ZA200208542B - Alkynyl phenyl heteroaromatic glucokinase activators. - Google Patents
Alkynyl phenyl heteroaromatic glucokinase activators. Download PDFInfo
- Publication number
- ZA200208542B ZA200208542B ZA200208542A ZA200208542A ZA200208542B ZA 200208542 B ZA200208542 B ZA 200208542B ZA 200208542 A ZA200208542 A ZA 200208542A ZA 200208542 A ZA200208542 A ZA 200208542A ZA 200208542 B ZA200208542 B ZA 200208542B
- Authority
- ZA
- South Africa
- Prior art keywords
- compound
- cyclopentyl
- phenyl
- carbon atom
- mmol
- Prior art date
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- 102000030595 Glucokinase Human genes 0.000 title description 37
- 108010021582 Glucokinase Proteins 0.000 title description 37
- 239000012190 activator Substances 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 107
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
- 229910052799 carbon Inorganic materials 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 125000004432 carbon atom Chemical group C* 0.000 claims description 34
- 125000001072 heteroaryl group Chemical group 0.000 claims description 34
- 229910052757 nitrogen Inorganic materials 0.000 claims description 29
- 238000000034 method Methods 0.000 claims description 23
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 20
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 239000011593 sulfur Substances 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000000335 thiazolyl group Chemical group 0.000 claims description 13
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 12
- 125000003277 amino group Chemical group 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 7
- 241001465754 Metazoa Species 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- UGZVQQWMVUYVHE-UHFFFAOYSA-N 3-cyclopentyl-2-(4-ethynylphenyl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1CCCC1CC(C=1C=CC(=CC=1)C#C)C(=O)NC1=NC=CS1 UGZVQQWMVUYVHE-UHFFFAOYSA-N 0.000 claims description 4
- ATIZYCJUBLAREU-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(2-pyridin-2-ylethynyl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1CCCC1CC(C=1C=CC(=CC=1)C#CC=1N=CC=CC=1)C(=O)NC1=NC=CS1 ATIZYCJUBLAREU-UHFFFAOYSA-N 0.000 claims description 4
- NRJVNKDOABGZSU-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(3-methoxyprop-1-ynyl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(C#CCOC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 NRJVNKDOABGZSU-UHFFFAOYSA-N 0.000 claims description 4
- KBYHEIXEMMBUSO-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(3-morpholin-4-ylprop-1-ynyl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1CCCC1CC(C=1C=CC(=CC=1)C#CCN1CCOCC1)C(=O)NC1=NC=CS1 KBYHEIXEMMBUSO-UHFFFAOYSA-N 0.000 claims description 4
- XWOZFNUZFINKTK-UHFFFAOYSA-N 3-cyclopentyl-2-[4-[2-(1-hydroxycyclohexyl)ethynyl]phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C=1C=C(C(CC2CCCC2)C(=O)NC=2SC=CN=2)C=CC=1C#CC1(O)CCCCC1 XWOZFNUZFINKTK-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000011321 prophylaxis Methods 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
- 230000001225 therapeutic effect Effects 0.000 claims description 4
