CA2681695A1 - 2-aminopyridine analogs as glucokinase activators - Google Patents

Info

Publication number

CA2681695A1

CA2681695A1 CA002681695A CA2681695A CA2681695A1 CA 2681695 A1 CA2681695 A1 CA 2681695A1 CA 002681695 A CA002681695 A CA 002681695A CA 2681695 A CA2681695 A CA 2681695A CA 2681695 A1 CA2681695 A1 CA 2681695A1

Authority

CA

Canada

Prior art keywords

alkyl

compound

formula

pyridin

mmol

Prior art date

2007-03-23

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 108010021582 Glucokinase Proteins 0.000 title claims abstract description 30
• 102000030595 Glucokinase Human genes 0.000 title claims abstract 10
• 150000003930 2-aminopyridines Chemical class 0.000 title description 14
• 239000012190 activator Substances 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims abstract description 335
• 238000000034 method Methods 0.000 claims abstract description 125
• 230000000694 effects Effects 0.000 claims abstract description 13
• 230000001404 mediated effect Effects 0.000 claims abstract description 10
• 230000003213 activating effect Effects 0.000 claims abstract description 8
• 230000002950 deficient Effects 0.000 claims abstract description 8
• 125000000217 alkyl group Chemical group 0.000 claims description 171
• -1 SO2NR e R f Inorganic materials 0.000 claims description 141
• 229910052794 bromium Inorganic materials 0.000 claims description 62
• 239000000460 chlorine Substances 0.000 claims description 58
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 46
• 229910052801 chlorine Inorganic materials 0.000 claims description 46
• 229910052757 nitrogen Inorganic materials 0.000 claims description 46
• 229910052731 fluorine Inorganic materials 0.000 claims description 39
• 125000004429 atom Chemical group 0.000 claims description 33
• 125000003118 aryl group Chemical group 0.000 claims description 31
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 30
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 26
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 25
• 239000003054 catalyst Substances 0.000 claims description 24
• 229910052739 hydrogen Inorganic materials 0.000 claims description 24
• 150000003839 salts Chemical class 0.000 claims description 24
• 150000003512 tertiary amines Chemical class 0.000 claims description 22
• 229910052740 iodine Inorganic materials 0.000 claims description 19
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 15
• 208000035475 disorder Diseases 0.000 claims description 14
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 13
• 229910006074 SO2NH2 Inorganic materials 0.000 claims description 13
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 13
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
• 229910052760 oxygen Inorganic materials 0.000 claims description 12
• 229910052751 metal Inorganic materials 0.000 claims description 11
• 239000002184 metal Substances 0.000 claims description 11
• 239000003153 chemical reaction reagent Substances 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 229910052763 palladium Inorganic materials 0.000 claims description 8
• 239000010949 copper Substances 0.000 claims description 7
