ES2378704T3 - Activadores de la glucocinasa - Google Patents
Activadores de la glucocinasa Download PDFInfo
- Publication number
- ES2378704T3 ES2378704T3 ES07716991T ES07716991T ES2378704T3 ES 2378704 T3 ES2378704 T3 ES 2378704T3 ES 07716991 T ES07716991 T ES 07716991T ES 07716991 T ES07716991 T ES 07716991T ES 2378704 T3 ES2378704 T3 ES 2378704T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- mmol
- saturated
- heteroaryl
- partially unsaturated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102000030595 Glucokinase Human genes 0.000 title claims abstract description 52
- 108010021582 Glucokinase Proteins 0.000 title claims abstract description 52
- 239000012190 activator Substances 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 246
- 238000011282 treatment Methods 0.000 claims abstract description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 43
- 230000003213 activating effect Effects 0.000 claims abstract description 9
- -1 2-tetrahydrofuranyl Chemical group 0.000 claims description 305
- 238000000034 method Methods 0.000 claims description 201
- 125000000623 heterocyclic group Chemical group 0.000 claims description 132
- 238000002360 preparation method Methods 0.000 claims description 132
- 229920006395 saturated elastomer Polymers 0.000 claims description 118
- 125000000217 alkyl group Chemical group 0.000 claims description 110
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 103
- 125000001072 heteroaryl group Chemical group 0.000 claims description 94
- 125000003342 alkenyl group Chemical group 0.000 claims description 81
- 125000000304 alkynyl group Chemical group 0.000 claims description 81
- 125000003118 aryl group Chemical group 0.000 claims description 79
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 71
- 229910052794 bromium Inorganic materials 0.000 claims description 49
- 239000000203 mixture Substances 0.000 claims description 48
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 47
- 229910052801 chlorine Inorganic materials 0.000 claims description 44
- 125000004429 atom Chemical group 0.000 claims description 30
- 229910052731 fluorine Inorganic materials 0.000 claims description 30
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 29
- 229910052717 sulfur Inorganic materials 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 229910052740 iodine Inorganic materials 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000004043 oxo group Chemical group O=* 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 125000002947 alkylene group Chemical group 0.000 claims description 20
- 201000010099 disease Diseases 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 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 16
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 13
- 239000003054 catalyst Substances 0.000 claims description 13
- 125000004450 alkenylene group Chemical group 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 11
- 125000002619 bicyclic group Chemical group 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 229910052799 carbon Inorganic materials 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 229910052751 metal Inorganic materials 0.000 claims description 7
- 239000002184 metal Substances 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000004419 alkynylene group Chemical group 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- 229910003827 NRaRb Inorganic materials 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 claims description 2
- 125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 2
- 108010081348 HRT1 protein Hairy Proteins 0.000 claims description 2
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 2
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 229910052701 rubidium Inorganic materials 0.000 claims description 2
- 125000004588 thienopyridyl group Chemical group S1C(=CC2=C1C=CC=N2)* 0.000 claims description 2
- ZRHUHDUEXWHZMA-UHFFFAOYSA-N 1,4-dihydropyrazol-5-one Chemical compound O=C1CC=NN1 ZRHUHDUEXWHZMA-UHFFFAOYSA-N 0.000 claims 1
- LJKOFHPXVQFIQA-UHFFFAOYSA-N 1-[4-[2-[[4-(2,6-dichlorophenyl)sulfanylpyridin-2-yl]amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CSC(NC=2N=CC=C(SC=3C(=CC=CC=3Cl)Cl)C=2)=N1 LJKOFHPXVQFIQA-UHFFFAOYSA-N 0.000 claims 1
- ZNEVZQJMMIYNCM-UHFFFAOYSA-N 1-[4-[2-[[4-(2,6-dimethylphenoxy)pyridin-2-yl]amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3C)C)C=2)=N1 ZNEVZQJMMIYNCM-UHFFFAOYSA-N 0.000 claims 1
- UTIDUWCJLKFEMM-UHFFFAOYSA-N 1-[4-[2-[[4-(2-chloro-6-methylphenoxy)pyridin-2-yl]amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3C)Cl)C=2)=N1 UTIDUWCJLKFEMM-UHFFFAOYSA-N 0.000 claims 1
- GBASZHHIBQYYME-UHFFFAOYSA-N 1-[4-[2-[[4-(2-chlorophenoxy)pyridin-2-yl]amino]-1,3-thiazol-4-yl]piperidin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCC1C1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3)Cl)C=2)=N1 GBASZHHIBQYYME-UHFFFAOYSA-N 0.000 claims 1
- GKGPSKQWWOBPCF-UHFFFAOYSA-N 3-[2-[[3-(1-acetylpiperidin-4-yl)-1,2,4-thiadiazol-5-yl]amino]-5-bromopyridin-4-yl]oxy-4-chloro-n-[2-(dimethylamino)ethyl]benzamide Chemical compound CN(C)CCNC(=O)C1=CC=C(Cl)C(OC=2C(=CN=C(NC=3SN=C(N=3)C3CCN(CC3)C(C)=O)C=2)Br)=C1 GKGPSKQWWOBPCF-UHFFFAOYSA-N 0.000 claims 1
- CJTXXGSSOGGONY-UHFFFAOYSA-N 3-[2-[[4-(1-acetylpiperidin-4-yl)-1,3-thiazol-2-yl]amino]pyridin-4-yl]oxypyridine-4-carbonitrile Chemical compound C1CN(C(=O)C)CCC1C1=CSC(NC=2N=CC=C(OC=3C(=CC=NC=3)C#N)C=2)=N1 CJTXXGSSOGGONY-UHFFFAOYSA-N 0.000 claims 1
- 206010011953 Decreased activity Diseases 0.000 claims 1
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 35
- 208000035475 disorder Diseases 0.000 abstract description 24
- 230000001404 mediated effect Effects 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 10
- 208000037765 diseases and disorders Diseases 0.000 abstract description 7
- 230000001771 impaired effect Effects 0.000 abstract description 6
- 206010056997 Impaired fasting glucose Diseases 0.000 abstract description 5
- 230000002950 deficient Effects 0.000 abstract description 5
- 208000002705 Glucose Intolerance Diseases 0.000 abstract description 4
- 230000006806 disease prevention Effects 0.000 abstract description 4
- 201000009104 prediabetes syndrome Diseases 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 242
- 238000005160 1H NMR spectroscopy Methods 0.000 description 223
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 150
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 136
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 127
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 121
- 239000007787 solid Substances 0.000 description 121
- 239000011541 reaction mixture Substances 0.000 description 119
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 96
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 94
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 89
- 235000019439 ethyl acetate Nutrition 0.000 description 89
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
- 229910001868 water Inorganic materials 0.000 description 79
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 78
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 75
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 72
- 238000001819 mass spectrum Methods 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 238000006243 chemical reaction Methods 0.000 description 57
- 239000000243 solution Substances 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- 229910000160 potassium phosphate Inorganic materials 0.000 description 47
- 235000011009 potassium phosphates Nutrition 0.000 description 47
- 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 45
- 239000008103 glucose Substances 0.000 description 44
- 239000000047 product Substances 0.000 description 42
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 41
- LIEPVGBDUYKPLC-UHFFFAOYSA-N 2-chloro-4-nitropyridine Chemical compound [O-][N+](=O)C1=CC=NC(Cl)=C1 LIEPVGBDUYKPLC-UHFFFAOYSA-N 0.000 description 39
- 229910000104 sodium hydride Inorganic materials 0.000 description 39
- 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 38
- 239000002480 mineral oil Substances 0.000 description 38
- 235000010446 mineral oil Nutrition 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 36
- 239000012312 sodium hydride Substances 0.000 description 36
- 239000012074 organic phase Substances 0.000 description 35
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 34
- 239000000460 chlorine Substances 0.000 description 33
- 239000003921 oil Substances 0.000 description 33
- 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 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 29
- OUQMXTJYCAJLGO-UHFFFAOYSA-N 4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(N)=N1 OUQMXTJYCAJLGO-UHFFFAOYSA-N 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 23
- HVHKUWRSDVJVIH-UHFFFAOYSA-N n-[5-bromo-4-(2,6-difluorophenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC(Br)=C(OC=3C(=CC=CC=3F)F)C=2)=N1 HVHKUWRSDVJVIH-UHFFFAOYSA-N 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 239000007983 Tris buffer Substances 0.000 description 21
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 20
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 19
- 102000004877 Insulin Human genes 0.000 description 19
- 108090001061 Insulin Proteins 0.000 description 19
- 239000012267 brine Substances 0.000 description 19
- 229940125396 insulin Drugs 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- 125000001424 substituent group Chemical group 0.000 description 19
- QMHIMXFNBOYPND-UHFFFAOYSA-N 4-methylthiazole Chemical compound CC1=CSC=N1 QMHIMXFNBOYPND-UHFFFAOYSA-N 0.000 description 18
- 238000004519 manufacturing process Methods 0.000 description 18
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 18
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
- 238000010898 silica gel chromatography Methods 0.000 description 17
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 16
- 150000004820 halides Chemical class 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- 150000003254 radicals Chemical class 0.000 description 15
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 14
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 239000013058 crude material Substances 0.000 description 13
- 239000012039 electrophile Substances 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 239000004215 Carbon black (E152) Substances 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 125000001309 chloro group Chemical group Cl* 0.000 description 12
- 229930195733 hydrocarbon Natural products 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 11
- 125000001246 bromo group Chemical group Br* 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 229940124597 therapeutic agent Drugs 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- 230000004913 activation Effects 0.000 description 10
- BAPJBEWLBFYGME-UHFFFAOYSA-N acrylic acid methyl ester Natural products COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 239000003112 inhibitor Substances 0.000 description 9
- 239000008194 pharmaceutical composition Substances 0.000 description 9
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 8
- RZKVGQCJNANFDR-UHFFFAOYSA-N 5-chloro-1,2,4-thiadiazole Chemical compound ClC1=NC=NS1 RZKVGQCJNANFDR-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 206010006895 Cachexia Diseases 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000012954 diazonium Substances 0.000 description 8
- 150000001989 diazonium salts Chemical class 0.000 description 8
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 8
- HAKVNWBUOCSHTR-UHFFFAOYSA-N (9,9-dimethylxanthen-1-yl)-diphenylphosphane Chemical compound C=12C(C)(C)C3=CC=CC=C3OC2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 HAKVNWBUOCSHTR-UHFFFAOYSA-N 0.000 description 7
- ADHDUTITAKAASJ-UHFFFAOYSA-N 1,2,4-oxadiazol-5-amine Chemical compound NC1=NC=NO1 ADHDUTITAKAASJ-UHFFFAOYSA-N 0.000 description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 7
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 7
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 7
- 206010020772 Hypertension Diseases 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 239000012458 free base Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 235000011181 potassium carbonates Nutrition 0.000 description 7
- 239000012453 solvate Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- ACTKAGSPIFDCMF-UHFFFAOYSA-N 1,3-oxazol-2-amine Chemical compound NC1=NC=CO1 ACTKAGSPIFDCMF-UHFFFAOYSA-N 0.000 description 6
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 6
- BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 6
- LWFOJAUNZSYKEN-UHFFFAOYSA-N 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoic acid Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=C(C=CC=3)C(O)=O)C=2)=N1 LWFOJAUNZSYKEN-UHFFFAOYSA-N 0.000 description 6
- NBUWEWMAYHNFMM-UHFFFAOYSA-N 4-chloro-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoic acid;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=CC=C(C=3)C(O)=O)Cl)C=2)=N1 NBUWEWMAYHNFMM-UHFFFAOYSA-N 0.000 description 6
- CNPURSDMOWDNOQ-UHFFFAOYSA-N 4-methoxy-7h-pyrrolo[2,3-d]pyrimidin-2-amine Chemical compound COC1=NC(N)=NC2=C1C=CN2 CNPURSDMOWDNOQ-UHFFFAOYSA-N 0.000 description 6
- UOOPXWRBLYPXBT-UHFFFAOYSA-N 5-chloro-1,2,4-oxadiazole Chemical compound ClC1=NC=NO1 UOOPXWRBLYPXBT-UHFFFAOYSA-N 0.000 description 6
- SOGZPBPMAOZHGR-UHFFFAOYSA-N 6-[(4-methyl-1,3-thiazol-2-yl)amino]-4-naphthalen-1-yloxypyridine-3-carbaldehyde Chemical compound CC1=CSC(NC=2N=CC(C=O)=C(OC=3C4=CC=CC=C4C=CC=3)C=2)=N1 SOGZPBPMAOZHGR-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 102000005548 Hexokinase Human genes 0.000 description 6
- 108700040460 Hexokinases Proteins 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- 150000001409 amidines Chemical class 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
- 238000004587 chromatography analysis Methods 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- KSVRGYWTCUZLIM-UHFFFAOYSA-N ethyl 4-fluoro-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoate Chemical compound CCOC(=O)C1=CC=C(F)C(OC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 KSVRGYWTCUZLIM-UHFFFAOYSA-N 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 230000003914 insulin secretion Effects 0.000 description 6