- MWRLZMKJPZXNEL-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(3-hydroxy-3-methylpent-1-ynyl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(C#CC(C)(O)CC)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 MWRLZMKJPZXNEL-UHFFFAOYSA-N 0.000 claims description 3
- MOWICLLAKVAVTB-UHFFFAOYSA-N 3-cyclopentyl-2-[4-(4-hydroxypent-1-ynyl)phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(C#CCC(O)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 MOWICLLAKVAVTB-UHFFFAOYSA-N 0.000 claims description 3
- QEWPVBVQRFJSFS-UHFFFAOYSA-N 3-cyclopentyl-2-[4-[3-(dimethylamino)prop-1-ynyl]phenyl]-n-(1,3-thiazol-2-yl)propanamide Chemical compound C1=CC(C#CCN(C)C)=CC=C1C(C(=O)NC=1SC=CN=1)CC1CCCC1 QEWPVBVQRFJSFS-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- RRLKYOITJIHSDO-UHFFFAOYSA-N ethyl 2-[[3-cyclopentyl-2-[4-(3-methoxyprop-1-ynyl)phenyl]propanoyl]amino]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(NC(=O)C(CC2CCCC2)C=2C=CC(=CC=2)C#CCOC)=N1 RRLKYOITJIHSDO-UHFFFAOYSA-N 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 3
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- 239000013543 active substance Substances 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
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- 125000005843 halogen group Chemical group 0.000 claims 3
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- 238000006243 chemical reaction Methods 0.000 description 80
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 74
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- 229920006395 saturated elastomer Polymers 0.000 description 57
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 56
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- 239000011780 sodium chloride Substances 0.000 description 45
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 44
- 229910052938 sodium sulfate Inorganic materials 0.000 description 44
- 235000011152 sodium sulphate Nutrition 0.000 description 44
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 30
- 238000003818 flash chromatography Methods 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 10
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- QXLPXWSKPNOQLE-UHFFFAOYSA-N methylpentynol Chemical compound CCC(C)(O)C#C QXLPXWSKPNOQLE-UHFFFAOYSA-N 0.000 description 1
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- ILBIXZPOMJFOJP-UHFFFAOYSA-N n,n-dimethylprop-2-yn-1-amine Chemical compound CN(C)CC#C ILBIXZPOMJFOJP-UHFFFAOYSA-N 0.000 description 1
- SGQYBUJEJYXKCH-UHFFFAOYSA-N n-(1,3-thiazol-2-yl)propanamide Chemical compound CCC(=O)NC1=NC=CS1 SGQYBUJEJYXKCH-UHFFFAOYSA-N 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000008012 organic excipient Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- JTHLRRZARWSHBE-UHFFFAOYSA-N pent-4-yn-2-ol Chemical compound CC(O)CC#C JTHLRRZARWSHBE-UHFFFAOYSA-N 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 230000029964 regulation of glucose metabolic process Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- GACTWZZMVMUKNG-ZXXMMSQZSA-N sorbitol 6-phosphate Chemical compound OC[C@@H](O)[C@H](O)[C@@H](O)[C@H](O)COP(O)(O)=O GACTWZZMVMUKNG-ZXXMMSQZSA-N 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/88—Nitrogen atoms, e.g. allantoin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| US20154600P | 2000-05-03 | 2000-05-03 |