• 125000005842 heteroatom Chemical group 0.000 claims description 7
• 125000006239 protecting group Chemical group 0.000 claims description 7
• 229910006069 SO3H Inorganic materials 0.000 claims description 6
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 6
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 5
• YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 5
• 239000012359 Methanesulfonyl chloride Substances 0.000 claims description 5
• 229910052802 copper Inorganic materials 0.000 claims description 5
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 5
• JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 claims description 5
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
• GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 claims description 5
• MVAXDKDOPWPFML-UHFFFAOYSA-N 2-(dimethylamino)acetyl chloride;hydrochloride Chemical compound [Cl-].C[NH+](C)CC(Cl)=O MVAXDKDOPWPFML-UHFFFAOYSA-N 0.000 claims description 4
• 230000008878 coupling Effects 0.000 claims description 4
• 238000010168 coupling process Methods 0.000 claims description 4
• 238000005859 coupling reaction Methods 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
• XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 claims description 3
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 2
• 230000003301 hydrolyzing effect Effects 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 claims 2
• 125000006164 6-membered heteroaryl group Chemical group 0.000 claims 1
• 206010012601 diabetes mellitus Diseases 0.000 abstract description 8
• 208000037765 diseases and disorders Diseases 0.000 abstract description 5
• 230000006806 disease prevention Effects 0.000 abstract description 2
• 206010011953 Decreased activity Diseases 0.000 abstract 1
• 238000006243 chemical reaction Methods 0.000 description 195
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 187
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 168
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 156
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 118
• 238000005481 NMR spectroscopy Methods 0.000 description 117
• 239000000243 solution Substances 0.000 description 100
• 239000007787 solid Substances 0.000 description 96
• 235000019439 ethyl acetate Nutrition 0.000 description 87
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 86
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 81
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 80
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 74
• 238000002360 preparation method Methods 0.000 description 73
• 239000000203 mixture Substances 0.000 description 69
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 66
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 64
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 63
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 58
• 239000002585 base Substances 0.000 description 54
• 238000005160 1H NMR spectroscopy Methods 0.000 description 50
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 50
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 50
• 229910052938 sodium sulfate Inorganic materials 0.000 description 50
• 235000011152 sodium sulphate Nutrition 0.000 description 50