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 230000000069 prophylactic effect Effects 0.000 description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 208000011580 syndromic disease Diseases 0.000 description 6
- JYFFFSZRWNGHHD-UHFFFAOYSA-N 2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoic acid Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3)C(O)=O)C=2)=N1 JYFFFSZRWNGHHD-UHFFFAOYSA-N 0.000 description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
- RVDOFHVTNXFOEK-UHFFFAOYSA-N 4-methyl-n-(4-phenylsulfanylpyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C=CC=CC=3)C=2)=N1 RVDOFHVTNXFOEK-UHFFFAOYSA-N 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
- 229920002527 Glycogen Polymers 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 206010022489 Insulin Resistance Diseases 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 150000002019 disulfides Chemical class 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 229940096919 glycogen Drugs 0.000 description 5
- 150000004678 hydrides Chemical class 0.000 description 5
- 210000003016 hypothalamus Anatomy 0.000 description 5
- 238000011065 in-situ storage Methods 0.000 description 5
- 239000013067 intermediate product Substances 0.000 description 5
- 125000005956 isoquinolyl group Chemical group 0.000 description 5
- 208000017169 kidney disease Diseases 0.000 description 5
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 229940095102 methyl benzoate Drugs 0.000 description 5
- NHEBDIWVHXNGMW-UHFFFAOYSA-N n-[4-(2-chlorophenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C(=CC=CC=3)Cl)C=2)=N1 NHEBDIWVHXNGMW-UHFFFAOYSA-N 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 125000006413 ring segment Chemical group 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 125000000335 thiazolyl group Chemical group 0.000 description 5
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 description 5
- JMYHHWKXFCFDSK-UHFFFAOYSA-N 2-(2,4-dimethylphenyl)indene-1,3-dione Chemical compound CC1=CC(C)=CC=C1C1C(=O)C2=CC=CC=C2C1=O JMYHHWKXFCFDSK-UHFFFAOYSA-N 0.000 description 4
- IVORPNVMYPQQMA-UHFFFAOYSA-N 2-chloro-4-(2,6-difluorophenoxy)pyridine Chemical compound FC1=CC=CC(F)=C1OC1=CC=NC(Cl)=C1 IVORPNVMYPQQMA-UHFFFAOYSA-N 0.000 description 4
- PSXZULQXUROAAM-UHFFFAOYSA-N 2-chloro-4-phenoxypyridine Chemical compound C1=NC(Cl)=CC(OC=2C=CC=CC=2)=C1 PSXZULQXUROAAM-UHFFFAOYSA-N 0.000 description 4
- DTWGZYZQUZUDLX-UHFFFAOYSA-N 2-chloro-4-phenylsulfanylpyridine Chemical compound C1=NC(Cl)=CC(SC=2C=CC=CC=2)=C1 DTWGZYZQUZUDLX-UHFFFAOYSA-N 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 4
- QQLKUJGWBUSGHW-UHFFFAOYSA-N 5-bromo-4-(2,6-difluorophenoxy)pyridin-2-amine Chemical compound C1=NC(N)=CC(OC=2C(=CC=CC=2F)F)=C1Br QQLKUJGWBUSGHW-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 description 4
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 208000008589 Obesity Diseases 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 4
- 125000005620 boronic acid group Chemical class 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- PJXRQEAIWNLFPR-UHFFFAOYSA-N ethyl 4-chloro-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(OC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 PJXRQEAIWNLFPR-UHFFFAOYSA-N 0.000 description 4
- IYJFHPMTZBJTNF-UHFFFAOYSA-N ethyl 6-[(4-methyl-1,3-thiazol-2-yl)amino]-4-naphthalen-1-yloxypyridine-3-carboxylate Chemical compound C1=C(OC=2C3=CC=CC=C3C=CC=2)C(C(=O)OCC)=CN=C1NC1=NC(C)=CS1 IYJFHPMTZBJTNF-UHFFFAOYSA-N 0.000 description 4
- MYLKAYRGMWSTHN-UHFFFAOYSA-N ethyl 6-[(4-methyl-1,3-thiazol-2-yl)amino]-4-phenoxypyridine-3-carboxylate Chemical compound C1=C(OC=2C=CC=CC=2)C(C(=O)OCC)=CN=C1NC1=NC(C)=CS1 MYLKAYRGMWSTHN-UHFFFAOYSA-N 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 201000001421 hyperglycemia Diseases 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 4
- PACOFIQUXCRVAD-UHFFFAOYSA-N n-(5-bromo-4-quinolin-5-yloxypyridin-2-yl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC(Br)=C(OC=3C4=CC=CN=C4C=CC=3)C=2)=N1 PACOFIQUXCRVAD-UHFFFAOYSA-N 0.000 description 4
- SPZVMOOOQIOAFT-UHFFFAOYSA-N n-[4-(3-methoxyphenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound COC1=CC=CC(OC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 SPZVMOOOQIOAFT-UHFFFAOYSA-N 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 210000000496 pancreas Anatomy 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 238000012746 preparative thin layer chromatography Methods 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000036186 satiety Effects 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 150000003568 thioethers Chemical class 0.000 description 4
- 150000003573 thiols Chemical class 0.000 description 4
- BXTWRMNZAGYXQQ-UHFFFAOYSA-N 1,2,4-oxadiazol-3-one Chemical compound O=C1N=CON1 BXTWRMNZAGYXQQ-UHFFFAOYSA-N 0.000 description 3
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 3
- ANZYSUCUCAKJSB-UHFFFAOYSA-N 2,6-dichloro-4-(2,6-difluorophenoxy)pyridine Chemical compound FC1=CC=CC(F)=C1OC1=CC(Cl)=NC(Cl)=C1 ANZYSUCUCAKJSB-UHFFFAOYSA-N 0.000 description 3
- HNUOAXKRCRARDI-UHFFFAOYSA-N 2-[(4-methyl-1,3-thiazol-2-yl)amino]-1h-pyridin-4-one Chemical compound CC1=CSC(NC=2N=CC=C(O)C=2)=N1 HNUOAXKRCRARDI-UHFFFAOYSA-N 0.000 description 3
- QVNLBUVZKXBZHW-UHFFFAOYSA-N 2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzonitrile Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3)C#N)C=2)=N1 QVNLBUVZKXBZHW-UHFFFAOYSA-N 0.000 description 3
- CHKKXYPPRMRFFD-UHFFFAOYSA-N 2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenol Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3)O)C=2)=N1 CHKKXYPPRMRFFD-UHFFFAOYSA-N 0.000 description 3
- NNTGMEABQDWVBU-UHFFFAOYSA-N 2-chloro-4-(1,2,3,4-tetrahydronaphthalen-1-yloxy)pyridine Chemical compound C1=NC(Cl)=CC(OC2C3=CC=CC=C3CCC2)=C1 NNTGMEABQDWVBU-UHFFFAOYSA-N 0.000 description 3
- PMMAVDWTURRMGN-UHFFFAOYSA-N 2-chloro-4-(2,6-dichlorophenyl)sulfanylpyridine Chemical compound C1=NC(Cl)=CC(SC=2C(=CC=CC=2Cl)Cl)=C1 PMMAVDWTURRMGN-UHFFFAOYSA-N 0.000 description 3
- AHBLZHXILGLMHB-UHFFFAOYSA-N 2-chloro-4-(2,6-dimethylphenoxy)pyridine Chemical compound CC1=CC=CC(C)=C1OC1=CC=NC(Cl)=C1 AHBLZHXILGLMHB-UHFFFAOYSA-N 0.000 description 3
- ZJGSREFSRODLLI-UHFFFAOYSA-N 2-chloro-4-(2,6-dimethylphenyl)sulfanylpyridine Chemical compound CC1=CC=CC(C)=C1SC1=CC=NC(Cl)=C1 ZJGSREFSRODLLI-UHFFFAOYSA-N 0.000 description 3
- ALOOKKQDCRJBSZ-UHFFFAOYSA-N 2-chloro-4-(2-chlorophenoxy)pyridine Chemical compound C1=NC(Cl)=CC(OC=2C(=CC=CC=2)Cl)=C1 ALOOKKQDCRJBSZ-UHFFFAOYSA-N 0.000 description 3
- XKWYCLNBPIFXKF-UHFFFAOYSA-N 2-chloro-4-(2-chlorophenyl)sulfanylpyridine Chemical compound C1=NC(Cl)=CC(SC=2C(=CC=CC=2)Cl)=C1 XKWYCLNBPIFXKF-UHFFFAOYSA-N 0.000 description 3
- AJVLUWIRLKEYEX-UHFFFAOYSA-N 2-chloro-4-(2-methylphenyl)sulfanylpyridine Chemical compound CC1=CC=CC=C1SC1=CC=NC(Cl)=C1 AJVLUWIRLKEYEX-UHFFFAOYSA-N 0.000 description 3
- OPOMFBDSFOAIAG-UHFFFAOYSA-N 2-chloro-4-(3-methoxyphenyl)sulfanylpyridine Chemical compound COC1=CC=CC(SC=2C=C(Cl)N=CC=2)=C1 OPOMFBDSFOAIAG-UHFFFAOYSA-N 0.000 description 3
- BUFNFADOSRVYAZ-UHFFFAOYSA-N 2-chloro-4-(4-chlorophenyl)sulfanylpyridine Chemical compound C1=CC(Cl)=CC=C1SC1=CC=NC(Cl)=C1 BUFNFADOSRVYAZ-UHFFFAOYSA-N 0.000 description 3
- UTBBTFACHGEZSK-UHFFFAOYSA-N 2-chloro-4-(4-methoxyphenoxy)pyridine Chemical compound C1=CC(OC)=CC=C1OC1=CC=NC(Cl)=C1 UTBBTFACHGEZSK-UHFFFAOYSA-N 0.000 description 3
- SBSLVJWNBABGPU-UHFFFAOYSA-N 2-chloro-4-cyclohexyloxypyridine Chemical compound C1=NC(Cl)=CC(OC2CCCCC2)=C1 SBSLVJWNBABGPU-UHFFFAOYSA-N 0.000 description 3
- XZLZQERVHJHMAL-UHFFFAOYSA-N 2-chloro-4-phenylmethoxypyridine Chemical compound C1=NC(Cl)=CC(OCC=2C=CC=CC=2)=C1 XZLZQERVHJHMAL-UHFFFAOYSA-N 0.000 description 3
- MAYSVJKOHYVHTH-UHFFFAOYSA-N 2-chloro-4-pyridin-3-yloxypyridine Chemical compound C1=NC(Cl)=CC(OC=2C=NC=CC=2)=C1 MAYSVJKOHYVHTH-UHFFFAOYSA-N 0.000 description 3
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 3
- UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 3
- MDAHCYDXIBCSRX-UHFFFAOYSA-N 4-(2,6-difluorophenoxy)-6-[(4-methyl-1,3-thiazol-2-yl)amino]pyridine-3-carbaldehyde Chemical compound CC1=CSC(NC=2N=CC(C=O)=C(OC=3C(=CC=CC=3F)F)C=2)=N1 MDAHCYDXIBCSRX-UHFFFAOYSA-N 0.000 description 3
- RHVFTZSBVFHFED-UHFFFAOYSA-N 4-methyl-n-(4-naphthalen-1-yloxypyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C4=CC=CC=C4C=CC=3)C=2)=N1 RHVFTZSBVFHFED-UHFFFAOYSA-N 0.000 description 3
- YCUOTYKRHLQUMR-UHFFFAOYSA-N 4-methyl-n-(4-naphthalen-1-ylsulfanylpyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C4=CC=CC=C4C=CC=3)C=2)=N1 YCUOTYKRHLQUMR-UHFFFAOYSA-N 0.000 description 3
- IAKNIUVASPWEAL-UHFFFAOYSA-N 4-methyl-n-(4-phenoxypyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=CC=CC=3)C=2)=N1 IAKNIUVASPWEAL-UHFFFAOYSA-N 0.000 description 3
- MPWFKZNDKISUOP-UHFFFAOYSA-N 4-methyl-n-(4-pyridin-2-ylsulfanylpyridin-2-yl)-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(SC=3N=CC=CC=3)C=2)=N1 MPWFKZNDKISUOP-UHFFFAOYSA-N 0.000 description 3
- KVFKUWCYMZOGDT-UHFFFAOYSA-N 4-methyl-n-(4-pyridin-3-yloxypyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=NC=CC=3)C=2)=N1 KVFKUWCYMZOGDT-UHFFFAOYSA-N 0.000 description 3
- RTHUVURUAUEROG-UHFFFAOYSA-N 4-methyl-n-[4-(1-methylimidazol-2-yl)sulfanylpyridin-2-yl]-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC=C(SC=3N(C=CN=3)C)C=2)=N1 RTHUVURUAUEROG-UHFFFAOYSA-N 0.000 description 3
- NESAZMRCKQUGTQ-UHFFFAOYSA-N 4-methyl-n-[4-(2-methylphenyl)sulfanylpyridin-2-yl]-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C(=CC=CC=3)C)C=2)=N1 NESAZMRCKQUGTQ-UHFFFAOYSA-N 0.000 description 3
- PQJAJRSUZVHLNX-UHFFFAOYSA-N 4-methyl-n-[4-[2-(trifluoromethyl)phenyl]sulfanylpyridin-2-yl]-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C(=CC=CC=3)C(F)(F)F)C=2)=N1 PQJAJRSUZVHLNX-UHFFFAOYSA-N 0.000 description 3
- QQFKAEQJOFCECU-UHFFFAOYSA-N 5-bromo-3-chloro-4-(2,6-difluorophenoxy)pyridin-2-amine Chemical compound NC1=NC=C(Br)C(OC=2C(=CC=CC=2F)F)=C1Cl QQFKAEQJOFCECU-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 201000001320 Atherosclerosis Diseases 0.000 description 3
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 3
- 208000002249 Diabetes Complications Diseases 0.000 description 3
- 206010012655 Diabetic complications Diseases 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010060378 Hyperinsulinaemia Diseases 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 108010025020 Nerve Growth Factor Proteins 0.000 description 3
- 229910019213 POCl3 Inorganic materials 0.000 description 3
- 206010041277 Sodium retention Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 3
- QKHDNYQVOKSVQQ-UHFFFAOYSA-N [2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]-phenylmethanol Chemical compound CC1=CSC(NC=2N=CC=C(C=2)C(O)C=2C=CC=CC=2)=N1 QKHDNYQVOKSVQQ-UHFFFAOYSA-N 0.000 description 3
- UREQCPCBVVWORR-UHFFFAOYSA-N [6-[(4-methyl-1,3-thiazol-2-yl)amino]-4-naphthalen-1-yloxypyridin-3-yl]methanol Chemical compound CC1=CSC(NC=2N=CC(CO)=C(OC=3C4=CC=CC=C4C=CC=3)C=2)=N1 UREQCPCBVVWORR-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 239000000883 anti-obesity agent Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 3
- 150000004832 aryl thioethers Chemical class 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 208000026106 cerebrovascular disease Diseases 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- NQAFOVLSHJCBAM-UHFFFAOYSA-N ethyl 4-chloro-3-(2-chloropyridin-4-yl)oxybenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(OC=2C=C(Cl)N=CC=2)=C1 NQAFOVLSHJCBAM-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 230000003451 hyperinsulinaemic effect Effects 0.000 description 3
- 201000008980 hyperinsulinism Diseases 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- WZMHQNQQNSPRAI-UHFFFAOYSA-N methyl 2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoate Chemical compound COC(=O)C1=CC=CC=C1OC1=CC=NC(NC=2SC=C(C)N=2)=C1 WZMHQNQQNSPRAI-UHFFFAOYSA-N 0.000 description 3
- GECXOBCCDDNFFT-UHFFFAOYSA-N methyl 3-(2-chloropyridin-4-yl)oxybenzoate Chemical compound COC(=O)C1=CC=CC(OC=2C=C(Cl)N=CC=2)=C1 GECXOBCCDDNFFT-UHFFFAOYSA-N 0.000 description 3
- CQHCHCYJGOKQEP-UHFFFAOYSA-N methyl 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]sulfanylbenzoate Chemical compound COC(=O)C1=CC=CC(SC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 CQHCHCYJGOKQEP-UHFFFAOYSA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- BRDIJHGBTFAGBS-UHFFFAOYSA-N n-(4-cyclohexyloxypyridin-2-yl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC3CCCCC3)C=2)=N1 BRDIJHGBTFAGBS-UHFFFAOYSA-N 0.000 description 3
- KYDRRSFGAHTGDF-UHFFFAOYSA-N n-[4-(2,3-dichlorophenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C(=C(Cl)C=CC=3)Cl)C=2)=N1 KYDRRSFGAHTGDF-UHFFFAOYSA-N 0.000 description 3
- YMRBZXCIBSNKRK-UHFFFAOYSA-N n-[4-(2,6-dichlorophenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3Cl)Cl)C=2)=N1 YMRBZXCIBSNKRK-UHFFFAOYSA-N 0.000 description 3
- YMBFYLDCAJVYCN-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3F)F)C=2)=N1 YMBFYLDCAJVYCN-UHFFFAOYSA-N 0.000 description 3
- MJKRQFUAUJQINP-UHFFFAOYSA-N n-[4-(2,6-dimethylphenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3C)C)C=2)=N1 MJKRQFUAUJQINP-UHFFFAOYSA-N 0.000 description 3
- KDFKXAQQFRBJGR-UHFFFAOYSA-N n-[4-(2,6-dimethylphenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C(=CC=CC=3C)C)C=2)=N1 KDFKXAQQFRBJGR-UHFFFAOYSA-N 0.000 description 3
- VPSOVPAOIHAJJC-UHFFFAOYSA-N n-[4-(2-chlorophenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3)Cl)C=2)=N1 VPSOVPAOIHAJJC-UHFFFAOYSA-N 0.000 description 3
- IBNLEIRKNFBCCF-UHFFFAOYSA-N n-[4-(2-methoxyphenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound COC1=CC=CC=C1OC1=CC=NC(NC=2SC=C(C)N=2)=C1 IBNLEIRKNFBCCF-UHFFFAOYSA-N 0.000 description 3
- HGCAVLCYWUKUET-UHFFFAOYSA-N n-[4-(3-methoxyphenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound COC1=CC=CC(SC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 HGCAVLCYWUKUET-UHFFFAOYSA-N 0.000 description 3
- IPTJVUPVQSSPHZ-UHFFFAOYSA-N n-[4-(4-methoxyphenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1=CC(OC)=CC=C1OC1=CC=NC(NC=2SC=C(C)N=2)=C1 IPTJVUPVQSSPHZ-UHFFFAOYSA-N 0.000 description 3