Publications (1)
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|---|---|
| ZA200208542B true ZA200208542B (en) | 2004-01-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200208542A ZA200208542B (en) | 2000-05-03 | 2002-10-22 | Alkynyl phenyl heteroaromatic glucokinase activators. |
Country Status (18)
| Country | Link |
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| US (1) | US6388071B2 (zh) |
| EP (1) | EP1282612B1 (zh) |
| JP (1) | JP3788935B2 (zh) |
| KR (1) | KR100502033B1 (zh) |
| CN (1) | CN1176915C (zh) |
| AR (1) | AR032453A1 (zh) |
| AT (1) | ATE286036T1 (zh) |
| AU (2) | AU2001270494B2 (zh) |
| BR (1) | BR0110573A (zh) |
| CA (1) | CA2407416C (zh) |
| DE (1) | DE60108108T2 (zh) |
| EC (1) | ECSP014054A (zh) |
| ES (1) | ES2233660T3 (zh) |
| MX (1) | MXPA02010745A (zh) |
| PE (1) | PE20011310A1 (zh) |
| PT (1) | PT1282612E (zh) |
| WO (1) | WO2001083465A2 (zh) |
| ZA (1) | ZA200208542B (zh) |
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| SE0102299D0 (sv) | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
| SE0102300D0 (sv) * | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
| SE0102764D0 (sv) * | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
| EP1336607A1 (en) * | 2002-02-19 | 2003-08-20 | Novo Nordisk A/S | Amide derivatives as glucokinase activators |
| GB2409678B (en) * | 2001-12-19 | 2005-09-21 | Hoffmann La Roche | Crystals of glucokinase and methods of growing them and ligands of glucokinase |
| US6911545B2 (en) | 2001-12-19 | 2005-06-28 | Hoffman-La Roche Inc. | Crystals of glucokinase and methods of growing them |
| KR101018318B1 (ko) | 2001-12-21 | 2011-03-04 | 노보 노르디스크 에이/에스 | Ｇｋ 활성제로서의 아미드 유도체 |
| MXPA05000130A (es) | 2002-06-27 | 2005-02-17 | Novo Nordisk As | Derivados de aril-carbonilo como agentes terapeuticos. |
| CN1678311A (zh) | 2002-06-27 | 2005-10-05 | 诺沃挪第克公司 | 用作治疗剂的芳基羰基衍生物 |
| KR20050074959A (ko) * | 2002-10-03 | 2005-07-19 | 노파르티스 아게 | 제ｉｉ형 당뇨병 치료에 유용한 글루코키나아제 활성인자로서의 치환된 (티아졸-２-일)-아미드 또는 술폰아미드 |
| GB0226930D0 (en) | 2002-11-19 | 2002-12-24 | Astrazeneca Ab | Chemical compounds |
| GB0226931D0 (en) | 2002-11-19 | 2002-12-24 | Astrazeneca Ab | Chemical compounds |
| PE20040801A1 (es) | 2002-12-12 | 2004-11-25 | Hoffmann La Roche | Derivados de pirazina y piridina 5-sustituidos como activadores de glucoquinasa |
| AU2003297291A1 (en) | 2003-01-06 | 2004-08-10 | Eli Lilly And Company | Substituted arylcyclopropylacetamides as glucokinase activators |
| PL378117A1 (pl) | 2003-02-11 | 2006-03-06 | Prosidion Limited | Tricyklopodstawione związki amidowe |
| CN102516240A (zh) | 2004-01-06 | 2012-06-27 | 诺和诺德公司 | 杂芳基脲及其作为葡糖激酶活化剂的用途 |
| BRPI0507734A (pt) * | 2004-02-18 | 2007-07-10 | Astrazeneca Ab | composto ou um sal, pró-droga ou solvato do mesmo, método de tratar doenças mediadas por glk, e, processo para a preparação de um composto |
| EP2048137A1 (en) * | 2004-02-18 | 2009-04-15 | AstraZeneca AB | Benzamide derivatives and their use as glucokinase activating agents. |
