TW200528440A - 2-cyanopyrrolidinecarboxamide compound - Google Patents
2-cyanopyrrolidinecarboxamide compound Download PDFInfo
- Publication number
- TW200528440A TW200528440A TW093132734A TW93132734A TW200528440A TW 200528440 A TW200528440 A TW 200528440A TW 093132734 A TW093132734 A TW 093132734A TW 93132734 A TW93132734 A TW 93132734A TW 200528440 A TW200528440 A TW 200528440A
- Authority
- TW
- Taiwan
- Prior art keywords
- group
- lower alkyl
- compound
- substituent
- substituted
- Prior art date
Links
- -1 2-cyanopyrrolidinecarboxamide compound Chemical class 0.000 title claims description 212
- 150000001875 compounds Chemical class 0.000 claims abstract description 355
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 183
- 125000001424 substituent group Chemical group 0.000 claims abstract description 127
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 16
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 9
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims description 101
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 84
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 56
- 150000001412 amines Chemical class 0.000 claims description 51
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 51
- 125000003277 amino group Chemical group 0.000 claims description 44
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 39
- 125000001072 heteroaryl group Chemical group 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 31
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 18
- 125000000468 ketone group Chemical group 0.000 claims description 15
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 229930194542 Keto Natural products 0.000 claims description 10
- 125000005241 heteroarylamino group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 8
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 8
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
- 239000003112 inhibitor Substances 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- WCQOBLXWLRDEQA-UHFFFAOYSA-N ethanimidamide;hydrochloride Chemical compound Cl.CC(N)=N WCQOBLXWLRDEQA-UHFFFAOYSA-N 0.000 claims description 6
- 150000002466 imines Chemical group 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000005421 aryl sulfonamido group Chemical group 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 3
- 150000004982 aromatic amines Chemical class 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 238000010586 diagram Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229940127557 pharmaceutical product Drugs 0.000 claims description 2
- 241001465754 Metazoa Species 0.000 claims 3
- 241000282412 Homo Species 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 125000006242 amine protecting group Chemical group 0.000 claims 1
- 125000005264 aryl amine group Chemical group 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- CSJDCSCTVDEHRN-UHFFFAOYSA-N methane;molecular oxygen Chemical compound C.O=O CSJDCSCTVDEHRN-UHFFFAOYSA-N 0.000 claims 1
- 238000004806 packaging method and process Methods 0.000 claims 1
- IIMRYECIBVWBPB-UHFFFAOYSA-N pyrrolidine-2-carbonitrile;dihydrochloride Chemical compound Cl.Cl.N#CC1CCCN1 IIMRYECIBVWBPB-UHFFFAOYSA-N 0.000 claims 1
- 239000010340 shenyuan Substances 0.000 claims 1
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 claims 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 abstract description 21
- 230000000694 effects Effects 0.000 abstract description 9
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract description 9
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 abstract 2
- 230000001404 mediated effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 249
- 239000000203 mixture Substances 0.000 description 149
- 238000005481 NMR spectroscopy Methods 0.000 description 126
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- 239000000243 solution Substances 0.000 description 113
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 99
- 101150041968 CDC13 gene Proteins 0.000 description 87
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 78
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 71
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 61
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 60
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 52
- 239000002904 solvent Substances 0.000 description 45
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 43
- 239000012044 organic layer Substances 0.000 description 41
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- 239000012267 brine Substances 0.000 description 36
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 36
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- 229960001701 chloroform Drugs 0.000 description 30
- 238000010898 silica gel chromatography Methods 0.000 description 29
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 28
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- 235000019341 magnesium sulphate Nutrition 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 27
- 229910052938 sodium sulfate Inorganic materials 0.000 description 27
- 235000011152 sodium sulphate Nutrition 0.000 description 27