- DMFGYLVSOBSRIN-UHFFFAOYSA-N n-[4-[3-[tert-butyl(dimethyl)silyl]oxyphenyl]sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C=C(O[Si](C)(C)C(C)(C)C)C=CC=3)C=2)=N1 DMFGYLVSOBSRIN-UHFFFAOYSA-N 0.000 description 3
- ZKEFQKHIEKRANN-UHFFFAOYSA-N n-[5-bromo-3-chloro-4-(2,6-difluorophenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2C(=C(OC=3C(=CC=CC=3F)F)C(Br)=CN=2)Cl)=N1 ZKEFQKHIEKRANN-UHFFFAOYSA-N 0.000 description 3
- RFCPVMSXGOHGRI-UHFFFAOYSA-N n-[[5-bromo-3-chloro-4-(2,6-difluorophenoxy)pyridin-2-yl]carbamothioyl]benzamide Chemical compound FC1=CC=CC(F)=C1OC1=C(Br)C=NC(NC(=S)NC(=O)C=2C=CC=CC=2)=C1Cl RFCPVMSXGOHGRI-UHFFFAOYSA-N 0.000 description 3
- YOGJSWASYRCLHJ-UHFFFAOYSA-N n-[[5-bromo-4-(2,6-difluorophenoxy)pyridin-2-yl]carbamothioyl]benzamide Chemical compound FC1=CC=CC(F)=C1OC1=CC(NC(=S)NC(=O)C=2C=CC=CC=2)=NC=C1Br YOGJSWASYRCLHJ-UHFFFAOYSA-N 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- 125000005936 piperidyl group Chemical group 0.000 description 3
- 150000003140 primary amides Chemical class 0.000 description 3
- FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- DIZAUAODINUDTA-UHFFFAOYSA-N tert-butyl 4-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxypiperidine-1-carboxylate Chemical compound CC1=CSC(NC=2N=CC=C(OC3CCN(CC3)C(=O)OC(C)(C)C)C=2)=N1 DIZAUAODINUDTA-UHFFFAOYSA-N 0.000 description 3
- VZDCNGBPNKYXOE-UHFFFAOYSA-N tert-butyl-[3-(2-chloropyridin-4-yl)sulfanylphenoxy]-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=CC(SC=2C=C(Cl)N=CC=2)=C1 VZDCNGBPNKYXOE-UHFFFAOYSA-N 0.000 description 3
- 150000003511 tertiary amides Chemical class 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 125000001425 triazolyl group Chemical group 0.000 description 3
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 3
- WAAPEIZFCHNLKK-UFBFGSQYSA-N (2s,4s)-6-fluoro-2',5'-dioxospiro[2,3-dihydrochromene-4,4'-imidazolidine]-2-carboxamide Chemical compound C([C@H](OC1=CC=C(F)C=C11)C(=O)N)[C@@]21NC(=O)NC2=O WAAPEIZFCHNLKK-UFBFGSQYSA-N 0.000 description 2
- VJHTZTZXOKVQRN-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine Chemical compound NC1=NC=NS1 VJHTZTZXOKVQRN-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 2
- CKKOVFGIBXCEIJ-UHFFFAOYSA-N 2,6-difluorophenol Chemical compound OC1=C(F)C=CC=C1F CKKOVFGIBXCEIJ-UHFFFAOYSA-N 0.000 description 2
- FIUFVLXDLQBXRW-UHFFFAOYSA-N 2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridine-4-carbaldehyde Chemical compound CC1=CSC(NC=2N=CC=C(C=O)C=2)=N1 FIUFVLXDLQBXRW-UHFFFAOYSA-N 0.000 description 2
- FHEYFIGWYQJVDR-ACJLOTCBSA-N 2-[[3-[(2r)-2-[[(2r)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1h-indol-7-yl]oxy]acetic acid Chemical compound C1([C@@H](O)CN[C@@H](CC=2C3=CC=CC(OCC(O)=O)=C3NC=2)C)=CC=CC(Cl)=C1 FHEYFIGWYQJVDR-ACJLOTCBSA-N 0.000 description 2
- ZUVHDLAVNXXPFX-UHFFFAOYSA-N 2-chloro-3-fluoro-4-phenylsulfanylpyridine Chemical compound C1=CN=C(Cl)C(F)=C1SC1=CC=CC=C1 ZUVHDLAVNXXPFX-UHFFFAOYSA-N 0.000 description 2
- PAWFRALNPUUDGC-UHFFFAOYSA-N 2-chloro-4-(1-methylimidazol-2-yl)sulfanylpyridine Chemical compound CN1C=CN=C1SC1=CC=NC(Cl)=C1 PAWFRALNPUUDGC-UHFFFAOYSA-N 0.000 description 2
- ANDAUMGOLYIIMM-UHFFFAOYSA-N 2-chloro-4-(2,3-dichlorophenyl)sulfanylpyridine Chemical compound C1=NC(Cl)=CC(SC=2C(=C(Cl)C=CC=2)Cl)=C1 ANDAUMGOLYIIMM-UHFFFAOYSA-N 0.000 description 2
- GXFNZHORHXUMEF-UHFFFAOYSA-N 2-chloro-4-(2-methoxyphenoxy)pyridine Chemical compound COC1=CC=CC=C1OC1=CC=NC(Cl)=C1 GXFNZHORHXUMEF-UHFFFAOYSA-N 0.000 description 2
- QDBRMJLTRUVYKJ-UHFFFAOYSA-N 2-chloro-4-(2-propan-2-ylphenyl)sulfanylpyridine Chemical compound CC(C)C1=CC=CC=C1SC1=CC=NC(Cl)=C1 QDBRMJLTRUVYKJ-UHFFFAOYSA-N 0.000 description 2
- WQYXWFNNLTVXSL-UHFFFAOYSA-N 2-chloro-4-(3-chlorophenyl)sulfanylpyridine Chemical compound ClC1=CC=CC(SC=2C=C(Cl)N=CC=2)=C1 WQYXWFNNLTVXSL-UHFFFAOYSA-N 0.000 description 2
- WYHUKLFKGRVQRZ-UHFFFAOYSA-N 2-chloro-4-(3-methoxyphenoxy)pyridine Chemical compound COC1=CC=CC(OC=2C=C(Cl)N=CC=2)=C1 WYHUKLFKGRVQRZ-UHFFFAOYSA-N 0.000 description 2
- ANTXOSQTTRWBQB-UHFFFAOYSA-N 2-chloro-4-(5,6,7,8-tetrahydronaphthalen-1-yloxy)pyridine Chemical compound C1=NC(Cl)=CC(OC=2C=3CCCCC=3C=CC=2)=C1 ANTXOSQTTRWBQB-UHFFFAOYSA-N 0.000 description 2
- GJTKJPMHCUGCSF-UHFFFAOYSA-N 2-chloro-4-[(4-methoxyphenyl)methylsulfanyl]pyridine Chemical compound C1=CC(OC)=CC=C1CSC1=CC=NC(Cl)=C1 GJTKJPMHCUGCSF-UHFFFAOYSA-N 0.000 description 2
- CIIUEEHIMGBIKW-UHFFFAOYSA-N 2-chloro-4-[2-(trifluoromethyl)phenyl]sulfanylpyridine Chemical compound FC(F)(F)C1=CC=CC=C1SC1=CC=NC(Cl)=C1 CIIUEEHIMGBIKW-UHFFFAOYSA-N 0.000 description 2
- XGJDRIYTMNXBHQ-UHFFFAOYSA-N 2-chloro-4-naphthalen-1-yloxypyridine Chemical compound C1=NC(Cl)=CC(OC=2C3=CC=CC=C3C=CC=2)=C1 XGJDRIYTMNXBHQ-UHFFFAOYSA-N 0.000 description 2
- HIWXQFCOBFFMQQ-UHFFFAOYSA-N 2-chloro-4-naphthalen-1-ylsulfanylpyridine Chemical compound C1=NC(Cl)=CC(SC=2C3=CC=CC=C3C=CC=2)=C1 HIWXQFCOBFFMQQ-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- KDRUIMNNZBMLJR-UHFFFAOYSA-N 2-isopropylaminoethylamine Chemical compound CC(C)NCCN KDRUIMNNZBMLJR-UHFFFAOYSA-N 0.000 description 2
- 125000004398 2-methyl-2-butyl group Chemical group CC(C)(CC)* 0.000 description 2
- 125000004918 2-methyl-2-pentyl group Chemical group CC(C)(CCC)* 0.000 description 2
- 125000004922 2-methyl-3-pentyl group Chemical group CC(C)C(CC)* 0.000 description 2
- OSJCYHAGZBUVIF-UHFFFAOYSA-N 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenol Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=C(O)C=CC=3)C=2)=N1 OSJCYHAGZBUVIF-UHFFFAOYSA-N 0.000 description 2
- NKANAHBQTNHUGB-UHFFFAOYSA-N 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]sulfanylphenol Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C=C(O)C=CC=3)C=2)=N1 NKANAHBQTNHUGB-UHFFFAOYSA-N 0.000 description 2
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 2
- 125000004917 3-methyl-2-butyl group Chemical group CC(C(C)*)C 0.000 description 2
- 125000004919 3-methyl-2-pentyl group Chemical group CC(C(C)*)CC 0.000 description 2
- 125000004921 3-methyl-3-pentyl group Chemical group CC(CC)(CC)* 0.000 description 2
- TXCZOLMHGLSPIF-UHFFFAOYSA-N 4-(2,6-dichlorophenyl)sulfanyl-6-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-3-ol Chemical compound CC1=CSC(NC=2N=CC(O)=C(SC=3C(=CC=CC=3Cl)Cl)C=2)=N1 TXCZOLMHGLSPIF-UHFFFAOYSA-N 0.000 description 2
- GCOQUSYRJNBELD-UHFFFAOYSA-N 4-(2,6-difluorophenoxy)pyridin-2-amine Chemical compound C1=NC(N)=CC(OC=2C(=CC=CC=2F)F)=C1 GCOQUSYRJNBELD-UHFFFAOYSA-N 0.000 description 2
- SFRJYTMDYQJDRR-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methylsulfanyl]pyridin-2-amine Chemical compound C1=CC(OC)=CC=C1CSC1=CC=NC(N)=C1 SFRJYTMDYQJDRR-UHFFFAOYSA-N 0.000 description 2
- VYBPEUZJHORROU-UHFFFAOYSA-N 4-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenol Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=CC(O)=CC=3)C=2)=N1 VYBPEUZJHORROU-UHFFFAOYSA-N 0.000 description 2
- YTFZMXFDZMAALK-UHFFFAOYSA-N 4-chloro-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxy-n-(3-morpholin-4-ylpropyl)benzamide;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=CC=C(C=3)C(=O)NCCCN3CCOCC3)Cl)C=2)=N1 YTFZMXFDZMAALK-UHFFFAOYSA-N 0.000 description 2
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 2
- 125000004920 4-methyl-2-pentyl group Chemical group CC(CC(C)*)C 0.000 description 2
- XDTJHZWPGWLGEC-UHFFFAOYSA-N 4-methyl-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoic acid;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=CC=C(C=3)C(O)=O)C)C=2)=N1 XDTJHZWPGWLGEC-UHFFFAOYSA-N 0.000 description 2
- HNMPEPGTTIGTTM-UHFFFAOYSA-N 4-methyl-n-(4-phenoxypyrimidin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=C(OC=3C=CC=CC=3)C=CN=2)=N1 HNMPEPGTTIGTTM-UHFFFAOYSA-N 0.000 description 2
- UVODOQIQPVABEQ-UHFFFAOYSA-N 4-methyl-n-(4-phenylmethoxypyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OCC=3C=CC=CC=3)C=2)=N1 UVODOQIQPVABEQ-UHFFFAOYSA-N 0.000 description 2
- PHODYAGBIYBQOB-UHFFFAOYSA-N 4-methyl-n-(6-phenoxypyrimidin-4-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CN=C(OC=3C=CC=CC=3)C=2)=N1 PHODYAGBIYBQOB-UHFFFAOYSA-N 0.000 description 2
- MRLJAXJWGWVADG-UHFFFAOYSA-N 4-methyl-n-[4-(1,2,3,4-tetrahydronaphthalen-1-yloxy)pyridin-2-yl]-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC3C4=CC=CC=C4CCC3)C=2)=N1 MRLJAXJWGWVADG-UHFFFAOYSA-N 0.000 description 2
- JVICVJCRTGTFJJ-UHFFFAOYSA-N 4-methyl-n-[4-(2-propan-2-ylphenyl)sulfanylpyridin-2-yl]-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.CC(C)C1=CC=CC=C1SC1=CC=NC(NC=2SC=C(C)N=2)=C1 JVICVJCRTGTFJJ-UHFFFAOYSA-N 0.000 description 2
- ZDKHIEVGROTZOL-UHFFFAOYSA-N 4-methyl-n-[4-(5,6,7,8-tetrahydronaphthalen-1-yloxy)pyridin-2-yl]-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C=4CCCCC=4C=CC=3)C=2)=N1 ZDKHIEVGROTZOL-UHFFFAOYSA-N 0.000 description 2
- RAFCWIXBEWVPGL-UHFFFAOYSA-N 4-phenylmethoxypyridin-2-amine Chemical compound C1=NC(N)=CC(OCC=2C=CC=CC=2)=C1 RAFCWIXBEWVPGL-UHFFFAOYSA-N 0.000 description 2
- LGPVXXJBWWYOSL-UHFFFAOYSA-N 4-propan-2-yl-1,3-thiazol-2-amine Chemical compound CC(C)C1=CSC(N)=N1 LGPVXXJBWWYOSL-UHFFFAOYSA-N 0.000 description 2
- NFGWPFHOAJYJIY-UHFFFAOYSA-N 5-bromo-4-phenylmethoxypyridin-2-amine Chemical compound C1=NC(N)=CC(OCC=2C=CC=CC=2)=C1Br NFGWPFHOAJYJIY-UHFFFAOYSA-N 0.000 description 2
- KYTSJYHJZIQKMD-UHFFFAOYSA-N 6-[(4-methyl-1,3-thiazol-2-yl)amino]-4-phenoxypyridine-3-carboxylic acid;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC(=C(OC=3C=CC=CC=3)C=2)C(O)=O)=N1 KYTSJYHJZIQKMD-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- 241000349731 Afzelia bipindensis Species 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 2
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 2
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 2
- YVIXXPCJZAUQHJ-YGRLFVJLSA-N Cp-114271 Chemical compound C([C@@H](C)NC[C@H](O)C=1N=C(SC=1)C(F)(F)F)C1=CC=C(OCC(O)=O)C=C1 YVIXXPCJZAUQHJ-YGRLFVJLSA-N 0.000 description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 description 2
- 102400000321 Glucagon Human genes 0.000 description 2
- 108060003199 Glucagon Proteins 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- 206010019708 Hepatic steatosis Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 206010020710 Hyperphagia Diseases 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 238000006411 Negishi coupling reaction Methods 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 102000007072 Nerve Growth Factors Human genes 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical class ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 208000004880 Polyuria Diseases 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 description 2
- 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 description 2
- 201000002661 Spondylitis Diseases 0.000 description 2
- 229940100389 Sulfonylurea Drugs 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- AHAWZRKEWDISIG-UHFFFAOYSA-N [2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]-phenylmethanone;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(C=2)C(=O)C=2C=CC=CC=2)=N1 AHAWZRKEWDISIG-UHFFFAOYSA-N 0.000 description 2
- KGCVJDUQNBGQPW-UHFFFAOYSA-N [5-bromo-4-(2,6-difluorophenoxy)pyridin-2-yl]thiourea Chemical compound C1=NC(NC(=S)N)=CC(OC=2C(=CC=CC=2F)F)=C1Br KGCVJDUQNBGQPW-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 229950003476 aminothiazole Drugs 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 239000003524 antilipemic agent Substances 0.000 description 2
- 229940125710 antiobesity agent Drugs 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
- 239000008228 bacteriostatic water for injection Substances 0.000 description 2
- UDSRUCAJZSIRHZ-UHFFFAOYSA-N benzamide dihydrochloride Chemical compound Cl.Cl.NC(=O)C1=CC=CC=C1.NC(=O)C1=CC=CC=C1 UDSRUCAJZSIRHZ-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 150000004283 biguanides Chemical class 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 235000013877 carbamide Nutrition 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 150000001723 carbon free-radicals Chemical class 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
- DZFSTAUMUPHORN-NRFANRHFSA-N cyclohexyl-[[4-[2-[[(2s)-2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethyl]phenoxy]methyl]phosphinic acid Chemical compound C([C@H](O)COC=1C=CC(O)=CC=1)NCCC(C=C1)=CC=C1OCP(O)(=O)C1CCCCC1 DZFSTAUMUPHORN-NRFANRHFSA-N 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 201000003146 cystitis Diseases 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 2
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- NMKUEPBHWWORJL-UHFFFAOYSA-N ethyl 3-(2-aminopyridin-4-yl)oxy-4-chlorobenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(OC=2C=C(N)N=CC=2)=C1 NMKUEPBHWWORJL-UHFFFAOYSA-N 0.000 description 2
- RFAZPRWOUABBAA-UHFFFAOYSA-N ethyl 3-(2-chloropyridin-4-yl)oxy-4-methylbenzoate Chemical compound CCOC(=O)C1=CC=C(C)C(OC=2C=C(Cl)N=CC=2)=C1 RFAZPRWOUABBAA-UHFFFAOYSA-N 0.000 description 2
- VLAYLJNWKAGNTB-UHFFFAOYSA-N ethyl 3-[5-bromo-2-[[4-(2-phenylethyl)-1,3-thiazol-2-yl]amino]pyridin-4-yl]oxy-4-chlorobenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(OC=2C(=CN=C(NC=3SC=C(CCC=4C=CC=CC=4)N=3)C=2)Br)=C1 VLAYLJNWKAGNTB-UHFFFAOYSA-N 0.000 description 2
- PFISJNBRAOSYPV-UHFFFAOYSA-N ethyl 4-chloro-3-hydroxybenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(O)=C1 PFISJNBRAOSYPV-UHFFFAOYSA-N 0.000 description 2
- QHHXWDUWCUCEIX-UHFFFAOYSA-N ethyl 6-chloro-4-naphthalen-1-yloxypyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1OC1=CC=CC2=CC=CC=C12 QHHXWDUWCUCEIX-UHFFFAOYSA-N 0.000 description 2
- XTEKENNBEPCICE-UHFFFAOYSA-N ethyl 6-chloro-4-phenoxypyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1OC1=CC=CC=C1 XTEKENNBEPCICE-UHFFFAOYSA-N 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 2
- 229960004666 glucagon Drugs 0.000 description 2
- 230000004190 glucose uptake Effects 0.000 description 2
- 230000002641 glycemic effect Effects 0.000 description 2
- 230000034659 glycolysis Effects 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 2
- 208000006575 hypertriglyceridemia Diseases 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
- 229960003105 metformin Drugs 0.000 description 2
