KR20060100390A - 디펩티딜 펩티다제-ⅳ 저해제로서의2-시아노피롤리딘카복사미드 - Google Patents

Info

Publication number

KR20060100390A

KR20060100390A KR1020067007974A KR20067007974A KR20060100390A KR 20060100390 A KR20060100390 A KR 20060100390A KR 1020067007974 A KR1020067007974 A KR 1020067007974A KR 20067007974 A KR20067007974 A KR 20067007974A KR 20060100390 A KR20060100390 A KR 20060100390A

Authority

KR

South Korea

Prior art keywords

compound

lower alkyl

substituent

amino

azabicyclo

Prior art date

2003-10-31

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Withdrawn

Links

• Espacenet
• Global Dossier
• Discuss

• LILNUAZFWDUXHX-UHFFFAOYSA-N 2-cyanopyrrolidine-1-carboxamide Chemical compound NC(=O)N1CCCC1C#N LILNUAZFWDUXHX-UHFFFAOYSA-N 0.000 title 1
• 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 title 1
• 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 358
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 148
• 125000001424 substituent group Chemical group 0.000 claims abstract description 142
• 150000003839 salts Chemical class 0.000 claims abstract description 25
• 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims abstract description 24
• 125000002947 alkylene group Chemical group 0.000 claims abstract description 18
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 12
• 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 claims abstract 3
• -1 aminosulfonylamino Chemical group 0.000 claims description 179
• 238000000034 method Methods 0.000 claims description 100
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 94
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 67
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 52
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 46
• 125000003545 alkoxy group Chemical group 0.000 claims description 44
• 125000001072 heteroaryl group Chemical group 0.000 claims description 38
• 238000006243 chemical reaction Methods 0.000 claims description 36
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 34
• 229910052736 halogen Inorganic materials 0.000 claims description 34
• 150000002367 halogens Chemical class 0.000 claims description 34
• 125000003118 aryl group Chemical group 0.000 claims description 29
• 125000001589 carboacyl group Chemical group 0.000 claims description 27
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 23
• 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 20
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 19
• 125000004043 oxo group Chemical group O=* 0.000 claims description 17
• 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 16
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims description 12
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 125000005241 heteroarylamino group Chemical group 0.000 claims description 10
• 125000005419 heteroarylsulfonylamino group Chemical group 0.000 claims description 10
• 125000000623 heterocyclic group Chemical group 0.000 claims description 10
• 125000003277 amino group Chemical group 0.000 claims description 9
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 9
• 230000008569 process Effects 0.000 claims description 9
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 8
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 8
• 239000003112 inhibitor Substances 0.000 claims description 8
• 125000004104 aryloxy group Chemical group 0.000 claims description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
• 125000001769 aryl amino group Chemical group 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 239000004480 active ingredient Substances 0.000 claims description 5
• 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 5
• 125000006239 protecting group Chemical group 0.000 claims description 5
• HBURXUXZLKNVTI-QSWPLQKNSA-N (2s)-1-[(1s,2s,4r,5r)-5-hydroxy-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@]2([H])[C@H](O)C[C@@]1(C2)[H])N1CCC[C@H]1C#N HBURXUXZLKNVTI-QSWPLQKNSA-N 0.000 claims description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
• 238000011282 treatment Methods 0.000 claims description 4
• UTSAVWUDUPXYMN-AFLYGPLOSA-N (2s)-1-[(1s,2s,4r,5r)-5-(2-hydroxyethoxy)-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@]2([H])[C@H](OCCO)C[C@@]1(C2)[H])N1CCC[C@H]1C#N UTSAVWUDUPXYMN-AFLYGPLOSA-N 0.000 claims description 3
• HBURXUXZLKNVTI-AZDRDEPNSA-N (2s)-1-[(1s,2s,4r,5s)-5-hydroxy-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@]2([H])[C@@H](O)C[C@@]1(C2)[H])N1CCC[C@H]1C#N HBURXUXZLKNVTI-AZDRDEPNSA-N 0.000 claims description 3
• BCSFFROFYZFBMX-JVDJTQHISA-N (2s)-1-[(1s,2s,4r,5z)-5-hydroxyimino-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@]2([H])C(=N\O)/C[C@@]1(C2)[H])N1CCC[C@H]1C#N BCSFFROFYZFBMX-JVDJTQHISA-N 0.000 claims description 3
• BSTOTEXATQCDHE-WMYFGTORSA-N (2s)-1-[(1s,3s,4s,5r)-5-hydroxy-2-azabicyclo[2.2.2]octane-3-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@@H]1[C@]2([H])CC[C@@](C[C@H]2O)(N1)[H])N1CCC[C@H]1C#N BSTOTEXATQCDHE-WMYFGTORSA-N 0.000 claims description 3
• 125000003342 alkenyl group Chemical group 0.000 claims description 3
• 238000002360 preparation method Methods 0.000 claims description 3
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 2
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
• 150000001805 chlorine compounds Chemical class 0.000 claims description 2
• ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 241001465754 Metazoa Species 0.000 claims 2
• 238000011321 prophylaxis Methods 0.000 claims 2
• XVBBDUMUVRNZJH-ROHXPCBUSA-N (2s)-1-[(1r,4r,5r,7s)-4-hydroxy-6-azabicyclo[3.2.1]octane-7-carbonyl]pyrrolidine-2-carbonitrile Chemical compound O=C([C@H]1N[C@@H]2C[C@H]1CC[C@H]2O)N1CCC[C@H]1C#N XVBBDUMUVRNZJH-ROHXPCBUSA-N 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 239000008177 pharmaceutical agent Substances 0.000 claims 1
• 230000000694 effects Effects 0.000 abstract description 8
• 230000001404 mediated effect Effects 0.000 abstract description 4
• 208000024891 symptom Diseases 0.000 abstract description 4
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 252
• 239000000203 mixture Substances 0.000 description 151
• 239000000243 solution Substances 0.000 description 116
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 70
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 56
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
• 239000002904 solvent Substances 0.000 description 44
• NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 43
