KR20110084339A - 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한 헤테로아릴 벤즈아미드 유도체 - Google Patents
당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한 헤테로아릴 벤즈아미드 유도체 Download PDFInfo
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- KR20110084339A KR20110084339A KR1020117015352A KR20117015352A KR20110084339A KR 20110084339 A KR20110084339 A KR 20110084339A KR 1020117015352 A KR1020117015352 A KR 1020117015352A KR 20117015352 A KR20117015352 A KR 20117015352A KR 20110084339 A KR20110084339 A KR 20110084339A
- Authority
- KR
- South Korea
- Prior art keywords
- oxy
- methyl
- ylcarbonyl
- azetidin
- benzamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
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- -1 Heteroaryl Benzamide Derivatives Chemical class 0.000 title claims abstract description 743
- 238000011282 treatment Methods 0.000 title claims abstract description 26
- 239000012190 activator Substances 0.000 title abstract description 10
- 206010012601 diabetes mellitus Diseases 0.000 title description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 281
- 150000003839 salts Chemical class 0.000 claims abstract description 79
- 238000000034 method Methods 0.000 claims abstract description 62
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 160
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 138
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 124
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 123
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 121
- 229910052757 nitrogen Inorganic materials 0.000 claims description 110
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 104
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 80
- 238000002360 preparation method Methods 0.000 claims description 72
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 53
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 49
- 125000001424 substituent group Chemical group 0.000 claims description 49
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 49
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
- 125000000335 thiazolyl group Chemical group 0.000 claims description 46
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 43
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 41
- 125000001153 fluoro group Chemical group F* 0.000 claims description 40
- 125000004076 pyridyl group Chemical group 0.000 claims description 40
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 39
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 38
- 229910052717 sulfur Inorganic materials 0.000 claims description 35
- 125000002393 azetidinyl group Chemical group 0.000 claims description 33
- 229910052799 carbon Inorganic materials 0.000 claims description 33
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 32
- 150000002148 esters Chemical class 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 27
- 125000003282 alkyl amino group Chemical group 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 230000008569 process Effects 0.000 claims description 25
- 229920006395 saturated elastomer Polymers 0.000 claims description 25
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 25
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 25
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 24
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 23
- 150000001721 carbon Chemical group 0.000 claims description 22
- 125000006239 protecting group Chemical group 0.000 claims description 22
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 20
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 20
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 19
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 19
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 17
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 13
- 230000001404 mediated effect Effects 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
- 239000002243 precursor Substances 0.000 claims description 11
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
- 125000005514 but-1-yn-3-yl group Chemical group 0.000 claims description 9
- 230000004048 modification Effects 0.000 claims description 8
- 238000012986 modification Methods 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 238000010640 amide synthesis reaction Methods 0.000 claims description 6
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 6
- 229940054066 benzamide antipsychotics Drugs 0.000 claims description 5
- 150000003936 benzamides Chemical class 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 238000010931 ester hydrolysis Methods 0.000 claims description 4
- 125000002524 organometallic group Chemical group 0.000 claims description 4
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
- XDMFAZAAXUCUSV-INIZCTEOSA-N 3-[5-(azetidin-1-ylsulfonyl)pyridin-2-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@@H](C)COC)=CC=1OC(N=C1)=CC=C1S(=O)(=O)N1CCC1 XDMFAZAAXUCUSV-INIZCTEOSA-N 0.000 claims description 3
- HCLWIRUHLMDAKD-UHFFFAOYSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-(1,3-difluoropropan-2-yloxy)-n-(1-methylpyrazol-3-yl)benzamide Chemical compound CN1C=CC(NC(=O)C=2C=C(OC=3C(=CC(=CN=3)C(=O)N3CCC3)Cl)C=C(OC(CF)CF)C=2)=N1 HCLWIRUHLMDAKD-UHFFFAOYSA-N 0.000 claims description 3
- LZMACOCFKKPYJC-AWEZNQCLSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-(difluoromethoxy)propan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@H](COC(F)F)C)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 LZMACOCFKKPYJC-AWEZNQCLSA-N 0.000 claims description 3
