AU771039B2 - A combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes - Google Patents
A combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes Download PDFInfo
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- AU771039B2 AU771039B2 AU20583/00A AU2058300A AU771039B2 AU 771039 B2 AU771039 B2 AU 771039B2 AU 20583/00 A AU20583/00 A AU 20583/00A AU 2058300 A AU2058300 A AU 2058300A AU 771039 B2 AU771039 B2 AU 771039B2
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- 229940122355 Insulin sensitizer Drugs 0.000 title claims abstract description 112
- 101710099475 3'-phosphoadenosine 5'-phosphate phosphatase Proteins 0.000 title claims abstract description 66
- 101710196411 Fructose-1,6-bisphosphatase Proteins 0.000 title claims abstract description 66
- 101710186733 Fructose-1,6-bisphosphatase, chloroplastic Proteins 0.000 title claims abstract description 66
- 101710109119 Fructose-1,6-bisphosphatase, cytosolic Proteins 0.000 title claims abstract description 66
- 101710198902 Fructose-1,6-bisphosphate aldolase/phosphatase Proteins 0.000 title claims abstract description 66
- 239000003112 inhibitor Substances 0.000 title claims abstract description 62
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 46
- 238000011282 treatment Methods 0.000 title claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 110
- 238000000034 method Methods 0.000 claims abstract description 107
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 25
- 201000010099 disease Diseases 0.000 claims abstract description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 379
- 125000003118 aryl group Chemical group 0.000 claims description 316
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- 125000002723 alicyclic group Chemical group 0.000 claims description 205
- 229910052739 hydrogen Inorganic materials 0.000 claims description 188
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 159
- 125000004122 cyclic group Chemical group 0.000 claims description 146
- 150000002148 esters Chemical class 0.000 claims description 106
- 125000005843 halogen group Chemical group 0.000 claims description 103
- 125000001072 heteroaryl group Chemical group 0.000 claims description 102
- 125000004429 atom Chemical group 0.000 claims description 98
- 229910052721 tungsten Inorganic materials 0.000 claims description 90
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 89
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 86
- 229940002612 prodrug Drugs 0.000 claims description 86
- 239000000651 prodrug Substances 0.000 claims description 86
- 125000005842 heteroatom Chemical group 0.000 claims description 76
- 125000004432 carbon atom Chemical group C* 0.000 claims description 74
- 229910052736 halogen Inorganic materials 0.000 claims description 69
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 65
- 150000002367 halogens Chemical class 0.000 claims description 63
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 62
- 125000000304 alkynyl group Chemical group 0.000 claims description 59
- 229910052698 phosphorus Inorganic materials 0.000 claims description 55
- 125000003342 alkenyl group Chemical group 0.000 claims description 54
- 125000003107 substituted aryl group Chemical group 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 53
- 229910052799 carbon Inorganic materials 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 50
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 49
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 43
- 239000011574 phosphorus Substances 0.000 claims description 43
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 36
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- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 34
- 229910052720 vanadium Inorganic materials 0.000 claims description 34
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 30
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- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 29
- 125000004423 acyloxy group Chemical group 0.000 claims description 28
- 125000001543 furan-2,5-diyl group Chemical group O1C(=CC=C1*)* 0.000 claims description 28
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 25
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
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- 239000000556 agonist Substances 0.000 claims description 22
