EA018988B1 - Активаторы глюкокиназы - Google Patents
Активаторы глюкокиназы Download PDFInfo
- Publication number
- EA018988B1 EA018988B1 EA201071320A EA201071320A EA018988B1 EA 018988 B1 EA018988 B1 EA 018988B1 EA 201071320 A EA201071320 A EA 201071320A EA 201071320 A EA201071320 A EA 201071320A EA 018988 B1 EA018988 B1 EA 018988B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- propanamide
- cyclopropylsulfonyl
- tetrahydro
- pyran
- indazol
- Prior art date
Links
- 102000030595 Glucokinase Human genes 0.000 title claims abstract description 54
- 108010021582 Glucokinase Proteins 0.000 title claims abstract description 54
- 239000012190 activator Substances 0.000 title description 55
- 150000001875 compounds Chemical class 0.000 claims abstract description 450
- 150000003839 salts Chemical class 0.000 claims abstract description 74
- 239000003814 drug Substances 0.000 claims abstract description 52
- 238000011282 treatment Methods 0.000 claims abstract description 52
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 35
- 201000010099 disease Diseases 0.000 claims abstract description 34
- 230000000694 effects Effects 0.000 claims abstract description 22
- 238000004519 manufacturing process Methods 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 9
- 201000001421 hyperglycemia Diseases 0.000 claims abstract description 8
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 7
- 208000008589 Obesity Diseases 0.000 claims abstract description 7
- 235000020824 obesity Nutrition 0.000 claims abstract description 7
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 7
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 6
- 208000001145 Metabolic Syndrome Diseases 0.000 claims abstract description 6
- 201000010390 abdominal obesity-metabolic syndrome 1 Diseases 0.000 claims abstract description 6
- 208000011661 metabolic syndrome X Diseases 0.000 claims abstract description 6
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims abstract description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 5
- -1 thiazolo [5,4-b] pyridinyl Chemical group 0.000 claims description 758
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 169
- NPMMXKUVLURCMA-UHFFFAOYSA-N n-(oxan-4-yl)propanamide Chemical compound CCC(=O)NC1CCOCC1 NPMMXKUVLURCMA-UHFFFAOYSA-N 0.000 claims description 78
- 125000000217 alkyl group Chemical group 0.000 claims description 63
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 61
- 229910052736 halogen Inorganic materials 0.000 claims description 54
- 150000002367 halogens Chemical class 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 45
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 44
- 125000004429 atom Chemical group 0.000 claims description 35
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 23
- 239000008103 glucose Substances 0.000 claims description 21
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 230000002829 reductive effect Effects 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 5
- 206010036049 Polycystic ovaries Diseases 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000010802 sludge Substances 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 4
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims description 4
- HAMZIZRSAJARRH-UHFFFAOYSA-N 4-cyclopropylsulfonyl-1-[1-[(5-fluoro-1,3-thiazol-2-yl)amino]-3-(oxan-4-yl)-1-oxopropan-2-yl]indazole-6-carboxylic acid Chemical compound C12=CC(C(=O)O)=CC(S(=O)(=O)C3CC3)=C2C=NN1C(C(=O)NC=1SC(F)=CN=1)CC1CCOCC1 HAMZIZRSAJARRH-UHFFFAOYSA-N 0.000 claims description 3
- 125000005518 carboxamido group Chemical group 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 5
- NEONVCXAZVYGDB-UHFFFAOYSA-N 1-cyclopropylpyrazole-3-carboxamide Chemical compound C1(CC1)N1N=C(C=C1)C(=O)N NEONVCXAZVYGDB-UHFFFAOYSA-N 0.000 claims 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 1
- 230000003213 activating effect Effects 0.000 abstract description 9
- 208000002705 Glucose Intolerance Diseases 0.000 abstract 1
- 201000009104 prediabetes syndrome Diseases 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 132
- 239000000203 mixture Substances 0.000 description 115
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- 239000000243 solution Substances 0.000 description 87
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- 238000000034 method Methods 0.000 description 84
- 235000002639 sodium chloride Nutrition 0.000 description 69
- 125000005842 heteroatom Chemical group 0.000 description 65
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- 239000007795 chemical reaction product Substances 0.000 description 55
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 51
- 125000003118 aryl group Chemical group 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 41
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 37
