BG107903A - Изоиндолин-1-он активатори на глюкокиназата - Google Patents

Изоиндолин-1-он активатори на глюкокиназата Download PDF

Info

Publication number: BG107903A
Authority: BG; Bulgaria
Prior art keywords: oxo; cyclohexyl; dihydro; isoindol; propionamide
Prior art date: 2000-12-13

Application number

BG107903A

Other languages

Bulgarian (bg)

English (en)

Inventor

Richard K. Guertin

Original Assignee

F. Hoffmann- La Roche Ag

Priority date (The priority date 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 date listed.)

2000-12-13

Filing date

2003-06-13

Publication date

2004-02-27

2003-06-13 Application filed by F. Hoffmann- La Roche Ag filed Critical F. Hoffmann- La Roche Ag

2004-02-27 Publication of BG107903A publication Critical patent/BG107903A/bg

Links

108010021582 Glucokinase Proteins 0.000 title abstract description 14
102000030595 Glucokinase Human genes 0.000 title abstract description 13
239000012190 activator Substances 0.000 title abstract description 12
PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 title abstract description 4
QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical class CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims abstract description 16
208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 11
-1 benzoimidazolyl Chemical group 0.000 claims description 151
229940080818 propionamide Drugs 0.000 claims description 88
150000001875 compounds Chemical class 0.000 claims description 85
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
125000001072 heteroaryl group Chemical group 0.000 claims description 36
229910052799 carbon Inorganic materials 0.000 claims description 35
238000002360 preparation method Methods 0.000 claims description 34
150000001721 carbon Chemical group 0.000 claims description 29
125000000217 alkyl group Chemical group 0.000 claims description 28
229910052757 nitrogen Chemical group 0.000 claims description 27
229910052736 halogen Inorganic materials 0.000 claims description 26
150000002367 halogens Chemical group 0.000 claims description 26
238000000034 method Methods 0.000 claims description 23
125000005842 heteroatom Chemical group 0.000 claims description 19
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 17
238000006243 chemical reaction Methods 0.000 claims description 16
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 15
125000004414 alkyl thio group Chemical group 0.000 claims description 14
150000001408 amides Chemical class 0.000 claims description 12
125000002950 monocyclic group Chemical group 0.000 claims description 12
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
125000004432 carbon atom Chemical group C* 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
239000001301 oxygen Chemical group 0.000 claims description 11
125000001424 substituent group Chemical group 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 11
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
125000001309 chloro group Chemical group Cl* 0.000 claims description 9
125000004076 pyridyl group Chemical group 0.000 claims description 9
239000011593 sulfur Substances 0.000 claims description 9
125000000335 thiazolyl group Chemical group 0.000 claims description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
125000003277 amino group Chemical group 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
150000001204 N-oxides Chemical class 0.000 claims description 7
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 7
239000003814 drug Substances 0.000 claims description 7
125000003373 pyrazinyl group Chemical group 0.000 claims description 7
125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
241001465754 Metazoa Species 0.000 claims description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
JFZLHUCEJYRSNM-HNNXBMFYSA-N (2s)-n-(5-chloro-1,3-thiazol-2-yl)-3-cyclohexyl-2-(4-fluoro-3-oxo-1h-isoindol-2-yl)propanamide Chemical compound C([C@H](N1CC=2C=CC=C(C=2C1=O)F)C(=O)NC=1SC(Cl)=CN=1)C1CCCCC1 JFZLHUCEJYRSNM-HNNXBMFYSA-N 0.000 claims description 5
239000002671 adjuvant Substances 0.000 claims description 5
239000001257 hydrogen Substances 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
230000002265 prevention Effects 0.000 claims description 5
239000013543 active substance Substances 0.000 claims description 4
125000001246 bromo group Chemical group Br* 0.000 claims description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
MOTYSUWGCCIXCJ-INIZCTEOSA-N (2s)-3-cyclohexyl-2-(4-fluoro-3-oxo-1h-isoindol-2-yl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C([C@H](N1CC=2C=CC=C(C=2C1=O)F)C(=O)NC=1SC=CN=1)C1CCCCC1 MOTYSUWGCCIXCJ-INIZCTEOSA-N 0.000 claims description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
125000005872 benzooxazolyl group Chemical group 0.000 claims description 3
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
NSCIJCDEXRVCMK-UHFFFAOYSA-N n-(5-chloro-1,3-thiazol-2-yl)-3-cycloheptyl-2-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound S1C(Cl)=CN=C1NC(=O)C(N1C(C2=CC=CC=C2C1)=O)CC1CCCCCC1 NSCIJCDEXRVCMK-UHFFFAOYSA-N 0.000 claims description 3
VPMSFNVPKXVXRA-UHFFFAOYSA-N n-(5-chloro-1,3-thiazol-2-yl)-3-cyclopentyl-2-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound S1C(Cl)=CN=C1NC(=O)C(N1C(C2=CC=CC=C2C1)=O)CC1CCCC1 VPMSFNVPKXVXRA-UHFFFAOYSA-N 0.000 claims description 3
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
KDUXDFOIUUGGRR-KRWDZBQOSA-N (2s)-3-cyclohexyl-2-(5-nitro-3-oxo-1h-isoindol-2-yl)-n-(1,3-thiazol-2-yl)propanamide Chemical compound C([C@H](N1CC2=CC=C(C=C2C1=O)[N+](=O)[O-])C(=O)NC=1SC=CN=1)C1CCCCC1 KDUXDFOIUUGGRR-KRWDZBQOSA-N 0.000 claims description 2
CLICAWXVUGZAHG-INIZCTEOSA-N (2s)-n-(5-chloro-1,3-thiazol-2-yl)-3-cyclohexyl-2-(6-nitro-3-oxo-1h-isoindol-2-yl)propanamide Chemical compound C([C@H](N1C(=O)C2=CC=C(C=C2C1)[N+](=O)[O-])C(=O)NC=1SC(Cl)=CN=1)C1CCCCC1 CLICAWXVUGZAHG-INIZCTEOSA-N 0.000 claims description 2
