WO1998046589B1 - Indazole amide compounds as serotoninergic agents - Google Patents
Indazole amide compounds as serotoninergic agentsInfo
- Publication number
- WO1998046589B1 WO1998046589B1 PCT/EP1998/002129 EP9802129W WO9846589B1 WO 1998046589 B1 WO1998046589 B1 WO 1998046589B1 EP 9802129 W EP9802129 W EP 9802129W WO 9846589 B1 WO9846589 B1 WO 9846589B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- formula
- hydrogen
- pharmaceutically acceptable
- isopropyl
- Prior art date
Links
- -1 Indazole amide compounds Chemical class 0.000 title claims 13
- 239000000952 serotonin receptor agonist Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract 23
- 150000003839 salts Chemical class 0.000 claims abstract 11
- 239000011780 sodium chloride Substances 0.000 claims abstract 11
- 239000002253 acid Substances 0.000 claims abstract 6
- 150000007522 mineralic acids Chemical class 0.000 claims abstract 5
- 150000007524 organic acids Chemical class 0.000 claims abstract 5
- 229910052739 hydrogen Inorganic materials 0.000 claims 15
- 239000001257 hydrogen Substances 0.000 claims 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 9
- 125000000217 alkyl group Chemical group 0.000 claims 6
- 150000002431 hydrogen Chemical class 0.000 claims 5
- 238000000034 method Methods 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 3
- 125000004076 pyridyl group Chemical group 0.000 claims 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 239000000460 chlorine Substances 0.000 claims 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical group 0.000 claims 2
- 125000005842 heteroatoms Chemical group 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000002757 morpholinyl group Chemical group 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N Methyl iodide Chemical group IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 230000002152 alkylating Effects 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- DYDNPESBYVVLBO-UHFFFAOYSA-N formanilide Chemical compound O=CNC1=CC=CC=C1 DYDNPESBYVVLBO-UHFFFAOYSA-N 0.000 claims 1
- 125000003838 furazanyl group Chemical group 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 claims 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000004193 piperazinyl group Chemical group 0.000 claims 1
- LTEKQAPRXFBRNN-UHFFFAOYSA-N piperidin-4-ylmethanamine Chemical compound NCC1CCNCC1 LTEKQAPRXFBRNN-UHFFFAOYSA-N 0.000 claims 1
- 125000006239 protecting group Chemical group 0.000 claims 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims 1
- 125000003373 pyrazinyl group Chemical group 0.000 claims 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims 1
- 125000002755 pyrazolinyl group Chemical group 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 125000002098 pyridazinyl group Chemical group 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 125000001422 pyrrolinyl group Chemical group 0.000 claims 1
- 125000000168 pyrrolyl group Chemical group 0.000 claims 1
- 125000001113 thiadiazolyl group Chemical group 0.000 claims 1
- 125000000335 thiazolyl group Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 125000004306 triazinyl group Chemical group 0.000 claims 1
Abstract
A compound having general formula (I) wherein R1, R2, R3, R'3, R4, R5 and R6 have the meanings stated in the description, acid addition salts thereof with pharmaceutically acceptable organic and inorganic acids and pharmaceutically acceptable quaternary salts thereof.
Claims
1. A compound having the general formula
(I) wherein:
R is hydrogen;
R2 is isopropyl;
R3 and R'3 are hydrogen;
R4 and R5 are hydrogen; Re is selected from the group comprising, C3.7 cycloalkyl, heterocyciic ring having from 5 to 6 members where 1 to 4 members are heteroatoms, the same or different from each other, selected from the group comprising N, O and S, dimethylamino Cι-3 alkyl, methoxy Cι-3 alkyl, N-phenyi amide, aminosuiphonylmethyl, dihydroxy C2.3 alkyl, aryl substituted by hydroxy; acid addition salts thereof with pharmaceutically acceptable organic and inorganic acids and pharmaceutically acceptable quaternary salts thereof.