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 26
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 26
- 235000017557 sodium bicarbonate Nutrition 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 23
- 239000007858 starting material Substances 0.000 description 22
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- 239000012074 organic phase Substances 0.000 description 20
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
- 238000001816 cooling Methods 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- DGBKTJIQJQNAIN-UHFFFAOYSA-N 2-butyl-3-methylbutanedioic acid Chemical compound CCCCC(C(O)=O)C(C)C(O)=O DGBKTJIQJQNAIN-UHFFFAOYSA-N 0.000 description 16
- 239000000843 powder Substances 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 239000003960 organic solvent Substances 0.000 description 10
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 10
- NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 9
- LLQHSBBZNDXTIV-UHFFFAOYSA-N 6-[5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-4,5-dihydro-1,2-oxazol-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC1CC(=NO1)C1=CC2=C(NC(O2)=O)C=C1 LLQHSBBZNDXTIV-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- NEAPKZHDYMQZCB-UHFFFAOYSA-N N-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]ethyl]-2-oxo-3H-1,3-benzoxazole-6-carboxamide Chemical compound C1CN(CCN1CCNC(=O)C2=CC3=C(C=C2)NC(=O)O3)C4=CN=C(N=C4)NC5CC6=CC=CC=C6C5 NEAPKZHDYMQZCB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000012230 colorless oil Substances 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 206010012601 diabetes mellitus Diseases 0.000 description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 238000007429 general method Methods 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000035484 reaction time Effects 0.000 description 8
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 7
- 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 7
- 102100040918 Pro-glucagon Human genes 0.000 description 7
- 238000007796 conventional method Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 7
- AJYDSJWVRJUFMI-UHFFFAOYSA-N tert-butyl 3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound C1CC2N(C(=O)OC(C)(C)C)CC1C2 AJYDSJWVRJUFMI-UHFFFAOYSA-N 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 125000004076 pyridyl group Chemical group 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- FQJRZOYTUCCBQR-UHFFFAOYSA-N tert-butyl 2-methylheptanoate Chemical compound CCCCCC(C)C(=O)OC(C)(C)C FQJRZOYTUCCBQR-UHFFFAOYSA-N 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- OBETXYAYXDNJHR-UHFFFAOYSA-N 2-Ethylhexanoic acid Chemical compound CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 4
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- VZKZGTZPGBJVOL-UHFFFAOYSA-N C(=O)=C1C(NCC1)C#N Chemical compound C(=O)=C1C(NCC1)C#N VZKZGTZPGBJVOL-UHFFFAOYSA-N 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 4
- 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 4
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- KICUISADAVMYCJ-UHFFFAOYSA-N methyl 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OC KICUISADAVMYCJ-UHFFFAOYSA-N 0.000 description 4
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 4
- 235000019345 sodium thiosulphate Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- AETVBWZVKDOWHH-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(1-ethylazetidin-3-yl)oxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OC1CN(C1)CC AETVBWZVKDOWHH-UHFFFAOYSA-N 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- DFGKGUXTPFWHIX-UHFFFAOYSA-N 6-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]acetyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)C1=CC2=C(NC(O2)=O)C=C1 DFGKGUXTPFWHIX-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 208000010444 Acidosis Diseases 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- ZITHNHPTZGVUMB-UHFFFAOYSA-N CC(C)(C)OC(=O)N1C2CCC(C2)C1=C=O Chemical compound CC(C)(C)OC(=O)N1C2CCC(C2)C1=C=O ZITHNHPTZGVUMB-UHFFFAOYSA-N 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
- 125000004185 ester group Chemical group 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 201000001119 neuropathy Diseases 0.000 description 3
- 230000007823 neuropathy Effects 0.000 description 3
- 208000033808 peripheral neuropathy Diseases 0.000 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 description 3
- 239000000047 product Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 208000037921 secondary disease Diseases 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000009518 sodium iodide Nutrition 0.000 description 3
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 3
- QSJTUXCBPTVKQZ-JEDNCBNOSA-N (2s)-pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.N#C[C@@H]1CCCN1 QSJTUXCBPTVKQZ-JEDNCBNOSA-N 0.000 description 2
- HHDQVBSXYDRQGD-DMTCNVIQSA-N (2s,4r)-4-hydroxypyrrolidine-1,2-dicarboxylic acid Chemical compound O[C@@H]1C[C@@H](C(O)=O)N(C(O)=O)C1 HHDQVBSXYDRQGD-DMTCNVIQSA-N 0.000 description 2
