DE69819311T2 - Neue benzimidazol inhibitoren der fructose-1,6-bisphosphatase - Google Patents
Neue benzimidazol inhibitoren der fructose-1,6-bisphosphatase Download PDFInfo
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- DE69819311T2 DE69819311T2 DE69819311T DE69819311T DE69819311T2 DE 69819311 T2 DE69819311 T2 DE 69819311T2 DE 69819311 T DE69819311 T DE 69819311T DE 69819311 T DE69819311 T DE 69819311T DE 69819311 T2 DE69819311 T2 DE 69819311T2
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- Prior art keywords
- alkyl
- group
- aryl
- alicyclic
- cyclic
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title claims abstract description 35
- 102000012195 Fructose-1,6-bisphosphatases Human genes 0.000 title claims abstract description 9
- 108010017464 Fructose-Bisphosphatase Proteins 0.000 title claims abstract description 9
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 title description 129
- 125000000217 alkyl group Chemical group 0.000 claims description 333
- 125000003118 aryl group Chemical group 0.000 claims description 256
- -1 perhaloalkoxy Chemical group 0.000 claims description 229
- 150000001875 compounds Chemical class 0.000 claims description 188
- 125000002723 alicyclic group Chemical group 0.000 claims description 148
- 125000004122 cyclic group Chemical group 0.000 claims description 144
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 117
- 150000002148 esters Chemical class 0.000 claims description 97
- 125000001072 heteroaryl group Chemical group 0.000 claims description 75
- 239000000651 prodrug Substances 0.000 claims description 68
- 229940002612 prodrug Drugs 0.000 claims description 68
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 67
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 51
- 125000002541 furyl group Chemical group 0.000 claims description 49
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 48
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 46
- 125000003342 alkenyl group Chemical group 0.000 claims description 43
- 125000000304 alkynyl group Chemical group 0.000 claims description 43
- 125000004432 carbon atom Chemical group C* 0.000 claims description 42
- 125000004423 acyloxy group Chemical group 0.000 claims description 41
- 125000004429 atom Chemical group 0.000 claims description 41
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 101710099475 3'-phosphoadenosine 5'-phosphate phosphatase Proteins 0.000 claims description 39
- 101710196411 Fructose-1,6-bisphosphatase Proteins 0.000 claims description 39
- 101710186733 Fructose-1,6-bisphosphatase, chloroplastic Proteins 0.000 claims description 39
- 101710109119 Fructose-1,6-bisphosphatase, cytosolic Proteins 0.000 claims description 39
- 101710198902 Fructose-1,6-bisphosphate aldolase/phosphatase Proteins 0.000 claims description 39
- 239000008103 glucose Substances 0.000 claims description 38
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 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 description 36
- 125000003282 alkyl amino group Chemical group 0.000 claims description 35
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
- 239000001301 oxygen Substances 0.000 claims description 34
- 229910052799 carbon Inorganic materials 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 33
- 210000004369 blood Anatomy 0.000 claims description 32
- 239000008280 blood Substances 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 125000003107 substituted aryl group Chemical group 0.000 claims description 32
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 30
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 27
- 125000004414 alkyl thio group Chemical group 0.000 claims description 27
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 27
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 27
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
- 125000001188 haloalkyl group Chemical group 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 24
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 24
- 125000005842 heteroatom Chemical group 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 21
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 19
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- 206010012601 diabetes mellitus Diseases 0.000 claims description 19
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 18
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 18
- 150000003462 sulfoxides Chemical class 0.000 claims description 18
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 18