- GDWFDENYUSWACI-UHFFFAOYSA-N methyl 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoate Chemical compound COC(=O)C1=CC=CC(OC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 GDWFDENYUSWACI-UHFFFAOYSA-N 0.000 description 2
- UYAKRHXSEOBYPJ-UHFFFAOYSA-N methyl 3-[4-(2,6-difluorophenoxy)-6-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-3-yl]sulfanylpropanoate Chemical compound C1=C(OC=2C(=CC=CC=2F)F)C(SCCC(=O)OC)=CN=C1NC1=NC(C)=CS1 UYAKRHXSEOBYPJ-UHFFFAOYSA-N 0.000 description 2
- YKUCHDXIBAQWSF-UHFFFAOYSA-N methyl 3-hydroxybenzoate Chemical compound COC(=O)C1=CC=CC(O)=C1 YKUCHDXIBAQWSF-UHFFFAOYSA-N 0.000 description 2
- LDTLDBDUBGAEDT-UHFFFAOYSA-N methyl 3-sulfanylpropanoate Chemical compound COC(=O)CCS LDTLDBDUBGAEDT-UHFFFAOYSA-N 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 0.000 description 2
- INHJHPSOZLMHOX-UHFFFAOYSA-N n-(3-fluoro-4-phenylsulfanylpyridin-2-yl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2C(=C(SC=3C=CC=CC=3)C=CN=2)F)=N1 INHJHPSOZLMHOX-UHFFFAOYSA-N 0.000 description 2
- DLOZAARWCDSPQI-UHFFFAOYSA-N n-[(5-bromo-4-phenylmethoxypyridin-2-yl)carbamothioyl]benzamide Chemical compound C1=C(OCC=2C=CC=CC=2)C(Br)=CN=C1NC(=S)NC(=O)C1=CC=CC=C1 DLOZAARWCDSPQI-UHFFFAOYSA-N 0.000 description 2
- YMUQQBSJUIAYDS-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]sulfanylbenzamide;dihydrochloride Chemical compound Cl.Cl.CN(C)CCNC(=O)C1=CC=CC(SC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 YMUQQBSJUIAYDS-UHFFFAOYSA-N 0.000 description 2
- CCGDRBKXGPAHJS-UHFFFAOYSA-N n-[4-(2,4-dichlorophenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C(=CC(Cl)=CC=3)Cl)C=2)=N1 CCGDRBKXGPAHJS-UHFFFAOYSA-N 0.000 description 2
- ZXGPDQIHDKAEGM-UHFFFAOYSA-N n-[4-(2,6-dichlorophenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C(=CC=CC=3Cl)Cl)C=2)=N1 ZXGPDQIHDKAEGM-UHFFFAOYSA-N 0.000 description 2
- GZPIXZRSEWRNHC-UHFFFAOYSA-N n-[4-(2,6-dichlorophenyl)sulfanylpyridin-2-yl]-4-propan-2-yl-1,3-thiazol-2-amine Chemical compound CC(C)C1=CSC(NC=2N=CC=C(SC=3C(=CC=CC=3Cl)Cl)C=2)=N1 GZPIXZRSEWRNHC-UHFFFAOYSA-N 0.000 description 2
- BXKJBXFBCCEKLY-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)-5-methoxypyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1=C(OC=2C(=CC=CC=2F)F)C(OC)=CN=C1NC1=NC(C)=CS1 BXKJBXFBCCEKLY-UHFFFAOYSA-N 0.000 description 2
- JROFAFABZUONFI-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)pyridin-2-yl]-5-methyl-[1,3]thiazolo[5,4-b]pyridin-2-amine;hydrochloride Chemical compound Cl.S1C2=NC(C)=CC=C2N=C1NC(N=CC=1)=CC=1OC1=C(F)C=CC=C1F JROFAFABZUONFI-UHFFFAOYSA-N 0.000 description 2
- GZFNEPIHLJQPGO-UHFFFAOYSA-N n-[4-(3-chlorophenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C=C(Cl)C=CC=3)C=2)=N1 GZFNEPIHLJQPGO-UHFFFAOYSA-N 0.000 description 2
- HPSWOAYOLFJXCW-UHFFFAOYSA-N n-[4-(4-chlorophenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C=CC(Cl)=CC=3)C=2)=N1 HPSWOAYOLFJXCW-UHFFFAOYSA-N 0.000 description 2
- XUORRRAFJIEDDW-UHFFFAOYSA-N n-[4-(benzenesulfinyl)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(C=2)S(=O)C=2C=CC=CC=2)=N1 XUORRRAFJIEDDW-UHFFFAOYSA-N 0.000 description 2
- NYNUXUILLDFCNK-UHFFFAOYSA-N n-[4-(benzenesulfonyl)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(C=2)S(=O)(=O)C=2C=CC=CC=2)=N1 NYNUXUILLDFCNK-UHFFFAOYSA-N 0.000 description 2
- XWLVOJZVWRCRMD-OFNKIYASSA-N n-[5-[(1r)-2-[[(1r)-1-[4-(difluoromethoxy)phenyl]-2-phenylethyl]amino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide Chemical compound C1=C(O)C(NS(=O)(=O)C)=CC([C@@H](O)CN[C@H](CC=2C=CC=CC=2)C=2C=CC(OC(F)F)=CC=2)=C1 XWLVOJZVWRCRMD-OFNKIYASSA-N 0.000 description 2
- IFIPUGLSGXICKY-UHFFFAOYSA-N n-[6-chloro-4-(2,6-difluorophenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=C(Cl)C=C(OC=3C(=CC=CC=3F)F)C=2)=N1 IFIPUGLSGXICKY-UHFFFAOYSA-N 0.000 description 2
- LOOUNJKLQFUYOT-UHFFFAOYSA-N n-[[5-bromo-4-[(4-methoxyphenyl)methylsulfanyl]pyridin-2-yl]carbamothioyl]benzamide Chemical compound C1=CC(OC)=CC=C1CSC1=CC(NC(=S)NC(=O)C=2C=CC=CC=2)=NC=C1Br LOOUNJKLQFUYOT-UHFFFAOYSA-N 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 239000003900 neurotrophic factor Substances 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- 231100000822 oral exposure Toxicity 0.000 description 2
- 238000007410 oral glucose tolerance test Methods 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 206010036067 polydipsia Diseases 0.000 description 2
- 208000022530 polyphagia Diseases 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 2
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229910052702 rhenium Inorganic materials 0.000 description 2
- 235000019627 satiety Nutrition 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class 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
- QPZCZRRXDONFPB-UHFFFAOYSA-N tert-butyl 3-(2-chloropyridin-4-yl)oxypiperidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC1OC1=CC=NC(Cl)=C1 QPZCZRRXDONFPB-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 0.000 description 2
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- 238000006478 transmetalation reaction Methods 0.000 description 2
- 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 2
- AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical compound N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 2
- DBGIVFWFUFKIQN-VIFPVBQESA-N (+)-Fenfluramine Chemical compound CCN[C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-VIFPVBQESA-N 0.000 description 1
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 1
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- IQHMQPYKHSIPOT-UHFFFAOYSA-N (2-chloropyridin-4-yl)sulfanyl benzoate Chemical compound C(C1=CC=CC=C1)(=O)OSC1=CC(=NC=C1)Cl IQHMQPYKHSIPOT-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- VLPIATFUUWWMKC-SNVBAGLBSA-N (2r)-1-(2,6-dimethylphenoxy)propan-2-amine Chemical compound C[C@@H](N)COC1=C(C)C=CC=C1C VLPIATFUUWWMKC-SNVBAGLBSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- VMDKRSNUUUUARH-MQDBWYGVSA-N (3s)-4-[[(2s)-1-[[(2s)-2-[[(2s)-3-(1h-indol-3-yl)-2-[[2-[[(2s)-2-[[2-(4-sulfooxyphenyl)acetyl]amino]hexanoyl]amino]acetyl]amino]propanoyl]amino]hexanoyl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(methylamino)-4-oxobutanoic acid Chemical compound N([C@@H](CCCC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCC)C(=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC)C(=O)CC1=CC=C(OS(O)(=O)=O)C=C1 VMDKRSNUUUUARH-MQDBWYGVSA-N 0.000 description 1
- OJOFWBDUKJKOMW-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenyl]methanone;dihydrochloride Chemical compound Cl.Cl.C1CN(CC)CCN1C(=O)C1=CC=CC=C1OC1=CC=NC(NC=2SC=C(C)N=2)=C1 OJOFWBDUKJKOMW-UHFFFAOYSA-N 0.000 description 1
- PMEFKAXDBMNKJW-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenyl]methanone;dihydrochloride Chemical compound Cl.Cl.C1CN(CC)CCN1C(=O)C1=CC=CC(OC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 PMEFKAXDBMNKJW-UHFFFAOYSA-N 0.000 description 1
- NALDFAVRVPVOSK-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[6-[(4-methyl-1,3-thiazol-2-yl)amino]-4-phenoxypyridin-3-yl]methanone;hydrochloride Chemical compound Cl.C1CN(CC)CCN1C(=O)C(C(=C1)OC=2C=CC=CC=2)=CN=C1NC1=NC(C)=CS1 NALDFAVRVPVOSK-UHFFFAOYSA-N 0.000 description 1
- PTDVPWWJRCOIIO-UHFFFAOYSA-N (4-methoxyphenyl)methanethiol Chemical compound COC1=CC=C(CS)C=C1 PTDVPWWJRCOIIO-UHFFFAOYSA-N 0.000 description 1
- QBWQVJNMQAFKRJ-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]sulfanylphenyl]methanone;dihydrochloride Chemical compound Cl.Cl.C1CN(C)CCN1C(=O)C1=CC=CC(SC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 QBWQVJNMQAFKRJ-UHFFFAOYSA-N 0.000 description 1
- BMHZAHGTGIZZCT-LJQANCHMSA-N (4r)-2-[(4-bromo-2-fluorophenyl)methyl]-6-fluorospiro[isoquinoline-4,3'-pyrrolidine]-1,2',3,5'-tetrone Chemical compound C1([C@]2(C(NC(=O)C2)=O)C2=O)=CC(F)=CC=C1C(=O)N2CC1=CC=C(Br)C=C1F BMHZAHGTGIZZCT-LJQANCHMSA-N 0.000 description 1
- DJSOGTCWYMPAIU-UHFFFAOYSA-N (5-bromo-4-phenylmethoxypyridin-2-yl)thiourea Chemical compound C1=NC(NC(=S)N)=CC(OCC=2C=CC=CC=2)=C1Br DJSOGTCWYMPAIU-UHFFFAOYSA-N 0.000 description 1
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 description 1
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 1
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- CEAFABGKSOIJLH-UHFFFAOYSA-M 1-phenyl-2-(1,3-thiazol-3-ium-3-yl)ethanone;bromide Chemical class [Br-].C=1C=CC=CC=1C(=O)C[N+]=1C=CSC=1 CEAFABGKSOIJLH-UHFFFAOYSA-M 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- QGRKONUHHGBHRB-UHFFFAOYSA-N 2,3-dichlorobenzenethiol Chemical compound SC1=CC=CC(Cl)=C1Cl QGRKONUHHGBHRB-UHFFFAOYSA-N 0.000 description 1
- KEQTWHPMSVAFDA-UHFFFAOYSA-N 2,3-dihydro-1h-pyrazole Chemical compound C1NNC=C1 KEQTWHPMSVAFDA-UHFFFAOYSA-N 0.000 description 1
- FJNNGKMAGDPVIU-UHFFFAOYSA-N 2,4,6-trichloropyridine Chemical compound ClC1=CC(Cl)=NC(Cl)=C1 FJNNGKMAGDPVIU-UHFFFAOYSA-N 0.000 description 1
- FFMBYMANYCDCMK-UHFFFAOYSA-N 2,5-dihydro-1h-imidazole Chemical compound C1NCN=C1 FFMBYMANYCDCMK-UHFFFAOYSA-N 0.000 description 1
- JBISHCXLCGVPGW-UHFFFAOYSA-N 2,6-dichlorobenzenethiol Chemical compound SC1=C(Cl)C=CC=C1Cl JBISHCXLCGVPGW-UHFFFAOYSA-N 0.000 description 1
- HOLHYSJJBXSLMV-UHFFFAOYSA-N 2,6-dichlorophenol Chemical compound OC1=C(Cl)C=CC=C1Cl HOLHYSJJBXSLMV-UHFFFAOYSA-N 0.000 description 1
- QCLJODDRBGKIRW-UHFFFAOYSA-N 2,6-dimethylbenzenethiol Chemical compound CC1=CC=CC(C)=C1S QCLJODDRBGKIRW-UHFFFAOYSA-N 0.000 description 1
- MZIWZDMEFARRSI-UHFFFAOYSA-N 2-(1,3-thiazol-2-yldisulfanyl)-1,3-thiazole Chemical compound N=1C=CSC=1SSC1=NC=CS1 MZIWZDMEFARRSI-UHFFFAOYSA-N 0.000 description 1
- OPLVDNKIJPDJBW-UHFFFAOYSA-N 2-(2-amino-1,3-thiazol-4-yl)ethyl acetate Chemical compound CC(=O)OCCC1=CSC(N)=N1 OPLVDNKIJPDJBW-UHFFFAOYSA-N 0.000 description 1
- VVKJJOUJMMVUDD-UHFFFAOYSA-N 2-(2-chloropyridin-4-yl)oxybenzonitrile Chemical compound C1=NC(Cl)=CC(OC=2C(=CC=CC=2)C#N)=C1 VVKJJOUJMMVUDD-UHFFFAOYSA-N 0.000 description 1
- YSBYEQVJUQJNFS-UHFFFAOYSA-N 2-(2-methoxyphenoxy)pyridine Chemical compound COC1=CC=CC=C1OC1=CC=CC=N1 YSBYEQVJUQJNFS-UHFFFAOYSA-N 0.000 description 1
- ADDWTJXNPUILNX-UHFFFAOYSA-N 2-(2-methylphenyl)sulfanylpyridine Chemical compound CC1=CC=CC=C1SC1=CC=CC=N1 ADDWTJXNPUILNX-UHFFFAOYSA-N 0.000 description 1
- AATIVJKUGFHMLD-UHFFFAOYSA-N 2-(3,4-dihydro-2h-pyrrol-5-yl)ethanamine Chemical compound NCCC1=NCCC1 AATIVJKUGFHMLD-UHFFFAOYSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- NYTFJVCRVVCOPP-UHFFFAOYSA-N 2-(3-methoxyphenoxy)pyridine Chemical compound COC1=CC=CC(OC=2N=CC=CC=2)=C1 NYTFJVCRVVCOPP-UHFFFAOYSA-N 0.000 description 1
- JQDNCGRNPYKRAO-UHFFFAOYSA-N 2-(bromomethyl)pyridine;hydron;bromide Chemical compound Br.BrCC1=CC=CC=N1 JQDNCGRNPYKRAO-UHFFFAOYSA-N 0.000 description 1
- LJINHMVNIBCANU-UHFFFAOYSA-N 2-(pyrimidin-2-yldisulfanyl)pyrimidine Chemical compound N=1C=CC=NC=1SSC1=NC=CC=N1 LJINHMVNIBCANU-UHFFFAOYSA-N 0.000 description 1
- XVGQHRKNXSUPEF-UHFFFAOYSA-N 2-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC=CC=C1S XVGQHRKNXSUPEF-UHFFFAOYSA-N 0.000 description 1
- LXUNZSDDXMPKLP-UHFFFAOYSA-N 2-Methylbenzenethiol Chemical compound CC1=CC=CC=C1S LXUNZSDDXMPKLP-UHFFFAOYSA-N 0.000 description 1
- QPJPJEXCXSQGKM-UHFFFAOYSA-N 2-[2-[(3-methyl-1,2,4-thiadiazol-5-yl)amino]pyridin-4-yl]oxybenzonitrile Chemical compound CC1=NSC(NC=2N=CC=C(OC=3C(=CC=CC=3)C#N)C=2)=N1 QPJPJEXCXSQGKM-UHFFFAOYSA-N 0.000 description 1
- IYRCMNUXAZJJGT-UHFFFAOYSA-N 2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxy-n-(2-pyrrolidin-1-ylethyl)benzamide;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3)C(=O)NCCN3CCCC3)C=2)=N1 IYRCMNUXAZJJGT-UHFFFAOYSA-N 0.000 description 1
- KJCOYROZHSJNJK-UHFFFAOYSA-N 2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxy-n-(3-morpholin-4-ylpropyl)benzamide;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3)C(=O)NCCCN3CCOCC3)C=2)=N1 KJCOYROZHSJNJK-UHFFFAOYSA-N 0.000 description 1
- AODFFPKKBSMOQR-UHFFFAOYSA-N 2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxy-n-[2-(propan-2-ylamino)ethyl]benzamide;dihydrochloride Chemical compound Cl.Cl.CC(C)NCCNC(=O)C1=CC=CC=C1OC1=CC=NC(NC=2SC=C(C)N=2)=C1 AODFFPKKBSMOQR-UHFFFAOYSA-N 0.000 description 1
- RGRCSRQPLLDGSG-UHFFFAOYSA-N 2-[2-[(4-naphthalen-1-yloxypyridin-2-yl)amino]-1,3-thiazol-4-yl]ethanol Chemical compound OCCC1=CSC(NC=2N=CC=C(OC=3C4=CC=CC=C4C=CC=3)C=2)=N1 RGRCSRQPLLDGSG-UHFFFAOYSA-N 0.000 description 1
- NQOHTHSNMBFJEP-UHFFFAOYSA-N 2-[2-[(4-phenylsulfanylpyridin-2-yl)amino]-1,3-thiazol-4-yl]ethanol Chemical compound OCCC1=CSC(NC=2N=CC=C(SC=3C=CC=CC=3)C=2)=N1 NQOHTHSNMBFJEP-UHFFFAOYSA-N 0.000 description 1
- ILNRQFBVVQUOLP-UHFFFAOYSA-N 2-[2-[[[4-(2-chlorophenyl)-2-thiazolyl]amino]-oxomethyl]-1-indolyl]acetic acid Chemical compound C=1C2=CC=CC=C2N(CC(=O)O)C=1C(=O)NC(SC=1)=NC=1C1=CC=CC=C1Cl ILNRQFBVVQUOLP-UHFFFAOYSA-N 0.000 description 1
- QNGORRQFGPZIFE-UHFFFAOYSA-N 2-[3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenoxy]acetic acid;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C=C(OCC(O)=O)C=CC=3)C=2)=N1 QNGORRQFGPZIFE-UHFFFAOYSA-N 0.000 description 1
- WCZZRXHZULNDFW-UHFFFAOYSA-N 2-[3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenoxy]ethanol Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=C(OCCO)C=CC=3)C=2)=N1 WCZZRXHZULNDFW-UHFFFAOYSA-N 0.000 description 1
- OTGCRKLWEUQYNU-UHFFFAOYSA-N 2-[5-bromo-2-[[4-(2-phenylethyl)-1,3-thiazol-2-yl]amino]pyridin-4-yl]acetic acid Chemical compound C1=C(Br)C(CC(=O)O)=CC(NC=2SC=C(CCC=3C=CC=CC=3)N=2)=N1 OTGCRKLWEUQYNU-UHFFFAOYSA-N 0.000 description 1
- LUACLLSCZRRTIH-UPHRSURJSA-N 2-[[4-[(z)-4-[4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy]but-2-enoxy]phenyl]methyl]-1,2,4-oxadiazolidine-3,5-dione Chemical compound O1C(=O)NC(=O)N1CC(C=C1)=CC=C1OC\C=C/COC(C=C1)=CC=C1CN1C(=O)NC(=O)O1 LUACLLSCZRRTIH-UPHRSURJSA-N 0.000 description 1
- NSVFSAJIGAJDMR-UHFFFAOYSA-N 2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OCCN(CC=2C=CC=CC=2)C=2C=CC=CC=2)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1P1(=O)OCC(C)(C)CO1 NSVFSAJIGAJDMR-UHFFFAOYSA-N 0.000 description 1
- RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical compound BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 1
- MJLVLHNXEOQASX-UHFFFAOYSA-M 2-bromo-3,3-dimethylbutanoate Chemical compound CC(C)(C)C(Br)C([O-])=O MJLVLHNXEOQASX-UHFFFAOYSA-M 0.000 description 1