- JIFNBRXKBJVHQZ-IMJSIDKUSA-N (2s,4s)-2-carbamoyl-4-fluoropyrrolidine-1-carboxylic acid Chemical compound NC(=O)[C@@H]1C[C@H](F)CN1C(O)=O JIFNBRXKBJVHQZ-IMJSIDKUSA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- UHVXBHRCGWKVOZ-UHFFFAOYSA-N 1-benzyl-4-methylpiperidin-4-ol Chemical compound C1CC(C)(O)CCN1CC1=CC=CC=C1 UHVXBHRCGWKVOZ-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- VWVRASTUFJRTHW-UHFFFAOYSA-N 2-[3-(azetidin-3-yloxy)-4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound O=C(CN1C=C(C(OC2CNC2)=N1)C1=CN=C(NC2CC3=C(C2)C=CC=C3)N=C1)N1CCC2=C(C1)N=NN2 VWVRASTUFJRTHW-UHFFFAOYSA-N 0.000 description 2
- IKOKHHBZFDFMJW-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(2-morpholin-4-ylethoxy)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCCN1CCOCC1 IKOKHHBZFDFMJW-UHFFFAOYSA-N 0.000 description 2
- WWSJZGAPAVMETJ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethoxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCC WWSJZGAPAVMETJ-UHFFFAOYSA-N 0.000 description 2
- HVTQDSGGHBWVTR-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-phenylmethoxypyrazol-1-yl]-1-morpholin-4-ylethanone Chemical compound C(C1=CC=CC=C1)OC1=NN(C=C1C=1C=NC(=NC=1)NC1CC2=CC=CC=C2C1)CC(=O)N1CCOCC1 HVTQDSGGHBWVTR-UHFFFAOYSA-N 0.000 description 2
- JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 2
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 2
- JVKRKMWZYMKVTQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JVKRKMWZYMKVTQ-UHFFFAOYSA-N 0.000 description 2
- UEWINXFENVHYDF-UHFFFAOYSA-N 2-butylheptanoic acid Chemical compound CCCCCC(C(O)=O)CCCC UEWINXFENVHYDF-UHFFFAOYSA-N 0.000 description 2
- MGGVALXERJRIRO-UHFFFAOYSA-N 4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-2-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-1H-pyrazol-5-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)O MGGVALXERJRIRO-UHFFFAOYSA-N 0.000 description 2
- OURXRFYZEOUCRM-UHFFFAOYSA-N 4-hydroxymorpholine Chemical compound ON1CCOCC1 OURXRFYZEOUCRM-UHFFFAOYSA-N 0.000 description 2
- WTFUTSCZYYCBAY-SXBRIOAWSA-N 6-[(E)-C-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-N-hydroxycarbonimidoyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C/C(=N/O)/C1=CC2=C(NC(O2)=O)C=C1 WTFUTSCZYYCBAY-SXBRIOAWSA-N 0.000 description 2
- JVRYNXFVLYZTAF-UHFFFAOYSA-N 6-hydroxy-2-azabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound C1C2C(O)CC1CN2C(O)=O JVRYNXFVLYZTAF-UHFFFAOYSA-N 0.000 description 2
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 206010027417 Metabolic acidosis Diseases 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- WWRUCFABCHBARW-HACHORDNSA-N ethyl (2s)-3-azabicyclo[2.2.2]octane-2-carboxylate Chemical compound C1CC2[C@@H](C(=O)OCC)NC1CC2 WWRUCFABCHBARW-HACHORDNSA-N 0.000 description 2
- JLFAHCIYUOZWRO-UHFFFAOYSA-N ethyl 2-ethylhept-4-enoate Chemical compound CCC=CCC(CC)C(=O)OCC JLFAHCIYUOZWRO-UHFFFAOYSA-N 0.000 description 2
- HRJHQOXWONBAJC-UHFFFAOYSA-N ethyl 2-methyloctanoate Chemical compound CCCCCCC(C)C(=O)OCC HRJHQOXWONBAJC-UHFFFAOYSA-N 0.000 description 2
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012025 fluorinating agent Substances 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- KLGSHNXEUZOKHH-JBUOLDKXSA-N hydron;methyl (2s,4r)-4-hydroxypyrrolidine-2-carboxylate;chloride Chemical compound Cl.COC(=O)[C@@H]1C[C@@H](O)CN1 KLGSHNXEUZOKHH-JBUOLDKXSA-N 0.000 description 2
- 125000000879 imine group Chemical group 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 230000003914 insulin secretion Effects 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 description 2
- 229910000032 lithium hydrogen carbonate Inorganic materials 0.000 description 2
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
- HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- DSWNRHCOGVRDOE-UHFFFAOYSA-N n,n-dimethylmethanimidamide Chemical compound CN(C)C=N DSWNRHCOGVRDOE-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 description 2
- 239000011736 potassium bicarbonate Substances 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 125000003226 pyrazolyl group Chemical group 0.000 description 2
- QJRYYOWARFCJQZ-UHFFFAOYSA-N pyrrolidine-1-carbonitrile Chemical class N#CN1CCCC1 QJRYYOWARFCJQZ-UHFFFAOYSA-N 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229940001593 sodium carbonate Drugs 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 2
- WBSWTIWOKFBHEE-UHFFFAOYSA-N (1-benzyl-4-methylpiperidin-4-yl)carbamic acid Chemical compound C1CC(C)(NC(O)=O)CCN1CC1=CC=CC=C1 WBSWTIWOKFBHEE-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
- UTZVHODLVIENHL-SLPGGIOYSA-N (1R,3R,4S,6R)-6-hydroxy-2-azabicyclo[2.2.1]heptane-2,3-dicarboxylic acid Chemical compound C1[C@@H]2[C@H](O)C[C@H]1[C@H](C(O)=O)N2C(O)=O UTZVHODLVIENHL-SLPGGIOYSA-N 0.000 description 1
- UTZVHODLVIENHL-KCDKBNATSA-N (1R,3S,4S,6R)-6-hydroxy-2-azabicyclo[2.2.1]heptane-2,3-dicarboxylic acid Chemical compound C1[C@@H]2[C@H](O)C[C@H]1[C@@H](C(O)=O)N2C(O)=O UTZVHODLVIENHL-KCDKBNATSA-N 0.000 description 1
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
- GXFAYZBQUMULJS-IMJSIDKUSA-N (2s,4s)-4-fluoropyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)[C@@H]1C[C@H](F)CN1C(O)=O GXFAYZBQUMULJS-IMJSIDKUSA-N 0.000 description 1