XDZPUUOXMDFXIF-IBGZPJMESA-N (2s)-n-(5-chloropyridin-2-yl)-3-cyclohexyl-2-(3-oxo-1h-isoindol-2-yl)propanamide Chemical compound N1=CC(Cl)=CC=C1NC(=O)[C@@H](N1C(C2=CC=CC=C2C1)=O)CC1CCCCC1 XDZPUUOXMDFXIF-IBGZPJMESA-N 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
230000008569 process Effects 0.000 claims description 2
201000006747 infectious mononucleosis Diseases 0.000 claims 8
GAHFFZDPDRNMNC-UHFFFAOYSA-N 4-fluoro-2,3-dihydroisoindol-1-one Chemical compound FC1=CC=CC2=C1CNC2=O GAHFFZDPDRNMNC-UHFFFAOYSA-N 0.000 claims 2
CAFYGEUIKNMVSG-SFHVURJKSA-N (2s)-3-cyclohexyl-2-(7-fluoro-3-oxo-1h-isoindol-2-yl)-n-pyrazin-2-ylpropanamide Chemical compound C([C@H](N1C(=O)C=2C=CC=C(C=2C1)F)C(=O)NC=1N=CC=NC=1)C1CCCCC1 CAFYGEUIKNMVSG-SFHVURJKSA-N 0.000 claims 1
LPQOADBMXVRBNX-UHFFFAOYSA-N ac1ldcw0 Chemical compound Cl.C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3CCSC1=C32 LPQOADBMXVRBNX-UHFFFAOYSA-N 0.000 claims 1
125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims 1
SGQYBUJEJYXKCH-UHFFFAOYSA-N n-(1,3-thiazol-2-yl)propanamide Chemical compound CCC(=O)NC1=NC=CS1 SGQYBUJEJYXKCH-UHFFFAOYSA-N 0.000 claims 1
230000003914 insulin secretion Effects 0.000 abstract description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 132
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 87
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 84
239000000203 mixture Substances 0.000 description 75
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
239000000243 solution Substances 0.000 description 49
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
230000008878 coupling Effects 0.000 description 35
238000010168 coupling process Methods 0.000 description 35
238000005859 coupling reaction Methods 0.000 description 35
239000003480 eluent Substances 0.000 description 34
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
238000003818 flash chromatography Methods 0.000 description 24
239000002253 acid Substances 0.000 description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
239000007787 solid Substances 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
239000006260 foam Substances 0.000 description 17
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
229910052938 sodium sulfate Inorganic materials 0.000 description 16
235000011152 sodium sulphate Nutrition 0.000 description 16
GEKUFTBQNVFPHS-HNNXBMFYSA-N (2s)-3-cyclohexyl-2-(3-oxo-1h-isoindol-2-yl)propanoic acid Chemical compound C([C@@H](C(=O)O)N1C(C2=CC=CC=C2C1)=O)C1CCCCC1 GEKUFTBQNVFPHS-HNNXBMFYSA-N 0.000 description 15
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 description 15
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 14
239000000284 extract Substances 0.000 description 14
239000008103 glucose Substances 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
239000011734 sodium Substances 0.000 description 12
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
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239000012267 brine Substances 0.000 description 10
150000002148 esters Chemical class 0.000 description 10
XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 10
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ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 6
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
239000002585 base Substances 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
BJDCWCLMFKKGEE-CMDXXVQNSA-N chembl252518 Chemical compound C([C@@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-CMDXXVQNSA-N 0.000 description 6
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125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
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229910052786 argon Inorganic materials 0.000 description 5
230000004071 biological effect Effects 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
238000007796 conventional method Methods 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
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238000010992 reflux Methods 0.000 description 5
238000004007 reversed phase HPLC Methods 0.000 description 5
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OWKBKSGHGBDMNC-HNNXBMFYSA-N (2s)-3-cyclohexyl-2-(6-nitro-3-oxo-1h-isoindol-2-yl)propanoic acid Chemical compound C([C@@H](C(=O)O)N1C(C2=CC=C(C=C2C1)[N+]([O-])=O)=O)C1CCCCC1 OWKBKSGHGBDMNC-HNNXBMFYSA-N 0.000 description 4
RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
241000271317 Gonystylus bancanus Species 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
230000004153 glucose metabolism Effects 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
238000011534 incubation Methods 0.000 description 4
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229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
229940002612 prodrug Drugs 0.000 description 4
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XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
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XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
125000004149 thio group Chemical group *S* 0.000 description 1
239000003104 tissue culture media Substances 0.000 description 1
230000000699 topical effect Effects 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
125000004954 trialkylamino group Chemical group 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
239000003981 vehicle Substances 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
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
- 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
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Diabetes (AREA)
Public Health (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (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)
Bioinformatics & Cheminformatics (AREA)
Endocrinology (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Breeding Of Plants And Reproduction By Means Of Culturing (AREA)