2. A compound according to claim 1 , characterized in that heterocyciic rings are thienyl, furanyl, pyranyl, pyrrolyl, imidazolyl, pyrazolyl, isoxazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, furazanyl, pyrrolinyl, imidazoiinyl, pyrazolidinyl, pyrazolinyl, pipehdinyl, piperazinyl, morpholinyl, triazinyl, thiazolyl, tetrazolyl and thiadiazolyl.
3. A compound according to claim 1 , characterized in that Re is selected from the group comprising cyclopropyl, cyclohexyl, pyridinyl, tetrazolyl,
mo holinyl, methoxymethyl, methoxypropyl, hydroxyphenyl, dimethylaminomethyl, and aminosulphonylmethyl.
4. A compound according to claim 1 , characterized in that R^ R3, R'3, R4 and R5 are hydrogen, R2 is isopropyl and Re is cyclohexyl.
5. A compound according to claim 1 , characterized in that R1f R3, R'3) RA and R5 are hydrogen, R2 is isopropyl and Re is pyridinyl.
6. A compound according to claim 1 , characterized in that R^ R3, R'3, ^ and R5 are hydrogen, R2 is isopropyl and Re is dimethylaminomethyl.
7. A compound according to claim 1 , characterized in that R1? R3, R'3, R4 and R5 are hydrogen, R2 is isopropyl and Re is morpholinyl.
8. A compound according to claim 1 , characterized in that R1( R3, R'3, R4 and R5 are hydrogen, R2 is isopropyl and Re is aminosulphonylmethyl.
9. A process for preparing a compound of the formula (I), acid addition salts thereof with pharmaceutically acceptable organic and inorganic acids and pharmaceutically acceptable quaternary salts thereof, comprising: a) acylating a 4-aminomethyl piperidine of the formula:
R3, R'3, R4 and R5 have the above mentioned meanings, and
P is a suitable protecting group; by means of a 1-alkyl-indazole-3-carboxylic acid halide of the formula:
(III) wherein
Ri and R2 have the above mentioned meanings, and
X is halogen, to give a compound of the formula:
(IV) wherein
Ri, 2, R3, R'3, R4, R5 and P have the above mentioned meanings, b) de-protecting a compound of the formula (IV) to give a compound of the formula:
(V) wherein R1f R2, R3, R'3, R and R5 have the above mentioned meanings, c) alkylating a compound of the formula (V) with a compound of the formula (VI) to give a compound of the formula (I) according to the following reaction scheme:
(V) (VI) wherein Ri, R2, R3, R'3, R , R5 and R5 have the above mentioned meanings, and
Y is halogen, d) optionally forming an acid addition salt of an indazole amide compound of the formula (I) with a pharmaceutically acceptable organic or inorganic acid, or a pharmaceutically acceptable quaternary salt of an indazole amide compound of the formula (I).
10. A process according to claim 9, characterized in that P is selected from the group comprising benzyloxycarbonyl, benzyl, terbutoxycarbonyl, trimethylsilylethoxycarbonyl.
11. A process according to claims 9 or 10, characterized in that step a) is carried out by reacting a compound of the formula (II) with a compound of the formula (III) in which X is chlorine, in the presence of a diluent and at a temperature of from 0 to 140°C for a period of time of from 0.5 to 20 hours.
12. A process according to claim 10, characterized in that when P is benzyl or benzyloxycarbonyl, step b) is carried out by catalytic hydrogenation.
13. A process according to any of the preceding claims from 9 to 11 , characterized in that when, in a compound of the formula (VI), Y is chlorine or bromine, step c) is performed in the presence of an acceptor of acids and in the presence of a diluent.
14. A process according to claim 9, characterized in that methyliodide forms a pharmaceutically acceptable quaternary salt of a compound of formula (I), step d).
15. An intermediate compound having the general formula:
(IV) wherein Ri is hydrogen; R2 is isopropyl; R3 and R'3 are hydrogen; R4 and R5 are hydrogen; and
P is selected from the group comprising benzyloxycarbonyl, terbutoxycarbonyl and trimethylsilylethoxycarbonyl.
