CN1740182A - 新的双氨基化膦酸酯前药 - Google Patents
新的双氨基化膦酸酯前药 Download PDFInfo
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- CN1740182A CN1740182A CNA2005100930590A CN200510093059A CN1740182A CN 1740182 A CN1740182 A CN 1740182A CN A2005100930590 A CNA2005100930590 A CN A2005100930590A CN 200510093059 A CN200510093059 A CN 200510093059A CN 1740182 A CN1740182 A CN 1740182A
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- alkyl
- aryl
- rudimentary
- aralkyl
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- 229940002612 prodrug Drugs 0.000 title abstract description 74
- 239000000651 prodrug Substances 0.000 title abstract description 74
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 title abstract description 10
- 239000003112 inhibitor Substances 0.000 claims abstract description 28
- 101710099475 3'-phosphoadenosine 5'-phosphate phosphatase Proteins 0.000 claims abstract description 26
- 101710196411 Fructose-1,6-bisphosphatase Proteins 0.000 claims abstract description 26
- 101710186733 Fructose-1,6-bisphosphatase, chloroplastic Proteins 0.000 claims abstract description 26
- 101710109119 Fructose-1,6-bisphosphatase, cytosolic Proteins 0.000 claims abstract description 26
- 101710198902 Fructose-1,6-bisphosphate aldolase/phosphatase Proteins 0.000 claims abstract description 26
- 239000008103 glucose Substances 0.000 claims abstract description 25
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 24
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 22
- 210000004369 blood Anatomy 0.000 claims abstract description 15
- 239000008280 blood Substances 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 338
- 125000003118 aryl group Chemical group 0.000 claims description 320
- 150000001875 compounds Chemical class 0.000 claims description 272
- 229910052757 nitrogen Inorganic materials 0.000 claims description 214
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 205
- -1 aralkoxy Chemical group 0.000 claims description 194
- 125000001188 haloalkyl group Chemical group 0.000 claims description 146
- 125000002723 alicyclic group Chemical group 0.000 claims description 136
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 107
- 229910052760 oxygen Inorganic materials 0.000 claims description 99
- 125000004429 atom Chemical group 0.000 claims description 96
- 125000001072 heteroaryl group Chemical group 0.000 claims description 86
- 125000004122 cyclic group Chemical group 0.000 claims description 82
- 229910052717 sulfur Inorganic materials 0.000 claims description 75
- 125000003545 alkoxy group Chemical group 0.000 claims description 71
- 238000002360 preparation method Methods 0.000 claims description 69
- 229910052799 carbon Inorganic materials 0.000 claims description 67
- 125000004432 carbon atom Chemical group C* 0.000 claims description 58
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 57
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 57
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 50
- 125000003342 alkenyl group Chemical group 0.000 claims description 47
- 229910052736 halogen Inorganic materials 0.000 claims description 45
- 125000000304 alkynyl group Chemical group 0.000 claims description 44
- 150000002367 halogens Chemical class 0.000 claims description 39
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 35
- 239000003814 drug Substances 0.000 claims description 34
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 33
- 229910052698 phosphorus Inorganic materials 0.000 claims description 32
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 125000004171 alkoxy aryl group Chemical group 0.000 claims description 28