- SVAZIMBLBHOVIR-UHFFFAOYSA-N 2-chloro-3-fluoropyridine Chemical compound FC1=CC=CN=C1Cl SVAZIMBLBHOVIR-UHFFFAOYSA-N 0.000 description 1
- JEFYJJWYKOFTHN-UHFFFAOYSA-N 2-chloro-3-isothiocyanatopyridine Chemical compound ClC1=NC=CC=C1N=C=S JEFYJJWYKOFTHN-UHFFFAOYSA-N 0.000 description 1
- QLLRUGRNZMPUIW-UHFFFAOYSA-N 2-chloro-3-phenylmethoxypyridine Chemical compound ClC1=NC=CC=C1OCC1=CC=CC=C1 QLLRUGRNZMPUIW-UHFFFAOYSA-N 0.000 description 1
- YYVUMOBNCILYDX-UHFFFAOYSA-N 2-chloro-4-(2,6-dichlorophenoxy)pyridine Chemical compound C1=NC(Cl)=CC(OC=2C(=CC=CC=2Cl)Cl)=C1 YYVUMOBNCILYDX-UHFFFAOYSA-N 0.000 description 1
- HCMUSBXMZQRDCA-UHFFFAOYSA-N 2-chloro-4-phenoxypyrimidine Chemical compound ClC1=NC=CC(OC=2C=CC=CC=2)=N1 HCMUSBXMZQRDCA-UHFFFAOYSA-N 0.000 description 1
- XQXWWFZTTYEYOL-UHFFFAOYSA-N 2-chloro-4-pyridin-2-ylsulfanylpyridine Chemical compound C1=NC(Cl)=CC(SC=2N=CC=CC=2)=C1 XQXWWFZTTYEYOL-UHFFFAOYSA-N 0.000 description 1
- SUMSBUDMYMYTLL-UHFFFAOYSA-N 2-chloro-6-methylpyridin-3-amine Chemical compound CC1=CC=C(N)C(Cl)=N1 SUMSBUDMYMYTLL-UHFFFAOYSA-N 0.000 description 1
- PWOBDMNCYMQTCE-UHFFFAOYSA-N 2-chlorobenzenethiol Chemical compound SC1=CC=CC=C1Cl PWOBDMNCYMQTCE-UHFFFAOYSA-N 0.000 description 1
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
- QXCOHSRHFCHCHN-UHFFFAOYSA-N 2-chloropyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(Cl)=C1 QXCOHSRHFCHCHN-UHFFFAOYSA-N 0.000 description 1
- GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 1
- 150000005749 2-halopyridines Chemical class 0.000 description 1
- 150000005695 2-halopyrimidines Chemical class 0.000 description 1
- BQDBYNDGHKZKIY-UHFFFAOYSA-N 2-methyl-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoic acid;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=C(C(O)=O)C=CC=3)C)C=2)=N1 BQDBYNDGHKZKIY-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- QEDRUXIMTJVXFL-UHFFFAOYSA-N 2-propan-2-ylbenzenethiol Chemical compound CC(C)C1=CC=CC=C1S QEDRUXIMTJVXFL-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- AQYNZOSCOWGGTP-UHFFFAOYSA-N 2-pyridin-2-ylsulfanylpyridine Chemical compound C=1C=CC=NC=1SC1=CC=CC=N1 AQYNZOSCOWGGTP-UHFFFAOYSA-N 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- BCOLNMGFOWHFNI-UHFFFAOYSA-N 2-trimethylsilylethanethiol Chemical compound C[Si](C)(C)CCS BCOLNMGFOWHFNI-UHFFFAOYSA-N 0.000 description 1
- 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- BCSVCWVQNOXFGL-UHFFFAOYSA-N 3,4-dihydro-4-oxo-3-((5-trifluoromethyl-2-benzothiazolyl)methyl)-1-phthalazine acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=NC2=CC(C(F)(F)F)=CC=C2S1 BCSVCWVQNOXFGL-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- SSWPSKSQQSJKKF-UHFFFAOYSA-M 3-(dimethylamino)propyl-triphenylphosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCN(C)C)C1=CC=CC=C1 SSWPSKSQQSJKKF-UHFFFAOYSA-M 0.000 description 1
- UYGZODVVDUIDDQ-UHFFFAOYSA-N 3-[(2,4-dichlorophenyl)methyl]-2-methyl-n-pentylsulfonylbenzimidazole-5-carboxamide Chemical compound C12=CC(C(=O)NS(=O)(=O)CCCCC)=CC=C2N=C(C)N1CC1=CC=C(Cl)C=C1Cl UYGZODVVDUIDDQ-UHFFFAOYSA-N 0.000 description 1
- JRSMWTXIABXFIW-UHFFFAOYSA-N 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxy-n-(2-pyrrolidin-1-ylethyl)benzamide;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC=C(OC=3C=C(C=CC=3)C(=O)NCCN3CCCC3)C=2)=N1 JRSMWTXIABXFIW-UHFFFAOYSA-N 0.000 description 1
- NJRFGHLEFMBERN-UHFFFAOYSA-N 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxy-n-(3-morpholin-4-ylpropyl)benzamide;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC=C(OC=3C=C(C=CC=3)C(=O)NCCCN3CCOCC3)C=2)=N1 NJRFGHLEFMBERN-UHFFFAOYSA-N 0.000 description 1
- JHWWMFZCTVRCQY-UHFFFAOYSA-N 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]sulfanylbenzoic acid Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C=C(C=CC=3)C(O)=O)C=2)=N1 JHWWMFZCTVRCQY-UHFFFAOYSA-N 0.000 description 1
- QAHOHVPDYXKFQC-UHFFFAOYSA-N 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]sulfanylbenzoic acid;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(SC=3C=C(C=CC=3)C(O)=O)C=2)=N1 QAHOHVPDYXKFQC-UHFFFAOYSA-N 0.000 description 1
- UUSYJIAXXLWSDU-UHFFFAOYSA-N 3-[2-[[5-bromo-4-(2,6-difluorophenoxy)pyridin-2-yl]amino]-1,3-thiazol-4-yl]propanoic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)CCC1=CSC(NC=2N=CC(Br)=C(OC=3C(=CC=CC=3F)F)C=2)=N1 UUSYJIAXXLWSDU-UHFFFAOYSA-N 0.000 description 1
- LXXPAVXDGZNBKJ-UHFFFAOYSA-N 3-[5-bromo-2-[[4-(2-phenylethyl)-1,3-thiazol-2-yl]amino]pyridin-4-yl]oxy-4-chloro-n-(2-pyrrolidin-1-ylethyl)benzamide;dihydrochloride Chemical compound Cl.Cl.ClC1=CC=C(C(=O)NCCN2CCCC2)C=C1OC(C(=CN=1)Br)=CC=1NC(SC=1)=NC=1CCC1=CC=CC=C1 LXXPAVXDGZNBKJ-UHFFFAOYSA-N 0.000 description 1
- LSJVRVLJYIJSFA-UHFFFAOYSA-N 3-[5-bromo-2-[[4-(2-phenylethyl)-1,3-thiazol-2-yl]amino]pyridin-4-yl]oxy-4-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C(OC=2C(=CN=C(NC=3SC=C(CCC=4C=CC=CC=4)N=3)C=2)Br)=C1 LSJVRVLJYIJSFA-UHFFFAOYSA-N 0.000 description 1
- CLOSAYOEXWMDJW-UHFFFAOYSA-N 3-[5-bromo-2-[[4-(2-phenylethyl)-1,3-thiazol-2-yl]amino]pyridin-4-yl]oxy-5-chloropyridine-4-carbonitrile Chemical compound ClC1=CN=CC(OC=2C(=CN=C(NC=3SC=C(CCC=4C=CC=CC=4)N=3)C=2)Br)=C1C#N CLOSAYOEXWMDJW-UHFFFAOYSA-N 0.000 description 1
- AJVQLGQBHWALPL-UHFFFAOYSA-N 3-[5-bromo-2-[[4-(2-phenylethyl)-1,3-thiazol-2-yl]amino]pyridin-4-yl]sulfanyl-5-chloropyridine-4-carbonitrile Chemical compound ClC1=CN=CC(SC=2C(=CN=C(NC=3SC=C(CCC=4C=CC=CC=4)N=3)C=2)Br)=C1C#N AJVQLGQBHWALPL-UHFFFAOYSA-N 0.000 description 1
- KRHCTXFJCFMFOR-UHFFFAOYSA-N 3-[tert-butyl(dimethyl)silyl]oxybenzenethiol Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=CC(S)=C1 KRHCTXFJCFMFOR-UHFFFAOYSA-N 0.000 description 1
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
- LKAYAMCKQCBSOU-UHFFFAOYSA-N 3-chloro-1,2,4-thiadiazole Chemical compound ClC=1N=CSN=1 LKAYAMCKQCBSOU-UHFFFAOYSA-N 0.000 description 1
- CQJDYPZUDYXHLM-UHFFFAOYSA-N 3-chlorobenzenethiol Chemical compound SC1=CC=CC(Cl)=C1 CQJDYPZUDYXHLM-UHFFFAOYSA-N 0.000 description 1
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 description 1
- QMVAZEHZOPDGHA-UHFFFAOYSA-N 3-methoxybenzenethiol Chemical compound COC1=CC=CC(S)=C1 QMVAZEHZOPDGHA-UHFFFAOYSA-N 0.000 description 1
- GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 description 1
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 description 1
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- FCTXEFOUDMXDPD-UHFFFAOYSA-N 3-sulfanylpropanenitrile Chemical compound SCCC#N FCTXEFOUDMXDPD-UHFFFAOYSA-N 0.000 description 1
- HTEXLZDJELUALQ-UHFFFAOYSA-N 4,5-dicyclohexyl-N-[4-(2,6-difluorophenoxy)pyridin-2-yl]-1,3-thiazol-2-amine Chemical compound Fc1cccc(F)c1Oc1ccnc(Nc2nc(C3CCCCC3)c(s2)C2CCCCC2)c1 HTEXLZDJELUALQ-UHFFFAOYSA-N 0.000 description 1
- LBELNRVJSALMSH-UHFFFAOYSA-N 4,5-dicyclopropyl-N-[4-(2,6-difluorophenoxy)pyridin-2-yl]-1,3-thiazol-2-amine Chemical compound Fc1cccc(F)c1Oc1ccnc(Nc2nc(C3CC3)c(s2)C2CC2)c1 LBELNRVJSALMSH-UHFFFAOYSA-N 0.000 description 1
- MCGBIXXDQFWVDW-UHFFFAOYSA-N 4,5-dihydro-1h-pyrazole Chemical compound C1CC=NN1 MCGBIXXDQFWVDW-UHFFFAOYSA-N 0.000 description 1
- YPJYEZWEVGESNC-UHFFFAOYSA-N 4-(2,6-difluorophenoxy)-6-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-3-ol Chemical compound CC1=CSC(NC=2N=CC(O)=C(OC=3C(=CC=CC=3F)F)C=2)=N1 YPJYEZWEVGESNC-UHFFFAOYSA-N 0.000 description 1
- NWENCZKBAWMPFO-UHFFFAOYSA-N 4-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzonitrile Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=CC(=CC=3)C#N)C=2)=N1 NWENCZKBAWMPFO-UHFFFAOYSA-N 0.000 description 1
- YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
- QBQLYIISSRXYKL-UHFFFAOYSA-N 4-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,2-oxazolidine-3,5-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1C(=O)NOC1=O QBQLYIISSRXYKL-UHFFFAOYSA-N 0.000 description 1
- OFXJACVSHOHAHQ-UHFFFAOYSA-N 4-butyl-n-[4-(2,6-difluorophenoxy)pyridin-2-yl]-1,3-thiazol-2-amine Chemical compound CCCCC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3F)F)C=2)=N1 OFXJACVSHOHAHQ-UHFFFAOYSA-N 0.000 description 1
- OPUGEGQBZGTDLG-UHFFFAOYSA-N 4-chloro-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]sulfanylbenzoic acid;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(SC=3C(=CC=C(C=3)C(O)=O)Cl)C=2)=N1 OPUGEGQBZGTDLG-UHFFFAOYSA-N 0.000 description 1
- KHGWFZBIISKKRP-UHFFFAOYSA-N 4-chloro-6-phenoxypyrimidine Chemical compound C1=NC(Cl)=CC(OC=2C=CC=CC=2)=N1 KHGWFZBIISKKRP-UHFFFAOYSA-N 0.000 description 1
- JAKYGHXGUDRIBH-UHFFFAOYSA-N 4-chloro-n-[2-(dimethylamino)ethyl]-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzamide;hydrochloride Chemical compound Cl.CN(C)CCNC(=O)C1=CC=C(Cl)C(OC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 JAKYGHXGUDRIBH-UHFFFAOYSA-N 0.000 description 1
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 1
- DFXBVTLCYZLJSZ-UHFFFAOYSA-N 4-fluoro-3-[[2-[(4-methyl-1,3-thiazol-2-yl)amino]-1h-pyridin-2-yl]oxy]benzoic acid;hydrochloride Chemical compound Cl.CC1=CSC(NC2(C=CC=CN2)OC=2C(=CC=C(C=2)C(O)=O)F)=N1 DFXBVTLCYZLJSZ-UHFFFAOYSA-N 0.000 description 1
- 150000005696 4-halopyrimidines Chemical class 0.000 description 1
- OHZUEFKOZYWUFF-UHFFFAOYSA-N 4-hydroxypiperidine-1-carboxylic acid Chemical compound OC1CCN(C(O)=O)CC1 OHZUEFKOZYWUFF-UHFFFAOYSA-N 0.000 description 1
- PGQURADDNMZQQD-UHFFFAOYSA-N 4-methyl-n-(4-piperidin-3-yloxypyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC3CNCCC3)C=2)=N1 PGQURADDNMZQQD-UHFFFAOYSA-N 0.000 description 1
- SNSTVMPHSIGATQ-UHFFFAOYSA-N 4-methyl-n-(4-piperidin-3-yloxypyridin-2-yl)-1,3-thiazol-2-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=CSC(NC=2N=CC=C(OC3CNCCC3)C=2)=N1 SNSTVMPHSIGATQ-UHFFFAOYSA-N 0.000 description 1
- ZACTYMQAAGNBEK-UHFFFAOYSA-N 4-methyl-n-(4-piperidin-4-yloxypyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC3CCNCC3)C=2)=N1 ZACTYMQAAGNBEK-UHFFFAOYSA-N 0.000 description 1
- TYCRYWQEXBBUMR-UHFFFAOYSA-N 4-methyl-n-(4-piperidin-4-yloxypyridin-2-yl)-1,3-thiazol-2-amine;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=CSC(NC=2N=CC=C(OC3CCNCC3)C=2)=N1 TYCRYWQEXBBUMR-UHFFFAOYSA-N 0.000 description 1
- QPKCJBJALZCRDF-UHFFFAOYSA-N 4-methyl-n-(4-pyridin-4-ylsulfanylpyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C=CN=CC=3)C=2)=N1 QPKCJBJALZCRDF-UHFFFAOYSA-N 0.000 description 1
- FQOKIMPQSAFJTF-UHFFFAOYSA-N 4-methyl-n-(4-quinolin-5-yloxypyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C4=CC=CN=C4C=CC=3)C=2)=N1 FQOKIMPQSAFJTF-UHFFFAOYSA-N 0.000 description 1
- KQVFDQGTRGSKHU-UHFFFAOYSA-N 4-methyl-n-(4-quinolin-6-yloxypyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=C4C=CC=NC4=CC=3)C=2)=N1 KQVFDQGTRGSKHU-UHFFFAOYSA-N 0.000 description 1
- NPJSCLFQZFRSQK-UHFFFAOYSA-N 4-methyl-n-(4-quinolin-7-yloxypyridin-2-yl)-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C=C4N=CC=CC4=CC=3)C=2)=N1 NPJSCLFQZFRSQK-UHFFFAOYSA-N 0.000 description 1
- LREDOTFICZMSAA-UHFFFAOYSA-N 4-methyl-n-(5-pyridin-2-ylsulfanyl-4-quinolin-5-yloxypyridin-2-yl)-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC(SC=3N=CC=CC=3)=C(OC=3C4=CC=CN=C4C=CC=3)C=2)=N1 LREDOTFICZMSAA-UHFFFAOYSA-N 0.000 description 1
- CHZFGWLVTMQAKC-UHFFFAOYSA-N 4-methyl-n-[4-(2-methylfuran-3-yl)sulfanylpyridin-2-yl]-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC3=C(OC=C3)C)C=2)=N1 CHZFGWLVTMQAKC-UHFFFAOYSA-N 0.000 description 1
- XIKWFKWULGTDGC-UHFFFAOYSA-N 4-methyl-n-[4-(3-phenylmethoxyphenoxy)pyridin-2-yl]-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=C(OCC=4C=CC=CC=4)C=CC=3)C=2)=N1 XIKWFKWULGTDGC-UHFFFAOYSA-N 0.000 description 1
- LIVUCMLUDLFMRV-BXUZGUMPSA-N 4-methyl-n-[4-[(1r,2r)-2-methylcyclohexyl]oxypyridin-2-yl]-1,3-thiazol-2-amine Chemical compound C[C@@H]1CCCC[C@H]1OC1=CC=NC(NC=2SC=C(C)N=2)=C1 LIVUCMLUDLFMRV-BXUZGUMPSA-N 0.000 description 1
- VGFYVEZIWVEHET-UHFFFAOYSA-N 4-methyl-n-[4-naphthalen-1-yloxy-5-(piperidin-1-ylmethyl)pyridin-2-yl]-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC(CN3CCCCC3)=C(OC=3C4=CC=CC=C4C=CC=3)C=2)=N1 VGFYVEZIWVEHET-UHFFFAOYSA-N 0.000 description 1
- WKCNGJYEULOJNM-UHFFFAOYSA-N 4-methyl-n-[5-(piperidin-4-ylmethylsulfanyl)-4-quinolin-5-yloxypyridin-2-yl]-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC(SCC3CCNCC3)=C(OC=3C4=CC=CN=C4C=CC=3)C=2)=N1 WKCNGJYEULOJNM-UHFFFAOYSA-N 0.000 description 1
- QNMWLKZUPMLKID-UHFFFAOYSA-N 4-methyl-n-pyridin-2-yl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=CC=2)=N1 QNMWLKZUPMLKID-UHFFFAOYSA-N 0.000 description 1
- ICGLPKIVTVWCFT-UHFFFAOYSA-N 4-methylbenzenesulfonohydrazide Chemical compound CC1=CC=C(S(=O)(=O)NN)C=C1 ICGLPKIVTVWCFT-UHFFFAOYSA-N 0.000 description 1
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- WFZHIPCBNKBNCB-UHFFFAOYSA-N 4-phenyl-n-[5-(piperidin-4-ylmethylsulfanyl)-4-quinolin-5-yloxypyridin-2-yl]-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1CSC(C(=C1)OC=2C3=CC=CN=C3C=CC=2)=CN=C1NC(SC=1)=NC=1C1=CC=CC=C1 WFZHIPCBNKBNCB-UHFFFAOYSA-N 0.000 description 1
- DOVNUEPFPBWTSV-UHFFFAOYSA-N 4-phenylmethoxy-1h-pyridin-2-one Chemical compound C1=CNC(=O)C=C1OCC1=CC=CC=C1 DOVNUEPFPBWTSV-UHFFFAOYSA-N 0.000 description 1
- PBBOXAYTFHPLTP-UHFFFAOYSA-N 4-quinolin-5-yloxypyridin-2-amine Chemical compound C1=NC(N)=CC(OC=2C3=CC=CN=C3C=CC=2)=C1 PBBOXAYTFHPLTP-UHFFFAOYSA-N 0.000 description 1
- JEFDBVSOHOTOJH-UHFFFAOYSA-N 4-tert-butyl-n-[4-(2,6-difluorophenoxy)pyridin-2-yl]-1,3-thiazol-2-amine Chemical compound CC(C)(C)C1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3F)F)C=2)=N1 JEFDBVSOHOTOJH-UHFFFAOYSA-N 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- 125000001826 4H-pyranyl group Chemical group O1C(=CCC=C1)* 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- NFFXEUUOMTXWCX-UHFFFAOYSA-N 5-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]-2-methoxy-n-[[4-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound C1=C(C(=O)NCC=2C=CC(=CC=2)C(F)(F)F)C(OC)=CC=C1CC1SC(=O)NC1=O NFFXEUUOMTXWCX-UHFFFAOYSA-N 0.000 description 1
- NKOHRVBBQISBSB-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1CC1C(=O)NC(=O)S1 NKOHRVBBQISBSB-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- SGCSNJNPPSSPKZ-UHFFFAOYSA-N 5-bromo-2,4-dichloropyridine Chemical compound ClC1=CC(Cl)=C(Br)C=N1 SGCSNJNPPSSPKZ-UHFFFAOYSA-N 0.000 description 1