- YIEACUBSPQGCLW-MMALYQPHSA-N (2s,4s)-4-fluoropyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.NC(=O)[C@@H]1C[C@H](F)CN1 YIEACUBSPQGCLW-MMALYQPHSA-N 0.000 description 1
- XUIOXDMJFRMYAV-UHFFFAOYSA-N (4-methylpiperidin-4-yl)carbamic acid Chemical compound OC(=O)NC1(C)CCNCC1 XUIOXDMJFRMYAV-UHFFFAOYSA-N 0.000 description 1
- DVGJCXKMICUSPU-HWKANZROSA-N (E)-2-ethylhex-4-enoic acid Chemical compound CCC(C(O)=O)C\C=C\C DVGJCXKMICUSPU-HWKANZROSA-N 0.000 description 1
- UZAOPTDGCXICDB-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinolin-4-amine Chemical compound C1=CC=C2C(N)CCNC2=C1 UZAOPTDGCXICDB-UHFFFAOYSA-N 0.000 description 1
- IXYABBFPMPPMPO-CFBFYNIHSA-N 1-[(1R,4R,5R,7S)-4-hydroxy-6-azabicyclo[3.2.1]octane-7-carbonyl]pyrrolidine-2-carbonitrile hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@H]2C[C@H]1CC[C@H]2O)N1CCCC1C#N IXYABBFPMPPMPO-CFBFYNIHSA-N 0.000 description 1
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- JVCBVWTTXCNJBJ-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCN1C2 JVCBVWTTXCNJBJ-UHFFFAOYSA-N 0.000 description 1
- YDQYORVMGACBMI-UHFFFAOYSA-N 1-benzyl-4-methylpiperidin-4-amine Chemical compound C1CC(C)(N)CCN1CC1=CC=CC=C1 YDQYORVMGACBMI-UHFFFAOYSA-N 0.000 description 1
- SSKBPPNEPSALEP-UHFFFAOYSA-N 1-fluoropyrrolidine-2-carbonitrile Chemical compound FN1CCCC1C#N SSKBPPNEPSALEP-UHFFFAOYSA-N 0.000 description 1
- LLURDEOOZCFXIQ-UHFFFAOYSA-N 1-hydroxy-2-azabicyclo[2.2.1]heptane-3-carboxylic acid Chemical compound OC12NC(C(CC1)C2)C(=O)O LLURDEOOZCFXIQ-UHFFFAOYSA-N 0.000 description 1
- CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical class ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- DLTZDKORVMYZEU-UHFFFAOYSA-N 2,6-dimethyl-4h-pyran Chemical compound CC1=CCC=C(C)O1 DLTZDKORVMYZEU-UHFFFAOYSA-N 0.000 description 1
- FZXBJPDVINOGBR-UHFFFAOYSA-N 2,6-dimethyloxan-4-one Chemical compound CC1CC(=O)CC(C)O1 FZXBJPDVINOGBR-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- VHDDOSLMSFXSPY-UHFFFAOYSA-N 2-[(dipropylamino)-propan-2-ylamino]-2-N,2-N-diethyl-1-N,1-N-dimethylpropane-1,2-diamine Chemical compound CCCN(CCC)N(C(C)C)C(C)(CN(C)C)N(CC)CC VHDDOSLMSFXSPY-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- VNPMDUDIDCXVCH-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(3-piperazin-1-ylpropyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound O=C(CN1C=C(C(CCCN2CCNCC2)=N1)C1=CN=C(NC2CC3=C(C2)C=CC=C3)N=C1)N1CCC2=C(C1)N=NN2 VNPMDUDIDCXVCH-UHFFFAOYSA-N 0.000 description 1
- XXZCIYUJYUESMD-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(morpholin-4-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCOCC1 XXZCIYUJYUESMD-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- IHCCLXNEEPMSIO-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 IHCCLXNEEPMSIO-UHFFFAOYSA-N 0.000 description 1
- VXZBYIWNGKSFOJ-UHFFFAOYSA-N 2-[4-[5-(2,3-dihydro-1H-inden-2-ylamino)pyrazin-2-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC=1N=CC(=NC=1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 VXZBYIWNGKSFOJ-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- DVGJCXKMICUSPU-UHFFFAOYSA-N 2-ethylhex-4-enoic acid Chemical compound CCC(C(O)=O)CC=CC DVGJCXKMICUSPU-UHFFFAOYSA-N 0.000 description 1
- MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 description 1
- SAOSCTYRONNFTC-UHFFFAOYSA-N 2-methyl-decanoic acid Chemical compound CCCCCCCCC(C)C(O)=O SAOSCTYRONNFTC-UHFFFAOYSA-N 0.000 description 1
- YSEQNZOXHCKLOG-UHFFFAOYSA-N 2-methyl-octanoic acid Chemical compound CCCCCCC(C)C(O)=O YSEQNZOXHCKLOG-UHFFFAOYSA-N 0.000 description 1
- TYEYBOSBBBHJIV-UHFFFAOYSA-M 2-oxobutanoate Chemical compound CCC(=O)C([O-])=O TYEYBOSBBBHJIV-UHFFFAOYSA-M 0.000 description 1
- HWXRWNDOEKHFTL-UHFFFAOYSA-N 2-propylhexanoic acid Chemical compound CCCCC(C(O)=O)CCC HWXRWNDOEKHFTL-UHFFFAOYSA-N 0.000 description 1
- JIDPHLLCKDISON-UHFFFAOYSA-N 2h-pyran-4-ol Chemical compound OC1=CCOC=C1 JIDPHLLCKDISON-UHFFFAOYSA-N 0.000 description 1
- KSNKQSPJFRQSEI-UHFFFAOYSA-N 3,3,3-trifluoropropanoic acid Chemical compound OC(=O)CC(F)(F)F KSNKQSPJFRQSEI-UHFFFAOYSA-N 0.000 description 1
- LCOFMNJNNXWKOC-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-4-amine Chemical group C1=CC=C2C(N)CCOC2=C1 LCOFMNJNNXWKOC-UHFFFAOYSA-N 0.000 description 1
- LNVWRBNPXCUYJI-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazol-4-amine Chemical compound CC1=NNC(C)=C1N LNVWRBNPXCUYJI-UHFFFAOYSA-N 0.000 description 1
- YRUCPAPUFQOPDX-UHFFFAOYSA-N 3-azabicyclo[2.2.1]heptane-2,3-dicarboxylic acid Chemical compound C1CC2N(C(O)=O)C(C(=O)O)C1C2 YRUCPAPUFQOPDX-UHFFFAOYSA-N 0.000 description 1
- BMVVXSIHLQYXJJ-UHFFFAOYSA-N 3-azoniabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1CC2C(C(=O)O)NC1C2 BMVVXSIHLQYXJJ-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- FIPCQYZRFKNBAJ-UHFFFAOYSA-N 4-O-benzyl 1-O-tert-butyl 3-butyl-2-methylbutanedioate Chemical compound CCCCC(C(C)C(=O)OC(C)(C)C)C(=O)OCC1=CC=CC=C1 FIPCQYZRFKNBAJ-UHFFFAOYSA-N 0.000 description 1
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 1
- JBTIPAKRVUCURY-UHFFFAOYSA-N 4-methyloxan-4-amine;hydrochloride Chemical compound Cl.CC1(N)CCOCC1 JBTIPAKRVUCURY-UHFFFAOYSA-N 0.000 description 1