- 125000004414 alkyl thio group Chemical group 0.000 claims description 28
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- 125000005842 heteroatom Chemical group 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 25
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 25
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 24
- 239000001301 oxygen Substances 0.000 claims description 24
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 23
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 22
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 21
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 20
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 20
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 20
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 19
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 19
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 19
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 18
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 18
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 16
- 125000004423 acyloxy group Chemical group 0.000 claims description 16
- 125000001769 aryl amino group Chemical group 0.000 claims description 16
- 125000004104 aryloxy group Chemical group 0.000 claims description 16
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 16
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 125000004437 phosphorous atom Chemical group 0.000 claims description 16
- 239000011574 phosphorus Substances 0.000 claims description 16
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 15
- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 14
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 14
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 14
- 125000000962 organic group Chemical group 0.000 claims description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
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- 241001465754 Metazoa Species 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 125000005647 linker group Chemical group 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 238000001727 in vivo Methods 0.000 claims description 8
- 150000003462 sulfoxides Chemical class 0.000 claims description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical group NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 7
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 7
- 150000001409 amidines Chemical class 0.000 claims description 7
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 6
- 230000004110 gluconeogenesis Effects 0.000 claims description 6
- 230000002440 hepatic effect Effects 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 4
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 4
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 4
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 230000000344 gluconeogenetic effect Effects 0.000 claims description 4
- 208000007345 glycogen storage disease Diseases 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 150000000182 1,3,5-triazines Chemical class 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 206010022489 Insulin Resistance Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 201000001421 hyperglycemia Diseases 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 2
- 230000001133 acceleration Effects 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 206010003497 Asphyxia Diseases 0.000 claims 1
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- 206010012655 Diabetic complications Diseases 0.000 claims 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