- URFISJPPUFBOMP-UHFFFAOYSA-N 5-bromo-2-[[4-(2-phenylethyl)-1,3-thiazol-2-yl]amino]-1h-pyridine-4-thione Chemical compound C1=C(Br)C(S)=CC(NC=2SC=C(CCC=3C=CC=CC=3)N=2)=N1 URFISJPPUFBOMP-UHFFFAOYSA-N 0.000 description 1
- YRVZFKHCVYXUFJ-UHFFFAOYSA-N 5-bromo-4-[(4-methoxyphenyl)methylsulfanyl]pyridin-2-amine Chemical compound C1=CC(OC)=CC=C1CSC1=CC(N)=NC=C1Br YRVZFKHCVYXUFJ-UHFFFAOYSA-N 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- LTTMCOHWLSCDCV-UHFFFAOYSA-N 5-methyl-4-propan-2-yl-1,3-thiazol-2-amine Chemical compound CC(C)C=1N=C(N)SC=1C LTTMCOHWLSCDCV-UHFFFAOYSA-N 0.000 description 1
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- YQXQCWDRFZRPTJ-UHFFFAOYSA-N 6-[(4-methyl-1,3-thiazol-2-yl)amino]-4-naphthalen-1-yloxypyridine-3-carboxylic acid Chemical compound CC1=CSC(NC=2N=CC(=C(OC=3C4=CC=CC=C4C=CC=3)C=2)C(O)=O)=N1 YQXQCWDRFZRPTJ-UHFFFAOYSA-N 0.000 description 1
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- IQRBNRFCRAJXJF-UHFFFAOYSA-N 9-benzyl-9-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1B2CC1=CC=CC=C1 IQRBNRFCRAJXJF-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 208000029483 Acquired immunodeficiency Diseases 0.000 description 1
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 description 1
- 229940127438 Amylin Agonists Drugs 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000002080 C09CA02 - Eprosartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002081 C09CA05 - Tasosartan Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 238000005653 Chichibabin synthesis reaction Methods 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- 101800001982 Cholecystokinin Proteins 0.000 description 1
- 102100025841 Cholecystokinin Human genes 0.000 description 1
- BMOVQUBVGICXQN-UHFFFAOYSA-N Clinofibrate Chemical compound C1=CC(OC(C)(CC)C(O)=O)=CC=C1C1(C=2C=CC(OC(C)(CC)C(O)=O)=CC=2)CCCCC1 BMOVQUBVGICXQN-UHFFFAOYSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 208000002230 Diabetic coma Diseases 0.000 description 1
- 206010070901 Diabetic dyslipidaemia Diseases 0.000 description 1
- 206010012665 Diabetic gangrene Diseases 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102100023374 Forkhead box protein M1 Human genes 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- 101100134925 Gallus gallus COR6 gene Proteins 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 229940121931 Gluconeogenesis inhibitor Drugs 0.000 description 1
- 102000003638 Glucose-6-Phosphatase Human genes 0.000 description 1
- 108010086800 Glucose-6-Phosphatase Proteins 0.000 description 1
- NMWQEPCLNXHPDX-UHFFFAOYSA-N Glybuzole Chemical compound S1C(C(C)(C)C)=NN=C1NS(=O)(=O)C1=CC=CC=C1 NMWQEPCLNXHPDX-UHFFFAOYSA-N 0.000 description 1
- 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
- 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 102000015779 HDL Lipoproteins Human genes 0.000 description 1
- 108010010234 HDL Lipoproteins Proteins 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 238000003445 Hantzsch reaction Methods 0.000 description 1
- 101000907578 Homo sapiens Forkhead box protein M1 Proteins 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 206010021518 Impaired gastric emptying Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010092277 Leptin Proteins 0.000 description 1
- 102000016267 Leptin Human genes 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 239000005574 MCPA Substances 0.000 description 1
- ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 208000029725 Metabolic bone disease Diseases 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- OBORCGYNZZCBAZ-UHFFFAOYSA-N N-[4-(2,6-difluorophenoxy)pyridin-2-yl]-4,5-bis(2-methylpropyl)-1,3-thiazol-2-amine Chemical compound CC(C)Cc1nc(Nc2cc(Oc3c(F)cccc3F)ccn2)sc1CC(C)C OBORCGYNZZCBAZ-UHFFFAOYSA-N 0.000 description 1
- OQWTXGZTJOFWSX-UHFFFAOYSA-N N-[4-(2,6-difluorophenoxy)pyridin-2-yl]-4,5-dipyridin-4-yl-1,3-thiazol-2-amine Chemical compound Fc1cccc(F)c1Oc1ccnc(Nc2nc(c(s2)-c2ccncc2)-c2ccncc2)c1 OQWTXGZTJOFWSX-UHFFFAOYSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 101001083189 Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100) Hexokinase-1 Proteins 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 101000840556 Oryza sativa subsp. japonica Hexokinase-4, chloroplastic Proteins 0.000 description 1
- 101000840634 Oryza sativa subsp. japonica Hexokinase-5 Proteins 0.000 description 1
- 206010049088 Osteopenia Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229940123973 Oxygen scavenger Drugs 0.000 description 1
- 229910020667 PBr3 Inorganic materials 0.000 description 1
- 229910019201 POBr3 Inorganic materials 0.000 description 1
- 229940126033 PPAR agonist Drugs 0.000 description 1
- 102000019280 Pancreatic lipases Human genes 0.000 description 1
- 108050006759 Pancreatic lipases Proteins 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 238000003482 Pinner synthesis reaction Methods 0.000 description 1
- GHUUBYQTCDQWRA-UHFFFAOYSA-N Pioglitazone hydrochloride Chemical compound Cl.N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 GHUUBYQTCDQWRA-UHFFFAOYSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100040918 Pro-glucagon Human genes 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 238000000297 Sandmeyer reaction Methods 0.000 description 1
- 208000020764 Sensation disease Diseases 0.000 description 1
- JLRNKCZRCMIVKA-UHFFFAOYSA-N Simfibrate Chemical compound C=1C=C(Cl)C=CC=1OC(C)(C)C(=O)OCCCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 JLRNKCZRCMIVKA-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000034972 Sudden Infant Death Diseases 0.000 description 1
- 206010042440 Sudden infant death syndrome Diseases 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- WHKUVVPPKQRRBV-UHFFFAOYSA-N Trasan Chemical compound CC1=CC(Cl)=CC=C1OCC(O)=O WHKUVVPPKQRRBV-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- 208000005946 Xerostomia Diseases 0.000 description 1
- NDPKMHOPLXSYOF-UHFFFAOYSA-N [2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]methanol Chemical compound CC1=CSC(NC=2N=CC=C(CO)C=2)=N1 NDPKMHOPLXSYOF-UHFFFAOYSA-N 0.000 description 1
- UDSMDZOXBHUDBE-UHFFFAOYSA-N [2-methyl-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenyl]methanol;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=C(CO)C=CC=3)C)C=2)=N1 UDSMDZOXBHUDBE-UHFFFAOYSA-N 0.000 description 1
- SYCYKWUBPUKLTJ-UHFFFAOYSA-N [3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenyl]-pyrrolidin-1-ylmethanone;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C=C(C=CC=3)C(=O)N3CCCC3)C=2)=N1 SYCYKWUBPUKLTJ-UHFFFAOYSA-N 0.000 description 1
- IKJYRHIXOVYIQI-UHFFFAOYSA-N [4-fluoro-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenyl]methanol;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=CC=C(CO)C=3)F)C=2)=N1 IKJYRHIXOVYIQI-UHFFFAOYSA-N 0.000 description 1
- HBOAUKCSCJMTTP-UHFFFAOYSA-N [4-methyl-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxyphenyl]methanol;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=CC=C(CO)C=3)C)C=2)=N1 HBOAUKCSCJMTTP-UHFFFAOYSA-N 0.000 description 1
- YJTAMBFCDFINBZ-UHFFFAOYSA-N [5-bromo-4-[(4-methoxyphenyl)methylsulfanyl]pyridin-2-yl]thiourea Chemical compound C1=CC(OC)=CC=C1CSC1=CC(NC(N)=S)=NC=C1Br YJTAMBFCDFINBZ-UHFFFAOYSA-N 0.000 description 1
- GTTHARXLMFTIDW-UHFFFAOYSA-N [6-[(4-methyl-1,3-thiazol-2-yl)amino]-4-phenoxypyridin-3-yl]methanol Chemical compound CC1=CSC(NC=2N=CC(CO)=C(OC=3C=CC=CC=3)C=2)=N1 GTTHARXLMFTIDW-UHFFFAOYSA-N 0.000 description 1
- SZPWXAOBLNYOHY-UHFFFAOYSA-N [C]1=CC=NC2=CC=CC=C12 Chemical group [C]1=CC=NC2=CC=CC=C12 SZPWXAOBLNYOHY-UHFFFAOYSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 229960001466 acetohexamide Drugs 0.000 description 1
- VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 201000009840 acute diarrhea Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003288 aldose reductase inhibitor Substances 0.000 description 1
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000002009 alkene group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 239000003888 alpha glucosidase inhibitor Substances 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 150000008378 aryl ethers Chemical class 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000005621 boronate group Chemical class 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 229960004111 buformin Drugs 0.000 description 1
- XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229960004349 candesartan cilexetil Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000004452 carbocyclyl group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-M carbonochloridate Chemical compound [O-]C(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-M 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 229960005110 cerivastatin Drugs 0.000 description 1
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- 229940107137 cholecystokinin Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 208000019902 chronic diarrheal disease Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229950003072 clinofibrate Drugs 0.000 description 1
- LRXXRIXDSAEIOR-ZDUSSCGKSA-N clobenzorex Chemical compound C([C@H](C)NCC=1C(=CC=CC=1)Cl)C1=CC=CC=C1 LRXXRIXDSAEIOR-ZDUSSCGKSA-N 0.000 description 1
- 229960002492 clobenzorex Drugs 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- PDXRQENMIVHKPI-UHFFFAOYSA-N cyclohexane-1,1-diol Chemical compound OC1(O)CCCCC1 PDXRQENMIVHKPI-UHFFFAOYSA-N 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 150000004691 decahydrates Chemical class 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- WOUOLAUOZXOLJQ-MBSDFSHPSA-N delapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N(CC(O)=O)C1CC2=CC=CC=C2C1)CC1=CC=CC=C1 WOUOLAUOZXOLJQ-MBSDFSHPSA-N 0.000 description 1
- 229960005227 delapril Drugs 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960004597 dexfenfluramine Drugs 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 description 1
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- 229960004890 diethylpropion Drugs 0.000 description 1
- XXEPPPIWZFICOJ-UHFFFAOYSA-N diethylpropion Chemical compound CCN(CC)C(C)C(=O)C1=CC=CC=C1 XXEPPPIWZFICOJ-UHFFFAOYSA-N 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- FUZBPOHHSBDTJQ-CFOQQKEYSA-L disodium;5-[(2r)-2-[[(2r)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate Chemical compound [Na+].[Na+].C1([C@@H](O)CN[C@@H](CC=2C=C3OC(OC3=CC=2)(C([O-])=O)C([O-])=O)C)=CC=CC(Cl)=C1 FUZBPOHHSBDTJQ-CFOQQKEYSA-L 0.000 description 1
- 125000005883 dithianyl group Chemical group 0.000 description 1
- 125000005411 dithiolanyl group Chemical group S1SC(CC1)* 0.000 description 1
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 229950003102 efonidipine Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 229950000269 emiglitate Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 description 1
- 229950010170 epalrestat Drugs 0.000 description 1
- CHNUOJQWGUIOLD-UHFFFAOYSA-N epalrestate Natural products C=1C=CC=CC=1C=C(C)C=C1SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-UHFFFAOYSA-N 0.000 description 1
- 229960004563 eprosartan Drugs 0.000 description 1
- OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- SHQNGLYXRFCPGZ-UHFFFAOYSA-N ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate Chemical compound CCOC(=O)CC1=CSC(N)=N1 SHQNGLYXRFCPGZ-UHFFFAOYSA-N 0.000 description 1
- UZDMTIAZUUODDY-UHFFFAOYSA-N ethyl 2-[2-[(4-naphthalen-1-yloxypyridin-2-yl)amino]-1,3-thiazol-4-yl]acetate Chemical compound CCOC(=O)CC1=CSC(NC=2N=CC=C(OC=3C4=CC=CC=C4C=CC=3)C=2)=N1 UZDMTIAZUUODDY-UHFFFAOYSA-N 0.000 description 1
- HNQSJROZDDLYEI-UHFFFAOYSA-N ethyl 3-(2-amino-5-bromopyridin-4-yl)oxy-4-chlorobenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(OC=2C(=CN=C(N)C=2)Br)=C1 HNQSJROZDDLYEI-UHFFFAOYSA-N 0.000 description 1
- TUZKOPASQNUIJD-UHFFFAOYSA-N ethyl 3-(2-chloropyridin-4-yl)oxy-4-fluorobenzoate Chemical compound CCOC(=O)C1=CC=C(F)C(OC=2C=C(Cl)N=CC=2)=C1 TUZKOPASQNUIJD-UHFFFAOYSA-N 0.000 description 1
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
- FIQYKFVJDSUWDE-UHFFFAOYSA-N ethyl 3-[2-(benzoylcarbamothioylamino)-5-bromopyridin-4-yl]oxy-4-chlorobenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(OC=2C(=CN=C(NC(=S)NC(=O)C=3C=CC=CC=3)C=2)Br)=C1 FIQYKFVJDSUWDE-UHFFFAOYSA-N 0.000 description 1
- DEMVMRGMYARXRE-UHFFFAOYSA-N ethyl 3-[2-[[5-bromo-4-(2,6-difluorophenoxy)pyridin-2-yl]amino]-1,3-thiazol-4-yl]propanoate Chemical compound CCOC(=O)CCC1=CSC(NC=2N=CC(Br)=C(OC=3C(=CC=CC=3F)F)C=2)=N1 DEMVMRGMYARXRE-UHFFFAOYSA-N 0.000 description 1
- MYCHPDPCDSAZBS-UHFFFAOYSA-N ethyl 3-[5-bromo-2-(carbamothioylamino)pyridin-4-yl]oxy-4-chlorobenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(OC=2C(=CN=C(NC(N)=S)C=2)Br)=C1 MYCHPDPCDSAZBS-UHFFFAOYSA-N 0.000 description 1
- WWTLEVOTRVPTOD-UHFFFAOYSA-N ethyl 3-hydroxy-2-methylbenzoate Chemical compound CCOC(=O)C1=CC=CC(O)=C1C WWTLEVOTRVPTOD-UHFFFAOYSA-N 0.000 description 1
- KDCZAKFTHLOVMV-UHFFFAOYSA-N ethyl 3-hydroxy-4-methylbenzoate Chemical compound CCOC(=O)C1=CC=C(C)C(O)=C1 KDCZAKFTHLOVMV-UHFFFAOYSA-N 0.000 description 1
- AAUBVINEXCCXOK-UHFFFAOYSA-N ethyl 4,6-dichloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1Cl AAUBVINEXCCXOK-UHFFFAOYSA-N 0.000 description 1
- NWWORXYTJRPSMC-QKPAOTATSA-N ethyl 4-[2-[(2r,3r,4r,5s)-3,4,5-trihydroxy-2-(hydroxymethyl)piperidin-1-yl]ethoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCCN1[C@H](CO)[C@@H](O)[C@H](O)[C@@H](O)C1 NWWORXYTJRPSMC-QKPAOTATSA-N 0.000 description 1
- IQQSATDJLYUYML-UHFFFAOYSA-N ethyl 4-chloro-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]-5-(pyridin-2-ylmethylsulfanyl)pyridin-4-yl]oxybenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(OC=2C(=CN=C(NC=3SC=C(C)N=3)C=2)SCC=2N=CC=CC=2)=C1 IQQSATDJLYUYML-UHFFFAOYSA-N 0.000 description 1
- RWBYCMPOFNRISR-UHFFFAOYSA-N ethyl 4-chlorobenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C=C1 RWBYCMPOFNRISR-UHFFFAOYSA-N 0.000 description 1
- QBOPWLOHFBLVGT-UHFFFAOYSA-N ethyl 4-fluoro-3-hydroxybenzoate Chemical compound CCOC(=O)C1=CC=C(F)C(O)=C1 QBOPWLOHFBLVGT-UHFFFAOYSA-N 0.000 description 1
- SQQSCBAXSBAWNN-UHFFFAOYSA-N ethyl 4-phenoxy-6-[(4-propan-2-yl-1,3-thiazol-2-yl)amino]pyridine-3-carboxylate Chemical compound C1=C(OC=2C=CC=CC=2)C(C(=O)OCC)=CN=C1NC1=NC(C(C)C)=CS1 SQQSCBAXSBAWNN-UHFFFAOYSA-N 0.000 description 1