• 239000012044 organic layer Substances 0.000 description 43
• 239000012267 brine Substances 0.000 description 40
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 39
• 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 39
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
• 239000011541 reaction mixture Substances 0.000 description 37
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
• 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 35
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 28
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 27
• 239000000741 silica gel Substances 0.000 description 26
• 229910002027 silica gel Inorganic materials 0.000 description 26
• 239000007787 solid Substances 0.000 description 26
• 229920006395 saturated elastomer Polymers 0.000 description 23
• 229910052938 sodium sulfate Inorganic materials 0.000 description 22
• 235000011152 sodium sulphate Nutrition 0.000 description 22
• 239000007858 starting material Substances 0.000 description 22
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
• 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 21
• 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 21
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
• 235000017557 sodium bicarbonate Nutrition 0.000 description 19
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
• 238000010898 silica gel chromatography Methods 0.000 description 18
• 239000012074 organic phase Substances 0.000 description 17
• 239000000843 powder Substances 0.000 description 16
• 238000001816 cooling Methods 0.000 description 15
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 15
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
• 239000011780 sodium chloride Substances 0.000 description 14
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 13
• 239000000706 filtrate Substances 0.000 description 13
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 11
• OBETXYAYXDNJHR-UHFFFAOYSA-N 2-Ethylhexanoic acid Chemical compound CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 10
• 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 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
• 239000003960 organic solvent Substances 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-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
• 239000002585 base Substances 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• 239000012230 colorless oil Substances 0.000 description 9
• 239000013078 crystal Substances 0.000 description 9
• YSEQNZOXHCKLOG-UHFFFAOYSA-N 2-methyl-octanoic acid Chemical compound CCCCCCC(C)C(O)=O YSEQNZOXHCKLOG-UHFFFAOYSA-N 0.000 description 8
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 229910052739 hydrogen Inorganic materials 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 230000035484 reaction time Effects 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
• 150000001412 amines Chemical class 0.000 description 7
• 238000007796 conventional method Methods 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• 229910052763 palladium Inorganic materials 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 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 7
• 238000012360 testing method Methods 0.000 description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• 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 6
• 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 6
• 102100040918 Pro-glucagon Human genes 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
• 206010012601 diabetes mellitus Diseases 0.000 description 6
• CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 6
• 238000007429 general method Methods 0.000 description 6
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 6
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 5
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 5
• 239000005977 Ethylene Substances 0.000 description 5
• 230000002378 acidificating effect Effects 0.000 description 5
• 239000000654 additive Substances 0.000 description 5
• 150000001298 alcohols Chemical class 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 230000003197 catalytic effect Effects 0.000 description 5
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
• 229910052757 nitrogen Inorganic materials 0.000 description 5
• 239000012299 nitrogen atmosphere Substances 0.000 description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
• 235000009518 sodium iodide Nutrition 0.000 description 5
• 238000005406 washing Methods 0.000 description 5
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 4
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 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 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
• 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 4
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
• 208000031226 Hyperlipidaemia Diseases 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 4
• UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 238000003776 cleavage reaction Methods 0.000 description 4
• GLNDAGDHSLMOKX-UHFFFAOYSA-N coumarin 120 Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2C GLNDAGDHSLMOKX-UHFFFAOYSA-N 0.000 description 4
• 201000010099 disease Diseases 0.000 description 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 125000001153 fluoro group Chemical group F* 0.000 description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 4
• 229910000027 potassium carbonate Inorganic materials 0.000 description 4
• 235000011181 potassium carbonates Nutrition 0.000 description 4
• ALSCEGDXFJIYES-UHFFFAOYSA-N pyrrolidine-2-carbonitrile Chemical class N#CC1CCCN1 ALSCEGDXFJIYES-UHFFFAOYSA-N 0.000 description 4
• 238000010791 quenching Methods 0.000 description 4
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 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
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
• 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
• 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 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
• XJWARUXLNARECD-JLIMGVALSA-N 3-o-tert-butyl 2-o-methyl (1s,2s,4r,5r)-5-hydroxy-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound C1[C@@H](O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])C2 XJWARUXLNARECD-JLIMGVALSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