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- 238000000034 method Methods 0.000 description 69
- 238000006243 chemical reaction Methods 0.000 description 63
- 125000003368 amide group Chemical group 0.000 description 49
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 47
- 239000000203 mixture Substances 0.000 description 42
- 125000001118 alkylidene group Chemical group 0.000 description 39
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 36
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
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- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 16
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 16
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 14
- YRMZUOPMHMPNPG-UHFFFAOYSA-N methyl 1,3-thiazole-2-carboxylate Chemical compound COC(=O)C1=NC=CS1 YRMZUOPMHMPNPG-UHFFFAOYSA-N 0.000 description 14
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
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- A61P3/00—Drugs for disorders of the metabolism
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/44—Amides thereof
- C07F9/4461—Amides thereof the amide moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4465—Amides thereof the amide moiety containing a substituent or a structure which is considered as characteristic of aliphatic amines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
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| US17186299P | 1999-12-22 | 1999-12-22 | |
| US60/171,862 | 1999-12-22 |
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| CN00819044A Division CN100595204C (zh) | 1999-12-22 | 2000-12-22 | 双氨基化膦酸酯前药 |
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| CNA2005100930590A Pending CN1740182A (zh) | 1999-12-22 | 2000-12-22 | 新的双氨基化膦酸酯前药 |
| CN00819044A Expired - Fee Related CN100595204C (zh) | 1999-12-22 | 2000-12-22 | 双氨基化膦酸酯前药 |
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| CN00819044A Expired - Fee Related CN100595204C (zh) | 1999-12-22 | 2000-12-22 | 双氨基化膦酸酯前药 |
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| US (3) | US6965033B2 (https=) |
| EP (1) | EP1240174A2 (https=) |
| JP (1) | JP2003519154A (https=) |
| KR (1) | KR100875335B1 (https=) |
| CN (2) | CN1740182A (https=) |
| AU (1) | AU784370B2 (https=) |
| BR (1) | BR0017048A (https=) |
| CA (1) | CA2396713A1 (https=) |
| CZ (1) | CZ301401B6 (https=) |
| HK (1) | HK1049841A1 (https=) |
| HU (1) | HUP0204092A3 (https=) |
| IL (1) | IL149887A0 (https=) |
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| PL (1) | PL356525A1 (https=) |
| RU (2) | RU2273642C2 (https=) |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107849071A (zh) * | 2015-08-10 | 2018-03-27 | 默沙东公司 | 抗病毒的β氨基酸酯膦酰二胺化合物 |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6284748B1 (en) * | 1997-03-07 | 2001-09-04 | Metabasis Therapeutics, Inc. | Purine inhibitors of fructose 1,6-bisphosphatase |
| KR100818845B1 (ko) | 1998-09-09 | 2008-04-01 | 메타베이시스 테라퓨틱스, 인크. | 신규한 프럭토스 1,6-비스포스파타제의 헤테로방향족 억제제 |
| US6756360B1 (en) * | 1998-12-24 | 2004-06-29 | Metabasis Therapeutics, Inc. | Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes |
| AU784370B2 (en) * | 1999-12-22 | 2006-03-23 | Metabasis Therapeutics, Inc. | Novel bisamidate phosphonate prodrugs |
| JP2003525944A (ja) | 2000-03-08 | 2003-09-02 | メタバシス・セラピューティクス・インコーポレイテッド | 新規アリールフルクトース−１，６−ビスホスファターゼ阻害剤 |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| EP1736478B1 (en) | 2000-05-26 | 2015-07-22 | IDENIX Pharmaceuticals, Inc. | Methods and compositions for treating flaviviruses and pestiviruses |
| US7563774B2 (en) | 2000-06-29 | 2009-07-21 | Metabasis Therapeutics, Inc. | Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes |
| EP1435974A4 (en) | 2001-09-28 | 2006-09-06 | Idenix Cayman Ltd | METHODS AND COMPOSITIONS FOR THE TREATMENT OF HEPATITIS C VIRUS USING 4 'MODIFIED NUCLEOSIDES |
| US7608600B2 (en) | 2002-06-28 | 2009-10-27 | Idenix Pharmaceuticals, Inc. | Modified 2′ and 3′-nucleoside prodrugs for treating Flaviviridae infections |
| TW200500375A (en) | 2002-06-28 | 2005-01-01 | Idenix Cayman Ltd | Modified 2' and 3'-nucleoside prodrugs for treating flaviviridae |
| NZ537662A (en) | 2002-06-28 | 2007-10-26 | Idenix Cayman Ltd | 2'-C-methyl-3'-O-L-valine ester ribofuranosyl cytidine for treatment of flaviviridae infections |
| CN1678326A (zh) | 2002-06-28 | 2005-10-05 | 埃迪尼克斯(开曼)有限公司 | 用于治疗黄病毒感染的2'－c－甲基－3'－o－l－缬氨酸酯核糖呋喃基胞苷 |
| AU2003252676A1 (en) * | 2002-07-23 | 2004-02-09 | Sankyo Company, Limited | Preventive for the onset of diabetes |
| LT1576138T (lt) | 2002-11-15 | 2017-06-26 | Idenix Pharmaceuticals Llc | 2`-šakoti nukleozidai derinyje su interferonu ir flaviviridae mutacija |
| AU2003300901A1 (en) | 2002-12-12 | 2004-06-30 | Idenix (Cayman) Limited | Process for the production of 2'-branched nucleosides |
| NZ540913A (en) * | 2002-12-23 | 2008-02-29 | Idenix Cayman Ltd | Process for the production of 3'-nucleoside prodrugs |
| SI1611112T1 (sl) * | 2003-02-11 | 2012-12-31 | Vernalis (R&D) Limited | Izoksazolne spojine kot inhibitorji vroäśinskih ĺ ok proteinov |
| EA014685B1 (ru) | 2003-04-25 | 2010-12-30 | Джилид Сайэнс, Инк. | Фосфонатсодержащие антивирусные соединения (варианты) и фармацевтическая композиция на их основе |
| JPWO2005030236A1 (ja) * | 2003-09-26 | 2006-12-07 | 株式会社スカイインターナショナル | 肝臓内糖新生阻害作用を有する物質及びそれを含有する食品又は食品配合剤 |
| US7129049B2 (en) * | 2003-12-22 | 2006-10-31 | Regents Of The University Of Minnesota | Method of detecting equine glycogen storage disease IV |
| JP4638355B2 (ja) * | 2003-12-26 | 2011-02-23 | 協和発酵キリン株式会社 | チアゾール誘導体 |
| US7819956B2 (en) | 2004-07-02 | 2010-10-26 | Siemens Water Technologies Corp. | Gas transfer membrane |
| EP1773477B1 (en) | 2004-07-05 | 2011-09-07 | Siemens Water Technologies Corp. | Hydrophilic membranes |
| JP2008510018A (ja) * | 2004-08-18 | 2008-04-03 | メタバシス・セラピューティクス・インコーポレイテッド | フルクトース−１，６−ビスホスファターゼの新規チアゾール阻害物質 |
| EP1827664B1 (en) | 2004-12-03 | 2011-06-08 | Siemens Industry, Inc. | Membrane post treatment |
| BRPI0519006A2 (pt) * | 2004-12-13 | 2008-12-23 | Daiichi Sankyo Co Ltd | uso de um inibidor de fbpase, kit de uma composiÇço farmacÊutica, uso de uma preparaÇço de biguanida e um inibidor de fbpase, agente terapÊutico para diabetes melito, e, combinaÇço de agentes terapÊuticos |
| EP1825854A1 (en) * | 2004-12-15 | 2007-08-29 | Daiichi Sankyo Company, Limited | MEDICINAL COMPOSITION CONTAINING FBPase INHIBITOR |
| WO2006123765A1 (ja) * | 2005-05-20 | 2006-11-23 | Daiichi Sankyo Company, Limited | フィルムコーティング製剤 |
| EP1894930A4 (en) * | 2005-06-23 | 2010-06-23 | Kyowa Hakko Kirin Co Ltd | THIAZOLE DERIVATIVE |
| KR20080031956A (ko) | 2005-07-14 | 2008-04-11 | 지멘스 워터 테크놀로지스 코포레이션 | 막의 모노퍼술페이트 처리 방법 |
| EP1752450A1 (en) | 2005-08-01 | 2007-02-14 | Merck Sante | Imidazole derivatives as fructose-1,6-bisphosphatase inhibitors and pharmaceutical compositions containing them |
| ES2422290T3 (es) | 2005-12-23 | 2013-09-10 | Idenix Pharmaceuticals Inc | Procedimiento para preparar un producto intermedio sintético para la preparación de nucleósidos ramificados |
| EP2032548A1 (en) | 2006-06-01 | 2009-03-11 | F.Hoffmann-La Roche Ag | Thiazole derivatives |
| WO2008028914A1 (en) | 2006-09-07 | 2008-03-13 | Nycomed Gmbh | Combination treatment for diabetes mellitus |