• 238000001819 mass spectrum Methods 0.000 description 48
• 239000012044 organic layer Substances 0.000 description 42
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 40
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
• 229920006395 saturated elastomer Polymers 0.000 description 38
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 37
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 37
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 36
• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 36
• 239000000741 silica gel Substances 0.000 description 32
• 229910002027 silica gel Inorganic materials 0.000 description 32
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 27
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
• 235000017557 sodium bicarbonate Nutrition 0.000 description 26
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 25
• 239000002904 solvent Substances 0.000 description 25
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
• ZVDDJPSHRNMSKV-UHFFFAOYSA-N acetaldehyde;hydrochloride Chemical compound Cl.CC=O ZVDDJPSHRNMSKV-UHFFFAOYSA-N 0.000 description 23
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 23
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 23
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 23
• 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 22
• 239000008103 glucose Substances 0.000 description 22
• 229910000104 sodium hydride Inorganic materials 0.000 description 22
• 102100029237 Hexokinase-4 Human genes 0.000 description 21
• 230000015572 biosynthetic process Effects 0.000 description 21
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• 238000003556 assay Methods 0.000 description 17
• 239000000463 material Substances 0.000 description 16
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 15
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 14
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
• 150000003840 hydrochlorides Chemical class 0.000 description 14
• 239000011541 reaction mixture Substances 0.000 description 14
• 238000010992 reflux Methods 0.000 description 14
• 239000012312 sodium hydride Substances 0.000 description 14
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
• 239000012267 brine Substances 0.000 description 13
• 239000013058 crude material Substances 0.000 description 13
• 239000000377 silicon dioxide Substances 0.000 description 13
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 12
• 239000000543 intermediate Substances 0.000 description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
• 238000003818 flash chromatography Methods 0.000 description 10
• 239000001257 hydrogen Substances 0.000 description 10
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000002002 slurry Substances 0.000 description 10
• 239000007832 Na2SO4 Substances 0.000 description 9
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 9
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
• 239000010410 layer Substances 0.000 description 9
• 239000003921 oil Substances 0.000 description 9
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• 229940124530 sulfonamide Drugs 0.000 description 9