- DCUYGCJQVJXUHU-UHFFFAOYSA-N 4-methyloxan-4-ol Chemical compound CC1(O)CCOCC1 DCUYGCJQVJXUHU-UHFFFAOYSA-N 0.000 description 1
- LGAQJENWWYGFSN-UHFFFAOYSA-N 4-methylpent-2-ene Chemical group CC=CC(C)C LGAQJENWWYGFSN-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- RYZAMMMGBAOMMC-UHFFFAOYSA-N 4-methylthian-4-ol Chemical compound CC1(O)CCSCC1 RYZAMMMGBAOMMC-UHFFFAOYSA-N 0.000 description 1
- SDTKFYMBKIVOOR-UHFFFAOYSA-N 5-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonyl]-2-azabicyclo[2.2.1]heptane-3-carboxylic acid Chemical compound C1C(O)C2C(C(O)=O)N(C(=O)OC(C)(C)C)C1C2 SDTKFYMBKIVOOR-UHFFFAOYSA-N 0.000 description 1
- YNAKPGRAPIXRFU-UHFFFAOYSA-N 5-hydroxy-2-azabicyclo[2.2.2]octane-2-carboxylic acid Chemical compound C1CC2CN(C1CC2O)C(=O)O YNAKPGRAPIXRFU-UHFFFAOYSA-N 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- DEXFNLNNUZKHNO-UHFFFAOYSA-N 6-[3-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperidin-1-yl]-3-oxopropyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1CCN(CC1)C(CCC1=CC2=C(NC(O2)=O)C=C1)=O DEXFNLNNUZKHNO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- OWCKULARZVLCSH-UHFFFAOYSA-N CC(C)(C)OC(=O)C1NC2CCC1C2 Chemical compound CC(C)(C)OC(=O)C1NC2CCC1C2 OWCKULARZVLCSH-UHFFFAOYSA-N 0.000 description 1
- HWUIZAPZQKBUHL-UHFFFAOYSA-N CC(C)(C)OC(=O)N1C2CC(C1=C=O)CC2=O Chemical compound CC(C)(C)OC(=O)N1C2CC(C1=C=O)CC2=O HWUIZAPZQKBUHL-UHFFFAOYSA-N 0.000 description 1
- WPRHNCNVLPEAOA-UHFFFAOYSA-N CC(C)(C)OC(N(CC(CC1)C2)C12OCC(NS(C)(=O)=O)=O)=O Chemical compound CC(C)(C)OC(N(CC(CC1)C2)C12OCC(NS(C)(=O)=O)=O)=O WPRHNCNVLPEAOA-UHFFFAOYSA-N 0.000 description 1
- 101100337060 Caenorhabditis elegans glp-1 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- VEDTXTNSFWUXGQ-UHFFFAOYSA-N Carbophenothion Chemical group CCOP(=S)(OCC)SCSC1=CC=C(Cl)C=C1 VEDTXTNSFWUXGQ-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010013883 Dwarfism Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- FRJIAZKQGSCKPQ-FSPLSTOPSA-N His-Ala Chemical group OC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CN=CN1 FRJIAZKQGSCKPQ-FSPLSTOPSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
- LEENHRHYVVNBTF-UHFFFAOYSA-N N-fluoren-4-ylidenehydroxylamine Chemical compound C1=CC=CC2=C3C(C=CC=C3C=C12)=NO LEENHRHYVVNBTF-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
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100023170 Nuclear receptor subfamily 1 group D member 1 Human genes 0.000 description 1
- YBOBHINAEIJRQH-UHFFFAOYSA-N ON=C1CC2CN(C1C2)C(=O)O Chemical compound ON=C1CC2CN(C1C2)C(=O)O YBOBHINAEIJRQH-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
- PICDIWZRYPWAIG-UHFFFAOYSA-N [Na].C(C)C(C)CCCC Chemical compound [Na].C(C)C(C)CCCC PICDIWZRYPWAIG-UHFFFAOYSA-N 0.000 description 1
- BDKZHNJTLHOSDW-UHFFFAOYSA-N [Na].CC(O)=O Chemical compound [Na].CC(O)=O BDKZHNJTLHOSDW-UHFFFAOYSA-N 0.000 description 1
- WJEIYVAPNMUNIU-UHFFFAOYSA-N [Na].OC(O)=O Chemical class [Na].OC(O)=O WJEIYVAPNMUNIU-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 1
- WJGAPUXHSQQWQF-UHFFFAOYSA-N acetic acid;hydrochloride Chemical compound Cl.CC(O)=O WJGAPUXHSQQWQF-UHFFFAOYSA-N 0.000 description 1
- PWUBONDMIMDOQY-UHFFFAOYSA-N acetonitrile;hydrochloride Chemical compound Cl.CC#N PWUBONDMIMDOQY-UHFFFAOYSA-N 0.000 description 1
- 230000007950 acidosis Effects 0.000 description 1
- 208000026545 acidosis disease Diseases 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 125000000747 amidyl group Chemical group [H][N-]* 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- QZPSXPBJTPJTSZ-UHFFFAOYSA-N aqua regia Chemical compound Cl.O[N+]([O-])=O QZPSXPBJTPJTSZ-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
- 150000001555 benzenes Chemical group 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- NRIMHVFWRMABGJ-UHFFFAOYSA-N bicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylic acid Chemical compound C1C2C(C(=O)O)=C(C(O)=O)C1C=C2 NRIMHVFWRMABGJ-UHFFFAOYSA-N 0.000 description 1
- IVVOCRBADNIWDM-UHFFFAOYSA-N bicyclo[2.2.1]heptane-2,3-dicarboxylic acid Chemical compound C1CC2C(C(O)=O)C(C(=O)O)C1C2 IVVOCRBADNIWDM-UHFFFAOYSA-N 0.000 description 1
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Substances FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 1
- 125000006251 butylcarbonyl group Chemical group 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000739 chaotic effect Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
- LNAMMBFJMYMQTO-FNEBRGMMSA-N chloroform;(1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].ClC(Cl)Cl.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 LNAMMBFJMYMQTO-FNEBRGMMSA-N 0.000 description 1
- KTRFZWJCHOQHMN-UHFFFAOYSA-N chloromethanethioic s-acid Chemical compound SC(Cl)=O KTRFZWJCHOQHMN-UHFFFAOYSA-N 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 125000004915 dibutylamino group Chemical group C(CCC)N(CCCC)* 0.000 description 1
- ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- HBNBMOGARBJBHS-UHFFFAOYSA-N dimethylarsane Chemical compound C[AsH]C HBNBMOGARBJBHS-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- JVQJWXWVPBKXGY-ORAJLSJDSA-N ethyl (1s,2s,4s,5r,6s)-5,6-dihydroxy-3-[(1r)-1-phenylethyl]-3-azabicyclo[2.2.2]octane-2-carboxylate Chemical compound C1([C@@H](C)N2[C@@]3([H])CC[C@]([C@@H]([C@@H]3O)O)([C@H]2C(=O)OCC)[H])=CC=CC=C1 JVQJWXWVPBKXGY-ORAJLSJDSA-N 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- BYEVBITUADOIGY-UHFFFAOYSA-N ethyl nonanoate Chemical compound CCCCCCCCC(=O)OCC BYEVBITUADOIGY-UHFFFAOYSA-N 0.000 description 1