• 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 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 241001274216 Naso Species 0.000 description 3
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 3
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
• 150000008065 acid anhydrides Chemical class 0.000 description 3
• 239000012131 assay buffer Substances 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• 125000004185 ester group Chemical group 0.000 description 3
• VHFZIBNRJPBOBX-SNVBAGLBSA-N ethyl 2-[(1r)-1-phenylethyl]iminoacetate Chemical compound CCOC(=O)C=N[C@H](C)C1=CC=CC=C1 VHFZIBNRJPBOBX-SNVBAGLBSA-N 0.000 description 3
• 239000008103 glucose Substances 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 125000004076 pyridyl group Chemical group 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 208000037921 secondary disease Diseases 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
• IFAMSTPTNRJBRG-VGMNWLOBSA-N (1r,2s,4s)-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound C1C[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(O)=O)[C@@]1([H])C2 IFAMSTPTNRJBRG-VGMNWLOBSA-N 0.000 description 2
• ARWLIMOJIMFGRX-KDXUFGMBSA-N (1s,2s,4r,5r)-5-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound C1[C@@H](O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(O)=O)[C@@]1([H])C2 ARWLIMOJIMFGRX-KDXUFGMBSA-N 0.000 description 2
• TYUQYVAXNUHBAT-JLIMGVALSA-N (1s,3s,4s,5r)-5-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonyl]-2-azabicyclo[2.2.2]octane-3-carboxylic acid Chemical compound C1C[C@]2([H])[C@H](O)C[C@@]1([H])N(C(=O)OC(C)(C)C)[C@@H]2C(O)=O TYUQYVAXNUHBAT-JLIMGVALSA-N 0.000 description 2
• RRRWAYWNXBSUFV-RTBKNWGFSA-N (2s)-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[2.2.2]octane-2-carboxylic acid Chemical compound C1CC2CCC1N(C(=O)OC(C)(C)C)[C@@H]2C(O)=O RRRWAYWNXBSUFV-RTBKNWGFSA-N 0.000 description 2
• QSJTUXCBPTVKQZ-JEDNCBNOSA-N (2s)-pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.N#C[C@@H]1CCCN1 QSJTUXCBPTVKQZ-JEDNCBNOSA-N 0.000 description 2
• 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 2
• 125000006729 (C2-C5) alkenyl group Chemical group 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
• YDQYORVMGACBMI-UHFFFAOYSA-N 1-benzyl-4-methylpiperidin-4-amine Chemical compound C1CC(C)(N)CCN1CC1=CC=CC=C1 YDQYORVMGACBMI-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
• HMCPFKPMDMJMGK-UHFFFAOYSA-N 1-methyl-3,4-dihydro-2h-quinolin-4-amine Chemical compound C1=CC=C2N(C)CCC(N)C2=C1 HMCPFKPMDMJMGK-UHFFFAOYSA-N 0.000 description 2
• MZMNEDXVUJLQAF-SFYZADRCSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-hydroxypyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@@H](O)CN1C(=O)OC(C)(C)C MZMNEDXVUJLQAF-SFYZADRCSA-N 0.000 description 2
• METPQQHVRNLTRX-YUMQZZPRSA-N 1-o-tert-butyl 2-o-methyl (2s,4s)-4-fluoropyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@H](F)CN1C(=O)OC(C)(C)C METPQQHVRNLTRX-YUMQZZPRSA-N 0.000 description 2
• WMIIHGCHQJIYTR-UHFFFAOYSA-N 2,4,6-trimethyloxan-4-amine Chemical compound CC1CC(C)(N)CC(C)O1 WMIIHGCHQJIYTR-UHFFFAOYSA-N 0.000 description 2
• VXZIIJNJEJTEOZ-UHFFFAOYSA-N 2,4,6-trimethyloxan-4-ol Chemical compound CC1CC(C)(O)CC(C)O1 VXZIIJNJEJTEOZ-UHFFFAOYSA-N 0.000 description 2
• FZXBJPDVINOGBR-UHFFFAOYSA-N 2,6-dimethyloxan-4-one Chemical compound CC1CC(=O)CC(C)O1 FZXBJPDVINOGBR-UHFFFAOYSA-N 0.000 description 2
• 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 2
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-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
• 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 2
• 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 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
• 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
• XZHODVBRILUJCW-UHFFFAOYSA-N 2-chloro-n-(2,4,6-trimethyloxan-4-yl)acetamide Chemical compound CC1CC(C)(NC(=O)CCl)CC(C)O1 XZHODVBRILUJCW-UHFFFAOYSA-N 0.000 description 2
• SCZLWAUHZWCVOS-UHFFFAOYSA-N 2-chloro-n-(4-methyloxan-4-yl)acetamide Chemical compound ClCC(=O)NC1(C)CCOCC1 SCZLWAUHZWCVOS-UHFFFAOYSA-N 0.000 description 2
• OBETXYAYXDNJHR-UHFFFAOYSA-M 2-ethylhexanoate Chemical compound CCCCC(CC)C([O-])=O OBETXYAYXDNJHR-UHFFFAOYSA-M 0.000 description 2
• SDBVUDYZBFDQKN-UHFFFAOYSA-N 2-o-tert-butyl 3-o-ethyl 5-hydroxy-2-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound C1C2CC(O)C1C(C(=O)OCC)N2C(=O)OC(C)(C)C SDBVUDYZBFDQKN-UHFFFAOYSA-N 0.000 description 2
• LCOFMNJNNXWKOC-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-4-amine Chemical compound C1=CC=C2C(N)CCOC2=C1 LCOFMNJNNXWKOC-UHFFFAOYSA-N 0.000 description 2
• BMVVXSIHLQYXJJ-UHFFFAOYSA-N 3-azoniabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1CC2C(C(=O)O)NC1C2 BMVVXSIHLQYXJJ-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
• FAMNSSUBWODQOM-UHFFFAOYSA-N 4-methyl-1-pyrazin-2-ylpiperidin-4-amine Chemical compound C1CC(C)(N)CCN1C1=CN=CC=N1 FAMNSSUBWODQOM-UHFFFAOYSA-N 0.000 description 2
• JBTIPAKRVUCURY-UHFFFAOYSA-N 4-methyloxan-4-amine;hydrochloride Chemical compound Cl.CC1(N)CCOCC1 JBTIPAKRVUCURY-UHFFFAOYSA-N 0.000 description 2
• DCUYGCJQVJXUHU-UHFFFAOYSA-N 4-methyloxan-4-ol Chemical compound CC1(O)CCOCC1 DCUYGCJQVJXUHU-UHFFFAOYSA-N 0.000 description 2
• RYZAMMMGBAOMMC-UHFFFAOYSA-N 4-methylthian-4-ol Chemical compound CC1(O)CCSCC1 RYZAMMMGBAOMMC-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 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 2
• 208000030507 AIDS Diseases 0.000 description 2
• 208000010444 Acidosis Diseases 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 208000007342 Diabetic Nephropathies Diseases 0.000 description 2
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
• VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 2
• 206010027417 Metabolic acidosis Diseases 0.000 description 2
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
• 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 2
• AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 2
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 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
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
• 150000001338 aliphatic hydrocarbons Chemical class 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
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 239000003637 basic solution Substances 0.000 description 2
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 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