• 206010006895 Cachexia Diseases 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 229910000024 caesium carbonate Inorganic materials 0.000 description 8
• 125000000623 heterocyclic group Chemical class 0.000 description 8
• DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 8
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 7
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
• 150000003927 aminopyridines Chemical class 0.000 description 7
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 7
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 6
• AQSRRZGQRFFFGS-UHFFFAOYSA-N 2-methylpyridin-3-ol Chemical compound CC1=NC=CC=C1O AQSRRZGQRFFFGS-UHFFFAOYSA-N 0.000 description 6
• KMYXHLABNWFDJV-UHFFFAOYSA-N 5-bromo-3-(2-methylpyridin-3-yl)oxypyridin-2-amine Chemical compound CC1=NC=CC=C1OC1=CC(Br)=CN=C1N KMYXHLABNWFDJV-UHFFFAOYSA-N 0.000 description 6
• 206010056997 Impaired fasting glucose Diseases 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• KUVIGJMFXWFQIC-UHFFFAOYSA-N [[(1-acetylpiperidin-4-yl)-chloromethylidene]amino] methanesulfonate Chemical compound CC(=O)N1CCC(C(Cl)=NOS(C)(=O)=O)CC1 KUVIGJMFXWFQIC-UHFFFAOYSA-N 0.000 description 6
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
• CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 6
• DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 6
• 239000012954 diazonium Substances 0.000 description 6
• 229910052736 halogen Inorganic materials 0.000 description 6
• 150000002367 halogens Chemical class 0.000 description 6
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
• DMRJRJOJUWXPQZ-UHFFFAOYSA-N methyl 3-[6-[[4-(1-acetylpiperidin-4-yl)-1,3-thiazol-2-yl]amino]-5-phenoxypyridin-3-yl]sulfanylpropanoate Chemical compound C=1C=CC=CC=1OC1=CC(SCCC(=O)OC)=CN=C1NC(SC=1)=NC=1C1CCN(C(C)=O)CC1 DMRJRJOJUWXPQZ-UHFFFAOYSA-N 0.000 description 6
• CEJAFGHCMUGZCO-UHFFFAOYSA-N n-[3-(2-methylpyridin-3-yl)oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]-3-piperidin-4-yl-1,2,4-thiadiazol-5-amine Chemical compound CC1=NC=CC=C1OC1=CC(SC=2N=CC=CC=2)=CN=C1NC1=NC(C2CCNCC2)=NS1 CEJAFGHCMUGZCO-UHFFFAOYSA-N 0.000 description 6
• 230000000069 prophylactic effect Effects 0.000 description 6
• 229940124597 therapeutic agent Drugs 0.000 description 6
• 150000003573 thiols Chemical class 0.000 description 6
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
• VJHTZTZXOKVQRN-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine Chemical compound NC1=NC=NS1 VJHTZTZXOKVQRN-UHFFFAOYSA-N 0.000 description 5
• SJHFANAAUIRSLR-UHFFFAOYSA-N 1-(1-acetylpiperidin-4-yl)-2-bromoethanone Chemical compound CC(=O)N1CCC(C(=O)CBr)CC1 SJHFANAAUIRSLR-UHFFFAOYSA-N 0.000 description 5
• 208000002705 Glucose Intolerance Diseases 0.000 description 5
• 150000001408 amides Chemical class 0.000 description 5
• 150000001989 diazonium salts Chemical class 0.000 description 5
• 239000006260 foam Substances 0.000 description 5
• 150000004820 halides Chemical class 0.000 description 5
• 235000019341 magnesium sulphate Nutrition 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 201000009104 prediabetes syndrome Diseases 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 125000004076 pyridyl group Chemical group 0.000 description 5