- KYRNEVFFGZVNBW-INIZCTEOSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-hydroxypropan-2-yl]oxy-n-(1-propan-2-ylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C=C2)C(C)C)=CC(O[C@H](CO)C)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 KYRNEVFFGZVNBW-INIZCTEOSA-N 0.000 claims description 3
- ULDXGWNESGXTMM-HNNXBMFYSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-butan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@@H](C)CC)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 ULDXGWNESGXTMM-HNNXBMFYSA-N 0.000 claims description 3
- TXOOXIIILDYWPT-KRWDZBQOSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-n-(1-methylpyrazol-3-yl)-5-[(3s)-oxolan-3-yl]oxybenzamide Chemical compound CN1C=CC(NC(=O)C=2C=C(OC=3C(=CC(=CN=3)C(=O)N3CCC3)Cl)C=C(O[C@@H]3COCC3)C=2)=N1 TXOOXIIILDYWPT-KRWDZBQOSA-N 0.000 claims description 3
- TZRCTNJSLXITNQ-UHFFFAOYSA-N 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-(1,3-difluoropropan-2-yloxy)-n-(1-methylpyrazol-3-yl)benzamide Chemical compound CN1C=CC(NC(=O)C=2C=C(OC=3N=CC(=NC=3)C(=O)N3CCC3)C=C(OC(CF)CF)C=2)=N1 TZRCTNJSLXITNQ-UHFFFAOYSA-N 0.000 claims description 3
- ZYCUSOFIMJTQJE-AWEZNQCLSA-N 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(2s)-1-(difluoromethoxy)propan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@H](COC(F)F)C)=CC=1OC(N=C1)=CN=C1C(=O)N1CCC1 ZYCUSOFIMJTQJE-AWEZNQCLSA-N 0.000 claims description 3
- GURWRZCJIOFOGW-HNNXBMFYSA-N 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@@H](C)COC)=CC=1OC(N=C1)=CN=C1C(=O)N1CCC1 GURWRZCJIOFOGW-HNNXBMFYSA-N 0.000 claims description 3
- QECHICISFOAFKJ-HNNXBMFYSA-N 3-[5-(azetidine-1-carbonyl)pyrazin-2-yl]oxy-5-[(2s)-butan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@@H](C)CC)=CC=1OC(N=C1)=CN=C1C(=O)N1CCC1 QECHICISFOAFKJ-HNNXBMFYSA-N 0.000 claims description 3
- HMWMNEGMNFNEKM-AWEZNQCLSA-N 3-[5-(azetidine-1-carbonyl)pyridin-2-yl]oxy-5-[(2s)-1-hydroxypropan-2-yl]oxy-n-(1,3-thiazol-2-yl)benzamide Chemical compound C=1C(C(=O)NC=2SC=CN=2)=CC(O[C@H](CO)C)=CC=1OC(N=C1)=CC=C1C(=O)N1CCC1 HMWMNEGMNFNEKM-AWEZNQCLSA-N 0.000 claims description 3
- CEWOJJDGYSJJOU-INIZCTEOSA-N 3-[5-(azetidine-1-carbonyl)pyridin-2-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@@H](C)COC)=CC=1OC(N=C1)=CC=C1C(=O)N1CCC1 CEWOJJDGYSJJOU-INIZCTEOSA-N 0.000 claims description 3
- KWWIQHCYQVGYNX-HNNXBMFYSA-N 3-[5-(azetidine-1-carbonyl)pyridin-2-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-(1h-pyrazol-5-yl)benzamide Chemical compound C=1C(C(=O)NC2=NNC=C2)=CC(O[C@@H](C)COC)=CC=1OC(N=C1)=CC=C1C(=O)N1CCC1 KWWIQHCYQVGYNX-HNNXBMFYSA-N 0.000 claims description 3
- KOPLWXCEFBVGGS-UHFFFAOYSA-N 3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-(1,3-difluoropropan-2-yloxy)-n-(1-methylpyrazol-3-yl)benzamide Chemical compound CN1C=CC(NC(=O)C=2C=C(OC=3C=NC(=CC=3)C(=O)N3CCC3)C=C(OC(CF)CF)C=2)=N1 KOPLWXCEFBVGGS-UHFFFAOYSA-N 0.000 claims description 3
- JTRIYLJPGMIYFG-HNNXBMFYSA-N 3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(2s)-1-(difluoromethoxy)propan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@H](COC(F)F)C)=CC=1OC(C=N1)=CC=C1C(=O)N1CCC1 JTRIYLJPGMIYFG-HNNXBMFYSA-N 0.000 claims description 3
- RBFKTFOSLZPFQY-INIZCTEOSA-N 3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@@H](C)COC)=CC=1OC(C=N1)=CC=C1C(=O)N1CCC1 RBFKTFOSLZPFQY-INIZCTEOSA-N 0.000 claims description 3
- BZOLDYZNKDRSNP-INIZCTEOSA-N 3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-5-[(2s)-butan-2-yl]oxy-n-(1-methylpyrazol-3-yl)benzamide Chemical compound C=1C(C(=O)NC2=NN(C)C=C2)=CC(O[C@@H](C)CC)=CC=1OC(C=N1)=CC=C1C(=O)N1CCC1 BZOLDYZNKDRSNP-INIZCTEOSA-N 0.000 claims description 3
- VUNFXTHGIDEEAX-SFHVURJKSA-N 3-[6-(azetidine-1-carbonyl)pyridin-3-yl]oxy-n-(1-methylpyrazol-3-yl)-5-[(3s)-oxolan-3-yl]oxybenzamide Chemical compound CN1C=CC(NC(=O)C=2C=C(OC=3C=NC(=CC=3)C(=O)N3CCC3)C=C(O[C@@H]3COCC3)C=2)=N1 VUNFXTHGIDEEAX-SFHVURJKSA-N 0.000 claims description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Chemical group C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
- HKXMYFNBGJSFMG-UHFFFAOYSA-N n-(1-methylpyrazol-3-yl)benzamide Chemical compound CN1C=CC(NC(=O)C=2C=CC=CC=2)=N1 HKXMYFNBGJSFMG-UHFFFAOYSA-N 0.000 claims description 3
- AAPMUPRTEALJSY-AWEZNQCLSA-N 3-[2-(azetidine-1-carbonyl)pyrimidin-5-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-(1,3-thiazol-2-yl)benzamide Chemical compound C=1C(C(=O)NC=2SC=CN=2)=CC(O[C@@H](C)COC)=CC=1OC(C=N1)=CN=C1C(=O)N1CCC1 AAPMUPRTEALJSY-AWEZNQCLSA-N 0.000 claims description 2
- JNLGDTCJFWZWGO-SFHVURJKSA-N 3-[3-chloro-5-(morpholine-4-carbonyl)pyridin-2-yl]oxy-n-(1-methylpyrazol-3-yl)-5-[(3s)-oxolan-3-yl]oxybenzamide Chemical compound CN1C=CC(NC(=O)C=2C=C(OC=3C(=CC(=CN=3)C(=O)N3CCOCC3)Cl)C=C(O[C@@H]3COCC3)C=2)=N1 JNLGDTCJFWZWGO-SFHVURJKSA-N 0.000 claims description 2
- UFUWOOIVADWLTG-UHFFFAOYSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-(1,3-difluoropropan-2-yloxy)-n-(1,5-dimethylpyrazol-3-yl)benzamide Chemical compound CN1C(C)=CC(NC(=O)C=2C=C(OC=3C(=CC(=CN=3)C(=O)N3CCC3)Cl)C=C(OC(CF)CF)C=2)=N1 UFUWOOIVADWLTG-UHFFFAOYSA-N 0.000 claims description 2
- XVEATFBWTITWLP-UHFFFAOYSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-(1,3-difluoropropan-2-yloxy)-n-(1h-pyrazol-5-yl)benzamide Chemical compound C=1C(C(=O)NC2=NNC=C2)=CC(OC(CF)CF)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 XVEATFBWTITWLP-UHFFFAOYSA-N 0.000 claims description 2
- XCNGNCFTRWXUJT-UHFFFAOYSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-(1,3-difluoropropan-2-yloxy)-n-(5-methylpyrazin-2-yl)benzamide Chemical compound C1=NC(C)=CN=C1NC(=O)C1=CC(OC(CF)CF)=CC(OC=2C(=CC(=CN=2)C(=O)N2CCC2)Cl)=C1 XCNGNCFTRWXUJT-UHFFFAOYSA-N 0.000 claims description 2