• 208000033679 diabetic kidney disease Diseases 0.000 description 2
• BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
• 239000003480 eluent 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
• GFFCSDRCCRGJKW-XBVQOTNRSA-N ethyl (1r,2s,4s)-3-[(1r)-1-phenylethyl]-3-azabicyclo[2.2.2]oct-5-ene-2-carboxylate Chemical compound C1([C@@H](C)N2[C@@]3([H])CC[C@](C=C3)([C@H]2C(=O)OCC)[H])=CC=CC=C1 GFFCSDRCCRGJKW-XBVQOTNRSA-N 0.000 description 2
• WUIAYXIFYFXSQX-BGZDPUMWSA-N ethyl (1r,4r,5r,7s)-4-hydroxy-6-azabicyclo[3.2.1]octane-7-carboxylate Chemical compound C1[C@@]2([H])N[C@H](C(=O)OCC)[C@]1([H])CC[C@H]2O WUIAYXIFYFXSQX-BGZDPUMWSA-N 0.000 description 2
• IXDCXTCQGXOSMU-OSMVPFSASA-N ethyl (1s,2s,4r,5r)-5-hydroxy-3-azabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@@H](O)[C@]2([H])N[C@H](C(=O)OCC)[C@@]1([H])C2 IXDCXTCQGXOSMU-OSMVPFSASA-N 0.000 description 2
• BSRNTNWGLCIJSC-VCQFTWBDSA-N ethyl (1s,2s,4s,5r,6s)-5,6-dihydroxy-3-azabicyclo[2.2.2]octane-2-carboxylate Chemical compound C1C[C@]2([H])[C@H](O)[C@H](O)[C@@]1([H])N[C@@H]2C(=O)OCC BSRNTNWGLCIJSC-VCQFTWBDSA-N 0.000 description 2
• JXWFWNBEIJRYAK-KDXUFGMBSA-N ethyl (1s,3s,4s,5r)-5-hydroxy-2-azabicyclo[2.2.2]octane-3-carboxylate Chemical compound C1C[C@]2([H])[C@H](O)C[C@@]1([H])N[C@@H]2C(=O)OCC JXWFWNBEIJRYAK-KDXUFGMBSA-N 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
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
• 125000006125 ethylsulfonyl group Chemical group 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 125000005843 halogen 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
• 238000001727 in vivo Methods 0.000 description 2
• 230000003914 insulin secretion Effects 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 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
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
• HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 description 2
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• SUWRFUCBJPWMRU-KDXUFGMBSA-N methyl (1s,2s,4r,5r)-5-acetyloxy-3-azabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@@H](OC(C)=O)[C@]2([H])N[C@H](C(=O)OC)[C@@]1([H])C2 SUWRFUCBJPWMRU-KDXUFGMBSA-N 0.000 description 2
• UXRHYUSIOTYRRH-SECBINFHSA-N methyl 2-[(1r)-1-phenylethyl]iminoacetate Chemical compound COC(=O)C=N[C@H](C)C1=CC=CC=C1 UXRHYUSIOTYRRH-SECBINFHSA-N 0.000 description 2
• 239000012046 mixed solvent 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
• AOSOPBKZGPYHCS-UHFFFAOYSA-N n-(1-benzyl-4-methylpiperidin-4-yl)acetamide Chemical compound C1CC(NC(=O)C)(C)CCN1CC1=CC=CC=C1 AOSOPBKZGPYHCS-UHFFFAOYSA-N 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 235000015497 potassium bicarbonate Nutrition 0.000 description 2
• 229910000028 potassium bicarbonate Inorganic materials 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
• 239000000047 product Substances 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 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
• 235000010265 sodium sulphite Nutrition 0.000 description 2
• VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
• HYPKHZYANLMKRK-QNSTZXKLSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-hydroxy-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N HYPKHZYANLMKRK-QNSTZXKLSA-N 0.000 description 2
• SQGNCVVKJIZGLC-BQBZGAKWSA-N tert-butyl (2s,4s)-2-carbamoyl-4-fluoropyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1C[C@@H](F)C[C@H]1C(N)=O SQGNCVVKJIZGLC-BQBZGAKWSA-N 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
• 230000009466 transformation Effects 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
• RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
• SXHAUJHLPXLQQA-KKOKHZNYSA-N (1r,2s,4r,5r)-3-[(2-methylpropan-2-yl)oxycarbonyl]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-3-azabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(O)=O)[C@@]1([H])C2 SXHAUJHLPXLQQA-KKOKHZNYSA-N 0.000 description 1
• BTLPJMSSOHNNQG-DBIOUOCHSA-N (1r,2s,4r,5r)-5-acetamido-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound C1[C@@H](NC(C)=O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(O)=O)[C@@]1([H])C2 BTLPJMSSOHNNQG-DBIOUOCHSA-N 0.000 description 1
• MOGVOEDMQKQNRS-KYXWUPHJSA-N (1r,4r,5r,7s)-4-hydroxy-6-[(2-methylpropan-2-yl)oxycarbonyl]-6-azabicyclo[3.2.1]octane-7-carboxylic acid Chemical compound C1[C@]2([H])[C@H](O)CC[C@@]1([H])[C@@H](C(O)=O)N2C(=O)OC(C)(C)C MOGVOEDMQKQNRS-KYXWUPHJSA-N 0.000 description 1
• FCYUPOCBNOAMHF-VGMFFHCQSA-N (1s)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1.C[C@H](N)C1=CC=CC=C1 FCYUPOCBNOAMHF-VGMFFHCQSA-N 0.000 description 1
• ARWLIMOJIMFGRX-JQCXWYLXSA-N (1s,2r,4r,5r)-5-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound C1[C@@H](O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@@H](C(O)=O)[C@@]1([H])C2 ARWLIMOJIMFGRX-JQCXWYLXSA-N 0.000 description 1
• WFQUYNVVACYPAW-SFTQSGBHSA-N (1s,2s,4r,5r)-5-(3-ethoxy-3-oxopropoxy)-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound C1[C@@H](OCCC(=O)OCC)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(O)=O)[C@@]1([H])C2 WFQUYNVVACYPAW-SFTQSGBHSA-N 0.000 description 1
• MSOFOJMCUKABJH-MIGQKNRLSA-N (1s,2s,4r,5r)-5-[(4-methylphenyl)sulfonylamino]-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound N([C@@H]1C[C@@]2(C[C@@]1([H])N([C@@H]2C(O)=O)C(=O)OC(C)(C)C)[H])S(=O)(=O)C1=CC=C(C)C=C1 MSOFOJMCUKABJH-MIGQKNRLSA-N 0.000 description 1
• PVRPQVLBJPONEB-BQHMLIOBSA-N (1s,2s,4s,5r,6s)-5,6-dihydroxy-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[2.2.2]octane-2-carboxylic acid Chemical compound C1C[C@@]2([H])[C@@H](O)[C@@H](O)[C@]1([H])[C@@H](C(O)=O)N2C(=O)OC(C)(C)C PVRPQVLBJPONEB-BQHMLIOBSA-N 0.000 description 1
• LJXOXNFLZSSFOM-HXLXBVJFSA-N (1s,2s,4s,5r,7r)-7-fluoro-5-hydroxy-3-[(2-methylpropan-2-yl)oxycarbonyl]-3-azabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound C1[C@@H](O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(O)=O)[C@@]1([H])[C@H]2F LJXOXNFLZSSFOM-HXLXBVJFSA-N 0.000 description 1
• NECGOUDAPCDBAB-AZGDMVHKSA-N (2s)-1-[(1r,2s,4r,5s)-5-hydroxy-1-methyl-4-propan-2-yl-3-azabicyclo[2.2.2]octane-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound O=C([C@@H]1[C@]2(C)CC[C@@]([C@H](C2)O)(N1)C(C)C)N1CCC[C@H]1C#N NECGOUDAPCDBAB-AZGDMVHKSA-N 0.000 description 1
• RQBRWBOIHGJMJJ-NORLLQMESA-N (2s)-1-[(1r,2s,4s)-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@@H]1[C@]2([H])CC[C@@](C2)(N1)[H])N1CCC[C@H]1C#N RQBRWBOIHGJMJJ-NORLLQMESA-N 0.000 description 1