BG107903A 2000-12-13 2003-06-13 Изоиндолин-1-он активатори на глюкокиназата BG107903A (bg)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US25527300P	2000-12-13	2000-12-13
US31871501P	2001-09-13	2001-09-13
PCT/EP2001/014404 WO2002048106A2 (en)	2000-12-13	2001-12-07	Isoindolin-1-one glucokinase activators

Publications (1)

Publication Number	Publication Date
BG107903A true BG107903A (bg)	2004-02-27

Family

ID=26944583

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG107903A BG107903A (bg)	2000-12-13	2003-06-13	Изоиндолин-1-он активатори на глюкокиназата

Country Status (35)

Country	Link
US (1)	US6482951B2 (hu)
EP (1)	EP1349856B1 (hu)
JP (1)	JP4021766B2 (hu)
KR (1)	KR100520651B1 (hu)
CN (1)	CN1247574C (hu)
AT (1)	ATE297922T1 (hu)
AU (2)	AU2002238415B2 (hu)
BG (1)	BG107903A (hu)
BR (1)	BR0116169A (hu)
CA (1)	CA2430579C (hu)
CY (1)	CY1105587T1 (hu)
CZ (1)	CZ20031882A3 (hu)
DE (1)	DE60111570T2 (hu)
DK (1)	DK1349856T3 (hu)
EG (1)	EG24358A (hu)
ES (1)	ES2243578T3 (hu)
HR (1)	HRP20030450B1 (hu)
HU (1)	HUP0400587A3 (hu)
IL (2)	IL156264A0 (hu)
MA (1)	MA26973A1 (hu)
MX (1)	MXPA03005170A (hu)
MY (1)	MY136741A (hu)
NO (1)	NO325810B1 (hu)
NZ (1)	NZ526236A (hu)
PA (1)	PA8534601A1 (hu)
PE (1)	PE20020593A1 (hu)
PL (1)	PL366006A1 (hu)
PT (1)	PT1349856E (hu)
RS (1)	RS50933B (hu)
RU (1)	RU2249590C2 (hu)
SI (1)	SI1349856T1 (hu)
SK (1)	SK8732003A3 (hu)
TW (1)	TWI294876B (hu)
UY (1)	UY27069A1 (hu)
WO (1)	WO2002048106A2 (hu)