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical group O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 21
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 21
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 18
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 18
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- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 17
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 16
- 150000003462 sulfoxides Chemical class 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 14
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 14
- 125000004414 alkyl thio group Chemical group 0.000 claims description 13
- 150000001409 amidines Chemical class 0.000 claims description 13
- 125000001246 bromo group Chemical group Br* 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 12
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims description 12
- 125000006366 methylene oxy carbonyl group Chemical group [H]C([H])([*:1])OC([*:2])=O 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 11
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 11
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 11
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 11
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 238000001727 in vivo Methods 0.000 claims description 11
- 125000005750 substituted cyclic group Chemical group 0.000 claims description 11
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 claims description 11
- 229960001641 troglitazone Drugs 0.000 claims description 11
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 claims description 11
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
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- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000004437 phosphorous atom Chemical group 0.000 claims description 10
- 201000001421 hyperglycemia Diseases 0.000 claims description 9
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 8
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
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- IRAAJHYKQDFNFO-SFHVURJKSA-N (2s)-3-[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]-2-(2,2,2-trifluoroethoxy)propanoic acid Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC1=CC=C(C[C@H](OCC(F)(F)F)C(O)=O)C=C1 IRAAJHYKQDFNFO-SFHVURJKSA-N 0.000 claims description 6
- MVDXXGIBARMXSA-PYUWXLGESA-N 5-[[(2r)-2-benzyl-3,4-dihydro-2h-chromen-6-yl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC1=CC=C(O[C@@H](CC=2C=CC=CC=2)CC2)C2=C1 MVDXXGIBARMXSA-PYUWXLGESA-N 0.000 claims description 6
- QQKNSPHAFATFNQ-UHFFFAOYSA-N darglitazone Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCC(=O)C(C=C1)=CC=C1CC1SC(=O)NC1=O QQKNSPHAFATFNQ-UHFFFAOYSA-N 0.000 claims description 6
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- AFSHNJLKCYAWRX-UHFFFAOYSA-N 4-[(5-chloronaphthalen-2-yl)methyl]-5h-1,2,3,5-oxathiadiazole 2-oxide Chemical compound C=1C=C2C(Cl)=CC=CC2=CC=1CC1=NS(=O)ON1 AFSHNJLKCYAWRX-UHFFFAOYSA-N 0.000 claims description 5
- YVQKIDLSVHRBGZ-UHFFFAOYSA-N 5-[[4-[2-hydroxy-2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(O)COC(C=C1)=CC=C1CC1SC(=O)NC1=O YVQKIDLSVHRBGZ-UHFFFAOYSA-N 0.000 claims description 5
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Reproductive Health (AREA)
- Child & Adolescent Psychology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11471898P | 1998-12-24 | 1998-12-24 | |
| US60/114718 | 1998-12-24 | ||
| PCT/US1999/030713 WO2000038666A2 (en) | 1998-12-24 | 1999-12-22 | A COMBINATION OF FBPase INHIBITORS AND INSULIN SENSITIZERS FOR THE TREATMENT OF DIABETES |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2058300A AU2058300A (en) | 2000-07-31 |
| AU771039B2 true AU771039B2 (en) | 2004-03-11 |
Family
ID=22357016
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU20583/00A Ceased AU771039B2 (en) | 1998-12-24 | 1999-12-22 | A combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP1143955B1 (https=) |
| JP (1) | JP2003515523A (https=) |
| KR (3) | KR20070046210A (https=) |
| CN (3) | CN1714866A (https=) |
| AT (1) | ATE300288T1 (https=) |
| AU (1) | AU771039B2 (https=) |
| BR (1) | BR9917005A (https=) |
| CA (1) | CA2354053A1 (https=) |
| CZ (1) | CZ20012353A3 (https=) |
| DE (1) | DE69926400T2 (https=) |
| DK (1) | DK1143955T3 (https=) |
| ES (1) | ES2246586T3 (https=) |