- OLKCXHIAJPIOTN-ZDUSSCGKSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-hydroxypropan-2-yl]oxy-n-(1,3-thiazol-2-yl)benzamide Chemical compound C=1C(C(=O)NC=2SC=CN=2)=CC(O[C@H](CO)C)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 OLKCXHIAJPIOTN-ZDUSSCGKSA-N 0.000 claims description 2
- YIYSJXYVLTVOGL-HNNXBMFYSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-hydroxypropan-2-yl]oxy-n-(5-methylpyrazin-2-yl)benzamide Chemical compound C=1C(C(=O)NC=2N=CC(C)=NC=2)=CC(O[C@H](CO)C)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 YIYSJXYVLTVOGL-HNNXBMFYSA-N 0.000 claims description 2
- AKKHGMVBTZTWKF-AWEZNQCLSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-hydroxypropan-2-yl]oxy-n-pyrazin-2-ylbenzamide Chemical compound C=1C(C(=O)NC=2N=CC=NC=2)=CC(O[C@H](CO)C)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 AKKHGMVBTZTWKF-AWEZNQCLSA-N 0.000 claims description 2
- ULVFYSVAHQNVIQ-HNNXBMFYSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-hydroxypropan-2-yl]oxy-n-pyridin-2-ylbenzamide Chemical compound C=1C(C(=O)NC=2N=CC=CC=2)=CC(O[C@H](CO)C)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 ULVFYSVAHQNVIQ-HNNXBMFYSA-N 0.000 claims description 2
- MUOAODPWWMJWAJ-AWEZNQCLSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-(1,3-thiazol-2-yl)benzamide Chemical compound C=1C(C(=O)NC=2SC=CN=2)=CC(O[C@@H](C)COC)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 MUOAODPWWMJWAJ-AWEZNQCLSA-N 0.000 claims description 2
- NEMHCDZRCNGUHJ-AWEZNQCLSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-(1h-pyrazol-5-yl)benzamide Chemical compound C=1C(C(=O)NC2=NNC=C2)=CC(O[C@@H](C)COC)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 NEMHCDZRCNGUHJ-AWEZNQCLSA-N 0.000 claims description 2
- LQBRZUJJKCBBRR-HNNXBMFYSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-pyrazin-2-ylbenzamide Chemical compound C=1C(C(=O)NC=2N=CC=NC=2)=CC(O[C@@H](C)COC)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 LQBRZUJJKCBBRR-HNNXBMFYSA-N 0.000 claims description 2
- HOLAFYAYRKPVFN-INIZCTEOSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-[(2s)-1-methoxypropan-2-yl]oxy-n-pyridin-2-ylbenzamide Chemical compound C=1C(C(=O)NC=2N=CC=CC=2)=CC(O[C@@H](C)COC)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 HOLAFYAYRKPVFN-INIZCTEOSA-N 0.000 claims description 2
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- HMUDPFUMSNPWAC-UHFFFAOYSA-N 3-[5-(azetidine-1-carbonyl)-3-chloropyridin-2-yl]oxy-5-propan-2-yloxy-n-(1h-pyrazol-5-yl)benzamide Chemical compound C=1C(C(=O)NC2=NNC=C2)=CC(OC(C)C)=CC=1OC(C(=C1)Cl)=NC=C1C(=O)N1CCC1 HMUDPFUMSNPWAC-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- KFGBVFJVWNZCAQ-SFHVURJKSA-N tert-butyl 3-[[3-[(2s)-1-methoxypropan-2-yl]oxy-5-phenylmethoxybenzoyl]amino]pyrazole-1-carboxylate Chemical compound C=1C(C(=O)NC2=NN(C=C2)C(=O)OC(C)(C)C)=CC(O[C@@H](C)COC)=CC=1OCC1=CC=CC=C1 KFGBVFJVWNZCAQ-SFHVURJKSA-N 0.000 description 1
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
-
- 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
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic 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
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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
- A61P3/04—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
- A61P3/06—Antihyperlipidemics
-
- 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
- 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
- C07D401/14—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 three or more hetero rings
-
- 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
- C07D403/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0514173A GB0514173D0 (en) | 2005-07-09 | 2005-07-09 | Chemical compounds |
| GB0514173.4 | 2005-07-09 | ||
| GB0516297A GB0516297D0 (en) | 2005-08-09 | 2005-08-09 | Chemical compounds |
| GB0516297.9 | 2005-08-09 | ||
| GB0523862.1 | 2005-11-24 | ||
| GB0523862A GB0523862D0 (en) | 2005-11-24 | 2005-11-24 | Chemical compounds |
| GB0524589.9 | 2005-12-02 | ||
| GB0524589A GB0524589D0 (en) | 2005-12-02 | 2005-12-02 | Chemical compounds |
| GB0607977.6 | 2006-04-22 | ||
| GB0607977A GB0607977D0 (en) | 2006-04-22 | 2006-04-22 | Chemical compounds |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087002533A Division KR101346902B1 (ko) | 2005-07-09 | 2006-07-03 | 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한헤테로아릴 벤즈아미드 유도체 |
Publications (1)
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| KR20110084339A true KR20110084339A (ko) | 2011-07-21 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1020087002533A Active KR101346902B1 (ko) | 2005-07-09 | 2006-07-03 | 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한헤테로아릴 벤즈아미드 유도체 |
| KR1020117015352A Ceased KR20110084339A (ko) | 2005-07-09 | 2006-07-03 | 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한 헤테로아릴 벤즈아미드 유도체 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087002533A Active KR101346902B1 (ko) | 2005-07-09 | 2006-07-03 | 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한헤테로아릴 벤즈아미드 유도체 |
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| AU (2) | AU2006268406C1 (enExample) |
| BR (3) | BRPI0613570B8 (enExample) |
| CA (1) | CA2614746C (enExample) |
| EC (1) | ECSP088164A (enExample) |
| ES (1) | ES2397648T3 (enExample) |
| IL (2) | IL188059A0 (enExample) |
| MX (1) | MX2008000172A (enExample) |
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| NO (1) | NO20076658L (enExample) |
| NZ (4) | NZ575512A (enExample) |
| SA (1) | SA06270215B1 (enExample) |