• 230000002441 reversible effect Effects 0.000 description 5
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• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 2
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 230000008961 swelling Effects 0.000 description 2
• DMAXDAGHXUAIPR-UHFFFAOYSA-N tert-butyl 3-[5-[[3-(2-ethylpyridin-3-yl)oxy-5-(2-methoxyethylsulfanyl)pyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound CCC1=NC=CC=C1OC1=CC(SCCOC)=CN=C1NC1=NC(C2CC3CCC(N3C(=O)OC(C)(C)C)C2)=NS1 DMAXDAGHXUAIPR-UHFFFAOYSA-N 0.000 description 2
• KYGIEKJMIGVYMA-UHFFFAOYSA-N tert-butyl 3-[5-[[3-(2-methylpyridin-3-yl)oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC1=NC=CC=C1OC1=CC(SC=2N=CC=CC=2)=CN=C1NC1=NC(C2CC3CCC(N3C(=O)OC(C)(C)C)C2)=NS1 KYGIEKJMIGVYMA-UHFFFAOYSA-N 0.000 description 2
• LMAJLKOFKLVHLQ-UHFFFAOYSA-N tert-butyl 3-[5-[[5-(2-methoxy-2-oxoethyl)sulfanyl-3-(2-methylpyridin-3-yl)oxypyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C=1C(SCC(=O)OC)=CN=C(NC=2SN=C(N=2)C2CC3CCC(N3C(=O)OC(C)(C)C)C2)C=1OC1=CC=CN=C1C LMAJLKOFKLVHLQ-UHFFFAOYSA-N 0.000 description 2
• GWCHWXGBUJDLSA-UHFFFAOYSA-N tert-butyl 3-[5-[[5-bromo-3-(2-ethylpyridin-3-yl)oxypyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound CCC1=NC=CC=C1OC1=CC(Br)=CN=C1NC1=NC(C2CC3CCC(N3C(=O)OC(C)(C)C)C2)=NS1 GWCHWXGBUJDLSA-UHFFFAOYSA-N 0.000 description 2
• RKEJUEOSAHCMGI-UHFFFAOYSA-N tert-butyl 3-[5-[[5-bromo-3-(2-methylpyridin-3-yl)oxypyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC1=NC=CC=C1OC1=CC(Br)=CN=C1NC1=NC(C2CC3CCC(N3C(=O)OC(C)(C)C)C2)=NS1 RKEJUEOSAHCMGI-UHFFFAOYSA-N 0.000 description 2
• HYRSGTXIVIMOOX-UHFFFAOYSA-N tert-butyl 4-(2-bromoacetyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(=O)CBr)CC1 HYRSGTXIVIMOOX-UHFFFAOYSA-N 0.000 description 2
• WRCNVYRLKORNCB-UHFFFAOYSA-N tert-butyl 4-(c-chloro-n-hydroxycarbonimidoyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(Cl)=NO)CC1 WRCNVYRLKORNCB-UHFFFAOYSA-N 0.000 description 2
• QZEXDYYNSSEBFH-UHFFFAOYSA-N tert-butyl 4-(c-chloro-n-methylsulfonyloxycarbonimidoyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(Cl)=NOS(C)(=O)=O)CC1 QZEXDYYNSSEBFH-UHFFFAOYSA-N 0.000 description 2
• CMUYBJHYEACLSY-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)azepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(CO)CC1 CMUYBJHYEACLSY-UHFFFAOYSA-N 0.000 description 2
• BRLYMACICGWYBH-UHFFFAOYSA-N tert-butyl 4-[2-[[3-(2-bromo-4-fluorophenoxy)-5-(3-methoxyphenyl)sulfanylpyridin-2-yl]amino]-1,3-thiazol-4-yl]piperidine-1-carboxylate Chemical compound COC1=CC=CC(SC=2C=C(OC=3C(=CC(F)=CC=3)Br)C(NC=3SC=C(N=3)C3CCN(CC3)C(=O)OC(C)(C)C)=NC=2)=C1 BRLYMACICGWYBH-UHFFFAOYSA-N 0.000 description 2
• XLYVNNFTLWKAIG-UHFFFAOYSA-N tert-butyl 4-[5-[(3-phenoxy-5-pyridin-2-ylsulfanylpyridin-2-yl)amino]-1,2,4-thiadiazol-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NSC(NC=2C(=CC(SC=3N=CC=CC=3)=CN=2)OC=2C=CC=CC=2)=N1 XLYVNNFTLWKAIG-UHFFFAOYSA-N 0.000 description 2
• NEFUZTQATCGTKQ-UHFFFAOYSA-N tert-butyl 4-[5-[(3-phenoxy-5-thieno[3,2-b]pyridin-7-ylsulfanylpyridin-2-yl)amino]-1,2,4-thiadiazol-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=NSC(NC=2C(=CC(SC=3C=4SC=CC=4N=CC=3)=CN=2)OC=2C=CC=CC=2)=N1 NEFUZTQATCGTKQ-UHFFFAOYSA-N 0.000 description 2
