJHFATNN-UHFFFAOYSA-N 5-methyl-1-naphthalen-1-ylpyrazole-4-carboxylic acid Chemical compound CC1=C(C(O)=O)C=NN1C1=CC=CC2=CC=CC=C12 HDPFDIUJHFATNN-UHFFFAOYSA-N 0.000 claims description 3
XAMARBFYCUIBJA-UHFFFAOYSA-N 5-methyl-2-naphthalen-1-yltriazole-4-carboxylic acid Chemical compound N1=C(C(O)=O)C(C)=NN1C1=CC=CC2=CC=CC=C12 XAMARBFYCUIBJA-UHFFFAOYSA-N 0.000 claims description 3
ILKNSPWBNNHYMC-UHFFFAOYSA-N 5-methyl-2-quinolin-5-yltriazole-4-carboxylic acid Chemical compound N1=C(C(O)=O)C(C)=NN1C1=CC=CC2=NC=CC=C12 ILKNSPWBNNHYMC-UHFFFAOYSA-N 0.000 claims description 3
125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 3
SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 claims description 3
239000002876 beta blocker Substances 0.000 claims description 3
229940097320 beta blocking agent Drugs 0.000 claims description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000004537 indazol-5-yl group Chemical group N1N=CC2=CC(=CC=C12)* 0.000 claims description 3
210000003734 kidney Anatomy 0.000 claims description 3
229960001289 prazosin Drugs 0.000 claims description 3
229960000103 thrombolytic agent Drugs 0.000 claims description 3
230000002792 vascular Effects 0.000 claims description 3
125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 claims description 2
JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 2
125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
YZLNQKMWEXOAPY-UHFFFAOYSA-N 5-cyclopropyl-n-(diaminomethylidene)-1-phenylpyrazole-4-carboxamide Chemical compound NC(=N)NC(=O)C=1C=NN(C=2C=CC=CC=2)C=1C1CC1 YZLNQKMWEXOAPY-UHFFFAOYSA-N 0.000 claims description 2
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 2
210000005013 brain tissue Anatomy 0.000 claims description 2
NRQBHARHWSTOEU-UHFFFAOYSA-N ethyl 5-cyclopropyl-1-[2-(trifluoromethyl)phenyl]pyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C=2C(=CC=CC=2)C(F)(F)F)C=1C1CC1 NRQBHARHWSTOEU-UHFFFAOYSA-N 0.000 claims description 2
GCSSMQVYMINFEI-UHFFFAOYSA-N ethyl 5-cyclopropyl-1-quinolin-8-ylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C=2C3=NC=CC=C3C=CC=2)C=1C1CC1 GCSSMQVYMINFEI-UHFFFAOYSA-N 0.000 claims description 2
ZTSMDLWTSJDXDJ-UHFFFAOYSA-N ethyl 5-methyl-1-naphthalen-1-ylpyrazole-4-carboxylate Chemical compound CC1=C(C(=O)OCC)C=NN1C1=CC=CC2=CC=CC=C12 ZTSMDLWTSJDXDJ-UHFFFAOYSA-N 0.000 claims description 2
IDZKPWASEWZONA-UHFFFAOYSA-N ethyl 5-methyl-1-quinolin-6-ylpyrazole-4-carboxylate Chemical compound CC1=C(C(=O)OCC)C=NN1C1=CC=C(N=CC=C2)C2=C1 IDZKPWASEWZONA-UHFFFAOYSA-N 0.000 claims description 2
210000005228 liver tissue Anatomy 0.000 claims description 2
DIDVCLKJLFLTTI-UHFFFAOYSA-N methyl 5-ethyl-1-quinolin-5-ylpyrazole-4-carboxylate Chemical compound CCC1=C(C(=O)OC)C=NN1C1=CC=CC2=NC=CC=C12 DIDVCLKJLFLTTI-UHFFFAOYSA-N 0.000 claims description 2
QRZKFORTHOZDTO-UHFFFAOYSA-N n-(diaminomethylidene)-3-methyl-1-phenylpyrazole-4-carboxamide Chemical compound C1=C(C(=O)NC(N)=N)C(C)=NN1C1=CC=CC=C1 QRZKFORTHOZDTO-UHFFFAOYSA-N 0.000 claims description 2
GSKLXGZWPHJZHX-UHFFFAOYSA-N n-(diaminomethylidene)-4-methyl-1-phenylpyrazole-3-carboxamide Chemical compound N1=C(C(=O)NC(N)=N)C(C)=CN1C1=CC=CC=C1 GSKLXGZWPHJZHX-UHFFFAOYSA-N 0.000 claims description 2
WXRXSMMKVWZIFU-UHFFFAOYSA-N n-(diaminomethylidene)-5-methyl-2-naphthalen-1-yltriazole-4-carboxamide Chemical compound N1=C(C(=O)NC(N)=N)C(C)=NN1C1=CC=CC2=CC=CC=C12 WXRXSMMKVWZIFU-UHFFFAOYSA-N 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
239000000546 pharmaceutical excipient Substances 0.000 claims description 2
125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 2
125000006413 ring segment Chemical group 0.000 claims description 2
210000001032 spinal nerve Anatomy 0.000 claims description 2
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229950004311 sorbinil Drugs 0.000 description 1
ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
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LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
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AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
238000003354 tissue distribution assay Methods 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
LUBHDINQXIHVLS-UHFFFAOYSA-N tolrestat Chemical compound OC(=O)CN(C)C(=S)C1=CC=CC2=C(C(F)(F)F)C(OC)=CC=C21 LUBHDINQXIHVLS-UHFFFAOYSA-N 0.000 description 1
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JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
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MTZBBNMLMNBNJL-UHFFFAOYSA-N xipamide Chemical compound CC1=CC=CC(C)=C1NC(=O)C1=CC(S(N)(=O)=O)=C(Cl)C=C1O MTZBBNMLMNBNJL-UHFFFAOYSA-N 0.000 description 1
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Classifications