| US20100076037A1 (en) | 2006-11-02 | 2010-03-25 | Chiang Lillian W | Methods of Treating Neuropathic Pain with Agonists of PPAR-gamma |
| KR101560844B1 (ko) | 2007-06-04 | 2015-10-15 | 벤-구리온 유니버시티 오브 더 네게브 리서치 앤드 디벨럽먼트 어쏘러티 | 트라이-아릴계 화합물 및 이를 포함하는 조성물 |
| EP2058308A1 (fr) | 2007-11-12 | 2009-05-13 | Merck Sante | Dérivés de benzimidazoledihydrothiadiazinone comme inhibiteurs de fructose-1,6-biphosphatase et compositions pharmaceutiques les contenant. |
| BRPI0821106A2 (pt) * | 2007-11-29 | 2015-06-16 | Ligand Pharm Inc | Pró-fármacos de nucleosídeo e usos dos mesmos |
| EP2227452A2 (en) | 2007-11-30 | 2010-09-15 | F. Hoffmann-La Roche AG | Pyridine compounds |
| WO2009129120A2 (en) | 2008-04-15 | 2009-10-22 | Rfs Pharma, Llc | Nucleoside derivatives for treatment of caliciviridae infections, including norovirus infections |
| RU2385870C1 (ru) * | 2009-01-29 | 2010-04-10 | Государственное образовательное учреждение высшего профессионального образования Волгоградский государственный технический университет (ВолгГТУ) | Способ получения n-замещенных (2-диалкоксифосфорил-4-циано)бутанамидинов |
| JP5690286B2 (ja) * | 2009-03-04 | 2015-03-25 | イデニク プハルマセウティカルス，インコーポレイテッド | ホスホチオフェン及びホスホチアゾールｈｃｖポリメラーゼ阻害剤 |
| EP2805951B1 (en) | 2009-03-20 | 2018-03-14 | Metabasis Therapeutics, Inc. | Inhibitors of diacylglycerol o-acyltransferase 1 (DGAT-1) and uses thereof |
| MX2016005995A (es) | 2013-11-05 | 2016-08-17 | Ben-Gurion Univ Of The Negev Res And Dev Authority | Compuestos para el tratamiento de diabetes y complicaciones de la enfermedad derivadas de la misma. |
| EP3078378B1 (en) | 2015-04-08 | 2020-06-24 | Vaiomer | Use of factor xa inhibitors for regulating glycemia |
| US10745428B2 (en) | 2015-12-10 | 2020-08-18 | Idenix Pharmaceuticals Llc | Antiviral phosphodiamide prodrugs of tenofovir |
| US10450335B2 (en) | 2015-12-15 | 2019-10-22 | Merck Sharp & Dohme Corp. | Antiviral oxime phosphoramide compounds |
| EP3532069A4 (en) | 2016-10-26 | 2020-05-13 | Merck Sharp & Dohme Corp. | ANTIVIRAL ARYL AMID PHOSPHODIAMID COMPOUNDS |
| US11123355B2 (en) | 2016-12-22 | 2021-09-21 | Idenix Pharmaceuticals Llc | Antiviral benzyl-amine phosphodiamide compounds |
| WO2020018399A1 (en) | 2018-07-19 | 2020-01-23 | Merck Sharp & Dohme Corp. | Phosphinic amide prodrugs of tenofovir |
| MX2021003904A (es) | 2018-10-05 | 2021-10-26 | Annapurna Bio Inc | Compuestos y composiciones para el tratamiento de afecciones asociadas con la actividad del receptor apj. |
Family Cites Families (70)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3454635A (en) * | 1965-07-27 | 1969-07-08 | Hoechst Ag | Benzenesulfonyl-ureas and process for their manufacture |
| US3551422A (en) * | 1968-03-27 | 1970-12-29 | Stevens & Co Inc J P | N-(oxymethyl) derivatives of phosphonopolyamino-s-triazines |
| US3822296A (en) * | 1969-01-23 | 1974-07-02 | Merck & Co Inc | 1-trifluoromethyl-1,2-epoxyethyl-1-phosphonic acid and its salts |
| US3657282A (en) * | 1969-01-23 | 1972-04-18 | Merck & Co Inc | Carboxyepoxyethyl-1-phosphonic acid and derivatives |
| GB1428137A (en) * | 1972-09-27 | 1976-03-17 | Ici Ltd | Prostanoic acid derivatives |
| US4000305A (en) * | 1972-09-27 | 1976-12-28 | Imperial Chemical Industries Limited | 15-, 16- AND 17-Indolyl or indolinyl nor prostanoic acid derivatives |
| GB1516347A (en) * | 1975-09-16 | 1978-07-05 | Ici Ltd | Process for the preparation of alkylphosphonate esters |
| US4092323A (en) * | 1975-09-16 | 1978-05-30 | Imperial Chemical Industries Limited | Hydrazine derivatives of pyridyl-ketones |
| DE2855659A1 (de) * | 1978-12-22 | 1980-07-03 | Bayer Ag | Benzimidazolyl-2-alkan-phosphonsaeuren |
| FR2531088B1 (fr) * | 1982-07-29 | 1987-08-28 | Sanofi Sa | Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation |
| DK277484A (da) * | 1983-06-23 | 1984-12-24 | Hoffmann La Roche | Thiazolidinderivater |
| DE3776880D1 (de) * | 1986-11-21 | 1992-04-02 | Ciba Geigy Ag | Neue substituierte alkandiphosphonsaeuren. |
| US4728739A (en) * | 1987-06-15 | 1988-03-01 | American Home Products Corporation | Hypoglycemic thiazolidinediones |
| US4791125A (en) * | 1987-12-02 | 1988-12-13 | Pfizer Inc. | Thiazolidinediones as hypoglycemic and anti-atherosclerosis agents |
| US4968790A (en) * | 1988-08-12 | 1990-11-06 | American Cyanamid Company | Antidiabetic phosphates |
| US5658889A (en) | 1989-01-24 | 1997-08-19 | Gensia Pharmaceuticals, Inc. | Method and compounds for aica riboside delivery and for lowering blood glucose |
| MX21452A (es) * | 1989-07-07 | 1994-01-31 | Ciba Geigy Ag | Preparaciones farmaceuticas que se administran en forma topica. |
| EP0438375B1 (de) * | 1990-01-18 | 1995-12-27 | Ciba-Geigy Ag | Phoshponsäure- und Thionophosphonsäure-Derivate |
| EP0533833B1 (en) | 1990-06-13 | 1995-12-20 | GLAZIER, Arnold | Phosphorous produgs |
| US5116919A (en) * | 1990-12-05 | 1992-05-26 | E. I. Du Pont De Nemours And Company | Process for increasing the relative viscosity of polyamides with reduced thermal degradation |
| JP3053490B2 (ja) * | 1991-02-25 | 2000-06-19 | 杏林製薬株式会社 | チアゾリジン−２，４−ジオン誘導体とその塩及び製造法 |
| US5142000A (en) * | 1991-08-28 | 1992-08-25 | E. I. Du Pont De Nemours And Company | Process for increasing polyamide molecular weight with organophosphonic acid or ester catalysts in the presence of alumina-containing titanium dioxide |
| US5302586A (en) * | 1991-12-19 | 1994-04-12 | G. D. Searle & Co. | Phosphonomethyl-imidazo[1,2-a]pyrimidine-2-carboxylic acid compounds for treatment of neurotoxic injury |
| US5731299A (en) * | 1992-05-29 | 1998-03-24 | The Procter & Gamble Company | Phosphonosulfonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism |
| US5236941A (en) * | 1992-06-30 | 1993-08-17 | American Home Products Corporation | 5-(2-hydroxy-1-arylethylidene)- and 5-(2-oxo-1-arylethylidene)-2,4-thiazolidinediones and derivatives thereof |
| US5728704A (en) * | 1992-09-28 | 1998-03-17 | Pfizer Inc. | Substituted pyridmidines for control of diabetic complications |
| US5478853A (en) * | 1992-10-12 | 1995-12-26 | Adir Et Compagnie | Thazolidinedione compounds |
| DE4303648A1 (de) * | 1993-02-09 | 1994-08-11 | Basf Ag | Verwendung von Aminovinylphosphonsäureestern als Lichtschutzmittel und Stabilisatoren für organisches Material |
| ATE199906T1 (de) * | 1993-06-29 | 2001-04-15 | Mitsubishi Chem Corp | Phosphonat-nukleotid ester-derivate |
| US5478852C1 (en) * | 1993-09-15 | 2001-03-13 | Sankyo Co | Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus |
| EP0719273B1 (en) * | 1993-09-17 | 2010-11-03 | Gilead Sciences, Inc. | Nucleotide analogs |
| US5798340A (en) | 1993-09-17 | 1998-08-25 | Gilead Sciences, Inc. | Nucleotide analogs |
| US5656745A (en) * | 1993-09-17 | 1997-08-12 | Gilead Sciences, Inc. | Nucleotide analogs |
| US5728650A (en) * | 1993-10-07 | 1998-03-17 | Zeneca Limited | Herbicidal aza bisphosphonic acids and compositions containing the same |
| US5468762A (en) * | 1994-05-18 | 1995-11-21 | American Home Products Corporation | Azolidinediones as antihyperglycemic agents |
| US5532256A (en) * | 1994-05-18 | 1996-07-02 | American Home Products Corporation | New azolidinediones and thiadiazolidinediones as antihyperglycemic agents |
| UA48150C2 (uk) * | 1994-11-02 | 2002-08-15 | Ай-Сі-Ен Фармасьютикалз | Похідні амінокислот або аміноспиртів, олігонуклеотид |