16. A compound according to claim 14, characterized in that R1t R3, R'3, R4 and R5 are hydrogen and R2 is isopropyl.
17. A pharmaceutical composition, characterized in that the said composition comprises an effective dose of at least one compound of the formula:
R4 and R5 are hydrogen;
Re is selected from the group comprising C1-3 alkyl, C3.7 cycloalkyi, heterocyciic ring having from 5 to 6 members where 1 to 3 members are heteroatoms, the same or different from each other, selected from the group comprising N, O and S, dimethylamino d.
3 alkyl, methoxy Cι-3 alkyl, N-phenyl amide, aminosulphonylmethyl, dihydroxy C2-3 alkyl, aryl, aryl substituted by hydroxy; acid addition salts thereof with pharmaceutically acceptable organic and inorganic acids and pharmaceutically acceptable quaternary salts thereof.
Priority Applications (17)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| UA99116211A UA58550C2 (en) | 1997-04-15 | 1998-02-04 | Indazole amide compounds as serotoninergic agents |
| EP98919257A EP0975623B1 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
| DK98919257T DK0975623T3 (en) | 1997-04-15 | 1998-04-02 | Indazolamide compounds as sertoninergic agents |
| SK1423-99A SK284731B6 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compound, process for producing it, intermediate product for its preparation and pharmaceutical composition containing it |
| IL13212798A IL132127A (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds, a process for their preparation, intermediates thereof and pharmaceutical compositions comprising them |
| SI9830218T SI0975623T1 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
| CA002286870A CA2286870C (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
| DE69806141T DE69806141T2 (en) | 1997-04-15 | 1998-04-02 | INDAZOLEAMIDE COMPOUNDS AS SEROTON INERGENS |
| HU0002057A HU227973B1 (en) | 1997-04-15 | 1998-04-02 | Indazole amides and pharmaceutical compositions containing them |
| US09/403,007 US6197769B1 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
| JP54347598A JP4578581B2 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotonin-like agonists |
| AT98919257T ATE219490T1 (en) | 1997-04-15 | 1998-04-02 | INDAZOLEAMIDE COMPOUNDS AS SEROTONINERGENIC AGENTS |
| EA199900935A EA002352B1 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
| AU72159/98A AU740360B2 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
| KR1019997009198A KR100563867B1 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
| BG103863A BG64006B1 (en) | 1997-04-15 | 1999-11-05 | Indazolamidine copmpounds as serotoninergic means |
| HK00107144A HK1027811A1 (en) | 1997-04-15 | 2000-11-09 | Indazole amide compounds as serotoninergic agents |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI97A000867 | 1997-04-15 | ||
| IT97MI000867A IT1291569B1 (en) | 1997-04-15 | 1997-04-15 | Indazolamides as serotonergic agents |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1998046589A2 WO1998046589A2 (en) | 1998-10-22 |
| WO1998046589A3 WO1998046589A3 (en) | 1999-01-28 |
| WO1998046589B1 true WO1998046589B1 (en) | 1999-03-04 |
Family
ID=11376888
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1998/002129 WO1998046589A2 (en) | 1997-04-15 | 1998-04-02 | Indazole amide compounds as serotoninergic agents |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US6197769B1 (en) |