| EP1737870A1 (en) * | 2004-04-02 | 2007-01-03 | Novartis AG | Thiazolopyridine derivates, pharmaceutical conditions containing them and methods of treating glucokinase mediated conditions |
| AU2005229416B2 (en) | 2004-04-02 | 2009-03-26 | Novartis Ag | Sulfonamide-thiazolpyridine derivatives as glucokinase activators useful the treatment of type 2 diabetes |
| TW200600086A (en) * | 2004-06-05 | 2006-01-01 | Astrazeneca Ab | Chemical compound |
| AU2005293343B2 (en) | 2004-10-16 | 2009-03-19 | Astrazeneca Ab | Process for making phenoxy benzamide compounds |
| GB0423043D0 (en) * | 2004-10-16 | 2004-11-17 | Astrazeneca Ab | Compounds |
| GB0423044D0 (en) * | 2004-10-16 | 2004-11-17 | Astrazeneca Ab | Compounds |
| EP1824835A1 (en) | 2004-12-03 | 2007-08-29 | Novo Nordisk A/S | Heteroaromatic glucokinase activators |
| US20110059941A1 (en) * | 2005-05-24 | 2011-03-10 | Peter William Rodney Caulkett | 2-phenyl substituted imidazol [4,5b] pyridine/pyrazine and purine derivatives as glucokinase modulators |
| TW200714597A (en) * | 2005-05-27 | 2007-04-16 | Astrazeneca Ab | Chemical compounds |
| EP1904466A1 (en) | 2005-07-08 | 2008-04-02 | Novo Nordisk A/S | Dicycloalkyl urea glucokinase activators |
| WO2007007040A1 (en) * | 2005-07-09 | 2007-01-18 | Astrazeneca Ab | 2 -heterocyclyloxybenzoyl amino heterocyclyl compounds as modulators of glucokinase for the treatment of type 2 diabetes |
| EP1902052B1 (en) * | 2005-07-09 | 2012-11-28 | AstraZeneca AB | Heteroaryl benzamide derivatives for use as glk activators in the treatment of diabetes |
| EP2027113A1 (en) * | 2005-07-09 | 2009-02-25 | AstraZeneca AB | Heteroaryl benzamide derivatives for use as glk activators in the treatment of diabetes |
| EP1910317B1 (en) | 2005-07-20 | 2013-07-03 | Eli Lilly And Company | 1-amino linked compounds |
| US9202182B2 (en) * | 2005-08-11 | 2015-12-01 | International Business Machines Corporation | Method and system for analyzing business architecture |
| JPWO2007026761A1 (ja) | 2005-08-31 | 2009-03-12 | アステラス製薬株式会社 | チアゾール誘導体 |
| JP2007063225A (ja) | 2005-09-01 | 2007-03-15 | Takeda Chem Ind Ltd | イミダゾピリジン化合物 |
| CN101272784A (zh) | 2005-09-29 | 2008-09-24 | 塞诺菲-安万特股份有限公司 | 苯基-和吡啶基-1,2,4-噁二唑酮衍生物、它们的制备方法和它们作为药物的用途 |
| GT200600429A (es) * | 2005-09-30 | 2007-04-30 | Compuestos organicos | |
| GT200600428A (es) * | 2005-09-30 | 2007-05-21 | Compuestos organicos | |
| EP1948644A1 (en) * | 2005-11-03 | 2008-07-30 | Prosidion Limited | Tricyclo substituted amides |
| CN101312940B (zh) | 2005-11-17 | 2012-11-14 | 伊莱利利公司 | 胰高血糖素受体拮抗剂、制备和治疗用途 |
| JP2009515997A (ja) * | 2005-11-18 | 2009-04-16 | タケダ サン ディエゴ インコーポレイテッド | グルコキナーゼ活性剤 |
| TW200738621A (en) * | 2005-11-28 | 2007-10-16 | Astrazeneca Ab | Chemical process |
| JP5302012B2 (ja) | 2006-03-08 | 2013-10-02 | タケダ カリフォルニア インコーポレイテッド | グルコキナーゼ活性剤 |
| US8211925B2 (en) | 2006-04-28 | 2012-07-03 | Transtech Pharma, Inc. | Benzamide glucokinase activators |
| PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
| EP2049518B1 (en) * | 2006-05-31 | 2011-08-31 | Takeda San Diego, Inc. | Indazole and isoindole derivatives as glucokinase activating agents. |
| CA2657566A1 (en) | 2006-07-24 | 2008-01-31 | F. Hoffmann-La Roche Ag | Pyrazoles as glucokinase activators |