Families Citing this family (49)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE0102299D0 (sv)	2001-06-26	2001-06-26	Astrazeneca Ab	Compounds
SE0102764D0 (sv)	2001-08-17	2001-08-17	Astrazeneca Ab	Compounds
NZ539013A (en)	2002-10-03	2007-05-31	Novartis Ag	Substituted (thiazol-2-yl) -amide or sulfonamide as glycokinase activators useful in the treatment of type 2 diabetes
DE60316709T2 (de)	2002-10-03	2008-07-17	F. Hoffmann-La Roche Ag	Indole-3-carbonsaüreamide als glucokinase (gk) aktivatoren
GB0226931D0 (en)	2002-11-19	2002-12-24	Astrazeneca Ab	Chemical compounds
WO2004063194A1 (en) *	2003-01-06	2004-07-29	Eli Lilly And Company	Heteroaryl compounds
PL378117A1 (pl) *	2003-02-11	2006-03-06	Prosidion Limited	Tricyklopodstawione związki amidowe
WO2004072066A1 (en) *	2003-02-11	2004-08-26	Prosidion Limited	Tri(cyclo) substituted amide glucokinase activator compounds
US7320992B2 (en) *	2003-08-25	2008-01-22	Amgen Inc.	Substituted 2,3-dihydro-1h-isoindol-1-one derivatives and methods of use
RU2412192C2 (ru)	2004-04-02	2011-02-20	Новартис Аг	Сульфонамидтиазолпиридиновые производные как активаторы глюкокиназы, пригодные для лечения диабета типа 2
CA2561157A1 (en) *	2004-04-02	2005-10-13	Novartis Ag	Thiazolopyridine derivatives, pharmaceutical conditions containing them and methods of treating glucokinase mediated conditions
JP4651714B2 (ja)	2005-07-09	2011-03-16	アストラゼネカアクチボラグ	糖尿病の治療においてｇｌｋ活性化剤として使用するためのヘテロアリールベンズアミド誘導体
AU2006285834A1 (en) *	2005-08-31	2007-03-08	Astellas Pharma Inc.	Thiazole derivative
JP2007063225A (ja) *	2005-09-01	2007-03-15	Takeda Chem Ind Ltd	イミダゾピリジン化合物
WO2007039177A2 (en)	2005-09-29	2007-04-12	Sanofi-Aventis	Phenyl- and pyridinyl- 1, 2 , 4 - oxadiazolone derivatives, processes for their preparation and their use as pharmaceuticals
GT200600429A (es) *	2005-09-30	2007-04-30		Compuestos organicos
GT200600428A (es) *	2005-09-30	2007-05-21		Compuestos organicos
JP2009513711A (ja) *	2005-11-01	2009-04-02	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	グルコキナーゼのアロステリックモジュレーターとしての置換ピロロン
EP1951706A1 (en)	2005-11-01	2008-08-06	Janssen Pharmaceutica N.V.	Dihydroisoindolones as allosteric modulators of glucokinase
CA2627910A1 (en) *	2005-11-01	2007-05-10	Janssen Pharmaceutica N.V.	Substituted cycloalkylpyrrolones as allosteric modulators of glucokinase
US8796313B2 (en)	2005-11-01	2014-08-05	Janssen Pharmaceutica N.V.	Substituted dihydroisoindolones as allosteric modulators of glucokinase
CA2626475A1 (en) *	2005-11-03	2007-05-10	Prosidion Limited	Tricyclo substituted amides
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
US8034822B2 (en)	2006-03-08	2011-10-11	Takeda San Diego, Inc.	Glucokinase activators