• IXYABBFPMPPMPO-OWMZXZORSA-N (2s)-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@@]2(C[C@]1(CC[C@H]2O)[H])[H])N1CCC[C@H]1C#N IXYABBFPMPPMPO-OWMZXZORSA-N 0.000 description 1
• HBURXUXZLKNVTI-RNJIMISSSA-N (2s)-1-[(1s,2r,4r,5r)-5-hydroxy-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@@H]1N[C@@]2([H])[C@H](O)C[C@@]1(C2)[H])N1CCC[C@H]1C#N HBURXUXZLKNVTI-RNJIMISSSA-N 0.000 description 1
• QAIICGZIQXUAPS-WWFNWRJBSA-N (2s)-1-[(1s,2s,4r)-5-oxo-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@]2([H])C(=O)C[C@@]1(C2)[H])N1CCC[C@H]1C#N QAIICGZIQXUAPS-WWFNWRJBSA-N 0.000 description 1
• JXYJKBKZVGLSON-GEPHSGDCSA-N (2s)-1-[(1s,2s,4r)-7-hydroxy-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile Chemical compound O=C([C@@H]1[C@]2([H])CC[C@](C2O)(N1)[H])N1CCC[C@H]1C#N JXYJKBKZVGLSON-GEPHSGDCSA-N 0.000 description 1
• BEQGTQLPSMKETH-LWTASJACSA-N (2s)-1-[(1s,2s,4r,5e)-5-phenylmethoxyimino-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.C([C@@]1(C[C@@]2([H])N[C@@H]1C(=O)N1[C@@H](CCC1)C#N)[H])\C2=N/OCC1=CC=CC=C1 BEQGTQLPSMKETH-LWTASJACSA-N 0.000 description 1
• QOJUIGVOIUQQHH-VJCFCCHNSA-N (2s)-1-[(1s,2s,4r,5r)-5-[(2e)-2-hydroxyiminoethoxy]-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@]2([H])[C@H](OC\C=N\O)C[C@@]1(C2)[H])N1CCC[C@H]1C#N QOJUIGVOIUQQHH-VJCFCCHNSA-N 0.000 description 1
• GAHABQNKHHJWLU-RCWPTPOPSA-N (2s)-1-[(1s,2s,4r,5r)-5-[(2r)-2,3-dihydroxypropoxy]-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@]2([H])[C@H](OC[C@H](O)CO)C[C@@]1(C2)[H])N1CCC[C@H]1C#N GAHABQNKHHJWLU-RCWPTPOPSA-N 0.000 description 1
• GAHABQNKHHJWLU-BPTLGQMOSA-N (2s)-1-[(1s,2s,4r,5r)-5-[(2s)-2,3-dihydroxypropoxy]-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@]2([H])[C@H](OC[C@@H](O)CO)C[C@@]1(C2)[H])N1CCC[C@H]1C#N GAHABQNKHHJWLU-BPTLGQMOSA-N 0.000 description 1
• MDTPLDVJCCZQGQ-VSLQPRDFSA-N (2s)-1-[(1s,2s,4s,5r,7r)-7-fluoro-5-hydroxy-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@]2([C@H](O)C[C@@]1([C@H]2F)[H])[H])N1CCC[C@H]1C#N MDTPLDVJCCZQGQ-VSLQPRDFSA-N 0.000 description 1
• OQHXBMAZHZXLRE-XLVUAHCWSA-N (2s)-1-[(2s)-3-azabicyclo[2.2.2]octane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@@H]1C2CCC(CC2)N1)N1CCC[C@H]1C#N OQHXBMAZHZXLRE-XLVUAHCWSA-N 0.000 description 1
• DMQSZIMWOFNPNR-WDSKDSINSA-N (2s,4s)-1-(2-chloroacetyl)-4-fluoropyrrolidine-2-carbonitrile Chemical compound F[C@H]1C[C@@H](C#N)N(C(=O)CCl)C1 DMQSZIMWOFNPNR-WDSKDSINSA-N 0.000 description 1
• AKILPJBDRGKDRC-VHBIQUBJSA-N (2s,4s)-1-[2-(3,4-dihydro-2h-chromen-4-ylamino)acetyl]-4-fluoropyrrolidine-2-carbonitrile Chemical compound C1[C@@H](F)C[C@@H](C#N)N1C(=O)CNC1C2=CC=CC=C2OCC1 AKILPJBDRGKDRC-VHBIQUBJSA-N 0.000 description 1
• YBIOAMCMYFCDEP-NEUMUYNTSA-N (2s,4s)-4-fluoro-1-[(1s,2s,4r,5r)-5-hydroxy-3-azabicyclo[2.2.1]heptane-2-carbonyl]pyrrolidine-2-carbonitrile;hydrochloride Chemical compound Cl.O=C([C@H]1N[C@@]2([H])[C@H](O)C[C@@]1(C2)[H])N1C[C@@H](F)C[C@H]1C#N YBIOAMCMYFCDEP-NEUMUYNTSA-N 0.000 description 1
• YGWZXQOYEBWUTH-BQBZGAKWSA-N (2s,4s)-4-fluoro-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1C[C@@H](F)C[C@H]1C(O)=O YGWZXQOYEBWUTH-BQBZGAKWSA-N 0.000 description 1
• VHSWHUJTHSXFTF-QNIGDANOSA-N (2s,4s)-4-fluoro-1-[2-[(1-methyl-3,4-dihydro-2h-quinolin-4-yl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C12=CC=CC=C2N(C)CCC1NCC(=O)N1C[C@@H](F)C[C@H]1C#N VHSWHUJTHSXFTF-QNIGDANOSA-N 0.000 description 1
• ZVQNANDNGCVHRE-XJKSFGJRSA-N (2s,4s)-4-fluoro-1-[2-[(2,4,6-trimethyloxan-4-yl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1C(C)OC(C)CC1(C)NCC(=O)N1[C@H](C#N)C[C@H](F)C1 ZVQNANDNGCVHRE-XJKSFGJRSA-N 0.000 description 1
• QELDLUWCRLBTJH-KBPBESRZSA-N (2s,4s)-4-fluoro-1-[2-[(4-methyl-1-pyrazin-2-ylpiperidin-4-yl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C1CC(C)(NCC(=O)N2[C@@H](C[C@H](F)C2)C#N)CCN1C1=CN=CC=N1 QELDLUWCRLBTJH-KBPBESRZSA-N 0.000 description 1
• JZHYMHQHCUGZFI-QWRGUYRKSA-N (2s,4s)-4-fluoro-1-[2-[(4-methyloxan-4-yl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](C[C@H](F)C1)C#N)C(=O)CNC1(C)CCOCC1 JZHYMHQHCUGZFI-QWRGUYRKSA-N 0.000 description 1
• CCBUDPLPYWKNGC-QWRGUYRKSA-N (2s,4s)-4-fluoro-1-[2-[(4-methylthian-4-yl)amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound N1([C@@H](C[C@H](F)C1)C#N)C(=O)CNC1(C)CCSCC1 CCBUDPLPYWKNGC-QWRGUYRKSA-N 0.000 description 1
• RTFJBSIJBPKECV-JKPQCYAASA-N (2s,4s)-4-fluoro-1-[2-[[(1r,5s)-3-methyl-8-pyrazin-2-yl-8-azabicyclo[3.2.1]octan-3-yl]amino]acetyl]pyrrolidine-2-carbonitrile Chemical compound C([C@]1(CC[C@@](C2)(N1C=1N=CC=NC=1)[H])[H])C2(C)NCC(=O)N1C[C@@H](F)C[C@H]1C#N RTFJBSIJBPKECV-JKPQCYAASA-N 0.000 description 1
• 125000006536 (C1-C2)alkoxy group Chemical group 0.000 description 1
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• CKNQOKQJFOLEAP-UHFFFAOYSA-N (hydroxyamino)oxysulfonylformic acid Chemical compound ONOS(=O)(=O)C(=O)O CKNQOKQJFOLEAP-UHFFFAOYSA-N 0.000 description 1
• RDZHCKRAHUPIFK-UHFFFAOYSA-N 1,3-diiodo-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(I)C(=O)N(I)C1=O RDZHCKRAHUPIFK-UHFFFAOYSA-N 0.000 description 1
• WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 1
• CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical class ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 1
• 125000006019 1-methyl-1-propenyl group Chemical group 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 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
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• VSYFZULSKMFUJJ-UHFFFAOYSA-N 2,6-dimethylpyran-4-one Chemical compound CC1=CC(=O)C=C(C)O1 VSYFZULSKMFUJJ-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
• 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
• RVIMNGJUHBVIDV-GVUVZJMGSA-N 2-[[(1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-3-azabicyclo[2.2.1]heptan-5-yl]oxy]-n-pyridin-2-ylacetamide;dihydrochloride Chemical compound Cl.Cl.O([C@@H]1C[C@@]2(C[C@@]1([H])N[C@@H]2C(=O)N1[C@@H](CCC1)C#N)[H])CC(=O)NC1=CC=CC=N1 RVIMNGJUHBVIDV-GVUVZJMGSA-N 0.000 description 1
• SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 description 1
• JBVSBLLOZVDAAZ-UHFFFAOYSA-N 2-diazonio-1-[(2-methylpropan-2-yl)oxy]ethenolate Chemical compound CC(C)(C)OC([O-])=C[N+]#N JBVSBLLOZVDAAZ-UHFFFAOYSA-N 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
• LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• BZISBHPCCPJHKB-IOJSHFJWSA-N 2-o-benzyl 3-o-tert-butyl (1s,2s,4r,5r)-5-[(e)-3-ethoxy-3-oxoprop-1-enoxy]-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](O\C=C\C(=O)OCC)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)OCC1=CC=CC=C1 BZISBHPCCPJHKB-IOJSHFJWSA-N 0.000 description 1