| US5925656A (en) * | 1995-04-10 | 1999-07-20 | Dr. Reddy's Research Foundation | Compounds having antidiabetic, hypolipidemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
| JP3144624B2 (ja) * | 1995-06-02 | 2001-03-12 | 杏林製薬株式会社 | Ｎ−ベンジルジオキソチアゾリジルベンズアミド誘導体及びその製造法 |
| US6001862A (en) * | 1995-06-02 | 1999-12-14 | Kyorin Pharameuticals Co., Ltd. | N-benzyldioxothiazolidylbenzamide derivatives and processes for preparing the same |
| US6147101A (en) * | 1995-06-02 | 2000-11-14 | Kyorin Pharmaceutical Co., Ltd. | N-benzyldioxothiazolidylbenzamide derivatives and process for producing the same |
| CA2204616C (en) * | 1995-09-18 | 2002-12-17 | Ranjan Mukherjee | Ppar gamma antagonists for treating obesity |
| DE69624143T2 (de) * | 1995-12-27 | 2003-06-12 | Otsuka Pharmaceutical Factory, Inc. | Phosphonsaurediester-derivate |
| US6249316B1 (en) * | 1996-08-23 | 2001-06-19 | Flashpoint Technology, Inc. | Method and system for creating a temporary group of images on a digital camera |
| US5861918A (en) * | 1997-01-08 | 1999-01-19 | Flashpoint Technology, Inc. | Method and system for managing a removable memory in a digital camera |
| US6054587A (en) | 1997-03-07 | 2000-04-25 | Metabasis Therapeutics, Inc. | Indole and azaindole inhibitors of fructose-1,6-bisphosphatase |
| US6284748B1 (en) | 1997-03-07 | 2001-09-04 | Metabasis Therapeutics, Inc. | Purine inhibitors of fructose 1,6-bisphosphatase |
| DE69819311T2 (de) | 1997-03-07 | 2004-07-29 | Metabasis Therapeutics Inc., San Diego | Neue benzimidazol inhibitoren der fructose-1,6-bisphosphatase |
| JP3610195B2 (ja) * | 1997-07-04 | 2005-01-12 | キヤノン株式会社 | 撮像装置 |
| US6008237A (en) * | 1997-12-19 | 1999-12-28 | Merck & Co., Inc. | Arylthiazolidinedione derivatives |
| CA2322487C (en) | 1998-03-06 | 2010-07-20 | Metabasis Therapeutics, Inc. | Novel prodrugs for phosphorus-containing compounds |
| US6312662B1 (en) * | 1998-03-06 | 2001-11-06 | Metabasis Therapeutics, Inc. | Prodrugs phosphorus-containing compounds |
| WO1999047549A1 (en) | 1998-03-16 | 1999-09-23 | Ontogen Corporation | PIPERAZINES AS INHIBITORS OF FRUCTOSE-1,6-BISPHOSPHATASE (FBPase) |
| KR100818845B1 (ko) | 1998-09-09 | 2008-04-01 | 메타베이시스 테라퓨틱스, 인크. | 신규한 프럭토스 1,6-비스포스파타제의 헤테로방향족 억제제 |
| US6756360B1 (en) * | 1998-12-24 | 2004-06-29 | Metabasis Therapeutics, Inc. | Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes |
| PL352756A1 (en) | 1998-12-24 | 2003-09-08 | Metabasis Therapeutics, Inc. | A combination of fbpase inhibitors and insulin sensitizers for the treatment of diabetes |
| US6284672B1 (en) * | 1999-03-02 | 2001-09-04 | Advanced Micro Devices, Inc. | Method of forming a super-shallow amorphous layer in silicon |
| JP2000278573A (ja) * | 1999-03-23 | 2000-10-06 | Minolta Co Ltd | データ記憶媒体の駆動システム |
| JP4393652B2 (ja) * | 1999-03-30 | 2010-01-06 | 株式会社リコー | 撮像装置および文書撮影方法 |
| AU784370B2 (en) * | 1999-12-22 | 2006-03-23 | Metabasis Therapeutics, Inc. | Novel bisamidate phosphonate prodrugs |
| JP2003525944A (ja) * | 2000-03-08 | 2003-09-02 | メタバシス・セラピューティクス・インコーポレイテッド | 新規アリールフルクトース−１，６−ビスホスファターゼ阻害剤 |
| US7563774B2 (en) * | 2000-06-29 | 2009-07-21 | Metabasis Therapeutics, Inc. | Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes |
| JP3914705B2 (ja) * | 2000-11-29 | 2007-05-16 | 富士フイルム株式会社 | ディジタル・カメラおよびその動作制御方法 |
| KR100814426B1 (ko) * | 2001-07-14 | 2008-03-18 | 삼성전자주식회사 | 다 채널 영상 중계 처리기 및 이를 적용한 다 채널 영상보안 시스템 |
| US7015941B2 (en) * | 2001-10-12 | 2006-03-21 | Malloy Desormeaux Stephen G | Hybrid cameras that download electronic images in selected geometric formats and methods |
| JP2003304482A (ja) * | 2002-02-08 | 2003-10-24 | Nikon Corp | 電子カメラ |
| JP2004038515A (ja) * | 2002-07-03 | 2004-02-05 | Sanyo Electric Co Ltd | データ記録装置 |