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| UY (1) | UY29656A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| SE0102764D0 (sv) | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
| JP2007523142A (ja) * | 2004-02-18 | 2007-08-16 | アストラゼネカ アクチボラグ | ベンズアミド誘導体、およびグルコキナーゼ活性化物質としてのそれらの使用 |
| TW200600086A (en) * | 2004-06-05 | 2006-01-01 | Astrazeneca Ab | Chemical compound |
| TW200714597A (en) * | 2005-05-27 | 2007-04-16 | Astrazeneca Ab | Chemical compounds |
| KR101346902B1 (ko) * | 2005-07-09 | 2014-01-02 | 아스트라제네카 아베 | 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한헤테로아릴 벤즈아미드 유도체 |
| PE20080251A1 (es) | 2006-05-04 | 2008-04-25 | Boehringer Ingelheim Int | Usos de inhibidores de dpp iv |
| US7910747B2 (en) | 2006-07-06 | 2011-03-22 | Bristol-Myers Squibb Company | Phosphonate and phosphinate pyrazolylamide glucokinase activators |
| JP2009544648A (ja) | 2006-07-24 | 2009-12-17 | エフ.ホフマン−ラ ロシュ アーゲー | グルコキナーゼ活性化剤としてのピラゾール類 |
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| 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. |
| TW200827346A (en) | 2006-11-03 | 2008-07-01 | Astrazeneca Ab | Chemical compounds |
| US20100094009A1 (en) * | 2006-12-21 | 2010-04-15 | Mccabe James | Novel crystalline compound useful as glk activator |
| TW200836719A (en) | 2007-02-12 | 2008-09-16 | Astrazeneca Ab | Chemical compounds |
| WO2008154563A1 (en) * | 2007-06-11 | 2008-12-18 | Bristol-Myers Squibb Company | 1, 3 - dihydroxy substituted phenylamide glucokinase activators |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| PT2197849E (pt) | 2007-10-09 | 2013-04-23 | Merck Patent Gmbh | Derivados de n-(pirazole-3-il)-benzamida como ativadores de glucoquinase |
| JP5567481B2 (ja) * | 2007-10-09 | 2014-08-06 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | グルコキナーゼアクチベーターとして有用なピリジン誘導体 |
| 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 |
| WO2010015849A2 (en) | 2008-08-04 | 2010-02-11 | Astrazeneca Ab | Therapeutic agents 414 |
| GB0902406D0 (en) * | 2009-02-13 | 2009-04-01 | Astrazeneca Ab | Crystalline polymorphic form |
| GB0902434D0 (en) * | 2009-02-13 | 2009-04-01 | Astrazeneca Ab | Chemical process |
| AR076220A1 (es) | 2009-04-09 | 2011-05-26 | Astrazeneca Ab | Derivados de pirazol [4,5 - e] pirimidina |
| AR076221A1 (es) * | 2009-04-09 | 2011-05-26 | Astrazeneca Ab | Derivado de pirazol [4,5-e] pirimidina y su uso para tratar diabetes y obesidad |
| US8222416B2 (en) | 2009-12-14 | 2012-07-17 | Hoffmann-La Roche Inc. | Azaindole glucokinase activators |
| WO2011095997A1 (en) | 2010-02-08 | 2011-08-11 | Advinus Therapeutics Private Limited | Benzamide compounds as glucokinase activators and their pharmaceutical application |
| WO2011135355A1 (en) | 2010-04-29 | 2011-11-03 | Astrazeneca Ab | 3-{ [5 -(azetidin-1-ylcarbonyl)pyrazin-2 -yl] oxy} -5-{ [(1s) -2 -hydroxy- 1 -methylethyl]oxy} -n- (5 -methylpyrazin-2-) benzamid monohydrate |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| WO2012007758A2 (en) | 2010-07-15 | 2012-01-19 | Astrazeneca Ab | Pharmaceutical formulations |
| US20160031907A1 (en) * | 2013-03-15 | 2016-02-04 | Epizyme, Inc. | Substituted Benzene Compounds |
| US9243001B2 (en) * | 2013-03-15 | 2016-01-26 | Epizyme, Inc. | Substituted benzene compounds |
| CN109715637B (zh) | 2016-07-22 | 2022-04-05 | 百时美施贵宝公司 | 葡萄糖激酶激活剂及其使用方法 |
| AU2022384750B2 (en) * | 2021-09-02 | 2024-07-11 | Conduit Uk Management Ltd | Therapeutic cocrystals of 3-{[5-(azetidine-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-{[(1 s)-1 -methyl-2- (methyloxy)ethyl]oxy)-n-(5-methylpyrazin-2-yl)benzamide |
Family Cites Families (210)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2750393A (en) * | 1954-12-01 | 1956-06-12 | Sterling Drug Inc | Iodinated 5-henzamidotetrazoles and preparation thereof |
| US2967194A (en) * | 1958-05-15 | 1961-01-03 | Pennsalt Chemicals Corp | 4-trifluoromethylsalicylamides |
| FR1526074A (fr) | 1967-03-22 | 1968-05-24 | Rech S Ind S O R I Soc D | Méthoxy-phényl-amino-2-thiazoles, leurs amides et leurs procédés de préparation |
| GB1352415A (en) | 1970-05-03 | 1974-05-08 | Boots Co Ltd | Esters of substituted nicotine acids |
| FR2088019A1 (en) | 1970-05-08 | 1972-01-07 | Rabot Ets David | Esters of 2 and 6-substituted nicotinic acids - with vasomotor active |
| CS173097B1 (enExample) | 1972-12-01 | 1977-02-28 | ||
| GB1400540A (en) * | 1972-12-06 | 1975-07-16 | Smith Kline French Lab | Salicylamides and compositions thereof |
| US4009174A (en) * | 1972-12-08 | 1977-02-22 | The Boots Company Limited | Esters of substituted nicotinic acids |
| GB1437800A (en) * | 1973-08-08 | 1976-06-03 | Phavic Sprl | Derivatives of 2-benzamido-5-nitro-thiazoles |
| JPS5734314B2 (enExample) | 1973-12-22 | 1982-07-22 | ||
| GB1561350A (en) | 1976-11-05 | 1980-02-20 | May & Baker Ltd | Benzamide derivatives |
| FR2344284A1 (fr) * | 1976-03-17 | 1977-10-14 | Cerm Cent Europ Rech Mauvernay | Nouveaux composes tricycliques a cycle furannique et leur application comme antidepresseurs |
| GB1588242A (en) | 1977-10-28 | 1981-04-23 | May & Baker Ltd | N-(tetrazol-5-yl)-salicylamide derivatives |
| US4474792A (en) * | 1979-06-18 | 1984-10-02 | Riker Laboratories, Inc. | N-Tetrazolyl benzamides and anti-allergic use thereof |
| JPS5721320A (en) | 1980-07-11 | 1982-02-04 | Chugai Pharmaceut Co Ltd | Blood sugar level depressing agent |
| JPS5775962A (en) | 1980-10-29 | 1982-05-12 | Shionogi & Co Ltd | 2-alkoxybenzamide derivative |
| FR2493848B2 (fr) * | 1980-11-07 | 1986-05-16 | Delalande Sa | Nouveaux derives des nor-tropane et granatane, leur procede de preparation et leur application en therapeutique |