- 125000001424 substituent group Chemical group 0.000 description 36
- 238000002360 preparation method Methods 0.000 description 34
- 230000015572 biosynthetic process Effects 0.000 description 33
- 239000002552 dosage form Substances 0.000 description 33
- 230000003178 anti-diabetic effect Effects 0.000 description 32
- 239000003472 antidiabetic agent Substances 0.000 description 32
- 239000012044 organic layer Substances 0.000 description 32
- 150000003254 radicals Chemical class 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
- 239000002904 solvent Substances 0.000 description 29
- 239000002253 acid Substances 0.000 description 27
- 239000003826 tablet Substances 0.000 description 27
- 229960001031 glucose Drugs 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- 239000002585 base Substances 0.000 description 24
- 239000003112 inhibitor Substances 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 238000003818 flash chromatography Methods 0.000 description 22
- 230000003993 interaction Effects 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
- 239000007788 liquid Substances 0.000 description 21
- 239000003921 oil Substances 0.000 description 21
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 20
- 235000019198 oils Nutrition 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- 239000002775 capsule Substances 0.000 description 19
- 235000001727 glucose Nutrition 0.000 description 19
- 239000000463 material Substances 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 18
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 17
- 125000001072 heteroaryl group Chemical group 0.000 description 17
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 17
- 229960003105 metformin Drugs 0.000 description 17
- 229940002612 prodrug Drugs 0.000 description 17
- 239000000651 prodrug Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 16
- 229910052799 carbon Inorganic materials 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 15
- 229910052794 bromium Inorganic materials 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
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- 239000000839 emulsion Substances 0.000 description 14
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- 229920006395 saturated elastomer Polymers 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 125000002947 alkylene group Chemical group 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
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- 229940079593 drug Drugs 0.000 description 11
- 229910052740 iodine Inorganic materials 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
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- 239000000126 substance Substances 0.000 description 11
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
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- XTEOJPUYZWEXFI-UHFFFAOYSA-N butyl n-[3-[4-(imidazol-1-ylmethyl)phenyl]-5-(2-methylpropyl)thiophen-2-yl]sulfonylcarbamate Chemical compound S1C(CC(C)C)=CC(C=2C=CC(CN3C=NC=C3)=CC=2)=C1S(=O)(=O)NC(=O)OCCCC XTEOJPUYZWEXFI-UHFFFAOYSA-N 0.000 description 8
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- 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
-
- 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
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- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Reproductive Health (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5405208P | 2008-05-16 | 2008-05-16 | |
| US10837008P | 2008-10-24 | 2008-10-24 | |
| PCT/US2009/044190 WO2009140624A2 (en) | 2008-05-16 | 2009-05-15 | Glucokinase activators |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201071320A1 EA201071320A1 (ru) | 2011-06-30 |
| EA018988B1 true EA018988B1 (ru) | 2013-12-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201071320A EA018988B1 (ru) | 2008-05-16 | 2009-05-15 | Активаторы глюкокиназы |
Country Status (27)
| Country | Link |
|---|---|
| US (4) | US8563730B2 (OSRAM) |
| EP (1) | EP2294053B1 (OSRAM) |
| JP (1) | JP5513492B2 (OSRAM) |
| KR (1) | KR20110018366A (OSRAM) |
| CN (1) | CN102105451B (OSRAM) |
| AR (1) | AR071811A1 (OSRAM) |
| AU (1) | AU2009246167B2 (OSRAM) |
| BR (1) | BRPI0912802A2 (OSRAM) |
| CA (1) | CA2724116A1 (OSRAM) |
| CL (1) | CL2009001203A1 (OSRAM) |
| CO (1) | CO6321274A2 (OSRAM) |
| CR (1) | CR11827A (OSRAM) |
| DO (1) | DOP2010000351A (OSRAM) |
| EA (1) | EA018988B1 (OSRAM) |
| EC (1) | ECSP10010688A (OSRAM) |
| GE (1) | GEP20135783B (OSRAM) |
| IL (1) | IL209062A (OSRAM) |
| MA (1) | MA32391B1 (OSRAM) |
| MX (1) | MX2010012298A (OSRAM) |
| MY (1) | MY152749A (OSRAM) |
| NZ (1) | NZ589084A (OSRAM) |
| PE (2) | PE20091901A1 (OSRAM) |
| SG (1) | SG190625A1 (OSRAM) |
| TW (1) | TWI445707B (OSRAM) |
| UY (1) | UY31830A (OSRAM) |
| WO (1) | WO2009140624A2 (OSRAM) |