• GSNHNJOFNJCUIQ-JJXSEGSLSA-N 2-o-benzyl 3-o-tert-butyl (1s,2s,4r,5r)-5-hydroxy-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)OCC1=CC=CC=C1 GSNHNJOFNJCUIQ-JJXSEGSLSA-N 0.000 description 1
• PKEFQSLNTJXAEE-UHFFFAOYSA-N 2-o-tert-butyl 3-o-ethyl 6-oxo-1,3,4,4a,5,7,8,8a-octahydroisoquinoline-2,3-dicarboxylate Chemical compound C1C(=O)CCC2CN(C(=O)OC(C)(C)C)C(C(=O)OCC)CC21 PKEFQSLNTJXAEE-UHFFFAOYSA-N 0.000 description 1
• KOJXEHRAIQNZGK-UHFFFAOYSA-N 2-oxo-3-azabicyclo[2.2.1]heptane-3-carboxylic acid Chemical compound C1CC2C(=O)N(C(=O)O)C1C2 KOJXEHRAIQNZGK-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
• 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
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• ZSZLTQSQRKYFTJ-ZDCRXTMVSA-N 3-o-tert-butyl 2-o-ethyl (1s,2s,4r,5r)-5-hydroxy-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound C1[C@@H](O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OCC)[C@@]1([H])C2 ZSZLTQSQRKYFTJ-ZDCRXTMVSA-N 0.000 description 1
• JLAWRHKSHDMZOV-KKOKHZNYSA-N 3-o-tert-butyl 2-o-methyl (1r,2s,4r,5r)-5-acetamido-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound C1[C@@H](NC(C)=O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])C2 JLAWRHKSHDMZOV-KKOKHZNYSA-N 0.000 description 1
• VLNSHXBDUCLEQZ-KYXWUPHJSA-N 3-o-tert-butyl 2-o-methyl (1r,2s,4r,5r)-5-amino-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound C1[C@@H](N)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])C2 VLNSHXBDUCLEQZ-KYXWUPHJSA-N 0.000 description 1
• AMWOORGVXJGKLE-UTLUCORTSA-N 3-o-tert-butyl 2-o-methyl (1r,2s,4s)-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound C1C[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])C2 AMWOORGVXJGKLE-UTLUCORTSA-N 0.000 description 1
• XJWARUXLNARECD-SGIHWFKDSA-N 3-o-tert-butyl 2-o-methyl (1s,2r,4r,5r)-5-hydroxy-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound C1[C@@H](O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@@H](C(=O)OC)[C@@]1([H])C2 XJWARUXLNARECD-SGIHWFKDSA-N 0.000 description 1
• OAEQUBLKYFGWIB-KYXWUPHJSA-N 3-o-tert-butyl 2-o-methyl (1s,2s,4r,5r)-5-azido-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound C1[C@@H](N=[N+]=[N-])[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])C2 OAEQUBLKYFGWIB-KYXWUPHJSA-N 0.000 description 1
• SPWRVTZXUBKZNX-ZDCRXTMVSA-N 3-o-tert-butyl 2-o-methyl (1s,2s,4r,5r)-5-methylsulfonyloxy-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound C1[C@@H](OS(C)(=O)=O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])C2 SPWRVTZXUBKZNX-ZDCRXTMVSA-N 0.000 description 1
• MDBVQNCEQBXDCL-XZDPQHSOSA-N 3-o-tert-butyl 2-o-methyl (1s,2s,4r,5r)-5-phenoxycarbothioyloxy-3-azabicyclo[2.2.1]heptane-2,3-dicarboxylate Chemical compound O([C@@H]1C[C@@]2(C[C@@]1([H])N([C@@H]2C(=O)OC)C(=O)OC(C)(C)C)[H])C(=S)OC1=CC=CC=C1 MDBVQNCEQBXDCL-XZDPQHSOSA-N 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
• YUCBLVFHJWOYDN-PPIALRKJSA-N 4-[(r)-[(2r,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]-1-[(r)-[(2r,4r,5s)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]phthalazine Chemical compound C1=C(OC)C=C2C([C@@H](OC=3C4=CC=CC=C4C(O[C@@H]([C@@H]4N5CC[C@@H]([C@@H](C5)CC)C4)C=4C5=CC(OC)=CC=C5N=CC=4)=NN=3)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 YUCBLVFHJWOYDN-PPIALRKJSA-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
• 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
• DTVPUONGFAPURI-KKOKHZNYSA-N 6-O-tert-butyl 7-O-ethyl (1R,4R,5R,7S)-4-hydroxy-6-azabicyclo[3.2.1]octane-6,7-dicarboxylate Chemical compound C1[C@]2([H])[C@H](O)CC[C@@]1([H])[C@@H](C(=O)OCC)N2C(=O)OC(C)(C)C DTVPUONGFAPURI-KKOKHZNYSA-N 0.000 description 1
• 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 1
• 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 1
• 125000006164 6-membered heteroaryl group Chemical group 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• CBDZOGRPAYBWLS-LESJPMCHSA-N C([C@@]1(C[C@@]2([H])N([C@@H]1C(=O)N1[C@@H](CCC1)C#N)C(=O)OC(C)(C)C)[H])\C2=N/OCC1=CC=CC=C1 Chemical compound C([C@@]1(C[C@@]2([H])N([C@@H]1C(=O)N1[C@@H](CCC1)C#N)C(=O)OC(C)(C)C)[H])\C2=N/OCC1=CC=CC=C1 CBDZOGRPAYBWLS-LESJPMCHSA-N 0.000 description 1
• UXBYSNXXUPLAPB-LPWJVIDDSA-N C1[C@@H](NC(=O)OC(C)(C)C)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])C2 Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])C2 UXBYSNXXUPLAPB-LPWJVIDDSA-N 0.000 description 1
• HVFXOEOOQNMAPI-VFCFLDTKSA-N C1[C@@H](O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])[C@H]2F Chemical compound C1[C@@H](O)[C@]2([H])N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)[C@@]1([H])[C@H]2F HVFXOEOOQNMAPI-VFCFLDTKSA-N 0.000 description 1
• 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
• WIKPFFAEXJRKIH-JSGCOSHPSA-N CC(C)S(N(CC1)CCC1NCC(N(C[C@H](C1)F)[C@@H]1C#N)=O)(=O)=O Chemical compound CC(C)S(N(CC1)CCC1NCC(N(C[C@H](C1)F)[C@@H]1C#N)=O)(=O)=O WIKPFFAEXJRKIH-JSGCOSHPSA-N 0.000 description 1
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 238000006646 Dess-Martin oxidation reaction Methods 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
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
• 108010016626 Dipeptides Proteins 0.000 description 1
• 206010013883 Dwarfism Diseases 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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 compound 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
• 206010020772 Hypertension Diseases 0.000 description 1
• 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 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-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
• 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 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
• XOYLNHKEOGOLKH-LPOAVQBDSA-N O=C([C@H]1N([C@@]2([H])[C@H](OC\C=N\O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OC\C=N\O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N XOYLNHKEOGOLKH-LPOAVQBDSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 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
• 238000010521 absorption reaction Methods 0.000 description 1
• ACQMQPOSUUWRJO-UHFFFAOYSA-N acetic acid;2,2,2-trifluoroethanol Chemical compound CC(O)=O.OCC(F)(F)F ACQMQPOSUUWRJO-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
• 230000000996 additive effect Effects 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