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- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- 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
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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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
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- 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
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
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General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
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Engineering & Computer Science (AREA)
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Chemical Kinetics & Catalysis (AREA)
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Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Epidemiology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
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Endocrinology (AREA)
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Obesity (AREA)
Emergency Medicine (AREA)
Physical Education & Sports Medicine (AREA)
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)
Steroid Compounds (AREA)

SK1234-2000A 1998-02-27 1999-02-05 Deriváty n-[(substituovaný päťčlenný di-alebo triáza-di- -nenasýtený kruh)karbonyl] guanidínu pre liečenie ischémie SK12342000A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US7636298P	1998-02-27	1998-02-27
PCT/IB1999/000206 WO1999043663A1 (en)	1998-02-27	1999-02-05	N-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives for the treatment of ischemia

Publications (1)

Publication Number	Publication Date
SK12342000A3 true SK12342000A3 (sk)	2001-03-12

Family

ID=22131525

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1234-2000A SK12342000A3 (sk)	1998-02-27	1999-02-05	Deriváty n-[(substituovaný päťčlenný di-alebo triáza-di- -nenasýtený kruh)karbonyl] guanidínu pre liečenie ischémie

Country Status (39)

Country	Link
US (2)	US6492401B1 (de)
EP (2)	EP1454902A1 (de)
JP (2)	JP2002504546A (de)
KR (4)	KR100449600B1 (de)
CN (1)	CN1289326A (de)
AP (1)	AP9901478A0 (de)
AR (1)	AR015526A1 (de)
AT (1)	ATE286034T1 (de)
AU (1)	AU739403B2 (de)
BG (1)	BG104803A (de)
BR (1)	BR9908332A (de)
CA (1)	CA2321642A1 (de)
CO (1)	CO4980897A1 (de)
DE (1)	DE69922930T2 (de)
DK (1)	DK1056729T3 (de)
DZ (1)	DZ2729A1 (de)
EA (1)	EA003603B1 (de)
ES (1)	ES2237080T3 (de)
GT (1)	GT199900022A (de)
HR (2)	HRP20010666A2 (de)
HU (1)	HUP0204418A3 (de)
ID (1)	ID25505A (de)
IL (1)	IL136588A0 (de)
IS (1)	IS5548A (de)
NO (1)	NO20004192D0 (de)
NZ (1)	NZ504769A (de)
OA (1)	OA11450A (de)
PA (1)	PA8468401A1 (de)
PE (1)	PE20000334A1 (de)
PL (1)	PL342444A1 (de)
PT (1)	PT1056729E (de)
SI (1)	SI1056729T1 (de)
SK (1)	SK12342000A3 (de)
TN (1)	TNSN99028A1 (de)
TR (1)	TR200002480T2 (de)
TW (1)	TWI226329B (de)
WO (1)	WO1999043663A1 (de)
YU (1)	YU46200A (de)
ZA (1)	ZA991578B (de)

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1999
- 1999-02-05 PT PT99901083T patent/PT1056729E/pt unknown
- 1999-02-05 DK DK99901083T patent/DK1056729T3/da active