| JPS5869812A (ja) | 1981-10-22 | 1983-04-26 | Chugai Pharmaceut Co Ltd | 血糖降下剤 |
| JPS59139357A (ja) * | 1983-01-28 | 1984-08-10 | Torii Yakuhin Kk | アミジン誘導体 |
| JPS61205937A (ja) | 1985-03-09 | 1986-09-12 | Konishiroku Photo Ind Co Ltd | ハロゲン化銀カラ−写真感光材料 |
| JPS62142168A (ja) | 1985-10-16 | 1987-06-25 | Mitsubishi Chem Ind Ltd | チアゾ−ル誘導体及びそれを有効成分とするロイコトリエンきつ抗剤 |
| JPS62158252A (ja) | 1985-12-28 | 1987-07-14 | Kirin Brewery Co Ltd | 4−アミノピリジンベンズアミド誘導体 |
| CA1327358C (en) | 1987-11-17 | 1994-03-01 | Morio Fujiu | Fluoro cytidine derivatives |
| JP2852659B2 (ja) | 1988-03-03 | 1999-02-03 | 富山化学工業株式会社 | ピペラジン誘導体およびその塩 |
| DE3822449A1 (de) | 1988-07-02 | 1990-01-04 | Henkel Kgaa | Oxidationshaarfaerbemittel mit neuen kupplern |
| JPH03181465A (ja) | 1989-12-11 | 1991-08-07 | Takeda Chem Ind Ltd | キノリン誘導体 |
| JPH04300874A (ja) | 1991-03-29 | 1992-10-23 | Tsumura & Co | 新規2,4−ジアミノ−1,3,5−トリアジン誘導体 |
| JPH04300832A (ja) | 1991-03-29 | 1992-10-23 | Tsumura & Co | 2,4−ジアミノ−1,3,5−トリアジン誘導体を有 効成分とするロイコトリエン拮抗剤 |
| US5258407A (en) * | 1991-12-31 | 1993-11-02 | Sterling Winthrop Inc. | 3,4-disubstituted phenols-immunomodulating agents |
| US5466715A (en) * | 1991-12-31 | 1995-11-14 | Sterling Winthrop Inc. | 3,4-disubstituted phenols-immunomodulating agents |
| US5273986A (en) * | 1992-07-02 | 1993-12-28 | Hoffmann-La Roche Inc. | Cycloalkylthiazoles |
| JPH0627025A (ja) | 1992-07-06 | 1994-02-04 | Toto Ltd | 分子認識機能膜及びこれを用いたセンサー |
| WO1994004525A1 (en) | 1992-08-20 | 1994-03-03 | Otsuka Pharmaceutical Company, Limited | Benzoheterocyclic compounds as oxytocin and vasopressin antagonists |
| EP0672031B1 (en) | 1992-12-02 | 2003-03-12 | Pfizer Inc. | Catechol diethers as selective pde iv inhibitors |
| EP0619116A3 (en) | 1993-04-05 | 1994-11-23 | Hoechst Japan | Use of synthetic retinoids for osteopathy. |
| GB9307527D0 (en) | 1993-04-13 | 1993-06-02 | Fujisawa Pharmaceutical Co | New venzamide derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same |
| GB9401460D0 (en) | 1994-01-26 | 1994-03-23 | Rhone Poulenc Rorer Ltd | Compositions of matter |
| PT714898E (pt) | 1994-06-21 | 2002-04-29 | Otsuka Pharma Co Ltd | Derivado de pirazolo¬1,5-a|pirimidina |
| US5661153A (en) * | 1994-07-19 | 1997-08-26 | Japan Energy Corporation | 1-arylpyrimidine derivatives and pharmaceutical use thereof |
| US5792109A (en) | 1994-09-01 | 1998-08-11 | Leland L. Ladd | Irrigation pump and system |
| GB9420557D0 (en) | 1994-10-12 | 1994-11-30 | Zeneca Ltd | Aromatic compounds |
| JPH08143565A (ja) | 1994-11-16 | 1996-06-04 | Fujisawa Pharmaceut Co Ltd | ベンズアミド化合物 |
| US5510478A (en) * | 1994-11-30 | 1996-04-23 | American Home Products Corporation | 2-arylamidothiazole derivatives with CNS activity |
| US5672750A (en) * | 1994-12-16 | 1997-09-30 | Eastman Chemical Company | Preparation of aromatic amides from carbon monoxide, an amine and an aromatic chloride |
| EP0799206B1 (en) | 1994-12-20 | 2002-09-11 | F. Hoffmann-La Roche Ag | Aryl- and hetaryl-sulfonamide derivatives, their preparation and their use as endothelin antagonists |
| US5700796A (en) | 1995-01-17 | 1997-12-23 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US5696112A (en) | 1995-01-17 | 1997-12-09 | American Cyanamid Company | Fused heterocyclic azepines as vasopressin antagonists |
| AR002459A1 (es) | 1995-01-17 | 1998-03-25 | American Cyanamid Co | Antagonistas de vasopresina de benzacepina triciclicos, una composicion farmaceutica que los contiene, un metodo para tratar enfermedades y unprocedimiento para su preparacion. |
| US5536718A (en) | 1995-01-17 | 1996-07-16 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US5849735A (en) * | 1995-01-17 | 1998-12-15 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US5753648A (en) | 1995-01-17 | 1998-05-19 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| US5532235A (en) | 1995-01-17 | 1996-07-02 | American Cyanamid Company | Tricyclic benzazepine vasopressin antagonists |
| JPH08301760A (ja) | 1995-05-10 | 1996-11-19 | Shiseido Co Ltd | 皮膚外用剤 |
| EP0870765B1 (en) | 1995-05-18 | 2003-11-19 | Zeria Pharmaceutical Co., Ltd. | Aminothiazole derivatives, drug containing the same and intermediate in the production of the compounds |
| JP3168915B2 (ja) | 1995-05-25 | 2001-05-21 | 田辺製薬株式会社 | 医薬組成物 |
| GB9511694D0 (en) | 1995-06-09 | 1995-08-02 | Fujisawa Pharmaceutical Co | Benzamide derivatives |
| US5712270A (en) * | 1995-11-06 | 1998-01-27 | American Home Products Corporation | 2-arylamidothiazole derivatives with CNS activity |
| JP3735741B2 (ja) | 1995-11-24 | 2006-01-18 | 株式会社大塚製薬工場 | 縮環ピリミジン誘導体 |
| GB9526558D0 (en) | 1995-12-27 | 1996-02-28 | Fujisawa Pharmaceutical Co | Heterobicyclic derivatives |
| AU2595697A (en) | 1996-03-29 | 1997-10-22 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| WO1997046560A1 (en) | 1996-06-06 | 1997-12-11 | Otsuka Pharmaceutical Factory, Inc. | Amide derivatives |
| JPH10101672A (ja) | 1996-08-06 | 1998-04-21 | Otsuka Pharmaceut Factory Inc | アデノシン増強剤 |
| JPH10101671A (ja) | 1996-08-08 | 1998-04-21 | Otsuka Pharmaceut Factory Inc | 一酸化窒素合成酵素阻害剤 |
| AUPO395396A0 (en) | 1996-12-02 | 1997-01-02 | Fujisawa Pharmaceutical Co., Ltd. | Benzamide derivatives |
| FR2757852B1 (fr) * | 1996-12-31 | 1999-02-19 | Cird Galderma | Composes stilbeniques a groupement adamantyl, compositions les contenant et utilisations |
| JPH10212271A (ja) | 1997-01-31 | 1998-08-11 | Zeria Pharmaceut Co Ltd | N−置換ベンゾイルアミン誘導体、それを含有する医薬及び該化合物の製造中間体 |
| EP0993831B1 (en) | 1997-02-07 | 2008-01-09 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| JPH10338658A (ja) | 1997-04-08 | 1998-12-22 | Hoechst Marion Roussel Kk | レチノイド作用調節剤 |