| TW200825063A (en) * | 2006-10-23 | 2008-06-16 | Astrazeneca Ab | Chemical compounds |
| CL2007003061A1 (es) * | 2006-10-26 | 2008-08-01 | Astrazeneca Ab | Compuestos derivados de 3,5-dioxi-benzamida; proceso de preparacion; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar una enfermedad mediada a traves de glk, tal como la diabetes tipo 2. |
| EP2091947A2 (en) | 2006-12-20 | 2009-08-26 | Takeda San Diego, Inc. | Glucokinase activators |
| BRPI0721143A2 (pt) * | 2006-12-21 | 2014-03-11 | Astrazeneca Ab | Forma cristalina do composto processo para a formação da mesma, uso de um composto, método para tratar doenças mediadas por ativador de glicocinase |
| TW200831081A (en) | 2006-12-25 | 2008-08-01 | Kyorin Seiyaku Kk | Glucokinase activator |
| WO2008104994A2 (en) | 2007-02-28 | 2008-09-04 | Advinus Therapeutics Private Limited | 2,2,2-tri-substituted acetamide derivatives as glucokinase activators, their process and pharmaceutical application |
| EP2116533B1 (en) * | 2007-03-07 | 2013-07-10 | Kyorin Pharmaceutical Co., Ltd. | Glucokinase activator |
| US8173645B2 (en) | 2007-03-21 | 2012-05-08 | Takeda San Diego, Inc. | Glucokinase activators |
| PE20091313A1 (es) * | 2008-01-15 | 2009-09-03 | Lilly Co Eli | (r)-2-(4-ciclopropansulfonil-fenil)-n-pirazin-2-il-3-(tetrahidropiran-4-il)-propionamida cristalina |
| BRPI0906888A2 (pt) | 2008-01-18 | 2015-11-03 | Astellas Pharma Inc | derivado de fenilacetamida |
| US8258134B2 (en) | 2008-04-16 | 2012-09-04 | Hoffmann-La Roche Inc. | Pyridazinone glucokinase activators |
| US7741327B2 (en) | 2008-04-16 | 2010-06-22 | Hoffmann-La Roche Inc. | Pyrrolidinone glucokinase activators |
| PT2275414E (pt) | 2008-04-28 | 2015-09-09 | Teijin Pharma Ltd | Derivado de amida do ácido ciclopentacrílico |
| AU2009278929B2 (en) | 2008-08-04 | 2012-07-05 | Astrazeneca Ab | Pyrazolo [3,4] pyrimidin-4-yl derivatives and their uses to treat diabetes and obesity |
| UA104742C2 (uk) | 2008-12-19 | 2014-03-11 | Эли Лилли Энд Компани | Похідні арилциклопропілацетаміду, застосовні як активатори глюкокінази |
| GB0902434D0 (en) * | 2009-02-13 | 2009-04-01 | Astrazeneca Ab | Chemical process |
| GB0902406D0 (en) * | 2009-02-13 | 2009-04-01 | Astrazeneca Ab | Crystalline polymorphic form |
| WO2010116176A1 (en) * | 2009-04-09 | 2010-10-14 | Astrazeneca Ab | Pyrazolo [4, 5-e] pyrimidine derivative and its use to treat diabetes and obesity |
| AR076220A1 (es) | 2009-04-09 | 2011-05-26 | Astrazeneca Ab | Derivados de pirazol [4,5 - e] pirimidina |
| US8222416B2 (en) | 2009-12-14 | 2012-07-17 | Hoffmann-La Roche Inc. | Azaindole glucokinase activators |
| AU2011235212B2 (en) | 2010-03-31 | 2014-07-31 | The Scripps Research Institute | Reprogramming cells |
| US8877754B2 (en) | 2010-09-06 | 2014-11-04 | Boehringer Ingelheim International Gmbh | Compounds, pharmaceutical compositions and uses thereof |
| WO2014035872A1 (en) * | 2012-08-27 | 2014-03-06 | Amgen Inc. | Tricyclic alkynes that interact with glucokinase regulatory protein |
| EP2878339A1 (en) | 2013-12-02 | 2015-06-03 | Siena Biotech S.p.A. | SIP3 antagonists |