- BGSFCOHRQUBESL-UHFFFAOYSA-N ethyl prop-2-enyl carbonate Chemical compound CCOC(=O)OCC=C BGSFCOHRQUBESL-UHFFFAOYSA-N 0.000 description 1
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 125000005817 fluorobutyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 208000020694 gallbladder disease Diseases 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid group Chemical group C(CCCCCC)(=O)O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 108010040030 histidinoalanine Proteins 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 229910003480 inorganic solid Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 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
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- AUEBEPQIIHJSHH-UHFFFAOYSA-N methyl 2-ethylhex-4-enoate Chemical compound COC(=O)C(CC=CC)CC AUEBEPQIIHJSHH-UHFFFAOYSA-N 0.000 description 1
- OVJJVYHDJVQFSF-UHFFFAOYSA-N methyl 2-hydroxy-2-methoxyacetate Chemical compound COC(O)C(=O)OC OVJJVYHDJVQFSF-UHFFFAOYSA-N 0.000 description 1
- YRHYCMZPEVDGFQ-UHFFFAOYSA-N methyl decanoate Chemical compound CCCCCCCCCC(=O)OC YRHYCMZPEVDGFQ-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 1
- DYLDHECBLHRVRX-OBAKHWDPSA-N n-[(1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-3-azabicyclo[2.2.1]heptan-5-yl]-4-methylbenzenesulfonamide;hydrochloride Chemical compound Cl.N([C@@H]1C[C@@]2(C[C@@]1([H])N[C@@H]2C(=O)N1[C@@H](CCC1)C#N)[H])S(=O)(=O)C1=CC=C(C)C=C1 DYLDHECBLHRVRX-OBAKHWDPSA-N 0.000 description 1
- FHTGZDVYPCEHFQ-UHFFFAOYSA-N n-methylpiperidin-4-amine Chemical compound CNC1CCNCC1 FHTGZDVYPCEHFQ-UHFFFAOYSA-N 0.000 description 1
- 125000006124 n-propyl sulfonyl group Chemical group 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000005184 naphthylamino group Chemical group C1(=CC=CC2=CC=CC=C12)N* 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- 230000003880 negative regulation of appetite Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
- 238000006146 oximation reaction Methods 0.000 description 1
- RWSZDLPYUAAMDO-UHFFFAOYSA-N pentanoic acid;sodium Chemical group [Na].CCCCC(O)=O RWSZDLPYUAAMDO-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000008855 peristalsis Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- QCRPJKHPRMATOD-UHFFFAOYSA-N pyridine-2-carbonitrile;hydrochloride Chemical compound Cl.N#CC1=CC=CC=N1 QCRPJKHPRMATOD-UHFFFAOYSA-N 0.000 description 1
- GKDLGIYCDXPTJS-UHFFFAOYSA-N pyridine-3-carbonitrile dihydrochloride Chemical compound Cl.Cl.N#CC1=CC=CN=C1 GKDLGIYCDXPTJS-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- ZVFZNMYLDRDSJE-UHFFFAOYSA-N pyrrolidine-1-carbonitrile;hydrochloride Chemical compound Cl.N#CN1CCCC1 ZVFZNMYLDRDSJE-UHFFFAOYSA-N 0.000 description 1
- LCDCPQHFCOBUEF-UHFFFAOYSA-N pyrrolidine-1-carboxamide Chemical compound NC(=O)N1CCCC1 LCDCPQHFCOBUEF-UHFFFAOYSA-N 0.000 description 1
- ALSCEGDXFJIYES-UHFFFAOYSA-N pyrrolidine-2-carbonitrile Chemical class N#CC1CCCN1 ALSCEGDXFJIYES-UHFFFAOYSA-N 0.000 description 1
- QSJTUXCBPTVKQZ-UHFFFAOYSA-N pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.N#CC1CCCN1 QSJTUXCBPTVKQZ-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000007347 radical substitution reaction Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N sodium azide Substances [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 1
- 235000017454 sodium diacetate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- OZWSLOKNPAWAFE-KAUDDPROSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-[2-oxo-2-(pyridin-2-ylamino)ethoxy]-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O([C@@H]1C[C@@]2(C[C@@]1([H])N([C@@H]2C(=O)N1[C@@H](CCC1)C#N)C(=O)OC(C)(C)C)[H])CC(=O)NC1=CC=CC=N1 OZWSLOKNPAWAFE-KAUDDPROSA-N 0.000 description 1
- UWNNZXDNLPNGQJ-UHFFFAOYSA-N tert-butyl 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OC(C)(C)C UWNNZXDNLPNGQJ-UHFFFAOYSA-N 0.000 description 1
- YIAGIPUMQSTQNW-UHFFFAOYSA-N tert-butyl 2-methyloctanoate Chemical compound CCCCCCC(C)C(=O)OC(C)(C)C YIAGIPUMQSTQNW-UHFFFAOYSA-N 0.000 description 1
- PGMLNVNMCQUYQU-UHFFFAOYSA-N tert-butyl 2-pentyloctanoate Chemical compound CCCCCCC(C(=O)OC(C)(C)C)CCCCC PGMLNVNMCQUYQU-UHFFFAOYSA-N 0.000 description 1
- PABFVGKPNHVSCG-UHFFFAOYSA-N tert-butyl 5-hydroxy-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound C1C(O)C2N(C(=O)OC(C)(C)C)CC1C2 PABFVGKPNHVSCG-UHFFFAOYSA-N 0.000 description 1
- AUKQEIHIPOHGHN-UHFFFAOYSA-N tert-butyl 5-oxo-2-azabicyclo[2.2.2]octane-2-carboxylate Chemical compound C1CC2N(C(=O)OC(C)(C)C)CC1C(=O)C2 AUKQEIHIPOHGHN-UHFFFAOYSA-N 0.000 description 1
- SCSLUABEVMLYEA-UHFFFAOYSA-N tert-butyl pentanoate Chemical compound CCCCC(=O)OC(C)(C)C SCSLUABEVMLYEA-UHFFFAOYSA-N 0.000 description 1
- UQCWXKSHRQJGPH-UHFFFAOYSA-M tetrabutylazanium;fluoride;hydrate Chemical compound O.[F-].CCCC[N+](CCCC)(CCCC)CCCC UQCWXKSHRQJGPH-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 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