| JPH1129480A (ja) | 1997-05-12 | 1999-02-02 | Otsuka Pharmaceut Factory Inc | 縮環ピリミジン誘導体を含有する医薬組成物 |
| EP0995742A4 (en) | 1997-06-27 | 2004-08-25 | Fujisawa Pharmaceutical Co | SULPHONAMIDE COMPOUNDS AND THEIR MEDICAL USE |
| EP1000932B9 (en) | 1997-06-27 | 2005-12-28 | Fujisawa Pharmaceutical Co., Ltd. | Aromatic ring derivatives |
| US6613942B1 (en) * | 1997-07-01 | 2003-09-02 | Novo Nordisk A/S | Glucagon antagonists/inverse agonists |
| US6114483A (en) | 1997-08-27 | 2000-09-05 | E. I. Du Pont De Nemours And Company | Polymerization of olefins |
| JPH11171848A (ja) | 1997-09-26 | 1999-06-29 | Fujirebio Inc | 芳香族アミド誘導体 |
| US6297239B1 (en) | 1997-10-08 | 2001-10-02 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| DE69801590T2 (de) | 1997-10-22 | 2002-07-11 | Astrazeneca Ab, Soedertaelje | Imidazolderivate und ihre verwendung als farnesylproteintransferase inhibitoren |
| CA2309331A1 (en) | 1997-11-12 | 1999-05-20 | Institute Of Medicinal Molecular Design, Inc. | Agent acting on retinoid receptor |
| EP1042320B1 (en) | 1997-11-21 | 2002-02-13 | AstraZeneca UK Limited | New compounds which are p2-purinoceptor 7-transmembrane (tm) g-protein coupled receptor antagonists |
| GB9725298D0 (en) | 1997-11-28 | 1998-01-28 | Zeneca Ltd | Insecticidal thiazole derivatives |
| CN1143855C (zh) | 1997-12-19 | 2004-03-31 | 舍林公开股份有限公司 | 作为抗凝剂的邻氨基苯甲酰胺衍生物 |
| ES2317688T3 (es) * | 1998-01-29 | 2009-04-16 | Amgen Inc. | Moduladores ppar-gamma. |
| JP3937367B2 (ja) | 1998-02-05 | 2007-06-27 | 株式会社大塚製薬工場 | 一酸化窒素合成酵素阻害剤 |
| JPH11292879A (ja) | 1998-04-08 | 1999-10-26 | Otsuka Pharmaceut Factory Inc | カルボキサミド誘導体 |
| DE19816780A1 (de) | 1998-04-16 | 1999-10-21 | Bayer Ag | Substituierte 2-Oxo-alkansäure-[2-(indol-3-yl)-ethyl]amide |
| GB9811969D0 (en) * | 1998-06-03 | 1998-07-29 | Celltech Therapeutics Ltd | Chemical compounds |
| DE19830431A1 (de) | 1998-07-08 | 2000-01-13 | Hoechst Marion Roussel De Gmbh | Sulfonylamino-carbonsäure-N-arylamide als Guanylatcyclase-Aktivatoren |
| US6197798B1 (en) * | 1998-07-21 | 2001-03-06 | Novartis Ag | Amino-benzocycloalkane derivatives |
| JP4191825B2 (ja) | 1998-09-10 | 2008-12-03 | あすか製薬株式会社 | 5−アミノイソキサゾール誘導体 |
| GB9823871D0 (en) | 1998-10-30 | 1998-12-23 | Pharmacia & Upjohn Spa | 2-Amino-thiazole derivatives, process for their preparation, and their use as antitumour agents |
| CA2361149A1 (en) | 1998-12-23 | 2000-07-06 | Eli Lilly And Company | Aromatic amides |
| WO2000046203A2 (en) | 1999-02-04 | 2000-08-10 | Millennium Pharmaceuticals, Inc. | G-protein coupled heptahelical receptor binding compounds and methods of use thereof |
| RU2242469C2 (ru) * | 1999-03-29 | 2004-12-20 | Ф.Хоффманн-Ля Рош Аг | Активаторы глюкокиназы |
| US6610846B1 (en) * | 1999-03-29 | 2003-08-26 | Hoffman-La Roche Inc. | Heteroaromatic glucokinase activators |
| SI1169312T1 (en) | 1999-03-29 | 2005-02-28 | F. Hoffmann-La Roche Ag | Glucokinase activators |
| US6320050B1 (en) * | 1999-03-29 | 2001-11-20 | Hoffmann-La Roche Inc. | Heteroaromatic glucokinase activators |
| DK1192137T3 (da) | 1999-06-30 | 2013-11-11 | Amgen Inc | Forbindelser til modulering af PPAR-gamma aktivitet |
| CZ2002534A3 (cs) | 1999-08-13 | 2002-07-17 | Vertex Pharmaceuticals Incorporated | Inhibitory protein-kináz, farmaceutické prostředky, které je obsahují, a jejich pouľití |
| IL148243A0 (en) | 1999-08-27 | 2002-09-12 | Sugen Inc | Trifluoromethyl sulfonyl and trifluoromethyl sulfonamido compounds and pharmaceutical compositions containing the same |
| GB9921684D0 (en) | 1999-09-15 | 1999-11-17 | Zeneca Ltd | Assays |
| DE60040676D1 (de) | 1999-09-17 | 2008-12-11 | Millennium Pharm Inc | BENZAMIDE UND ÄHNLICHE INHIBITOREN VON FAKTOR Xa |
| AU7866300A (en) | 1999-10-08 | 2001-04-23 | Smithkline Beecham Corporation | Fab i inhibitors |
| CZ20021492A3 (cs) | 1999-11-04 | 2003-06-18 | Ortho-Mcneil Pharmaceutical, Inc. | Nepeptidové substituované benzothiazepiny jako antagonisté vazopresinu |
| AU1917201A (en) * | 1999-11-18 | 2001-05-30 | Centaur Pharmaceuticals, Inc. | Amide therapeutics and methods for treating inflammatory bowel disease |
| US6353111B1 (en) | 1999-12-15 | 2002-03-05 | Hoffmann-La Roche Inc. | Trans olefinic glucokinase activators |
| CA2401778C (en) | 2000-02-29 | 2010-12-21 | Cor Therapeutics, Inc. | Benzamides and related inhibitors of factor xa |
| EP1132381A1 (en) | 2000-03-08 | 2001-09-12 | Cermol S.A. | Ester derivatives of dimethylpropionic acid and pharmaceutical compositions containing them |
| AU776053B2 (en) | 2000-03-31 | 2004-08-26 | Astellas Pharma Inc. | Diazepan derivatives or salts thereof |
| US6534651B2 (en) * | 2000-04-06 | 2003-03-18 | Inotek Pharmaceuticals Corp. | 7-Substituted isoindolinone inhibitors of inflammation and reperfusion injury and methods of use thereof |
| ES2233660T3 (es) | 2000-05-03 | 2005-06-16 | F. Hoffmann-La Roche Ag | Activadores de glucokinasa alquinil fenil heteroaromaticos. |
| ATE304011T1 (de) | 2000-05-03 | 2005-09-15 | Hoffmann La Roche | Hydantoin-enthaltende glucokinase aktivatoren |
| PT1282611E (pt) | 2000-05-08 | 2005-02-28 | Hoffmann La Roche | Fenilacetamidas substituidas e sua utilizacao como activadores da glucocinase |
| DK1283830T3 (da) | 2000-05-08 | 2008-08-25 | Hoffmann La Roche | Para-amin-substituerede phenylamidglucokinase-aktivatorer |
| ES2265435T3 (es) | 2000-06-28 | 2007-02-16 | Amgen Inc. | Moduladores benzotiazolilo de ppar-gamma. |
| CA2416229C (en) | 2000-07-20 | 2007-09-18 | F. Hoffmann-La Roche Ag | Alpha-acyl and alpha-heteroatom-substituted benzene acetamide glucokinase activators |