| HK (1) | HK1046863B (https=) |
| HU (1) | HUP0402506A3 (https=) |
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| IL (2) | IL143569A0 (https=) |
| MX (1) | MXPA01006511A (https=) |
| NO (1) | NO20013115L (https=) |
| NZ (1) | NZ512219A (https=) |
| PL (1) | PL352756A1 (https=) |
| PT (1) | PT1143955E (https=) |
| RU (2) | RU2227749C2 (https=) |
| SK (1) | SK9172001A3 (https=) |
| WO (1) | WO2000038666A2 (https=) |
| ZA (1) | ZA200105016B (https=) |
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| US6284748B1 (en) | 1997-03-07 | 2001-09-04 | Metabasis Therapeutics, Inc. | Purine inhibitors of fructose 1,6-bisphosphatase |
| US6312662B1 (en) | 1998-03-06 | 2001-11-06 | Metabasis Therapeutics, Inc. | Prodrugs phosphorus-containing compounds |
| KR100818845B1 (ko) | 1998-09-09 | 2008-04-01 | 메타베이시스 테라퓨틱스, 인크. | 신규한 프럭토스 1,6-비스포스파타제의 헤테로방향족 억제제 |
| 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 |
| EP1372660A2 (en) * | 2000-07-06 | 2004-01-02 | Metabasis Therapeutics, Inc. | A combination of fbpase inhibitors and antidiabetic agents useful for the treatment of diabetes |
| EP1340749A4 (en) * | 2000-11-17 | 2007-09-05 | Takeda Pharmaceutical | ISOXAZOLE DERIVATIVES |
| EP2223927B1 (en) | 2002-05-13 | 2014-10-15 | Metabasis Therapeutics, Inc. | Salts of a phosphonic acid based prodrug of PMEA |
| WO2003095665A2 (en) | 2002-05-13 | 2003-11-20 | Metabasis Therapeutics, Inc. | Pmea and pmpa cyclic producing synthesis |
| AU2003264256A1 (en) * | 2002-09-04 | 2004-03-29 | Dsm Ip Assets B.V. | A nutritional and therapeutic composition of an insulin sensitizer and a peptide fraction |
| UA80991C2 (en) | 2002-10-07 | 2007-11-26 | Solid preparation containing an insulin resistance improving drug and an active ingredient useful as a remedy for diabetes | |
| SI1611112T1 (sl) * | 2003-02-11 | 2012-12-31 | Vernalis (R&D) Limited | Izoksazolne spojine kot inhibitorji vroäśinskih ĺ ok proteinov |
| 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 |
| 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 |
| 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 |
| EP1889618A4 (en) * | 2005-05-27 | 2010-11-24 | Daiichi Sankyo Co Ltd | Combined drug for treating diabetes |
| EP1894930A4 (en) | 2005-06-23 | 2010-06-23 | Kyowa Hakko Kirin Co Ltd | THIAZOLE DERIVATIVE |
| US20100076037A1 (en) | 2006-11-02 | 2010-03-25 | Chiang Lillian W | Methods of Treating Neuropathic Pain with Agonists of PPAR-gamma |
| CN103665043B (zh) | 2012-08-30 | 2017-11-10 | 江苏豪森药业集团有限公司 | 一种替诺福韦前药及其在医药上的应用 |
| US9631825B2 (en) | 2012-12-18 | 2017-04-25 | Nortek Air Solutions, Llc | Air filter assembly |
| AU2015217221A1 (en) | 2014-02-13 | 2016-08-11 | Ligand Pharmaceuticals, Inc. | Prodrug compounds and their uses |
| CN106687118A (zh) | 2014-07-02 | 2017-05-17 | 配体药物公司 | 前药化合物及其用途 |
| CN105481896A (zh) * | 2015-12-03 | 2016-04-13 | 浙江大学 | 一种地马格列的制备方法 |
| CN113416739B (zh) * | 2021-06-24 | 2022-04-19 | 黑龙江八一农垦大学 | 鲁氏酵母菌基因在提高微生物产hdmf的产量中的应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4968790A (en) * | 1988-08-12 | 1990-11-06 | American Cyanamid Company | Antidiabetic phosphates |
| JPH03157377A (ja) * | 1988-11-18 | 1991-07-05 | Takeda Chem Ind Ltd | チオ尿素誘導体及びａｇｅ生成阻害剤 |
| DE69014562T2 (de) * | 1989-01-24 | 1995-06-22 | Gensia Pharma | Verfahren und verbindungen zur verabreichung von aica ribosiden und zur erniedrigung des blutglucose gehaltes. |
| TWI238064B (en) * | 1995-06-20 | 2005-08-21 | Takeda Chemical Industries Ltd | A pharmaceutical composition for prophylaxis and treatment of diabetes |
| US5859037A (en) * | 1997-02-19 | 1999-01-12 | Warner-Lambert Company | Sulfonylurea-glitazone combinations for diabetes |
| 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 |
| US6054587A (en) * | 1997-03-07 | 2000-04-25 | Metabasis Therapeutics, Inc. | Indole and azaindole inhibitors of fructose-1,6-bisphosphatase |
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1999
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- 1999-12-22 CN CNA2007101628889A patent/CN101164618A/zh active Pending
- 1999-12-22 WO PCT/US1999/030713 patent/WO2000038666A2/en not_active Ceased
- 1999-12-22 SK SK917-2001A patent/SK9172001A3/sk unknown
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2003
- 2003-10-31 RU RU2003132054/14A patent/RU2003132054A/ru not_active Application Discontinuation
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