| JP3781017B2 (ja) * | 2002-07-22 | 2006-05-31 | カシオ計算機株式会社 | 画像管理システム及び画像管理方法、デジタルカメラ |
| US20040156615A1 (en) * | 2002-07-25 | 2004-08-12 | Fuji Photo Film Co., Ltd | Method and apparatus for image reproduction, method and apparatus for image recording, and programs therefor |
| US20050093998A1 (en) * | 2003-11-03 | 2005-05-05 | Haas William R. | Digital camera with variable size delete buffer |
-
2000
- 2000-12-22 AU AU52447/01A patent/AU784370B2/en not_active Ceased
- 2000-12-22 CZ CZ20022172A patent/CZ301401B6/cs not_active IP Right Cessation
- 2000-12-22 CN CNA2005100930590A patent/CN1740182A/zh active Pending
- 2000-12-22 HU HU0204092A patent/HUP0204092A3/hu unknown
- 2000-12-22 RU RU2002119708/04A patent/RU2273642C2/ru not_active IP Right Cessation
- 2000-12-22 CN CN00819044A patent/CN100595204C/zh not_active Expired - Fee Related
- 2000-12-22 JP JP2001549405A patent/JP2003519154A/ja active Pending
- 2000-12-22 NZ NZ519219A patent/NZ519219A/en not_active IP Right Cessation
- 2000-12-22 HK HK03101952.1A patent/HK1049841A1/zh unknown
- 2000-12-22 KR KR1020027008017A patent/KR100875335B1/ko not_active Expired - Fee Related
- 2000-12-22 PL PL00356525A patent/PL356525A1/xx not_active Application Discontinuation
- 2000-12-22 WO PCT/IB2000/002071 patent/WO2001047935A2/en not_active Ceased
- 2000-12-22 CA CA002396713A patent/CA2396713A1/en not_active Abandoned
- 2000-12-22 EP EP00993135A patent/EP1240174A2/en not_active Withdrawn
- 2000-12-22 SK SK889-2002A patent/SK8892002A3/sk not_active Application Discontinuation
- 2000-12-22 MX MXPA02006156A patent/MXPA02006156A/es active IP Right Grant
- 2000-12-22 BR BR0017048-8A patent/BR0017048A/pt not_active Application Discontinuation
- 2000-12-22 IL IL14988700A patent/IL149887A0/xx unknown
- 2000-12-22 US US09/747,182 patent/US6965033B2/en not_active Expired - Lifetime
-
2002
- 2002-05-31 ZA ZA200204399A patent/ZA200204399B/xx unknown
- 2002-06-18 NO NO20022932A patent/NO20022932L/no not_active Application Discontinuation
-
2004
- 2004-07-28 US US10/900,718 patent/US20050004077A1/en not_active Abandoned
-
2005
- 2005-12-12 RU RU2005138719/04A patent/RU2005138719A/ru not_active Application Discontinuation
-
2009
- 2009-03-26 US US12/411,951 patent/US20090192121A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107849071A (zh) * | 2015-08-10 | 2018-03-27 | 默沙东公司 | 抗病毒的β氨基酸酯膦酰二胺化合物 |
| CN107849071B (zh) * | 2015-08-10 | 2021-03-09 | 默沙东公司 | 抗病毒的β氨基酸酯膦酰二胺化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA02006156A (es) | 2003-09-22 |
| KR20020063248A (ko) | 2002-08-01 |
| HUP0204092A3 (en) | 2005-02-28 |
| BR0017048A (pt) | 2002-11-05 |
| CZ20022172A3 (cs) | 2003-01-15 |
| US6965033B2 (en) | 2005-11-15 |
| IL149887A0 (en) | 2002-11-10 |
| PL356525A1 (en) | 2004-06-28 |
| JP2003519154A (ja) | 2003-06-17 |
| NO20022932D0 (no) | 2002-06-18 |
| HK1049841A1 (zh) | 2003-05-30 |
| NO20022932L (no) | 2002-08-22 |
| WO2001047935A3 (en) | 2002-03-21 |
| KR100875335B1 (ko) | 2008-12-22 |
| RU2273642C2 (ru) | 2006-04-10 |
| CZ301401B6 (cs) | 2010-02-17 |
| ZA200204399B (en) | 2003-11-26 |
| RU2005138719A (ru) | 2007-06-20 |
| US20090192121A1 (en) | 2009-07-30 |
| CN100595204C (zh) | 2010-03-24 |
| SK8892002A3 (en) | 2003-04-01 |
| RU2002119708A (ru) | 2004-03-20 |
| WO2001047935A2 (en) | 2001-07-05 |
| US20020173490A1 (en) | 2002-11-21 |
| HUP0204092A2 (hu) | 2003-03-28 |
| US20050004077A1 (en) | 2005-01-06 |
| NZ519219A (en) | 2004-03-26 |
| CA2396713A1 (en) | 2001-07-05 |
| CN1434828A (zh) | 2003-08-06 |
| AU5244701A (en) | 2001-07-09 |
| EP1240174A2 (en) | 2002-09-18 |
| AU784370B2 (en) | 2006-03-23 |
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