• 238000010976 amide bond formation reaction Methods 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 229940024606 amino acid Drugs 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000019270 ammonium chloride Nutrition 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
• 230000036528 appetite Effects 0.000 description 1
• 235000019789 appetite Nutrition 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
• 206010003246 arthritis Diseases 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 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
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 229910052801 chlorine Inorganic materials 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
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 230000001934 delay Effects 0.000 description 1
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
• 150000004985 diamines Chemical class 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• 235000018823 dietary intake Nutrition 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 239000007884 disintegrant Substances 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
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 150000002118 epoxides Chemical class 0.000 description 1
• ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
• URJFTFDBBNOERE-WSTLGDPDSA-N ethyl (1r,2s,4s)-1,4-dimethyl-3-[(1r)-1-phenylethyl]-3-azabicyclo[2.2.2]oct-5-ene-2-carboxylate Chemical compound C1([C@@H](C)N2[C@@H]([C@]3(C)CC[C@@]2(C)C=C3)C(=O)OCC)=CC=CC=C1 URJFTFDBBNOERE-WSTLGDPDSA-N 0.000 description 1
• JWBYFKNJJLQNLA-IVOMFYJKSA-N ethyl (1r,2s,4s)-1-methyl-3-[(1r)-1-phenylethyl]-4-propan-2-yl-3-azabicyclo[2.2.2]oct-5-ene-2-carboxylate Chemical compound C1([C@@H](C)N2[C@@H]([C@]3(C)CC[C@@]2(C=C3)C(C)C)C(=O)OCC)=CC=CC=C1 JWBYFKNJJLQNLA-IVOMFYJKSA-N 0.000 description 1
• WPVULUCPUMGINO-BVUBDWEXSA-N ethyl (1r,2s,4s)-3-[(1r)-1-phenylethyl]-3-azabicyclo[2.2.1]hept-5-ene-2-carboxylate Chemical compound C1([C@@H](C)N2[C@@]3([H])C[C@](C=C3)([C@H]2C(=O)OCC)[H])=CC=CC=C1 WPVULUCPUMGINO-BVUBDWEXSA-N 0.000 description 1
• VJTWVZLCYCMKLW-NHMWIVBRSA-N ethyl (1r,4r,5r,7s)-4-hydroxy-6-[(1r)-1-phenylethyl]-6-azabicyclo[3.2.1]octane-7-carboxylate Chemical compound C1([C@@H](C)N2[C@]3([H])C[C@@](CC[C@H]3O)([C@H]2C(=O)OCC)[H])=CC=CC=C1 VJTWVZLCYCMKLW-NHMWIVBRSA-N 0.000 description 1
• LFJLFJCNXZNNFU-ZIRHEVKLSA-N ethyl (1s,2s,4r,5r)-5-hydroxy-3-[(1r)-1-phenylethyl]-3-azabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1([C@@H](C)N2[C@@]3([H])[C@H](O)C[C@](C3)([C@H]2C(=O)OCC)[H])=CC=CC=C1 LFJLFJCNXZNNFU-ZIRHEVKLSA-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
• JBOBMYRWNYJELX-LBWNCTQTSA-N ethyl (1s,3s,4s,5r)-5-hydroxy-2-[(1r)-1-phenylethyl]-2-azabicyclo[2.2.2]octane-3-carboxylate Chemical compound C1([C@@H](C)N2[C@@H]([C@]3([H])CC[C@]2(C[C@H]3O)[H])C(=O)OCC)=CC=CC=C1 JBOBMYRWNYJELX-LBWNCTQTSA-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
• FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 239000011737 fluorine Substances 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
• 238000009472 formulation Methods 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 208000020694 gallbladder disease Diseases 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• RKGLLHCSSVJTAN-YYICOITRSA-N glucagen Chemical compound Cl.C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 RKGLLHCSSVJTAN-YYICOITRSA-N 0.000 description 1
• 229940095886 glucagen Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000008282 halocarbons Chemical class 0.000 description 1
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
• 150000004677 hydrates Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 229960002591 hydroxyproline Drugs 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 230000000415 inactivating effect Effects 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
• 238000011835 investigation Methods 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
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 239000006210 lotion Substances 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
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 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
• PWUWUKQPSOGOPL-BEAPCOKYSA-N methyl (1r,2s,4s)-3-[(1r)-1-phenylethyl]-3-azabicyclo[2.2.1]hept-5-ene-2-carboxylate Chemical compound C1([C@@H](C)N2[C@@]3([H])C[C@](C=C3)([C@H]2C(=O)OC)[H])=CC=CC=C1 PWUWUKQPSOGOPL-BEAPCOKYSA-N 0.000 description 1
• CJDNRDGDUKJZQE-WTBGCVQCSA-N methyl (1s,2s,4r,5r)-5-acetyloxy-3-[(1r)-1-phenylethyl]-3-azabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1([C@@H](C)N2[C@@]3([H])[C@H](OC(C)=O)C[C@](C3)([C@H]2C(=O)OC)[H])=CC=CC=C1 CJDNRDGDUKJZQE-WTBGCVQCSA-N 0.000 description 1
• GJNBNGMIKKUMCR-OVHBTUCOSA-N methyl (1s,2s,4s,5r,7r)-7-fluoro-5-hydroxy-3-azabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@@H](O)[C@]2([H])N[C@H](C(=O)OC)[C@@]1([H])[C@H]2F GJNBNGMIKKUMCR-OVHBTUCOSA-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
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical compound Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 1
• WCLMVRQMQZRRMU-UHFFFAOYSA-N n-(1-methyl-2,3-dihydroquinolin-4-ylidene)hydroxylamine Chemical compound C1=CC=C2N(C)CCC(=NO)C2=C1 WCLMVRQMQZRRMU-UHFFFAOYSA-N 0.000 description 1
• LOWLISSVPQGXNV-UHFFFAOYSA-N n-(2,3-dihydrochromen-4-ylidene)hydroxylamine Chemical compound C1=CC=C2C(=NO)CCOC2=C1 LOWLISSVPQGXNV-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
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• KOSYAAIZOGNATQ-UHFFFAOYSA-N o-phenyl chloromethanethioate Chemical compound ClC(=S)OC1=CC=CC=C1 KOSYAAIZOGNATQ-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 210000004798 organs belonging to the digestive system Anatomy 0.000 description 1
• JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000002572 peristaltic effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 239000012071 phase 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
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 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(=O)NCC(O)=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 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
• 230000002265 prevention 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
• YYFIGOPUHPDIBO-UHFFFAOYSA-N propanoic acid;hydrochloride Chemical compound Cl.CCC(O)=O YYFIGOPUHPDIBO-UHFFFAOYSA-N 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([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