| EP (1) | EP0975623B1 (en) |
| JP (2) | JP4578581B2 (en) |
| KR (1) | KR100563867B1 (en) |
| CN (1) | CN1318416C (en) |
| AR (1) | AR012426A1 (en) |
| AT (1) | ATE219490T1 (en) |
| AU (1) | AU740360B2 (en) |
| BG (1) | BG64006B1 (en) |
| CA (1) | CA2286870C (en) |
| CZ (1) | CZ295190B6 (en) |
| DE (1) | DE69806141T2 (en) |
| DK (1) | DK0975623T3 (en) |
| EA (1) | EA002352B1 (en) |
| ES (1) | ES2178205T3 (en) |
| GE (1) | GEP20022654B (en) |
| HK (1) | HK1027811A1 (en) |
| HU (1) | HU227973B1 (en) |
| IL (1) | IL132127A (en) |
| IT (1) | IT1291569B1 (en) |
| PL (1) | PL193308B1 (en) |
| PT (1) | PT975623E (en) |
| SK (1) | SK284731B6 (en) |
| TR (1) | TR199902546T2 (en) |
| UA (1) | UA58550C2 (en) |
| WO (1) | WO1998046589A2 (en) |
| ZA (1) | ZA982926B (en) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1291569B1 (en) * | 1997-04-15 | 1999-01-11 | Angelini Ricerche Spa | Indazolamides as serotonergic agents |
| IL157254A0 (en) | 2001-02-23 | 2004-02-19 | Merck & Co Inc | N-substituted nonaryl-heterocyclic nmda/mr2b antagonists |
| WO2002080928A1 (en) * | 2001-04-03 | 2002-10-17 | Merck & Co., Inc. | N-substituted nonaryl-heterocyclo amidyl nmda/nr2b antagonists |
| ITMI20030287A1 (en) | 2003-02-18 | 2004-08-19 | Acraf | INDAZOLAMIDS EQUIPPED WITH ANALGESIC ACTIVITY METHOD, FOR |
| ITMI20030972A1 (en) * | 2003-05-15 | 2004-11-16 | Acraf | INDAZOLO EQUIPPED WITH ANALGESIC ACTIVITY, METHOD TO PREPARE IT AND PHARMACEUTICAL COMPOSITION THAT INCLUDES IT. |
| ITMI20031468A1 (en) | 2003-07-18 | 2005-01-19 | Acraf | ATIVE DRUG IN NEUROPATHIC PAIN |
| TW200533348A (en) * | 2004-02-18 | 2005-10-16 | Theravance Inc | Indazole-carboxamide compounds as 5-ht4 receptor agonists |
| US7728006B2 (en) * | 2004-04-07 | 2010-06-01 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| US8309575B2 (en) | 2004-04-07 | 2012-11-13 | Theravance, Inc. | Quinolinone-carboxamide compounds as 5-HT4 receptor agonists |
| TWI351282B (en) | 2004-04-07 | 2011-11-01 | Theravance Inc | Quinolinone-carboxamide compounds as 5-ht4 recepto |
| WO2006052640A1 (en) * | 2004-11-05 | 2006-05-18 | Theravance, Inc. | 5-ht4 receptor agonist compounds |
| ES2327142T3 (en) * | 2004-11-05 | 2009-10-26 | Theravance, Inc. | QUINOLINONA-CARBOXAMIDA COMPOUNDS. |
| NZ555180A (en) * | 2004-12-22 | 2010-09-30 | Theravance Inc | Indazole-carboxamide compounds useful as 5-HT4 receptor agonists |
| JP2008530225A (en) * | 2005-02-17 | 2008-08-07 | セラヴァンス， インコーポレーテッド | Crystal form of indazole-carboxamide compound |
| NZ560828A (en) * | 2005-03-02 | 2011-01-28 | Theravance Inc | Quinolinone compounds as 5-HT4 receptor agonists |
| ITMI20062230A1 (en) * | 2006-11-22 | 2008-05-23 | Acraf | 2-ALCHIL-INDAZOLIC COMPOUND PROCEDURE FOR PREPARATION AND PHARMACEUTICAL COMPOSITION THAT INCLUDES IT |
| UA99927C2 (en) * | 2007-11-12 | 2012-10-25 | Ацьенде Кимике Риуните Анджелини Франческо А.Чи.Р.А.Ф. С.П.А. | Pharmaceutical composition that is active in the treatment of neuropathic pain |
| US8377968B2 (en) * | 2008-06-02 | 2013-02-19 | Zalicus Pharmaceuticals, Ltd. | N-piperidinyl acetamide derivatives as calcium channel blockers |
| EP2718283A4 (en) * | 2011-06-07 | 2014-10-29 | Sumitomo Dainippon Pharma Co Ltd | Indazole- and pyrrolopyridine-derivative and pharmaceutical use thereof |