PE20080251A1 (es)	2006-05-04	2008-04-25	Boehringer Ingelheim Int	Usos de inhibidores de dpp iv
EP2049518B1 (en) *	2006-05-31	2011-08-31	Takeda San Diego, Inc.	Indazole and isoindole derivatives as glucokinase activating agents.
WO2008079787A2 (en)	2006-12-20	2008-07-03	Takeda San Diego, Inc.	Glucokinase activators
WO2008074694A1 (en) *	2006-12-20	2008-06-26	F. Hoffmann-La Roche Ag	Crystallization of glucokinase activators
TW200831081A (en) *	2006-12-25	2008-08-01	Kyorin Seiyaku Kk	Glucokinase activator
EP2116533B1 (en) *	2007-03-07	2013-07-10	Kyorin Pharmaceutical Co., Ltd.	Glucokinase activator
WO2008116107A2 (en) *	2007-03-21	2008-09-25	Takeda San Diego, Inc.	Piperazine derivatives as glucokinase activators
AR070107A1 (es) *	2008-01-15	2010-03-17	Lilly Co Eli	R-2-(4-ciclopropansulfonil-fenil)-n-pirazin-2-il-3-(tetrahidropiran-4-il)-propionamida en forma cristalina, composicion farmaceutica que la comprende y su uso para la manufactura de un medicamento util para la prevencion o tratamiento de hiperglicemia
WO2009092432A1 (en) *	2008-01-24	2009-07-30	Merck Patent Gmbh	Beta-amino acid derivatives for treatment of diabetes
NZ588462A (en)	2008-04-28	2012-07-27	Kyorin Seiyaku Kk	Cyclopentylacrylic acid amide derivative
PE20141375A1 (es) *	2008-05-16	2014-10-23	Takeda San Diego Inc	Activadores de glucoquinasa
CA2735184C (en) *	2008-09-11	2013-05-28	Pfizer Inc.	Heteroaryls amide derivatives and their use as glucokinase activators
CN105176930B (zh)	2010-03-31	2021-05-04	斯克里普斯研究所	重编程细胞
US8178689B2 (en) *	2010-06-17	2012-05-15	Hoffman-La Roche Inc.	Tricyclic compounds
US20130156720A1 (en)	2010-08-27	2013-06-20	Ironwood Pharmaceuticals, Inc.	Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
CN103764672A (zh)	2011-03-01	2014-04-30	辛纳吉制药公司	制备鸟苷酸环化酶c激动剂的方法
US8470866B2 (en) *	2011-05-03	2013-06-25	Hoffmann-La Roche Inc.	Isoindolinone derivatives
EP3004076B1 (en) *	2013-05-27	2019-10-23	F.Hoffmann-La Roche Ag	New 3,4-dihydro-2h-isoquinoline-1-one and 2,3-dihydro-isoindol-1-one compounds
RS65632B1 (sr)	2013-06-05	2024-07-31	Bausch Health Ireland Ltd	Ultra-prečišćeni agonisti guanilat-ciklaze c, postupak njihove pripreme i upotrebe
CN113121450A (zh)	2014-08-29	2021-07-16	Tes制药有限责任公司	α-氨基-β-羧基粘康酸半醛脱羧酶抑制剂
US20180134667A1 (en)	2016-10-14	2018-05-17	TES Pharma S.r.I.	Inhibitors of alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase
IL283182B2 (en)	2018-11-20	2025-10-01	Tes Pharma S R L	Alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase inhibitors
CN116283717B (zh) *	2023-01-06	2025-04-08	暨南大学	一种藁本内酯衍生物及其制备方法和应用
WO2024229228A2 (en) *	2023-05-02	2024-11-07	The Rockefeller University	1-oxoisoindolin-2-yl amide activators of vcp and derivatives thereof