- OHHBFEVZJLBKEH-UHFFFAOYSA-N ethylenediamine dihydrochloride Chemical compound Cl.Cl.NCCN OHHBFEVZJLBKEH-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 229960001582 fenfluramine Drugs 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 229950007256 fidarestat Drugs 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000001288 gastroparesis Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229960000346 gliclazide Drugs 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229960001381 glipizide Drugs 0.000 description 1
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- VHHHONWQHHHLTI-UHFFFAOYSA-N hexachloroethane Chemical compound ClC(Cl)(Cl)C(Cl)(Cl)Cl VHHHONWQHHHLTI-UHFFFAOYSA-N 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000000910 hyperinsulinemic effect Effects 0.000 description 1
- 208000020346 hyperlipoproteinemia Diseases 0.000 description 1
- 230000002727 hyperosmolar Effects 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 210000003692 ilium Anatomy 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- MGXWVYUBJRZYPE-YUGYIWNOSA-N incretin Chemical class C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)[C@@H](C)O)[C@@H](C)CC)C1=CC=C(O)C=C1 MGXWVYUBJRZYPE-YUGYIWNOSA-N 0.000 description 1
- 239000000859 incretin Substances 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- APNSGVMLAYLYCT-UHFFFAOYSA-N isobutyl nitrite Chemical compound CC(C)CON=O APNSGVMLAYLYCT-UHFFFAOYSA-N 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical group C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 1
- 229940039781 leptin Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 229950003977 lintitript Drugs 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- ANEBWFXPVPTEET-UHFFFAOYSA-N manidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ANEBWFXPVPTEET-UHFFFAOYSA-N 0.000 description 1
- 229960003963 manidipine Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 1
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- QPGWSHBWXXVEPG-UHFFFAOYSA-N methyl 2-(2-chloropyridin-4-yl)oxybenzoate Chemical compound COC(=O)C1=CC=CC=C1OC1=CC=NC(Cl)=C1 QPGWSHBWXXVEPG-UHFFFAOYSA-N 0.000 description 1
- NTNUDYROPUKXNA-UHFFFAOYSA-N methyl 2-(triphenyl-$l^{5}-phosphanylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC)C1=CC=CC=C1 NTNUDYROPUKXNA-UHFFFAOYSA-N 0.000 description 1
- XSNBKACCKXDZLN-UHFFFAOYSA-N methyl 3-[2-[(4-propan-2-yl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzoate Chemical compound COC(=O)C1=CC=CC(OC=2C=C(NC=3SC=C(N=3)C(C)C)N=CC=2)=C1 XSNBKACCKXDZLN-UHFFFAOYSA-N 0.000 description 1
- GMGKDUBBAHSGLI-UHFFFAOYSA-N methyl 3-[4-(2,6-difluorophenoxy)-6-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-3-yl]propanoate Chemical compound C1=C(OC=2C(=CC=CC=2F)F)C(CCC(=O)OC)=CN=C1NC1=NC(C)=CS1 GMGKDUBBAHSGLI-UHFFFAOYSA-N 0.000 description 1
- 229940120152 methyl 3-hydroxybenzoate Drugs 0.000 description 1
- SRGOMBXXNIVIPR-UHFFFAOYSA-N methyl 3-sulfanylbenzoate Chemical compound COC(=O)C1=CC=CC(S)=C1 SRGOMBXXNIVIPR-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- OLXYLDUSSBULGU-UHFFFAOYSA-N methyl pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC=C1 OLXYLDUSSBULGU-UHFFFAOYSA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229960003404 mexiletine Drugs 0.000 description 1
- 206010062198 microangiopathy Diseases 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 229950002259 minalrestat Drugs 0.000 description 1
- 229960003365 mitiglinide Drugs 0.000 description 1
- WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical class CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- DEBOSDVZRKNQNU-UHFFFAOYSA-N n-(2-chloroethyl)propan-2-amine Chemical compound CC(C)NCCCl DEBOSDVZRKNQNU-UHFFFAOYSA-N 0.000 description 1
- WKASDHRGJOMVIN-UHFFFAOYSA-N n-(4-cyclohexylsulfanylpyridin-2-yl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC3CCCCC3)C=2)=N1 WKASDHRGJOMVIN-UHFFFAOYSA-N 0.000 description 1
- OZQULYARBDQAHC-UHFFFAOYSA-N n-(4-cyclopentylsulfanylpyridin-2-yl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC3CCCC3)C=2)=N1 OZQULYARBDQAHC-UHFFFAOYSA-N 0.000 description 1
- REMNUJJLCFYOBF-UHFFFAOYSA-N n-(4-isoquinolin-5-yloxypyridin-2-yl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C4=CC=NC=C4C=CC=3)C=2)=N1 REMNUJJLCFYOBF-UHFFFAOYSA-N 0.000 description 1
- OQPGUAYCUAXAJQ-UHFFFAOYSA-N n-(4-isoquinolin-7-yloxypyridin-2-yl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C=C4C=NC=CC4=CC=3)C=2)=N1 OQPGUAYCUAXAJQ-UHFFFAOYSA-N 0.000 description 1
- DNKXYAWWNVVXDW-UHFFFAOYSA-N n-(4-quinolin-5-yloxypyridin-2-yl)-[1,3]thiazolo[5,4-b]pyridin-2-amine Chemical compound C1=CC=C2C(OC=3C=C(N=CC=3)NC=3SC4=NC=CC=C4N=3)=CC=CC2=N1 DNKXYAWWNVVXDW-UHFFFAOYSA-N 0.000 description 1
- ZAMAQZQFXVNHPD-UHFFFAOYSA-N n-(5-benzyl-4-quinolin-5-yloxypyridin-2-yl)-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC(CC=3C=CC=CC=3)=C(OC=3C4=CC=CN=C4C=CC=3)C=2)=N1 ZAMAQZQFXVNHPD-UHFFFAOYSA-N 0.000 description 1
- UUBKBRVSURMORN-UHFFFAOYSA-N n-(5-bromo-4-quinolin-5-yloxypyridin-2-yl)-4-(2-phenylethyl)-1,3-thiazol-2-amine Chemical compound C1=C(OC=2C3=CC=CN=C3C=CC=2)C(Br)=CN=C1NC(SC=1)=NC=1CCC1=CC=CC=C1 UUBKBRVSURMORN-UHFFFAOYSA-N 0.000 description 1
- ZAHCBXBWQVUKSU-UHFFFAOYSA-N n-(5-bromo-4-thieno[3,2-b]pyridin-7-ylsulfanylpyridin-2-yl)-4-(2-phenylethyl)-1,3-thiazol-2-amine Chemical compound C1=C(SC=2C=3SC=CC=3N=CC=2)C(Br)=CN=C1NC(SC=1)=NC=1CCC1=CC=CC=C1 ZAHCBXBWQVUKSU-UHFFFAOYSA-N 0.000 description 1
- FDOUKSLRADYQTO-UHFFFAOYSA-N n-[2-(1h-imidazol-5-yl)ethyl]-2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzamide;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3)C(=O)NCCC=3N=CNC=3)C=2)=N1 FDOUKSLRADYQTO-UHFFFAOYSA-N 0.000 description 1
- CAKOVFRJZCZAOB-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-methyl-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzamide;dihydrochloride Chemical compound Cl.Cl.CN(C)CCNC(=O)C1=CC=C(C)C(OC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 CAKOVFRJZCZAOB-UHFFFAOYSA-N 0.000 description 1
- UVBMOZCMDKKETL-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-6-[(4-methyl-1,3-thiazol-2-yl)amino]-4-phenoxypyridine-3-carboxamide;hydrochloride Chemical compound Cl.C1=C(OC=2C=CC=CC=2)C(C(=O)NCCN(C)C)=CN=C1NC1=NC(C)=CS1 UVBMOZCMDKKETL-UHFFFAOYSA-N 0.000 description 1
- DVKOEZJSPBUIDH-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-methyl-2-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzamide;dihydrochloride Chemical compound Cl.Cl.CN(C)CCN(C)C(=O)C1=CC=CC=C1OC1=CC=NC(NC=2SC=C(C)N=2)=C1 DVKOEZJSPBUIDH-UHFFFAOYSA-N 0.000 description 1
- YJMAZJSNFUXTJE-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-n-methyl-3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxybenzamide;dihydrochloride Chemical compound Cl.Cl.CN(C)CCN(C)C(=O)C1=CC=CC(OC=2C=C(NC=3SC=C(C)N=3)N=CC=2)=C1 YJMAZJSNFUXTJE-UHFFFAOYSA-N 0.000 description 1
- FQIFAFUIXHQQBS-UHFFFAOYSA-N n-[4-(2,4-difluorophenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C(=CC(F)=CC=3)F)C=2)=N1 FQIFAFUIXHQQBS-UHFFFAOYSA-N 0.000 description 1
- FPJRVHREWAPRSG-UHFFFAOYSA-N n-[4-(2,6-dichlorophenyl)sulfanylpyridin-2-yl]-3-methyl-1,2,4-thiadiazol-5-amine Chemical compound CC1=NSC(NC=2N=CC=C(SC=3C(=CC=CC=3Cl)Cl)C=2)=N1 FPJRVHREWAPRSG-UHFFFAOYSA-N 0.000 description 1
- GNGDMTVVGZIQGK-UHFFFAOYSA-N n-[4-(2,6-dichlorophenyl)sulfanylpyridin-2-yl]-3-phenyl-1,2,4-thiadiazol-5-amine Chemical compound ClC1=CC=CC(Cl)=C1SC1=CC=NC(NC=2SN=C(N=2)C=2C=CC=CC=2)=C1 GNGDMTVVGZIQGK-UHFFFAOYSA-N 0.000 description 1
- PELNPONCZDDBQM-UHFFFAOYSA-N n-[4-(2,6-dichlorophenyl)sulfanylpyridin-2-yl]-[1,3]thiazolo[5,4-b]pyridin-2-amine Chemical compound ClC1=CC=CC(Cl)=C1SC1=CC=NC(NC=2SC3=NC=CC=C3N=2)=C1 PELNPONCZDDBQM-UHFFFAOYSA-N 0.000 description 1
- CVJBDQZWJWGVEN-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)-5-(1,3-thiazol-2-ylsulfanyl)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC(SC=3SC=CN=3)=C(OC=3C(=CC=CC=3F)F)C=2)=N1 CVJBDQZWJWGVEN-UHFFFAOYSA-N 0.000 description 1
- ASXSDPYDRSEUDM-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)-5-[4-(dimethylamino)but-1-enyl]pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.C1=C(OC=2C(=CC=CC=2F)F)C(C=CCCN(C)C)=CN=C1NC1=NC(C)=CS1 ASXSDPYDRSEUDM-UHFFFAOYSA-N 0.000 description 1
- USRUGKNVSPGQFA-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)-5-phenylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC(=C(OC=3C(=CC=CC=3F)F)C=2)C=2C=CC=CC=2)=N1 USRUGKNVSPGQFA-UHFFFAOYSA-N 0.000 description 1
- QCMFOQQVSPJSQT-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)-5-phenylsulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC(SC=3C=CC=CC=3)=C(OC=3C(=CC=CC=3F)F)C=2)=N1 QCMFOQQVSPJSQT-UHFFFAOYSA-N 0.000 description 1
- SDFWYUICUNQHBE-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)-5-pyridin-4-ylsulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.CC1=CSC(NC=2N=CC(SC=3C=CN=CC=3)=C(OC=3C(=CC=CC=3F)F)C=2)=N1 SDFWYUICUNQHBE-UHFFFAOYSA-N 0.000 description 1
- YFCRLRMLDZBNEG-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)pyridin-2-yl]-4-(trifluoromethyl)-1,3-thiazol-2-amine Chemical compound FC1=CC=CC(F)=C1OC1=CC=NC(NC=2SC=C(N=2)C(F)(F)F)=C1 YFCRLRMLDZBNEG-UHFFFAOYSA-N 0.000 description 1
- KYBPSSFPOQZSFQ-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)pyridin-2-yl]-4-ethyl-1,3-thiazol-2-amine Chemical compound CCC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3F)F)C=2)=N1 KYBPSSFPOQZSFQ-UHFFFAOYSA-N 0.000 description 1
- OMCATXLJSVRYPP-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)pyridin-2-yl]-4-phenyl-1,3-thiazol-2-amine Chemical compound FC1=CC=CC(F)=C1OC1=CC=NC(NC=2SC=C(N=2)C=2C=CC=CC=2)=C1 OMCATXLJSVRYPP-UHFFFAOYSA-N 0.000 description 1
- BVOLKHDVULFSLF-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)pyridin-2-yl]-4-thiophen-3-yl-1,3-thiazol-2-amine Chemical compound FC1=CC=CC(F)=C1OC1=CC=NC(NC=2SC=C(N=2)C2=CSC=C2)=C1 BVOLKHDVULFSLF-UHFFFAOYSA-N 0.000 description 1
- DGEYUCFDULAOFB-UHFFFAOYSA-N n-[4-(2,6-difluorophenoxy)pyridin-2-yl]-[1,3]thiazolo[5,4-b]pyridin-2-amine;hydrochloride Chemical compound Cl.FC1=CC=CC(F)=C1OC1=CC=NC(NC=2SC3=NC=CC=C3N=2)=C1 DGEYUCFDULAOFB-UHFFFAOYSA-N 0.000 description 1
- NHDDGBKYPBRVMS-UHFFFAOYSA-N n-[4-(2,6-difluorophenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C(=CC=CC=3F)F)C=2)=N1 NHDDGBKYPBRVMS-UHFFFAOYSA-N 0.000 description 1
- VIBXNHDRPLCRRU-UHFFFAOYSA-N n-[4-(2-chloro-6-methylphenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(OC=3C(=CC=CC=3C)Cl)C=2)=N1 VIBXNHDRPLCRRU-UHFFFAOYSA-N 0.000 description 1
- OZVAHQYTNKLKGR-UHFFFAOYSA-N n-[4-(2-chloro-6-methylphenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC=C(SC=3C(=CC=CC=3C)Cl)C=2)=N1 OZVAHQYTNKLKGR-UHFFFAOYSA-N 0.000 description 1
- GNVZYXWGLVENPM-UHFFFAOYSA-N n-[4-[(4-methoxyphenyl)methylsulfanyl]pyridin-2-yl]-1,1-diphenylmethanimine Chemical compound C1=CC(OC)=CC=C1CSC1=CC=NC(N=C(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 GNVZYXWGLVENPM-UHFFFAOYSA-N 0.000 description 1
- BYTZLVNLFJMWGP-UHFFFAOYSA-N n-[5-[(cyclohexylamino)methyl]-4-naphthalen-1-yloxypyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC(CNC3CCCCC3)=C(OC=3C4=CC=CC=C4C=CC=3)C=2)=N1 BYTZLVNLFJMWGP-UHFFFAOYSA-N 0.000 description 1
- HJZJFFDFWFISSS-UHFFFAOYSA-N n-[5-[(dimethylamino)methyl]-4-naphthalen-1-yloxypyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1=C(OC=2C3=CC=CC=C3C=CC=2)C(CN(C)C)=CN=C1NC1=NC(C)=CS1 HJZJFFDFWFISSS-UHFFFAOYSA-N 0.000 description 1
- ZPHDMCMUMWPNGQ-UHFFFAOYSA-N n-[5-[(dimethylamino)methyl]-4-naphthalen-1-yloxypyridin-2-yl]-4-methyl-1,3-thiazol-2-amine;dihydrochloride Chemical compound Cl.Cl.C1=C(OC=2C3=CC=CC=C3C=CC=2)C(CN(C)C)=CN=C1NC1=NC(C)=CS1 ZPHDMCMUMWPNGQ-UHFFFAOYSA-N 0.000 description 1
- AIHZHIKWWBIUHF-UHFFFAOYSA-N n-[5-bromo-4-(2,6-dichlorophenyl)sulfanylpyridin-2-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound CC1=CSC(NC=2N=CC(Br)=C(SC=3C(=CC=CC=3Cl)Cl)C=2)=N1 AIHZHIKWWBIUHF-UHFFFAOYSA-N 0.000 description 1
- KEAZKLQVBRHHMI-UHFFFAOYSA-N n-[5-bromo-4-[(3-methyl-1,2,4-oxadiazol-5-yl)methyl]pyridin-2-yl]-4-(2-phenylethyl)-1,3-thiazol-2-amine Chemical compound CC1=NOC(CC=2C(=CN=C(NC=3SC=C(CCC=4C=CC=CC=4)N=3)C=2)Br)=N1 KEAZKLQVBRHHMI-UHFFFAOYSA-N 0.000 description 1
- OWGBWLSVZAMWEM-UHFFFAOYSA-N n-[5-bromo-4-[(3-methyl-[1,2]oxazolo[5,4-b]pyridin-4-yl)sulfanyl]pyridin-2-yl]-4-(2-phenylethyl)-1,3-thiazol-2-amine Chemical compound C=12C(C)=NOC2=NC=CC=1SC(C(=CN=1)Br)=CC=1NC(SC=1)=NC=1CCC1=CC=CC=C1 OWGBWLSVZAMWEM-UHFFFAOYSA-N 0.000 description 1
- IVPQXRMTJDJURN-UHFFFAOYSA-N n-[5-bromo-4-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]pyridin-2-yl]-4-(2-phenylethyl)-1,3-thiazol-2-amine Chemical compound O1C(C)=NN=C1CC1=CC(NC=2SC=C(CCC=3C=CC=CC=3)N=2)=NC=C1Br IVPQXRMTJDJURN-UHFFFAOYSA-N 0.000 description 1
- RMKBDUAYWOKUHY-UHFFFAOYSA-N n-[5-cyclohexylsulfanyl-4-(2,6-difluorophenoxy)pyridin-2-yl]-4-methyl-1,3-thiazol-2-amine;hydrochloride Chemical compound Cl.CC1=CSC(NC=2N=CC(SC3CCCCC3)=C(OC=3C(=CC=CC=3F)F)C=2)=N1 RMKBDUAYWOKUHY-UHFFFAOYSA-N 0.000 description 1
- DQMWMUMCNOJLSI-UHFFFAOYSA-N n-carbamothioylbenzamide Chemical compound NC(=S)NC(=O)C1=CC=CC=C1 DQMWMUMCNOJLSI-UHFFFAOYSA-N 0.000 description 1
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
- SEXOVMIIVBKGGM-UHFFFAOYSA-N naphthalene-1-thiol Chemical compound C1=CC=C2C(S)=CC=CC2=C1 SEXOVMIIVBKGGM-UHFFFAOYSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- 201000009925 nephrosclerosis Diseases 0.000 description 1
- PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 description 1
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 description 1
- ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
- BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003551 oxepanyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229940116369 pancreatic lipase Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004108 pentose phosphate pathway Effects 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- RYFZYYUIAZYQLC-UHFFFAOYSA-N perchloromethyl mercaptan Chemical compound ClSC(Cl)(Cl)Cl RYFZYYUIAZYQLC-UHFFFAOYSA-N 0.000 description 1
- 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 229960003562 phentermine Drugs 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960002827 pioglitazone hydrochloride Drugs 0.000 description 1