- 229910052727 yttrium Inorganic materials 0.000 claims description 18
- 241001465754 Metazoa Species 0.000 claims description 17
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 15
- 125000004104 aryloxy group Chemical group 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 15
- 150000002576 ketones Chemical class 0.000 claims description 15
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 14
- 125000001769 aryl amino group Chemical group 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 230000004110 gluconeogenesis Effects 0.000 claims description 13
- 102000004877 Insulin Human genes 0.000 claims description 12
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- 125000001691 aryl alkyl amino group Chemical group 0.000 claims description 11
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000005343 heterocyclic alkyl group Chemical group 0.000 claims description 11
- 229940125396 insulin Drugs 0.000 claims description 11
- 150000001409 amidines Chemical class 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 9
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 9
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 9
- 125000004171 alkoxy aryl group Chemical group 0.000 claims description 9
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 9
- 125000005518 carboxamido group Chemical group 0.000 claims description 9
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 9
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
- VEQDEMWUVGAJKG-UHFFFAOYSA-N 1-amino-1-azidoguanidine Chemical compound N(=[N+]=[N-])N(C(=N)N)N VEQDEMWUVGAJKG-UHFFFAOYSA-N 0.000 claims description 8
- 150000002596 lactones Chemical class 0.000 claims description 8
- 229920002527 Glycogen Polymers 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 229940096919 glycogen Drugs 0.000 claims description 7
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 150000001336 alkenes Chemical group 0.000 claims description 6
- VAYTZRYEBVHVLE-UHFFFAOYSA-N 1,3-dioxol-2-one Chemical class O=C1OC=CO1 VAYTZRYEBVHVLE-UHFFFAOYSA-N 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 5
- AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical compound [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 claims description 4
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 4
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 2
- 229920005557 bromobutyl Polymers 0.000 claims description 2
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- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 abstract description 9
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
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- 150000003871 sulfonates Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- ZTCGGBIFOFASKI-UHFFFAOYSA-N tert-butyl acetate;lithium Chemical compound [Li].CC(=O)OC(C)(C)C ZTCGGBIFOFASKI-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- YLGRTLMDMVAFNI-UHFFFAOYSA-N tributyl(prop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC=C YLGRTLMDMVAFNI-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- POSZUTFLHGNLHX-KSBRXOFISA-N tris maleate Chemical compound OCC(N)(CO)CO.OCC(N)(CO)CO.OC(=O)\C=C/C(O)=O POSZUTFLHGNLHX-KSBRXOFISA-N 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 238000013293 zucker diabetic fatty rat Methods 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- 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
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
- C07F9/65068—Five-membered rings having the nitrogen atoms in positions 1 and 3 condensed with carbocyclic rings or carbocyclic ring systems
-
- 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
- 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
-
- 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
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4062797P | 1997-03-07 | 1997-03-07 | |
| US40627P | 1997-03-07 | ||
| PCT/US1998/004498 WO1998039343A1 (en) | 1997-03-07 | 1998-03-06 | Novel benzimidazole inhibitors of fructose-1,6-bisphosphatase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69819311D1 DE69819311D1 (de) | 2003-12-04 |
| DE69819311T2 true DE69819311T2 (de) | 2004-07-29 |
Family
ID=21912034
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69819311T Expired - Fee Related DE69819311T2 (de) | 1997-03-07 | 1998-03-06 | Neue benzimidazol inhibitoren der fructose-1,6-bisphosphatase |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US6110903A (https=) |
| EP (1) | EP0970095B1 (https=) |
| JP (1) | JP2001515482A (https=) |
| AT (1) | ATE253073T1 (https=) |
| AU (1) | AU6691498A (https=) |