| US6369232B1 (en) | 2000-08-15 | 2002-04-09 | Hoffmann-La Roche Inc. | Tetrazolyl-phenyl acetamide glucokinase activators |
| AU2001293826A1 (en) | 2000-09-25 | 2002-04-02 | Janssen Pharmaceutica N.V. | Farnesyl transferase inhibiting quinoline and quinazoline derivatives as farnesyl transferase inhibitors |
| WO2002026731A2 (en) | 2000-09-29 | 2002-04-04 | Millenium Pharmaceuticals, Inc. | Quaternary amidino based inhibitors of factor xa |
| AU2002214546A1 (en) | 2000-09-29 | 2002-04-08 | Cor Therapeutics, Inc. | Bicyclic pyrimidin-4-one based inhibitors of factor xa |
| MXPA03003002A (es) | 2000-10-05 | 2004-12-06 | Fujisawa Pharmaceutical Co | Compuestos de benzamina como inhibidores de la secrecion de la apo b. |
| MXPA03003572A (es) | 2000-11-22 | 2003-07-14 | Yamanouchi Pharma Co Ltd | Derivados de benceno sustituidos o sales de los mismos. |
| DK1341774T3 (da) | 2000-12-06 | 2006-06-12 | Hoffmann La Roche | Kondenserede heteroaromatiske glucokinase-aktivatorer |
| US6482951B2 (en) | 2000-12-13 | 2002-11-19 | Hoffmann-La Roche Inc. | Isoindolin-1-one glucokinase activators |
| GB0031301D0 (en) | 2000-12-21 | 2001-01-31 | Ici Plc | Process for the production of fluoromethyl hexafluoroisopropyl ether |
| WO2002051397A1 (en) * | 2000-12-22 | 2002-07-04 | Ishihara Sangyo Kaisha, Ltd. | Aniline derivatives or salts thereof and cytokine production inhibitors containing the same |
| EP1217000A1 (en) | 2000-12-23 | 2002-06-26 | Aventis Pharma Deutschland GmbH | Inhibitors of factor Xa and factor VIIa |
| US20040077697A1 (en) | 2001-02-02 | 2004-04-22 | Hiroyuki Koshio | 2-Acylaminothiazole derivative or its salt |
| TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
| EP1373194B1 (en) | 2001-03-30 | 2007-08-01 | Millennium Pharmaceuticals, Inc. | BENZAMIDE INHIBITORS OF FACTOR Xa |
| SE0102300D0 (sv) | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
| SE0102299D0 (sv) | 2001-06-26 | 2001-06-26 | Astrazeneca Ab | Compounds |
| PL368129A1 (en) * | 2001-08-09 | 2005-03-21 | Ono Pharmaceutical Co, Ltd. | Carboxylic acid derivative compounds and drugs comprising these compounds as the active ingredient |
| TWI325302B (en) | 2001-08-13 | 2010-06-01 | Du Pont | Benzoxazinone compounds |
| SE0102764D0 (sv) | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
| WO2003022856A1 (en) | 2001-09-12 | 2003-03-20 | Pharmacia & Upjohn Company | Substituted 7-aza[2.2.1] bicycloheptanes for the treatment of diseases |
| TWI283164B (en) | 2001-09-21 | 2007-07-01 | Du Pont | Anthranilamide arthropodicide treatment |
| SI1427415T1 (sl) | 2001-09-21 | 2009-12-31 | Bristol Myers Squibb Co | Sestavine, ki vsebujejo laktame in njihovi derivati kot inhibitorji faktorja xa |
| WO2003028641A2 (en) | 2001-10-01 | 2003-04-10 | Taisho Pharmaceutical Co., Ltd. | Mch receptor antagonists |
| AU2002349299A1 (en) | 2001-12-03 | 2003-06-17 | Novo Nordisk A/S | Use of a glucokinase activator in combination with a glucagon antagonist for treating type 2 diabetes |
| EP1336607A1 (en) | 2002-02-19 | 2003-08-20 | Novo Nordisk A/S | Amide derivatives as glucokinase activators |
| AR037641A1 (es) | 2001-12-05 | 2004-11-17 | Tularik Inc | Moduladores de inflamacion |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| DE10161765A1 (de) * | 2001-12-15 | 2003-07-03 | Bayer Cropscience Gmbh | Substituierte Phenylderivate |
| US6911545B2 (en) | 2001-12-19 | 2005-06-28 | Hoffman-La Roche Inc. | Crystals of glucokinase and methods of growing them |
| EP1458382A1 (en) | 2001-12-21 | 2004-09-22 | Novo Nordisk A/S | Amide derivatives as gk activators |
| GB0202873D0 (en) | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
| DE60328671D1 (de) | 2002-03-26 | 2009-09-17 | Banyu Pharma Co Ltd | Neue aminobenzamidderivate |
| CN100357283C (zh) | 2002-04-02 | 2007-12-26 | 中国科学院上海药物研究所 | 一类甲硫氨酰氨肽酶抑制剂 |
| EA011297B1 (ru) | 2002-04-26 | 2009-02-27 | Ф. Хоффманн-Ля Рош Аг | Замещённые фенилацетамиды и их применение в качестве активаторов глюкокиназы |
| WO2003097824A1 (en) | 2002-05-16 | 2003-11-27 | Banyu Pharmaceutical Co., Ltd. | Crystal of glucokinase protein, and method for drug design using the crystal |
| CA2488642C (en) | 2002-06-27 | 2011-09-06 | Dharma Rao Polisetti | Aryl carbonyl derivatives as glucokinase activators |
| WO2004007472A1 (ja) | 2002-07-10 | 2004-01-22 | Ono Pharmaceutical Co., Ltd. | Ccr4アンタゴニストおよびその医薬用途 |
| WO2004022536A1 (en) | 2002-09-04 | 2004-03-18 | Glenmark Pharmaceuticals Limited | New heterocyclic amide compounds useful for the treatment of inflammatory and allergic disorders: process for their preparation and pharmaceutical compositions containing them |
| HK1079788A1 (zh) | 2002-10-03 | 2006-04-13 | Novartis Ag | 适用於治疗2型糖尿病的作为葡萄糖激酶活化剂的取代的(噻唑-2-基)-酰胺或磺胺 |
| EP1549638B1 (en) | 2002-10-03 | 2007-10-03 | F. Hoffmann-La Roche Ag | Indole-3-carboxamides as glucokinase (gk) activators |
| GB0226931D0 (en) | 2002-11-19 | 2002-12-24 | Astrazeneca Ab | Chemical compounds |
| GB0226930D0 (en) | 2002-11-19 | 2002-12-24 | Astrazeneca Ab | Chemical compounds |
| MY141521A (en) | 2002-12-12 | 2010-05-14 | Hoffmann La Roche | 5-substituted-six-membered heteroaromatic glucokinase activators |
| AU2003294376A1 (en) | 2003-01-06 | 2004-08-10 | Eli Lilly And Company | Heteroaryl compounds |
| WO2004063179A1 (en) | 2003-01-06 | 2004-07-29 | Eli Lilly And Company | Substituted arylcyclopropylacetamides as glucokinase activators |
| EP1594863A1 (en) | 2003-02-11 | 2005-11-16 | Prosidion Limited | Tri(cyclo) substituted amide glucokinase activator compounds |