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2687147A1 (fr) *	1992-02-11	1993-08-13	Union Pharma Scient Appl	Nouveaux derives d'alpha-amino n-pyridyl benzene propanamide, leurs procedes de preparation, compositions pharmaceutiques les contenant.
CA2224062C (en) *	1995-06-06	2001-09-04	Pfizer Limited	Substituted n-(indole-2-carbonyl)-glycinamides and derivatives as glycogen phosphorylase inhibitors
TR200102805T2 (tr)	1999-03-29	2002-04-22	F.Hoffmann-La Roche Ag	Glikokinaz aktivatörleri
AU2001252270B2 (en)	2000-05-03	2005-12-15	F. Hoffmann-La Roche Ag	Hydantoin-containing glucokinase activators
BR0110704A (pt)	2000-05-08	2003-01-28	Hoffmann La Roche	Fenil - acetamidas substituìdas e seu uso como ativadores de glicocinase

2001
- 2001-12-06 US US10/010,978 patent/US6482951B2/en not_active Expired - Fee Related
- 2001-12-07 RS YUP-477/03A patent/RS50933B/sr unknown
- 2001-12-07 DK DK01986857T patent/DK1349856T3/da active
- 2001-12-07 SI SI200130381T patent/SI1349856T1/xx unknown
- 2001-12-07 NZ NZ526236A patent/NZ526236A/xx unknown
- 2001-12-07 BR BR0116169-5A patent/BR0116169A/pt not_active Application Discontinuation
- 2001-12-07 RU RU2003120512/04A patent/RU2249590C2/ru not_active IP Right Cessation
- 2001-12-07 AU AU2002238415A patent/AU2002238415B2/en not_active Ceased
- 2001-12-07 AT AT01986857T patent/ATE297922T1/de active
- 2001-12-07 HR HR20030450A patent/HRP20030450B1/xx not_active IP Right Cessation
- 2001-12-07 JP JP2002549637A patent/JP4021766B2/ja not_active Expired - Fee Related
- 2001-12-07 CZ CZ20031882A patent/CZ20031882A3/cs unknown
- 2001-12-07 IL IL15626401A patent/IL156264A0/xx unknown
- 2001-12-07 ES ES01986857T patent/ES2243578T3/es not_active Expired - Lifetime
- 2001-12-07 PT PT01986857T patent/PT1349856E/pt unknown
- 2001-12-07 PL PL01366006A patent/PL366006A1/xx unknown
- 2001-12-07 HU HU0400587A patent/HUP0400587A3/hu unknown
- 2001-12-07 EP EP01986857A patent/EP1349856B1/en not_active Expired - Lifetime
- 2001-12-07 WO PCT/EP2001/014404 patent/WO2002048106A2/en not_active Ceased
- 2001-12-07 AU AU3841502A patent/AU3841502A/xx active Pending
- 2001-12-07 KR KR10-2003-7007869A patent/KR100520651B1/ko not_active Expired - Fee Related
- 2001-12-07 CA CA2430579A patent/CA2430579C/en not_active Expired - Fee Related
- 2001-12-07 DE DE60111570T patent/DE60111570T2/de not_active Expired - Lifetime
- 2001-12-07 MX MXPA03005170A patent/MXPA03005170A/es active IP Right Grant
- 2001-12-07 CN CNB018206107A patent/CN1247574C/zh not_active Expired - Fee Related
- 2001-12-07 SK SK873-2003A patent/SK8732003A3/sk unknown
- 2001-12-10 TW TW090130510A patent/TWI294876B/zh not_active IP Right Cessation
- 2001-12-10 EG EG20011316A patent/EG24358A/xx active
- 2001-12-10 PA PA20018534601A patent/PA8534601A1/es unknown
- 2001-12-11 PE PE2001001234A patent/PE20020593A1/es not_active Application Discontinuation
- 2001-12-11 MY MYPI20015613A patent/MY136741A/en unknown
- 2001-12-12 UY UY27069A patent/UY27069A1/es not_active Application Discontinuation
2003
- 2003-06-02 IL IL156264A patent/IL156264A/en not_active IP Right Cessation
- 2003-06-12 MA MA27197A patent/MA26973A1/fr unknown
- 2003-06-12 NO NO20032674A patent/NO325810B1/no not_active IP Right Cessation
- 2003-06-13 BG BG107903A patent/BG107903A/bg unknown
2005
- 2005-09-15 CY CY20051101133T patent/CY1105587T1/el unknown