| DE (1) | DE69819311T2 (https=) |
| DK (1) | DK0970095T3 (https=) |
| ES (1) | ES2210728T3 (https=) |
| PT (1) | PT970095E (https=) |
| WO (1) | WO1998039343A1 (https=) |
| ZA (1) | ZA981936B (https=) |
Families Citing this family (120)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU6452098A (en) | 1997-03-07 | 1998-09-22 | Metabasis Therapeutics, Inc. | Novel 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 |
| WO1999045016A2 (en) | 1998-03-06 | 1999-09-10 | Metabasis Therapeutics, Inc. | Novel prodrugs for phosphorus-containing compounds |
| US6312662B1 (en) | 1998-03-06 | 2001-11-06 | Metabasis Therapeutics, Inc. | Prodrugs phosphorus-containing compounds |
| ATE246197T1 (de) | 1998-09-09 | 2003-08-15 | Metabasis Therapeutics Inc | Neue heteroaromatische fructose 1,6- bisphosphatase inhibitoren |
| DE59911249D1 (de) | 1998-11-03 | 2005-01-13 | Abbott Gmbh & Co Kg | Substituierte 2-phenylbenzimidazole, deren herstellung und anwendung |
| IL143569A0 (en) * | 1998-12-24 | 2002-04-21 | Metabasis Therapeutics Inc | A combination of fbpase inhibitors and insulin sensitizers for the treatment of diabetes |
| US6756360B1 (en) | 1998-12-24 | 2004-06-29 | Metabasis Therapeutics, Inc. | Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes |
| US7205404B1 (en) * | 1999-03-05 | 2007-04-17 | Metabasis Therapeutics, Inc. | Phosphorus-containing prodrugs |
| HUP0200260A3 (en) | 1999-03-05 | 2002-11-28 | Metabasis Therapeutics Inc San | Novel phosphorus-containing prodrugs, their preparation and their use |
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| CA2396713A1 (en) * | 1999-12-22 | 2001-07-05 | Metabasis Therapeutics, Inc. | Novel bisamidate phosphonate prodrugs |
| AU2006202624B2 (en) * | 1999-12-22 | 2008-08-14 | Metabasis Therapeutics, Inc. | Novel bisamidate phosphonate prodrugs |
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| US7563774B2 (en) * | 2000-06-29 | 2009-07-21 | Metabasis Therapeutics, Inc. | Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes |
| IL153513A0 (en) * | 2000-07-06 | 2003-07-06 | Metabasis Therapeutics Inc | A COMBINATION OF FBPase INHIBITORS AND ANTIDIABETIC AGENTS USEFUL FOR THE TREATMENT OF DIABETES |
| AU2003235501A1 (en) * | 2002-05-13 | 2003-11-11 | Metabasis Therapeutics, Inc. | PMEA and PMPA cyclic producing synthesis |
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| US7129049B2 (en) * | 2003-12-22 | 2006-10-31 | Regents Of The University Of Minnesota | Method of detecting equine glycogen storage disease IV |
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| 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 |
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| TW260664B (https=) * | 1993-02-15 | 1995-10-21 | Otsuka Pharma Factory Inc | |
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| US6054587A (en) | 1997-03-07 | 2000-04-25 | Metabasis Therapeutics, Inc. | Indole and azaindole 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 |
| KR20010033811A (ko) * | 1997-12-31 | 2001-04-25 | 토마스 안 빅토리아 | 2차 및 3차 아민을 함유하는 약제의 물에 용해가능한프로드럭 및 그것의 제조방법 |
-
1998
- 1998-03-06 DE DE69819311T patent/DE69819311T2/de not_active Expired - Fee Related
- 1998-03-06 EP EP98909031A patent/EP0970095B1/en not_active Expired - Lifetime
- 1998-03-06 ZA ZA9801936A patent/ZA981936B/xx unknown
- 1998-03-06 AT AT98909031T patent/ATE253073T1/de not_active IP Right Cessation
- 1998-03-06 DK DK98909031T patent/DK0970095T3/da active
- 1998-03-06 ES ES98909031T patent/ES2210728T3/es not_active Expired - Lifetime
- 1998-03-06 PT PT98909031T patent/PT970095E/pt unknown
- 1998-03-06 WO PCT/US1998/004498 patent/WO1998039343A1/en not_active Ceased
- 1998-03-06 AU AU66914/98A patent/AU6691498A/en not_active Abandoned
- 1998-03-06 US US09/036,329 patent/US6110903A/en not_active Expired - Fee Related
- 1998-03-06 JP JP53888798A patent/JP2001515482A/ja active Pending
-
2000
- 2000-04-11 US US09/547,282 patent/US6399782B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0970095B1 (en) | 2003-10-29 |
| AU6691498A (en) | 1998-09-22 |
| DE69819311D1 (de) | 2003-12-04 |
| US6399782B1 (en) | 2002-06-04 |
| ATE253073T1 (de) | 2003-11-15 |
| DK0970095T3 (da) | 2004-03-08 |
| ES2210728T3 (es) | 2004-07-01 |
| EP0970095A1 (en) | 2000-01-12 |
| ZA981936B (en) | 1999-09-06 |
| JP2001515482A (ja) | 2001-09-18 |
| US6110903A (en) | 2000-08-29 |
| PT970095E (pt) | 2004-03-31 |
| WO1998039343A1 (en) | 1998-09-11 |
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Owner name: METABASIS THERAPEUTICS, INC., LA JOLLA, CALIF., US |
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