• KQFVGNXUDBTEJL-UHFFFAOYSA-N tert-butyl 4-[5-[[3-(2-methylpyridin-3-yl)oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]azepane-1-carboxylate Chemical compound CC1=NC=CC=C1OC1=CC(SC=2N=CC=CC=2)=CN=C1NC1=NC(C2CCN(CCC2)C(=O)OC(C)(C)C)=NS1 KQFVGNXUDBTEJL-UHFFFAOYSA-N 0.000 description 2
• LDVAPGZRTALTIP-UHFFFAOYSA-N tert-butyl 4-[5-[[3-(2-methylpyridin-3-yl)oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidine-1-carboxylate Chemical compound CC1=NC=CC=C1OC1=CC(SC=2N=CC=CC=2)=CN=C1NC1=NC(C2CCN(CC2)C(=O)OC(C)(C)C)=NS1 LDVAPGZRTALTIP-UHFFFAOYSA-N 0.000 description 2
• FUIMMOPURJQOKF-UHFFFAOYSA-N tert-butyl 4-[5-[[5-bromo-3-(2-methylpyridin-3-yl)oxypyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]azepane-1-carboxylate Chemical compound CC1=NC=CC=C1OC1=CC(Br)=CN=C1NC1=NC(C2CCN(CCC2)C(=O)OC(C)(C)C)=NS1 FUIMMOPURJQOKF-UHFFFAOYSA-N 0.000 description 2
• APPVUKMQCPHPGN-UHFFFAOYSA-N tert-butyl 4-[5-[[5-bromo-3-(2-methylpyridin-3-yl)oxypyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidine-1-carboxylate Chemical compound CC1=NC=CC=C1OC1=CC(Br)=CN=C1NC1=NC(C2CCN(CC2)C(=O)OC(C)(C)C)=NS1 APPVUKMQCPHPGN-UHFFFAOYSA-N 0.000 description 2
• PJGLIJYHRJWIKF-UHFFFAOYSA-N tert-butyl 4-formylazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(C=O)CC1 PJGLIJYHRJWIKF-UHFFFAOYSA-N 0.000 description 2
• JQKQFYWVGVTDHM-UHFFFAOYSA-N tert-butyl n-[4-[2-[(3-phenoxy-5-pyridin-2-ylsulfanylpyridin-2-yl)amino]-1,3-thiazol-4-yl]piperidin-1-yl]sulfonylcarbamate Chemical compound C1CN(S(=O)(=O)NC(=O)OC(C)(C)C)CCC1C1=CSC(NC=2C(=CC(SC=3N=CC=CC=3)=CN=2)OC=2C=CC=CC=2)=N1 JQKQFYWVGVTDHM-UHFFFAOYSA-N 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• DKGYESBFCGKOJC-UHFFFAOYSA-N thiophen-3-amine Chemical compound NC=1C=CSC=1 DKGYESBFCGKOJC-UHFFFAOYSA-N 0.000 description 2
• 125000001425 triazolyl group Chemical group 0.000 description 2
• GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 239000011701 zinc Substances 0.000 description 2
• OGTIVLDRXVBTPJ-QGZVFWFLSA-N (2r)-2-hydroxy-1-[4-[5-[(3-phenoxy-5-pyridin-2-ylsulfanylpyridin-2-yl)amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]propan-1-one Chemical compound C1CN(C(=O)[C@H](O)C)CCC1C1=NSC(NC=2C(=CC(SC=3N=CC=CC=3)=CN=2)OC=2C=CC=CC=2)=N1 OGTIVLDRXVBTPJ-QGZVFWFLSA-N 0.000 description 1
• HFTSPKIAXHZROA-UHFFFAOYSA-N (6-chloropyridin-2-yl)hydrazine Chemical compound NNC1=CC=CC(Cl)=N1 HFTSPKIAXHZROA-UHFFFAOYSA-N 0.000 description 1
• LDQBLOQVAAYWLW-UHFFFAOYSA-N (C-chloro-N-methylsulfonyloxycarbonimidoyl) 8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound ClC(=NOS(=O)(=O)C)OC(=O)N1C2CCCC1CC2 LDQBLOQVAAYWLW-UHFFFAOYSA-N 0.000 description 1
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
• KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• GLVMLJCMUBZVTJ-UHFFFAOYSA-N 1,4-dibromo-2,5-difluorobenzene Chemical compound FC1=CC(Br)=C(F)C=C1Br GLVMLJCMUBZVTJ-UHFFFAOYSA-N 0.000 description 1
• VFZXZEJGLKOTBW-UHFFFAOYSA-N 1-(1-acetylpiperidin-4-yl)ethanone Chemical compound CC(=O)C1CCN(C(C)=O)CC1 VFZXZEJGLKOTBW-UHFFFAOYSA-N 0.000 description 1
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 1