Also Published As

Publication number	Publication date
DE60111570T2 (de)	2006-05-11
KR20030064817A (ko)	2003-08-02
HUP0400587A3 (en)	2011-03-28
PE20020593A1 (es)	2002-07-06
CA2430579A1 (en)	2002-06-20
NO20032674L (no)	2003-06-12
ES2243578T3 (es)	2005-12-01
CN1481382A (zh)	2004-03-10
EG24358A (en)	2009-03-04
PA8534601A1 (es)	2002-08-26
MY136741A (en)	2008-11-28
PL366006A1 (en)	2005-01-24
PT1349856E (pt)	2005-09-30
RU2249590C2 (ru)	2005-04-10
EP1349856B1 (en)	2005-06-15
UY27069A1 (es)	2002-07-31
YU47703A (sh)	2006-05-25
HRP20030450B1 (en)	2006-02-28
AU2002238415B2 (en)	2007-01-04
TWI294876B (en)	2008-03-21
CN1247574C (zh)	2006-03-29
DK1349856T3 (da)	2005-10-17
JP4021766B2 (ja)	2007-12-12
SK8732003A3 (en)	2004-04-06
NZ526236A (en)	2004-12-24
HRP20030450A2 (en)	2005-04-30
US20020082260A1 (en)	2002-06-27
IL156264A0 (en)	2004-01-04
CY1105587T1 (el)	2010-07-28
RS50933B (sr)	2010-08-31
AU3841502A (en)	2002-06-24
HK1063314A1 (en)	2004-12-24
SI1349856T1 (en)	2005-10-31
MA26973A1 (fr)	2004-12-20
JP2004521095A (ja)	2004-07-15
NO20032674D0 (no)	2003-06-12
KR100520651B1 (ko)	2005-10-11
US6482951B2 (en)	2002-11-19
BR0116169A (pt)	2003-12-23
MXPA03005170A (es)	2003-09-22
WO2002048106A2 (en)	2002-06-20
IL156264A (en)	2010-11-30
CA2430579C (en)	2010-01-26
EP1349856A2 (en)	2003-10-08
HUP0400587A2 (hu)	2004-06-28
NO325810B1 (no)	2008-07-21
ATE297922T1 (de)	2005-07-15
WO2002048106A3 (en)	2002-11-28
CZ20031882A3 (cs)	2003-12-17
DE60111570D1 (de)	2005-07-21

Publication	Publication Date	Title
EP1349856B1 (en)	2005-06-15	Isoindolin-1-one glucokinase activators
EP1549638B1 (en)	2007-10-03	Indole-3-carboxamides as glucokinase (gk) activators
AU2002238415A1 (en)	2002-08-29	Isoindolin-1-one glucokinase activators
KR100519826B1 (ko)	2005-10-06	파라-아민 치환된 페닐아미드 글루코키나제 활성화제
EP1282612B1 (en)	2004-12-29	Alkynyl phenyl heteroaromatic glucokinase activators
AU2001270494A1 (en)	2002-01-31	Alkynyl phenyl heteroaromatic glucokinase activators
AU2001265914A1 (en)	2002-02-07	Para-amine substituted phenylamide glucokinase activators
HK1083098B (en)	2008-02-22	Indole-3-carboxamides as glucokinase (gk) activators