| ZA (1) | ZA201007975B (OSRAM) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2770775C1 (ru) * | 2018-05-31 | 2022-04-21 | Хуа Медсин (Шанхай) Лтд. | Фармацевтическая комбинация, композиция и комбинированный состав, содержащий активатор глюкокиназы и ингибитор dpp-iv, и способ его приготовления и применения |
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| MY152749A (en) | 2008-05-16 | 2014-11-28 | Takeda California Inc | Pyrazole and fused pyrazole glucokinase activators |
| CA2735162C (en) | 2008-08-27 | 2015-06-23 | Takeda Pharmaceutical Company Limited | Pyrrole compounds |
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| CN102471330A (zh) | 2009-07-06 | 2012-05-23 | 巴斯夫欧洲公司 | 用于防治无脊椎动物害虫的哒嗪化合物 |
| CN102471321A (zh) | 2009-07-06 | 2012-05-23 | 巴斯夫欧洲公司 | 用于防治无脊椎动物害虫的哒嗪化合物 |
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| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| AU2011235212B2 (en) | 2010-03-31 | 2014-07-31 | The Scripps Research Institute | Reprogramming cells |
| BR112012029844A2 (pt) | 2010-05-26 | 2015-10-13 | Transtech Pharma Inc | uso de metamorfina em combinação com um ativador de glucoquinase e combinações compreendendo metamorfina com um ativador de glucoquinase |
| 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 |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| US20130197229A1 (en) * | 2010-10-13 | 2013-08-01 | Christopher Matthews | Method of making azaindazole derivatives |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2760862B1 (en) | 2011-09-27 | 2015-10-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2849776B1 (en) | 2012-05-17 | 2021-04-21 | vTv Therapeutics LLC | Glucokinase activator compositions for the treatment of diabetes |
| EP2964198A2 (en) * | 2013-03-04 | 2016-01-13 | vTv Therapeutics LLC | Stable glucokinase activator compositions |
| EP2878339A1 (en) | 2013-12-02 | 2015-06-03 | Siena Biotech S.p.A. | SIP3 antagonists |
| TWI667233B (zh) | 2013-12-19 | 2019-08-01 | 德商拜耳製藥公司 | 新穎吲唑羧醯胺,其製備方法、含彼等之醫藥製劑及其製造醫藥之用途 |
| SG10201912805SA (en) * | 2014-12-19 | 2020-02-27 | Aragon Pharmaceuticals Inc | Process for the preparation of a diarylthiohydantoin compound |
| CN105092770B (zh) * | 2015-01-12 | 2017-03-29 | 上海中医药大学 | 一种筛选二肽基肽酶四抑制剂的方法 |
| JP2018522846A (ja) | 2015-06-15 | 2018-08-16 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | ハロゲン置換フェノキシフェニルアミジン類及び殺菌剤としてのそれらの使用 |
| US10252977B2 (en) | 2015-06-15 | 2019-04-09 | Bayer Cropscience Aktiengesellschaft | Halogen-substituted phenoxyphenylamidines and the use thereof as fungicides |
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| EP4487909A3 (en) | 2018-06-12 | 2025-03-19 | vTv Therapeutics LLC | Therapeutic uses of glucokinase activators in combination with insulin or insulin analogs |
| US12391658B2 (en) | 2020-02-18 | 2025-08-19 | Vtv Therapeutics Llc | Sulfoxide and sulfone glucokinase activators and methods of use thereof |
| CA3181722A1 (en) | 2020-06-08 | 2021-12-16 | Jing TENG | Salts or co-crystals of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid and uses thereof |
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2009
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- 2009-05-15 WO PCT/US2009/044190 patent/WO2009140624A2/en not_active Ceased
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- 2009-05-15 SG SG2013034012A patent/SG190625A1/en unknown
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- 2009-05-15 TW TW98116300A patent/TWI445707B/zh not_active IP Right Cessation
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2010
- 2010-11-01 IL IL209062A patent/IL209062A/en not_active IP Right Cessation
- 2010-11-08 ZA ZA2010/07975A patent/ZA201007975B/en unknown
- 2010-11-15 DO DO2010000351A patent/DOP2010000351A/es unknown
- 2010-12-07 CR CR11827A patent/CR11827A/es unknown
- 2010-12-07 CO CO10154094A patent/CO6321274A2/es not_active Application Discontinuation
- 2010-12-10 MA MA33420A patent/MA32391B1/fr unknown
- 2010-12-16 EC ECSP10010688 patent/ECSP10010688A/es unknown
-
2012
- 2012-04-10 US US13/443,774 patent/US20120225887A1/en not_active Abandoned
-
2013
- 2013-10-02 US US14/044,687 patent/US9139598B2/en not_active Expired - Fee Related
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2015
- 2015-09-21 US US14/860,573 patent/US20160009735A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007143434A2 (en) * | 2006-05-31 | 2007-12-13 | Takeda San Diego, Inc. | Indazole and isoindole derivatives as glucokinase activating agents |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2770775C1 (ru) * | 2018-05-31 | 2022-04-21 | Хуа Медсин (Шанхай) Лтд. | Фармацевтическая комбинация, композиция и комбинированный состав, содержащий активатор глюкокиназы и ингибитор dpp-iv, и способ его приготовления и применения |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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