• FRYKCACAZRFJFE-UHFFFAOYSA-N 1-[3-[5-[[3-(2-methylpyridin-3-yl)oxy-5-(trifluoromethyl)pyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]-8-azabicyclo[3.2.1]octan-8-yl]ethanone;hydrochloride Chemical compound Cl.CC(=O)N1C(C2)CCC1CC2C(N=1)=NSC=1NC1=NC=C(C(F)(F)F)C=C1OC1=CC=CN=C1C FRYKCACAZRFJFE-UHFFFAOYSA-N 0.000 description 1
• XLBZNXIITUXKDS-UHFFFAOYSA-N 1-[3-[5-[[3-(2-methylpyridin-3-yl)oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]-8-azabicyclo[3.2.1]octan-8-yl]ethanone;hydrochloride Chemical compound Cl.CC(=O)N1C(C2)CCC1CC2C(N=1)=NSC=1NC(C(=C1)OC=2C(=NC=CC=2)C)=NC=C1SC1=CC=CC=N1 XLBZNXIITUXKDS-UHFFFAOYSA-N 0.000 description 1
• NXXIGVOORSNMNX-UHFFFAOYSA-N 1-[3-[5-[[5-(2-hydroxy-2-methylpropyl)sulfanyl-3-(2-methylpyridin-3-yl)oxypyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]-8-azabicyclo[3.2.1]octan-8-yl]ethanone Chemical compound CC(=O)N1C(C2)CCC1CC2C(N=1)=NSC=1NC1=NC=C(SCC(C)(C)O)C=C1OC1=CC=CN=C1C NXXIGVOORSNMNX-UHFFFAOYSA-N 0.000 description 1
• GLCFUIPAEHONBC-UHFFFAOYSA-N 1-[3-methyl-4-[2-[(3-phenoxy-5-pyridin-2-ylsulfanylpyridin-2-yl)amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone;dihydrochloride Chemical compound Cl.Cl.CC1CN(C(C)=O)CCC1C1=CSC(NC=2C(=CC(SC=3N=CC=CC=3)=CN=2)OC=2C=CC=CC=2)=N1 GLCFUIPAEHONBC-UHFFFAOYSA-N 0.000 description 1
• NFOKKRBKJATCEB-UHFFFAOYSA-N 1-[4-[2-[(3-phenoxy-5-pyridin-2-ylsulfanylpyridin-2-yl)amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone;dihydrochloride Chemical compound Cl.Cl.C1CN(C(=O)C)CCC1C1=CSC(NC=2C(=CC(SC=3N=CC=CC=3)=CN=2)OC=2C=CC=CC=2)=N1 NFOKKRBKJATCEB-UHFFFAOYSA-N 0.000 description 1
• NGRCJFXYCYWMLU-UHFFFAOYSA-N 1-[4-[2-[(5-bromo-3-cyclopentyloxypyridin-2-yl)amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CSC(NC=2C(=CC(Br)=CN=2)OC2CCCC2)=N1 NGRCJFXYCYWMLU-UHFFFAOYSA-N 0.000 description 1
• DEKNGHFCSXNXFR-UHFFFAOYSA-N 1-[4-[2-[[3-(4-fluorophenoxy)-5-thieno[3,2-b]pyridin-7-ylsulfanylpyridin-2-yl]amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CSC(NC=2C(=CC(SC=3C=4SC=CC=4N=CC=3)=CN=2)OC=2C=CC(F)=CC=2)=N1 DEKNGHFCSXNXFR-UHFFFAOYSA-N 0.000 description 1
• OVMNXWXKRPPZNK-UHFFFAOYSA-N 1-[4-[2-[[5-(5-chlorothieno[3,2-b]pyridin-7-yl)sulfanyl-3-phenoxypyridin-2-yl]amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CSC(NC=2C(=CC(SC=3C=4SC=CC=4N=C(Cl)C=3)=CN=2)OC=2C=CC=CC=2)=N1 OVMNXWXKRPPZNK-UHFFFAOYSA-N 0.000 description 1
• JWAYGVXTEZAJBO-UHFFFAOYSA-N 1-[4-[2-[[5-bromo-3-(2-methylpyridin-3-yl)oxypyridin-2-yl]amino]-1,3-thiazol-4-yl]azepan-1-yl]ethanone;dihydrochloride Chemical compound Cl.Cl.C1CN(C(=O)C)CCCC1C1=CSC(NC=2C(=CC(Br)=CN=2)OC=2C(=NC=CC=2)C)=N1 JWAYGVXTEZAJBO-UHFFFAOYSA-N 0.000 description 1
• VXFSEELNTKPJQM-UHFFFAOYSA-N 1-[4-[2-[[5-thieno[3,2-b]pyridin-7-ylsulfanyl-3-[2-(trifluoromethyl)phenoxy]pyridin-2-yl]amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CSC(NC=2C(=CC(SC=3C=4SC=CC=4N=CC=3)=CN=2)OC=2C(=CC=CC=2)C(F)(F)F)=N1 VXFSEELNTKPJQM-UHFFFAOYSA-N 0.000 description 1
• ZTUWEJHVNPSXBD-UHFFFAOYSA-N 1-[4-[5-[(3-phenoxy-5-thieno[3,2-b]pyridin-7-ylsulfanylpyridin-2-yl)amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone;dihydrochloride Chemical compound Cl.Cl.C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(SC=3C=4SC=CC=4N=CC=3)=CN=2)OC=2C=CC=CC=2)=N1 ZTUWEJHVNPSXBD-UHFFFAOYSA-N 0.000 description 1