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
- 229960002797 pitavastatin Drugs 0.000 description 1
- VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- ZEMKJNLEYQVKEL-UHFFFAOYSA-N potassium;tri(propan-2-yl)-sulfidosilane Chemical compound [K+].CC(C)[Si]([S-])(C(C)C)C(C)C ZEMKJNLEYQVKEL-UHFFFAOYSA-N 0.000 description 1
- 229960003611 pramlintide Drugs 0.000 description 1
- 108010029667 pramlintide Proteins 0.000 description 1
- NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000001749 primary amide group Chemical group 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000006410 propenylene group Chemical group 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
- 125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical class [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
- 108010022711 pyroglutamyl-histidyl-glycine Proteins 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000010656 regulation of insulin secretion Effects 0.000 description 1
- 230000007363 regulatory process Effects 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- CRPGRUONUFDYBG-UHFFFAOYSA-N risarestat Chemical compound C1=C(OCC)C(OCCCCC)=CC=C1C1C(=O)NC(=O)S1 CRPGRUONUFDYBG-UHFFFAOYSA-N 0.000 description 1
- XMSXOLDPMGMWTH-UHFFFAOYSA-N rivoglitazone Chemical compound CN1C2=CC(OC)=CC=C2N=C1COC(C=C1)=CC=C1CC1SC(=O)NC1=O XMSXOLDPMGMWTH-UHFFFAOYSA-N 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- 229960004058 simfibrate Drugs 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- RROSXLCQOOGZBR-UHFFFAOYSA-N sodium;isothiocyanate Chemical compound [Na+].[N-]=C=S RROSXLCQOOGZBR-UHFFFAOYSA-N 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000004059 squalene synthase inhibitor Substances 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960000651 tasosartan Drugs 0.000 description 1
- ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- XXUBCCIIIIAKPR-UHFFFAOYSA-N tert-butyl 3-[2-[(4-methyl-1,3-thiazol-2-yl)amino]pyridin-4-yl]oxypiperidine-1-carboxylate Chemical compound CC1=CSC(NC=2N=CC=C(OC3CN(CCC3)C(=O)OC(C)(C)C)C=2)=N1 XXUBCCIIIIAKPR-UHFFFAOYSA-N 0.000 description 1
- UIJXHKXIOCDSEB-UHFFFAOYSA-N tert-butyl 3-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(O)C1 UIJXHKXIOCDSEB-UHFFFAOYSA-N 0.000 description 1
- QJGJETWHNOHKQR-UHFFFAOYSA-N tert-butyl 4-(2-chloropyridin-4-yl)oxypiperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=NC(Cl)=C1 QJGJETWHNOHKQR-UHFFFAOYSA-N 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 description 1
- 125000001583 thiepanyl group Chemical group 0.000 description 1
- 125000002053 thietanyl group Chemical group 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- LUBHDINQXIHVLS-UHFFFAOYSA-N tolrestat Chemical compound OC(=O)CN(C)C(=S)C1=CC=CC2=C(C(F)(F)F)C(OC)=CC=C21 LUBHDINQXIHVLS-UHFFFAOYSA-N 0.000 description 1
- 229960003069 tolrestat Drugs 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
- 230000009466 transformation Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- DHWBYAACHDUFAT-UHFFFAOYSA-N tricyclopentylphosphane Chemical compound C1CCCC1P(C1CCCC1)C1CCCC1 DHWBYAACHDUFAT-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- VPAYJEUHKVESSD-UHFFFAOYSA-N trifluoroiodomethane Chemical compound FC(F)(F)I VPAYJEUHKVESSD-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- XPEMYYBBHOILIJ-UHFFFAOYSA-N trimethyl(trimethylsilylperoxy)silane Chemical compound C[Si](C)(C)OO[Si](C)(C)C XPEMYYBBHOILIJ-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- WQEVDHBJGNOKKO-UHFFFAOYSA-K vanadic acid Chemical compound O[V](O)(O)=O WQEVDHBJGNOKKO-UHFFFAOYSA-K 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000005167 vascular cell Anatomy 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
- SXONDGSPUVNZLO-UHFFFAOYSA-N zenarestat Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F SXONDGSPUVNZLO-UHFFFAOYSA-N 0.000 description 1
- 229950006343 zenarestat Drugs 0.000 description 1
- 229950005346 zopolrestat Drugs 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- 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
- C07D513/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US76317306P | 2006-01-27 | 2006-01-27 | |
| US763173P | 2006-01-27 | ||
| PCT/US2007/001956 WO2007089512A1 (en) | 2006-01-27 | 2007-01-24 | Glucokinase activators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2378704T3 true ES2378704T3 (es) | 2012-04-17 |
Family
ID=38109991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07716991T Active ES2378704T3 (es) | 2006-01-27 | 2007-01-24 | Activadores de la glucocinasa |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US8022222B2 (enExample) |
| EP (1) | EP1986645B1 (enExample) |
| JP (1) | JP5236499B2 (enExample) |
| CN (1) | CN101437512A (enExample) |
| AT (1) | ATE539748T1 (enExample) |
| CA (1) | CA2637172A1 (enExample) |
| ES (1) | ES2378704T3 (enExample) |
| TW (1) | TW200740804A (enExample) |
| WO (1) | WO2007089512A1 (enExample) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008091770A1 (en) * | 2007-01-24 | 2008-07-31 | Array Biopharma Inc. | 2-aminopyridine derivatives as glucokinase activators |
| CA2681695A1 (en) * | 2007-03-23 | 2008-10-02 | Array Biopharma Inc. | 2-aminopyridine analogs as glucokinase activators |
| UY31281A1 (es) * | 2007-08-13 | 2009-03-31 | Aminas, benzamidas y sulfonamidas {[4-(5,6-dimetil-2-piridin-2-il-piridin-3-il) oxipiridin-2-il]amino} sustituidas, sus sales farmacéuticamente aceptables, composiciones contenniéndolas y aplicaciones. | |
| WO2009022179A2 (en) * | 2007-08-14 | 2009-02-19 | Astrazeneca Ab | Glucokinase activators in the treatment of osteoarthritis |
| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| SI2209778T1 (sl) | 2007-09-21 | 2012-12-31 | Array Biopharma, Inc. | Piridin-2-il-amino-I, 2,4-tiadiazol derivati kot aktivatorji glukokinaze za zdravljenje sladkorne bolezni |
| AU2008310097B2 (en) | 2007-10-09 | 2013-05-16 | Merck Patent Gmbh | Pyridine derivatives useful as glucokinase activators |
| KR101608096B1 (ko) | 2008-01-23 | 2016-03-31 | 브리스톨-마이어스 스큅 컴퍼니 | ４-피리디논 화합물 및 암을 위한 그의 용도 |
| US7741327B2 (en) | 2008-04-16 | 2010-06-22 | Hoffmann-La Roche Inc. | Pyrrolidinone glucokinase activators |
| BRPI0920707A2 (pt) | 2008-10-02 | 2015-12-29 | Respivert Ltd | compostos |
| JPWO2010058846A1 (ja) * | 2008-11-21 | 2012-04-19 | アステラス製薬株式会社 | ４，６−ジアミノニコチンアミド化合物 |
| US8299074B2 (en) | 2008-12-11 | 2012-10-30 | Respivert Ltd. | P38 MAP kinase inhibitors |
| GB0905955D0 (en) | 2009-04-06 | 2009-05-20 | Respivert Ltd | Novel compounds |
| GB0921731D0 (en) | 2009-12-11 | 2010-01-27 | Respivert Ltd | Theraputic uses |
| GB0921730D0 (en) | 2009-12-11 | 2010-01-27 | Respivert Ltd | Method of treatment |
| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| CA2800498C (en) | 2010-03-31 | 2021-11-16 | The Scripps Research Institute | Reprogramming cells |
| GB201005589D0 (en) | 2010-04-01 | 2010-05-19 | Respivert Ltd | Novel compounds |
| US9260410B2 (en) | 2010-04-08 | 2016-02-16 | Respivert Ltd. | P38 MAP kinase inhibitors |
| JP5787977B2 (ja) | 2010-04-08 | 2015-09-30 | レスピバート・リミテツド | Ｐ３８ｍａｐキナーゼ阻害剤 |
| US8178689B2 (en) | 2010-06-17 | 2012-05-15 | Hoffman-La Roche Inc. | Tricyclic compounds |
| EP2582709B1 (de) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-on-derivate als inhibitoren von lipasen und phospholipasen |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| 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 |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| MX366318B (es) | 2010-11-19 | 2019-07-05 | Ligand Pharm Inc | Derivados de aminas heterocíclicas que inhiben la transducción de señal mediana por cinasa asociada con el receptor de interleucina-1. |
| WO2012120056A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683699B1 (de) | 2011-03-08 | 2015-06-24 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2766349B1 (de) | 2011-03-08 | 2016-06-01 | Sanofi | Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| WO2012120054A1 (de) | 2011-03-08 | 2012-09-13 | Sanofi | Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| EP2683704B1 (de) | 2011-03-08 | 2014-12-17 | Sanofi | Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung |
| JPWO2012121314A1 (ja) | 2011-03-09 | 2014-07-17 | 第一三共株式会社 | ジピリジルアミン誘導体 |
| CN102786517B (zh) * | 2011-05-18 | 2017-06-06 | 中国医学科学院药物研究所 | Gk和ppar双重激动活性的嘧啶噻唑胺类衍生物 |
| JP5748210B2 (ja) * | 2011-05-26 | 2015-07-15 | 日本化薬株式会社 | 複素環化合物の製造方法 |
| SG10201604682VA (en) * | 2011-06-10 | 2016-07-28 | Merck Patent Gmbh | Compositions and methods for the production of pyrimidine and pyridine compounds with btk inhibitory activity |
| JP6061856B2 (ja) * | 2011-09-05 | 2017-01-18 | 中外製薬株式会社 | クマリン誘導体の製造方法 |
| 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 |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| TW201329067A (zh) * | 2011-12-08 | 2013-07-16 | Amgen Inc | 作為ｇｋａ活化劑之脲化合物 |
| JP6177894B2 (ja) | 2012-05-18 | 2017-08-09 | アムジェン インコーポレイテッド | チアジアゾールの調製方法 |
| WO2014074657A1 (en) * | 2012-11-08 | 2014-05-15 | Bristol-Myers Squibb Company | Bicyclic heterocycle substituted pyridyl compounds useful as kinase modulators |
| US9732063B2 (en) | 2012-11-16 | 2017-08-15 | Respivert Limited | Kinase inhibitors |
| WO2014159938A1 (en) | 2013-03-13 | 2014-10-02 | The Broad Institute, Inc. | Substituted aminothiazoles for the treatment of tuberculosis |
| WO2016001341A1 (en) * | 2014-07-03 | 2016-01-07 | F. Hoffmann-La Roche Ag | Sulfonylaminopyridine compounds, compositions and methods of use |
| CN106749002A (zh) * | 2015-02-12 | 2017-05-31 | 佛山市赛维斯医药科技有限公司 | 一种含硝基喹啉结构的葡萄糖激酶活化剂及其用途 |
| JP6483272B2 (ja) * | 2015-02-17 | 2019-03-13 | グアンジョウ インスティテュート オブ バイオメディスン アンド ヘルス，チャイニーズ アカデミー オブ サイエンスィズ | 白色脂肪組織の褐色化を誘導するための化合物および方法 |
| US10807983B2 (en) | 2015-03-16 | 2020-10-20 | Ligand Pharmaceuticals, Inc. | Imidazo-fused heterocycles and uses thereof |
| ES2912276T3 (es) * | 2015-04-07 | 2022-05-25 | Ela Pharma Ltd | Composiciones para tratar y/o prevenir necrosis celular o tisular que seleccionan como diana específicamente catepsina C y/o CELA1 y/o CELA3A y/o enzimas estructuralmente relacionadas con las mismas |
| AU2016274576A1 (en) | 2015-06-11 | 2017-12-21 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | p62-ZZ chemical inhibitor |
| EP3390387B1 (en) | 2015-12-18 | 2021-11-17 | Bayer Pharma Aktiengesellschaft | Heteroarylbenzimidazole compounds |
| WO2017207534A1 (en) | 2016-06-03 | 2017-12-07 | Bayer Pharma Aktiengesellschaft | Substituted heteroarylbenzimidazole compounds |
| TWI825663B (zh) * | 2016-10-14 | 2023-12-11 | 美商林伯士拉克許米公司 | Tyk2抑制劑及其用途 |
| EP3846793B1 (en) | 2018-09-07 | 2024-01-24 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
| JP7499284B2 (ja) | 2019-06-25 | 2024-06-13 | インベンティスバイオ カンパニー リミテッド | 複素環化合物、その製造方法及びその使用方法 |
| CN110898049B (zh) * | 2019-11-29 | 2021-09-14 | 华中师范大学 | 二硫化合物在制备药物中的应用、fbp酶抑制剂及用于预防和/或治疗糖尿病的药剂 |
| AU2021230289A1 (en) | 2020-03-03 | 2022-09-29 | PIC Therapeutics, Inc. | eIF4E inhibitors and uses thereof |
| WO2022147694A1 (en) * | 2021-01-06 | 2022-07-14 | Beijing Erai Therapeutics Co., Ltd. | Aminoheteroaryl compounds and uses thereof |
| CA3229560A1 (en) | 2021-08-25 | 2023-03-02 | Christopher L. Vandeusen | Eif4e inhibitors and uses thereof |
| JP2024532276A (ja) | 2021-08-25 | 2024-09-05 | ピク セラピューティクス， インコーポレイテッド | ｅＩＦ４Ｅ阻害剤及びその使用 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP0202682A3 (en) * | 1999-09-10 | 2003-03-28 | Merck & Co Inc | Tyrosine kinase inhibitors, pharmaceutical compositions containing them and their use |
| JP2004535437A (ja) * | 2001-06-22 | 2004-11-25 | メルク エンド カムパニー インコーポレーテッド | チロシンキナーゼ阻害剤 |
| ES2289279T3 (es) | 2002-03-15 | 2008-02-01 | Vertex Pharmaceuticals Incorporated | Composiciones utiles como inhibidores de proteinquinasas. |
| US20040023978A1 (en) * | 2002-07-24 | 2004-02-05 | Yu Ren | Active salt forms with tyrosine kinase activity |
| US20040023981A1 (en) * | 2002-07-24 | 2004-02-05 | Yu Ren | Salt forms with tyrosine kinase activity |
| 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 |
| JP2006507302A (ja) | 2002-10-30 | 2006-03-02 | メルク エンド カムパニー インコーポレーテッド | キナーゼ阻害剤 |
| PL378117A1 (pl) * | 2003-02-11 | 2006-03-06 | Prosidion Limited | Tricyklopodstawione związki amidowe |
| GB0328178D0 (en) | 2003-12-05 | 2004-01-07 | Astrazeneca Ab | Compounds |
| AU2005264213A1 (en) * | 2004-05-21 | 2006-01-26 | Msd K.K. | Selective inhibitors against Cdk4 and Cdk6 having aminothiazole skeleton |
| NZ556433A (en) * | 2005-01-14 | 2010-10-29 | Cgi Pharmaceuticals Inc | 1, 3-diaryl substituted ureas as modulators of kinase activity |
| CA2593803A1 (en) | 2005-01-26 | 2006-08-03 | Irm Llc | Thiazole-amide compounds and compsitions as protein kinase inhibitors |
| WO2006135604A2 (en) * | 2005-06-09 | 2006-12-21 | Merck & Co., Inc. | Inhibitors of checkpoint kinases |
-
2007
- 2007-01-24 CN CNA2007800107261A patent/CN101437512A/zh active Pending
- 2007-01-24 ES ES07716991T patent/ES2378704T3/es active Active
- 2007-01-24 WO PCT/US2007/001956 patent/WO2007089512A1/en not_active Ceased
- 2007-01-24 AT AT07716991T patent/ATE539748T1/de active
- 2007-01-24 JP JP2008552395A patent/JP5236499B2/ja not_active Expired - Fee Related
- 2007-01-24 US US12/161,366 patent/US8022222B2/en not_active Expired - Fee Related
- 2007-01-24 EP EP07716991A patent/EP1986645B1/en not_active Not-in-force
- 2007-01-24 CA CA002637172A patent/CA2637172A1/en not_active Abandoned
- 2007-01-25 TW TW096102803A patent/TW200740804A/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ATE539748T1 (de) | 2012-01-15 |
| US8022222B2 (en) | 2011-09-20 |
| WO2007089512A1 (en) | 2007-08-09 |
| EP1986645A1 (en) | 2008-11-05 |
| CN101437512A (zh) | 2009-05-20 |
| EP1986645B1 (en) | 2012-01-04 |
| US20090247526A1 (en) | 2009-10-01 |
| JP2009524670A (ja) | 2009-07-02 |
| CA2637172A1 (en) | 2007-08-09 |
| JP5236499B2 (ja) | 2013-07-17 |
| TW200740804A (en) | 2007-11-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2378704T3 (es) | Activadores de la glucocinasa | |
| AU2007235558B2 (en) | 2 -aminopyridine analogs as glucokinase activators | |
| US8933077B2 (en) | Glucokinase activators | |
| HK1178901A (en) | 2-aminopyridine analogs as glucokinase activators |