| EP3053834B1 (en) | 2015-02-04 | 2019-03-27 | Tetra Laval Holdings & Finance S.A. | Forming assembly and method for forming a plurality of sealed packs for pourable food products starting from a tube of packaging material |
| MX2020008905A (es) | 2018-06-12 | 2020-12-03 | Vtv Therapeutics Llc | Usos terapeuticos de activadores de glucoquinasa en combinacion con insulina o analogos de insulinas. |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61115054A (ja) * | 1984-11-08 | 1986-06-02 | Taisho Pharmaceut Co Ltd | スチレンアルカン酸誘導体 |
| EP0831795A2 (en) * | 1995-06-07 | 1998-04-01 | Sugen, Inc. | Phosphatase inhibitors |
| ES2198719T3 (es) * | 1997-06-24 | 2004-02-01 | Zeria Pharmaceutical Co., Ltd. | Procedimiento de produccion de los derivados de 2-hidroxibenzamida. |
-
2001
- 2001-04-25 KR KR10-2002-7014725A patent/KR100502033B1/ko not_active IP Right Cessation
- 2001-04-25 AU AU2001270494A patent/AU2001270494B2/en not_active Ceased
- 2001-04-25 CN CNB018089127A patent/CN1176915C/zh not_active Expired - Fee Related
- 2001-04-25 AT AT01949294T patent/ATE286036T1/de not_active IP Right Cessation
- 2001-04-25 CA CA002407416A patent/CA2407416C/en not_active Expired - Fee Related
- 2001-04-25 US US09/841,983 patent/US6388071B2/en not_active Expired - Fee Related
- 2001-04-25 PT PT01949294T patent/PT1282612E/pt unknown
- 2001-04-25 WO PCT/EP2001/004654 patent/WO2001083465A2/en active IP Right Grant
- 2001-04-25 ES ES01949294T patent/ES2233660T3/es not_active Expired - Lifetime
- 2001-04-25 BR BR0110573-6A patent/BR0110573A/pt not_active IP Right Cessation
- 2001-04-25 MX MXPA02010745A patent/MXPA02010745A/es active IP Right Grant
- 2001-04-25 JP JP2001580894A patent/JP3788935B2/ja not_active Expired - Fee Related
- 2001-04-25 EP EP01949294A patent/EP1282612B1/en not_active Expired - Lifetime
- 2001-04-25 AU AU7049401A patent/AU7049401A/xx active Pending
- 2001-04-25 DE DE60108108T patent/DE60108108T2/de not_active Expired - Lifetime
- 2001-04-27 PE PE2001000383A patent/PE20011310A1/es not_active Application Discontinuation
- 2001-04-30 AR ARP010102035A patent/AR032453A1/es not_active Application Discontinuation
- 2001-05-03 EC EC2001004054A patent/ECSP014054A/es unknown
-
2002
- 2002-10-22 ZA ZA200208542A patent/ZA200208542B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA02010745A (es) | 2003-03-10 |
| ECSP014054A (es) | 2002-01-25 |
| EP1282612B1 (en) | 2004-12-29 |
| BR0110573A (pt) | 2003-04-01 |
| ES2233660T3 (es) | 2005-06-16 |
| CA2407416A1 (en) | 2001-11-08 |
| EP1282612A2 (en) | 2003-02-12 |
| DE60108108D1 (de) | 2005-02-03 |
| WO2001083465A2 (en) | 2001-11-08 |
| KR100502033B1 (ko) | 2005-07-25 |
| JP3788935B2 (ja) | 2006-06-21 |
| DE60108108T2 (de) | 2005-12-08 |
| KR20020093117A (ko) | 2002-12-12 |
| PT1282612E (pt) | 2005-04-29 |
| CN1176915C (zh) | 2004-11-24 |
| CN1432004A (zh) | 2003-07-23 |
| PE20011310A1 (es) | 2001-12-31 |
| AU7049401A (en) | 2001-11-12 |
| ATE286036T1 (de) | 2005-01-15 |
| CA2407416C (en) | 2006-07-18 |
| AU2001270494B2 (en) | 2005-11-10 |
| JP2003531898A (ja) | 2003-10-28 |
| US20010053851A1 (en) | 2001-12-20 |
| WO2001083465A3 (en) | 2002-05-16 |
| US6388071B2 (en) | 2002-05-14 |
| AR032453A1 (es) | 2003-11-12 |
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