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- HPNURIVGONRLQI-UHFFFAOYSA-K trifluoroeuropium Chemical compound F[Eu](F)F HPNURIVGONRLQI-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 238000003828 vacuum filtration Methods 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
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/10—Drugs for disorders of the endocrine system of the posterior pituitary hormones, e.g. oxytocin, ADH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- 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
- C07D471/08—Bridged systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Virology (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Transplantation (AREA)
- Gastroenterology & Hepatology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Vascular Medicine (AREA)
- AIDS & HIV (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2003906010A AU2003906010A0 (en) | 2003-10-31 | DPP-IV Inhibitor | |
| AU2004900961A AU2004900961A0 (en) | 2004-02-25 | DPP-IV inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW200528440A true TW200528440A (en) | 2005-09-01 |
Family
ID=34553068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW093132734A TW200528440A (en) | 2003-10-31 | 2004-10-28 | 2-cyanopyrrolidinecarboxamide compound |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US7186731B2 (https=) |
| EP (1) | EP1737863B1 (https=) |
| JP (1) | JP4636021B2 (https=) |
| KR (1) | KR20060100390A (https=) |
| AR (1) | AR046313A1 (https=) |
| AT (1) | ATE419250T1 (https=) |
| BR (1) | BRPI0415587A (https=) |
| CA (1) | CA2543533A1 (https=) |
| CO (1) | CO5690603A2 (https=) |
| DE (1) | DE602004018837D1 (https=) |
| ES (1) | ES2320557T3 (https=) |
| IL (1) | IL175214A0 (https=) |
| MX (1) | MXPA06004797A (https=) |
| NO (1) | NO20062517L (https=) |
| RU (1) | RU2006118789A (https=) |
| TW (1) | TW200528440A (https=) |
| WO (1) | WO2005042533A2 (https=) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL1753748T3 (pl) | 2004-05-12 | 2010-01-29 | Pfizer Prod Inc | Pochodne proliny i ich zastosowanie jako inhibitorów peptydazy dipeptylowej IV |
| JP2008530197A (ja) * | 2005-02-18 | 2008-08-07 | イノディア インク． | ４−ヒドロキシイソロイシンの類似体及びその使用 |
| EP1874287A2 (en) * | 2005-03-22 | 2008-01-09 | Innodia Inc. | Compounds and compositions for use in the prevention and treatment of obesity and related syndromes |
| KR20080000665A (ko) | 2005-04-22 | 2008-01-02 | 알란토스 파마슈티컬즈 홀딩, 인코포레이티드 | 디펩티딜 펩티다아제-ⅳ 억제제 |
| CA2617715A1 (en) * | 2005-08-11 | 2007-02-15 | F. Hoffmann-La Roche Ag | Pharmaceutical composition comprising a dpp-iv inhibitor |
| GB0526291D0 (en) | 2005-12-23 | 2006-02-01 | Prosidion Ltd | Therapeutic method |
| US20100048545A1 (en) * | 2006-03-22 | 2010-02-25 | Innodia Inc. | Compounds and Compositions for Use in the Prevention and Treatment of Disorders of Fat Metabolism and Obesity |
| PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| US7727978B2 (en) * | 2006-08-24 | 2010-06-01 | Bristol-Myers Squibb Company | Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| GB0713602D0 (en) * | 2007-07-12 | 2007-08-22 | Syngenta Participations Ag | Chemical compounds |
| US8338450B2 (en) * | 2007-09-21 | 2012-12-25 | Lupin Limited | Compounds as dipeptidyl peptidase IV (DPP IV) inhibitors |
| JP5305704B2 (ja) * | 2008-03-24 | 2013-10-02 | 富士フイルム株式会社 | 新規化合物、光重合性組成物、カラーフィルタ用光重合性組成物、カラーフィルタ、及びその製造方法、固体撮像素子、並びに、平版印刷版原版 |
| EP2108960A1 (en) | 2008-04-07 | 2009-10-14 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditons modulated by PYY |
| WO2010146597A1 (en) | 2009-06-18 | 2010-12-23 | Lupin Limited | 2-amino-2- [8-(dimethyl carbamoyl)- 8-aza- bicyclo [3.2.1] oct-3-yl]-exo- ethanoyl derivatives as potent dpp-iv inhibitors |
| US8999975B2 (en) | 2011-09-19 | 2015-04-07 | Boehringer Ingelheim International Gmbh | Substituted N- [1-cyano-2- (phenyl) ethyl] -2-azabicyclo [2.2.1] heptane-3-carboxamide inhibitors of cathepsin C |
| EA030003B1 (ru) | 2012-12-21 | 2018-06-29 | Джилид Сайэнс, Инк. | Полициклическое карбамоилпиридоновое соединение и его фармацевтическое применение для лечения вич-инфекции |
| EP2970252B1 (en) | 2013-03-14 | 2020-06-03 | Boehringer Ingelheim International GmbH | Substituted 2-aza-bicyclo[2.2.2]octane-3-carboxylic acid (benzyl-cyano-methyl)-amides inhibitors of cathepsin c |
| ES2845473T3 (es) | 2013-03-14 | 2021-07-26 | Boehringer Ingelheim Int | (Bencil-ciano-metil)-amidas sustituidas de ácido 2-aza-biciclo[2.2.1]heptano-3-carboxílico inhibidores de la catepsina- C |
| NO2865735T3 (https=) | 2013-07-12 | 2018-07-21 | ||
| ES2859102T3 (es) | 2013-07-12 | 2021-10-01 | Gilead Sciences Inc | Compuestos de carbamoilpiridona policíclica y su uso para el tratamiento de infecciones por VIH |
| TW201613936A (en) | 2014-06-20 | 2016-04-16 | Gilead Sciences Inc | Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide |
| TWI677489B (zh) | 2014-06-20 | 2019-11-21 | 美商基利科學股份有限公司 | 多環型胺甲醯基吡啶酮化合物之合成 |
| NO2717902T3 (https=) | 2014-06-20 | 2018-06-23 | ||
| JP6529575B2 (ja) | 2014-08-01 | 2019-06-12 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 置換オキセタンおよびそれらのカテプシンｃの阻害薬としての使用 |