• HQHQNEQEMURMOD-UHFFFAOYSA-N 1-[4-[5-[(5-bromo-3-hydroxypyridin-2-yl)amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(Br)=CN=2)O)=N1 HQHQNEQEMURMOD-UHFFFAOYSA-N 0.000 description 1
• KJKJHXMWKUNILS-UHFFFAOYSA-N 1-[4-[5-[(5-bromo-3-phenoxypyridin-2-yl)amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(Br)=CN=2)OC=2C=CC=CC=2)=N1 KJKJHXMWKUNILS-UHFFFAOYSA-N 0.000 description 1
• SBRGWDJNHINHFM-UHFFFAOYSA-N 1-[4-[5-[[3-(1-methylpyrazol-4-yl)oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(SC=3N=CC=CC=3)=CN=2)OC2=CN(C)N=C2)=N1 SBRGWDJNHINHFM-UHFFFAOYSA-N 0.000 description 1
• QLWHYMHKEWULPR-UHFFFAOYSA-N 1-[4-[5-[[3-(2-methylpyridin-3-yl)oxy-5-(3-methylpyridin-2-yl)sulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone;hydrochloride Chemical compound Cl.C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(SC=3C(=CC=CN=3)C)=CN=2)OC=2C(=NC=CC=2)C)=N1 QLWHYMHKEWULPR-UHFFFAOYSA-N 0.000 description 1
• ZCNKPJGDOXPOCW-UHFFFAOYSA-N 1-[4-[5-[[3-(2-methylpyridin-3-yl)oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]azepan-1-yl]ethanone;dihydrochloride Chemical compound Cl.Cl.C1CN(C(=O)C)CCCC1C1=NSC(NC=2C(=CC(SC=3N=CC=CC=3)=CN=2)OC=2C(=NC=CC=2)C)=N1 ZCNKPJGDOXPOCW-UHFFFAOYSA-N 0.000 description 1
• ROMJYJIQWBMNBW-UHFFFAOYSA-N 1-[4-[5-[[3-(4-fluorophenoxy)-5-thieno[3,2-b]pyridin-7-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone;dihydrochloride Chemical compound Cl.Cl.C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(SC=3C=4SC=CC=4N=CC=3)=CN=2)OC=2C=CC(F)=CC=2)=N1 ROMJYJIQWBMNBW-UHFFFAOYSA-N 0.000 description 1
• QYPRAKILUZIWBP-UHFFFAOYSA-N 1-[4-[5-[[3-[2-(hydroxymethyl)pyridin-3-yl]oxy-5-pyridin-2-ylsulfanylpyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone;hydrochloride Chemical compound Cl.C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(SC=3N=CC=CC=3)=CN=2)OC=2C(=NC=CC=2)CO)=N1 QYPRAKILUZIWBP-UHFFFAOYSA-N 0.000 description 1
• QESVFCDIAXJQLU-UHFFFAOYSA-N 1-[4-[5-[[5-(2,6-dimethylphenyl)sulfanyl-3-(2-methylpyridin-3-yl)oxypyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(SC=3C(=CC=CC=3C)C)=CN=2)OC=2C(=NC=CC=2)C)=N1 QESVFCDIAXJQLU-UHFFFAOYSA-N 0.000 description 1
• JFCKULRDSMEDAX-UHFFFAOYSA-N 1-[4-[5-[[5-(2-hydroxy-2-methylpropyl)sulfanyl-3-([1,2,4]triazolo[1,5-a]pyridin-8-yloxy)pyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone;hydrochloride Chemical compound Cl.C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(SCC(C)(C)O)=CN=2)OC=2C3=NC=NN3C=CC=2)=N1 JFCKULRDSMEDAX-UHFFFAOYSA-N 0.000 description 1
• IBOHTCSUBUPCIM-UHFFFAOYSA-N 1-[4-[5-[[5-(2-hydroxyethylsulfanyl)-3-(2-methylpyridin-3-yl)oxypyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]-4-methylpiperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1(C)C1=NSC(NC=2C(=CC(SCCO)=CN=2)OC=2C(=NC=CC=2)C)=N1 IBOHTCSUBUPCIM-UHFFFAOYSA-N 0.000 description 1
• QCQGBPNHVGKEIE-UHFFFAOYSA-N 1-[4-[5-[[5-bromo-3-(6,7-dihydro-5h-cyclopenta[b]pyridin-5-yloxy)pyridin-2-yl]amino]-1,2,4-thiadiazol-3-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=NSC(NC=2C(=CC(Br)=CN=2)OC2C3=CC=CN=C3CC2)=N1 QCQGBPNHVGKEIE-UHFFFAOYSA-N 0.000 description 1
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