- 1999-02-05 KR KR10-2000-7009529A patent/KR100449600B1/ko not_active Expired - Fee Related
- 1999-02-05 EA EA200000789A patent/EA003603B1/ru not_active IP Right Cessation
- 1999-02-05 PL PL99342444A patent/PL342444A1/xx not_active Application Discontinuation
- 1999-02-05 AU AU20706/99A patent/AU739403B2/en not_active Ceased
- 1999-02-05 YU YU46200A patent/YU46200A/sh unknown
- 1999-02-05 AT AT99901083T patent/ATE286034T1/de not_active IP Right Cessation
- 1999-02-05 HU HU0204418A patent/HUP0204418A3/hu not_active Application Discontinuation
- 1999-02-05 KR KR10-2003-7012300A patent/KR20030083004A/ko not_active Ceased
- 1999-02-05 IL IL13658899A patent/IL136588A0/xx unknown
- 1999-02-05 US US09/367,731 patent/US6492401B1/en not_active Expired - Fee Related
- 1999-02-05 EP EP04008203A patent/EP1454902A1/de not_active Withdrawn
- 1999-02-05 HR HR20010666A patent/HRP20010666A2/hr not_active Application Discontinuation
- 1999-02-05 EP EP99901083A patent/EP1056729B1/de not_active Expired - Lifetime
- 1999-02-05 CA CA002321642A patent/CA2321642A1/en not_active Abandoned
- 1999-02-05 KR KR10-2003-7009644A patent/KR20030078886A/ko not_active Ceased
- 1999-02-05 NZ NZ504769A patent/NZ504769A/en unknown
- 1999-02-05 ES ES99901083T patent/ES2237080T3/es not_active Expired - Lifetime
- 1999-02-05 BR BR9908332-9A patent/BR9908332A/pt not_active IP Right Cessation
- 1999-02-05 SK SK1234-2000A patent/SK12342000A3/sk unknown
- 1999-02-05 KR KR10-2002-7017553A patent/KR100407903B1/ko not_active Expired - Fee Related
- 1999-02-05 JP JP2000533420A patent/JP2002504546A/ja active Pending
- 1999-02-05 DE DE69922930T patent/DE69922930T2/de not_active Expired - Fee Related
- 1999-02-05 CN CN99802628A patent/CN1289326A/zh active Pending
- 1999-02-05 WO PCT/IB1999/000206 patent/WO1999043663A1/en not_active Ceased
- 1999-02-05 HR HR20000550A patent/HRP20000550A2/hr not_active Application Discontinuation
- 1999-02-05 TR TR2000/02480T patent/TR200002480T2/xx unknown
- 1999-02-05 SI SI9930743T patent/SI1056729T1/xx unknown
- 1999-02-05 ID IDW20001633A patent/ID25505A/id unknown
- 1999-02-22 GT GT199900022A patent/GT199900022A/es unknown
- 1999-02-22 TW TW088102574A patent/TWI226329B/zh active
- 1999-02-23 PE PE1999000156A patent/PE20000334A1/es not_active Application Discontinuation
- 1999-02-24 DZ DZ990032A patent/DZ2729A1/xx active
- 1999-02-24 TN TNTNSN99028A patent/TNSN99028A1/fr unknown
- 1999-02-24 PA PA19998468401A patent/PA8468401A1/es unknown
- 1999-02-25 AR ARP990100791A patent/AR015526A1/es unknown
- 1999-02-25 AP APAP/P/1999/001478A patent/AP9901478A0/en unknown
- 1999-02-26 ZA ZA9901578A patent/ZA991578B/xx unknown
- 1999-03-01 CO CO99012526A patent/CO4980897A1/es unknown
2000
- 2000-06-27 IS IS5548A patent/IS5548A/is unknown
- 2000-08-18 OA OA1200000223A patent/OA11450A/en unknown
- 2000-08-22 NO NO20004192A patent/NO20004192D0/no not_active Application Discontinuation
- 2000-09-27 BG BG104803A patent/BG104803A/bg unknown
2002
- 2002-12-09 US US10/315,369 patent/US6974813B2/en not_active Expired - Fee Related
2004
- 2004-08-27 JP JP2004248129A patent/JP2005041879A/ja not_active Withdrawn