| EP3511331A1 (en) | 2014-09-12 | 2019-07-17 | Boehringer Ingelheim International GmbH | Spirocyclic inhibitors of cathepsin c |
| TWI695003B (zh) | 2014-12-23 | 2020-06-01 | 美商基利科學股份有限公司 | 多環胺甲醯基吡啶酮化合物及其醫藥用途 |
| EA201791982A1 (ru) | 2015-03-09 | 2020-02-17 | Интекрин Терапьютикс, Инк. | Способы лечения неалкогольной жировой болезни печени и/или липодистрофии |
| KR20190057158A (ko) | 2015-04-02 | 2019-05-27 | 길리애드 사이언시즈, 인코포레이티드 | 폴리시클릭-카르바모일피리돈 화합물 및 그의 제약 용도 |
| JP2020515639A (ja) | 2017-04-03 | 2020-05-28 | コヒラス・バイオサイエンシズ・インコーポレイテッド | 進行性核上性麻痺の処置のためのＰＰＡＲγアゴニスト |
| IT201700059292A1 (it) | 2017-05-31 | 2018-12-01 | Univ Pisa | Derivati 1,3-diaza-4-ossa-[3.3.1]-biciclici, loro preparazione e uso come medicinale, in particolare per il trattamento del diabete |
| ES2991898T3 (es) | 2018-08-08 | 2024-12-05 | Sumitomo Pharma Co Ltd | Derivado de piperidina con puente ópticamente activo |
| KR102779601B1 (ko) | 2018-08-27 | 2025-03-12 | 스미토모 파마 가부시키가이샤 | 광학 활성인 아자비시클로환 유도체 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2002360732A1 (en) * | 2001-12-26 | 2003-07-24 | Guilford Pharmaceuticals | Change inhibitors of dipeptidyl peptidase iv |
| TW200401635A (en) * | 2002-07-23 | 2004-02-01 | Yamanouchi Pharma Co Ltd | 2-Cyano-4-fluoropyrrolidine derivative or salt thereof |
-
2004
- 2004-10-28 TW TW093132734A patent/TW200528440A/zh unknown
- 2004-10-29 DE DE602004018837T patent/DE602004018837D1/de not_active Expired - Fee Related
- 2004-10-29 KR KR1020067007974A patent/KR20060100390A/ko not_active Withdrawn
- 2004-10-29 US US10/975,524 patent/US7186731B2/en not_active Expired - Fee Related
- 2004-10-29 MX MXPA06004797A patent/MXPA06004797A/es not_active Application Discontinuation
- 2004-10-29 JP JP2006518489A patent/JP4636021B2/ja not_active Expired - Fee Related
- 2004-10-29 RU RU2006118789/04A patent/RU2006118789A/ru not_active Application Discontinuation
- 2004-10-29 ES ES04793389T patent/ES2320557T3/es not_active Expired - Lifetime
- 2004-10-29 WO PCT/JP2004/016469 patent/WO2005042533A2/en not_active Ceased
- 2004-10-29 AR ARP040104001A patent/AR046313A1/es not_active Application Discontinuation
- 2004-10-29 EP EP04793389A patent/EP1737863B1/en not_active Expired - Lifetime
- 2004-10-29 AT AT04793389T patent/ATE419250T1/de not_active IP Right Cessation
- 2004-10-29 CA CA002543533A patent/CA2543533A1/en not_active Abandoned
- 2004-10-29 BR BRPI0415587-4A patent/BRPI0415587A/pt not_active IP Right Cessation
-
2006
- 2006-04-26 IL IL175214A patent/IL175214A0/en unknown
- 2006-04-26 CO CO06039525A patent/CO5690603A2/es not_active Application Discontinuation
- 2006-05-31 NO NO20062517A patent/NO20062517L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| AR046313A1 (es) | 2005-11-30 |
| WO2005042533A3 (en) | 2005-09-01 |
| WO2005042533A2 (en) | 2005-05-12 |
| CO5690603A2 (es) | 2006-10-31 |
| ATE419250T1 (de) | 2009-01-15 |
| US20050137224A1 (en) | 2005-06-23 |
| EP1737863B1 (en) | 2008-12-31 |
| CA2543533A1 (en) | 2005-05-12 |
| DE602004018837D1 (de) | 2009-02-12 |
| KR20060100390A (ko) | 2006-09-20 |
| MXPA06004797A (es) | 2006-07-03 |
| ES2320557T3 (es) | 2009-05-25 |
| US7186731B2 (en) | 2007-03-06 |
| NO20062517L (no) | 2006-07-21 |
| IL175214A0 (en) | 2006-09-05 |
| RU2006118789A (ru) | 2007-12-10 |
| JP4636021B2 (ja) | 2011-02-23 |
| JP2007510619A (ja) | 2007-04-26 |
| BRPI0415587A (pt) | 2007-01-02 |
| EP1737863A2 (en) | 2007-01-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW200528440A (en) | 2-cyanopyrrolidinecarboxamide compound | |
| JP7829523B2 (ja) | 多環式ｔｌｒ７／８アンタゴニスト及び免疫障害の治療におけるそれらの使用 | |
| US11459327B1 (en) | Cycloalkyl and hetero-cycloalkyl inhibitors, preparation methods therefor, and use thereof | |
| JP7367169B2 (ja) | Ｒｉｐ１阻害剤化合物並びにそれを製造及び使用するための方法 | |
| JP6553748B2 (ja) | 縮合環化合物、医薬組成物およびその使用 | |
| CN105102451B (zh) | N-苯基-氨甲酰衍生物及其作为药物用于治疗乙型肝炎的用途 | |
| TW202043217A (zh) | Ｂｃｌ－２抑制劑 | |
| DE602004010708T2 (de) | Imidazopyridinsubstituierte tropanderivate mit ccr5-rezeptorantagonistischer wirkung zur behandlung von hiv und entzündungen | |
| JP6908536B2 (ja) | ムスカリンｍ２受容体の正のアロステリックモジュレーター | |
| TW201249842A (en) | Dispiropyrrolidine derivatives | |
| EA020815B1 (ru) | Ингибиторы вируса гепатита с | |
| TW202128699A (zh) | 治療性化合物 | |
| TW202333663A (zh) | Rxfp1促效劑 | |
| TWI869058B (zh) | 經取代四氫環戊[c]吡咯、經取代二氫吡咯，其類似物及使用其之方法 | |
| RU2852021C2 (ru) | Новые ингибиторы JAK1-киназ | |
| CN115650974B (zh) | N-[5-(嘧啶-2-氨基)-2,4-二取代苯基]-顺式戊二烯酰胺衍生物及应用 | |
| AU2004285809A1 (en) | 2-cyanopyrrolidinecarboxamides as dipeptidyl peptidase-IV inhibitors | |
| WO2025077825A1 (en) | Methods and compositions for treating cardio-pulmonary disorders | |
| AU2024358558A1 (en) | Methods and compositions for treating cardio-pulmonary disorders | |
| HK1262126A1 (en) | Polycyclic tlr7/8 antagonists and use thereof in the treatment of immune disorders | |
| HK1262126B (en) | Polycyclic tlr7/8 antagonists and use thereof in the treatment of immune disorders | |
| HK1216174A1 (zh) | 氨基取代的咪唑并[1，2-a]吡啶羧酰胺和它们的用途 | |
| HK1216174B (en) | Amino-substituted imidazo[1,2-a]pyridinecarboxamides and their use | |
| HK1196353A (en) | Compounds useful as inhibitors of choline kinase |