| MX351288B (en) * | 2012-02-21 | 2017-10-09 | Acraf | Use of 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors. |
| PL2817302T3 (en) * | 2012-02-21 | 2016-06-30 | Acraf | 1h-indazole-3-carboxamide compounds as glycogen synthase kinase 3 beta inhibitors |
| WO2014134306A1 (en) | 2013-03-01 | 2014-09-04 | Zalicus Pharmaceuticals, Ltd. | Heterocyclic inhibitors of the sodium channel |
| CN114340670A (en) | 2019-07-11 | 2022-04-12 | 普拉克西斯精密药物股份有限公司 | Formulations of T-type calcium channel modulators and methods of use thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9103862D0 (en) * | 1991-02-25 | 1991-04-10 | Glaxo Group Ltd | Chemical compounds |
| AU2435092A (en) * | 1991-08-20 | 1993-03-16 | Smithkline Beecham Plc | 5-ht4 receptor antagonists |
| IL117438A (en) * | 1995-03-16 | 2001-12-23 | Lilly Co Eli | Indazolecarboxamides, their preparation and pharmaceutical compositions containing them |
| KR19990022096A (en) * | 1995-05-31 | 1999-03-25 | 쇼다 오사무 | Indazole derivatives with monocyclic amino groups |
| IT1291569B1 (en) * | 1997-04-15 | 1999-01-11 | Angelini Ricerche Spa | Indazolamides as serotonergic agents |
-
1997
- 1997-04-15 IT IT97MI000867A patent/IT1291569B1/en active IP Right Grant
-
1998
- 1998-02-04 UA UA99116211A patent/UA58550C2/en unknown
- 1998-04-02 ES ES98919257T patent/ES2178205T3/en not_active Expired - Lifetime
- 1998-04-02 AU AU72159/98A patent/AU740360B2/en not_active Ceased
- 1998-04-02 SK SK1423-99A patent/SK284731B6/en not_active IP Right Cessation
- 1998-04-02 AT AT98919257T patent/ATE219490T1/en active
- 1998-04-02 JP JP54347598A patent/JP4578581B2/en not_active Expired - Fee Related
- 1998-04-02 CZ CZ19993625A patent/CZ295190B6/en not_active IP Right Cessation
- 1998-04-02 TR TR1999/02546T patent/TR199902546T2/en unknown
- 1998-04-02 EP EP98919257A patent/EP0975623B1/en not_active Expired - Lifetime
- 1998-04-02 CA CA002286870A patent/CA2286870C/en not_active Expired - Fee Related
- 1998-04-02 DE DE69806141T patent/DE69806141T2/en not_active Expired - Lifetime
- 1998-04-02 GE GEAP19985083A patent/GEP20022654B/en unknown
- 1998-04-02 WO PCT/EP1998/002129 patent/WO1998046589A2/en active IP Right Grant
- 1998-04-02 DK DK98919257T patent/DK0975623T3/en active
- 1998-04-02 IL IL13212798A patent/IL132127A/en not_active IP Right Cessation
- 1998-04-02 EA EA199900935A patent/EA002352B1/en not_active IP Right Cessation
- 1998-04-02 CN CNB988041987A patent/CN1318416C/en not_active Expired - Fee Related
- 1998-04-02 PL PL336348A patent/PL193308B1/en unknown
- 1998-04-02 KR KR1019997009198A patent/KR100563867B1/en not_active IP Right Cessation
- 1998-04-02 HU HU0002057A patent/HU227973B1/en not_active IP Right Cessation
- 1998-04-02 PT PT98919257T patent/PT975623E/en unknown
- 1998-04-02 US US09/403,007 patent/US6197769B1/en not_active Expired - Lifetime
- 1998-04-06 ZA ZA982926A patent/ZA982926B/en unknown
- 1998-04-15 AR ARP980101721A patent/AR012426A1/en active IP Right Grant
-
1999
- 1999-11-05 BG BG103863A patent/BG64006B1/en unknown
-
2000
- 2000-11-09 HK HK00107144A patent/HK1027811A1/en not_active IP Right Cessation
-
2010
- 2010-04-26 JP JP2010100701A patent/JP5237324B2/en not_active Expired - Fee Related
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