Also Published As

Publication number	Publication date
DE69922930D1 (de)	2005-02-03
IS5548A (is)	2000-06-27
AU739403B2 (en)	2001-10-11
TR200002480T2 (tr)	2000-12-21
BR9908332A (pt)	2000-11-07
EA003603B1 (ru)	2003-06-26
KR20030078886A (ko)	2003-10-08
US20030149043A1 (en)	2003-08-07
TNSN99028A1 (fr)	2005-11-10
KR100407903B1 (ko)	2003-12-01
US6974813B2 (en)	2005-12-13
SI1056729T1 (en)	2005-04-30
CO4980897A1 (es)	2000-11-27
GT199900022A (es)	2000-08-15
JP2005041879A (ja)	2005-02-17
IL136588A0 (en)	2001-06-14
AU2070699A (en)	1999-09-15
PE20000334A1 (es)	2000-05-13
KR20030009548A (ko)	2003-01-29
HRP20010666A2 (en)	2001-10-31
EA200000789A1 (ru)	2001-02-26
HUP0204418A3 (en)	2003-10-28
AP9901478A0 (en)	1999-03-31
PA8468401A1 (es)	2000-09-29
US6492401B1 (en)	2002-12-10
YU46200A (sh)	2003-02-28
EP1454902A1 (de)	2004-09-08
HRP20000550A2 (en)	2001-02-28
KR20010041397A (ko)	2001-05-15
CN1289326A (zh)	2001-03-28
BG104803A (bg)	2001-05-31
AR015526A1 (es)	2001-05-02
EP1056729B1 (de)	2004-12-29
ATE286034T1 (de)	2005-01-15
KR100449600B1 (ko)	2004-09-21
KR20030083004A (ko)	2003-10-23
EP1056729A1 (de)	2000-12-06
NO20004192L (no)	2000-08-22
CA2321642A1 (en)	1999-09-02
TWI226329B (en)	2005-01-11
PT1056729E (pt)	2005-04-29
DK1056729T3 (da)	2005-04-11
DE69922930T2 (de)	2005-12-29
HUP0204418A2 (hu)	2003-04-28
JP2002504546A (ja)	2002-02-12
DZ2729A1 (fr)	2005-03-01
NZ504769A (en)	2005-04-29
OA11450A (en)	2003-12-04
PL342444A1 (en)	2001-06-04
NO20004192D0 (no)	2000-08-22
ID25505A (id)	2000-10-05
WO1999043663A1 (en)	1999-09-02
ZA991578B (en)	2000-08-28
ES2237080T3 (es)	2005-07-16

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