| PL378117A1 (pl) | 2003-02-11 | 2006-03-06 | Prosidion Limited | Tricyklopodstawione związki amidowe |
| CA2515841C (en) | 2003-02-13 | 2010-06-01 | Banyu Pharmaceutical Co., Ltd. | Novel 2-pyridine carboxamide derivatives |
| MXPA05009059A (es) * | 2003-02-26 | 2005-10-19 | Banyu Pharma Co Ltd | Derivados de heteroarilcarbamoilbenceno. |
| EP2385040A1 (en) | 2003-03-14 | 2011-11-09 | ONO Pharmaceutical Co., Ltd. | Nitrogen-containing heterocyclic derivatives and drugs containing the same as the active ingredient |
| AR043633A1 (es) | 2003-03-20 | 2005-08-03 | Schering Corp | Ligandos de receptores de canabinoides |
| CA2518823A1 (en) | 2003-03-24 | 2004-10-07 | F.Hoffmann-La Roche Ag | Benzyl-pyridazinons as reverse transcriptase inhibitors |
| WO2004110350A2 (en) | 2003-05-14 | 2004-12-23 | Torreypines Therapeutics, Inc. | Compouds and uses thereof in modulating amyloid beta |
| EP1635832A2 (en) | 2003-06-06 | 2006-03-22 | Merck & Co., Inc. | Combination therapy for the treatment of diabetes |
| EP1673355A1 (en) | 2003-09-22 | 2006-06-28 | Pfizer Limited | Substituted triazole derivatives as oxytocin antagonists |
| EP1675844A1 (en) | 2003-10-23 | 2006-07-05 | Sterix Limited | Phenyl carboxamide and sulfonamide derivatives for use as 11-beta-hydroxysteroid dehydrogenase |
| GB0325402D0 (en) * | 2003-10-31 | 2003-12-03 | Astrazeneca Ab | Compounds |
| US20050165031A1 (en) * | 2003-11-13 | 2005-07-28 | Ambit Biosciences Corporation | Urea derivatives as ABL modulators |
| EP1532980A1 (en) | 2003-11-24 | 2005-05-25 | Novo Nordisk A/S | N-heteroaryl indole carboxamides and analogues thereof, for use as glucokinase activators in the treatment of diabetes |
| GB0327761D0 (en) | 2003-11-29 | 2003-12-31 | Astrazeneca Ab | Compounds |
| GB0327760D0 (en) | 2003-11-29 | 2003-12-31 | Astrazeneca Ab | Compounds |
| GB0328178D0 (en) | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Compounds |
| KR20060105872A (ko) | 2003-12-29 | 2006-10-11 | 반유 세이야꾸 가부시끼가이샤 | 신규한 2-헤테로아릴 치환된 벤즈이미다졸 유도체 |
| PL1723128T3 (pl) | 2004-01-06 | 2013-04-30 | Novo Nordisk As | Pochodne heteroarylowe mocznika oraz ich zastosowanie jako aktywatory glukokinazy |
| JP2007523142A (ja) * | 2004-02-18 | 2007-08-16 | アストラゼネカ アクチボラグ | ベンズアミド誘導体、およびグルコキナーゼ活性化物質としてのそれらの使用 |
| AU2005214137B2 (en) | 2004-02-18 | 2008-05-29 | Astrazeneca Ab | Compounds |
| CN1934100A (zh) | 2004-03-23 | 2007-03-21 | 万有制药株式会社 | 取代喹唑啉或吡啶并嘧啶衍生物 |
| EP1735322B1 (en) | 2004-04-02 | 2011-09-14 | Novartis AG | Sulfonamide-thiazolpyridine derivatives as glucokinase activators useful for the treatment of type 2 diabetes |
| WO2005095417A1 (en) | 2004-04-02 | 2005-10-13 | Novartis Ag | Thiazolopyridine derivates, pharmaceutical conditions containing them and methods of treating glucokinase mediated conditions |
| BRPI0510163A (pt) | 2004-04-21 | 2007-10-02 | Prosidion Ltd | compostos de amidas tri(ciclo)-substituìdas |
| TW200600086A (en) | 2004-06-05 | 2006-01-01 | Astrazeneca Ab | Chemical compound |
| JP2008502658A (ja) | 2004-06-17 | 2008-01-31 | ノボ ノルディスク アクティーゼルスカブ | 肝臓選択的グルコキナーゼ活性化因子の使用 |
| GB0418058D0 (en) | 2004-08-12 | 2004-09-15 | Prosidion Ltd | Fluorination process |
| KR100890695B1 (ko) | 2004-08-12 | 2009-03-26 | 프로시디온 리미티드 | 치환된 페닐아세트아미드 및 글루코키나제 활성화제로서의그의 용도 |
| GB0418046D0 (en) | 2004-08-12 | 2004-09-15 | Prosidion Ltd | Eantioselective process |
| WO2006030925A1 (ja) | 2004-09-13 | 2006-03-23 | Ono Pharmaceutical Co., Ltd. | 含窒素複素環誘導体およびそれらを有効成分とする薬剤 |
| GB0423043D0 (en) | 2004-10-16 | 2004-11-17 | Astrazeneca Ab | Compounds |
| KR20070085371A (ko) | 2004-10-16 | 2007-08-27 | 아스트라제네카 아베 | 페녹시 벤즈아미드 화합물의 제조 방법 |
| GB0423044D0 (en) | 2004-10-16 | 2004-11-17 | Astrazeneca Ab | Compounds |
| DE602004018552D1 (de) | 2004-12-24 | 2009-01-29 | Telecom Italia Spa | Verfahren zur optimierung des webseitenzugangs in drahtlosen netzwerken |
| CA2605738C (en) | 2005-04-25 | 2013-10-01 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Novel azaheterocyclic compounds as kinase inhibitors |
| EP1891069A1 (en) | 2005-05-24 | 2008-02-27 | AstraZeneca AB | 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 |
| KR101346902B1 (ko) | 2005-07-09 | 2014-01-02 | 아스트라제네카 아베 | 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한헤테로아릴 벤즈아미드 유도체 |
| 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 |
| US20080234273A1 (en) | 2005-07-09 | 2008-09-25 | Mckerrecher Darren | Heteroaryl Benzamide Derivatives for Use as Glk Activators in the Treatment of Diabetes |
| WO2007017649A1 (en) | 2005-08-09 | 2007-02-15 | Astrazeneca Ab | Heteroarylcarbamoylbenzene derivatives for the treatment of diabetes |
| JP2007063225A (ja) | 2005-09-01 | 2007-03-15 | Takeda Chem Ind Ltd | イミダゾピリジン化合物 |
| RU2008108221A (ru) | 2005-09-07 | 2009-10-20 | Плекссикон, Инк. (Us) | Соединения, активные в отношении ppar (рецепторов активаторов пролиферации пероксисом) |
| US20090105263A1 (en) | 2005-09-16 | 2009-04-23 | Peter William Rodney Caulkett | Heterobicyclic compounds as glucokinase activators |
| CA2627813A1 (en) | 2005-11-01 | 2007-05-10 | Janssen Pharmaceutica N.V. | Substituted pyrrolones as allosteric modulators of glucokinase |
| TW200738621A (en) | 2005-11-28 | 2007-10-16 | Astrazeneca Ab | Chemical process |
| US8003642B2 (en) | 2006-03-10 | 2011-08-23 | Ono Pharmaceutical Co., Ltd. | Nitrogenated heterocyclic derivative, and pharmaceutical agent comprising the derivative as active ingredient |
| 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. |
| US20100094009A1 (en) | 2006-12-21 | 2010-04-15 | Mccabe James | Novel crystalline compound useful as glk activator |
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