• 230000001681 protective effect Effects 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 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
• 150000003235 pyrrolidines Chemical class 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 230000006340 racemization Effects 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical class [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 238000005055 short column chromatography Methods 0.000 description 1
• 229910052708 sodium Inorganic materials 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
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000000126 substance Substances 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000003786 synthesis reaction Methods 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
• NOZUNIDVLPGMSG-ZHCJQAHYSA-N tert-butyl (1r,2r,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@@H]1N([C@@]2([H])[C@H](NC(=O)OC(C)(C)C)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N NOZUNIDVLPGMSG-ZHCJQAHYSA-N 0.000 description 1
• IYKKJAFRNIXJLK-YIDVYQOGSA-N tert-butyl (1r,2r,4r,5r)-5-acetamido-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@@H]1N([C@@]2([H])[C@H](NC(C)=O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N IYKKJAFRNIXJLK-YIDVYQOGSA-N 0.000 description 1
• DSLUEXUVSPUYRQ-ILOCAZANSA-N tert-butyl (1r,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-pyrrolidin-1-yl-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound N1([C@@H]2C[C@@]3(C[C@@]2([H])N([C@@H]3C(=O)N2[C@@H](CCC2)C#N)C(=O)OC(C)(C)C)[H])CCCC1 DSLUEXUVSPUYRQ-ILOCAZANSA-N 0.000 description 1
• CYQBBCNLYPTLAE-RFGFWPKPSA-N tert-butyl (1r,2s,4s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])CC[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N CYQBBCNLYPTLAE-RFGFWPKPSA-N 0.000 description 1
• UUPORAXPVQIMQB-KHMAMNHCSA-N tert-butyl (1r,4r,5r,7s)-7-[(2s)-2-cyanopyrrolidine-1-carbonyl]-4-hydroxy-6-azabicyclo[3.2.1]octane-6-carboxylate Chemical compound O=C([C@H]1N([C@]2([H])C[C@]1(CC[C@H]2O)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N UUPORAXPVQIMQB-KHMAMNHCSA-N 0.000 description 1
• NKYUZXZSGKKDFE-DOEOUOAPSA-N tert-butyl (1s,2r,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-(3-ethoxy-3-oxopropoxy)-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@@H]1N([C@@]2([H])[C@H](OCCC(=O)OCC)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N NKYUZXZSGKKDFE-DOEOUOAPSA-N 0.000 description 1
• YCCJXMMXGIDVTB-CXUGJCBMSA-N tert-butyl (1s,2r,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-[(4-methylphenyl)sulfonylamino]-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound N([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])S(=O)(=O)C1=CC=C(C)C=C1 YCCJXMMXGIDVTB-CXUGJCBMSA-N 0.000 description 1
• HYPKHZYANLMKRK-ODXJTPSBSA-N tert-butyl (1s,2r,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-hydroxy-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@@H]1N([C@@]2([H])[C@H](O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N HYPKHZYANLMKRK-ODXJTPSBSA-N 0.000 description 1
• QDKZJBAERQETJG-FMSGJZPZSA-N tert-butyl (1s,2s,4r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-oxo-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])C(=O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N QDKZJBAERQETJG-FMSGJZPZSA-N 0.000 description 1
• VCBABMCBQSRLAZ-UJHHCITNSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-(2-ethoxy-2-oxoethoxy)-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OCC(=O)OCC)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N VCBABMCBQSRLAZ-UJHHCITNSA-N 0.000 description 1
• MKPTVCLOFHCYSH-RBZJEDDUSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-(2-hydroxyethoxy)-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OCCO)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N MKPTVCLOFHCYSH-RBZJEDDUSA-N 0.000 description 1
• MDDUIWHQDOFKDD-RBZJEDDUSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-(2-oxoethoxy)-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OCC=O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N MDDUIWHQDOFKDD-RBZJEDDUSA-N 0.000 description 1
• LURLRZOFPASJSY-SIRPWMCASA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-(2-oxopropoxy)-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OCC(C)=O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N LURLRZOFPASJSY-SIRPWMCASA-N 0.000 description 1
• BTFWTIUKGCTRPL-UBVLKLFISA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-(4-nitrophenoxy)-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])C1=CC=C([N+]([O-])=O)C=C1 BTFWTIUKGCTRPL-UBVLKLFISA-N 0.000 description 1
• KBJLSLPUYHNGGT-UJHHCITNSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-[2-(dimethylsulfamoylamino)-2-oxoethoxy]-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OCC(=O)NS(=O)(=O)N(C)C)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N KBJLSLPUYHNGGT-UJHHCITNSA-N 0.000 description 1
• MWVRADRSALRRNC-XGYYKPKNSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-[2-(methanesulfonamido)-2-oxoethoxy]-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OCC(=O)NS(C)(=O)=O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N MWVRADRSALRRNC-XGYYKPKNSA-N 0.000 description 1
• MVOSRQSRHDNXBM-NRUGXNMXSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OCC(=O)OC(C)(C)C)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N MVOSRQSRHDNXBM-NRUGXNMXSA-N 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
• VDIHPAUBKAZIKB-AHDPXTMNSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-methylsulfonyloxy-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OS(C)(=O)=O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N VDIHPAUBKAZIKB-AHDPXTMNSA-N 0.000 description 1
• SUXRDHWADLWYFL-NRUGXNMXSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-pyridin-2-yloxy-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])C1=CC=CC=N1 SUXRDHWADLWYFL-NRUGXNMXSA-N 0.000 description 1
• DBBGECAVTFMLQS-QQKNPXLJSA-N tert-butyl (1s,2s,4r,5r)-2-[(2s,4s)-2-cyano-4-fluoropyrrolidine-1-carbonyl]-5-hydroxy-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1C[C@@H](F)C[C@H]1C#N DBBGECAVTFMLQS-QQKNPXLJSA-N 0.000 description 1
• LYEDRXWFHDJQKC-JAAXMTQOSA-N tert-butyl (1s,2s,4r,5r)-5-(2-amino-2-oxoethoxy)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](OCC(N)=O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N LYEDRXWFHDJQKC-JAAXMTQOSA-N 0.000 description 1
• DCFPBZKCAUNHAQ-IPLXSBJHSA-N tert-butyl (1s,2s,4r,5r)-5-(5-cyanopyridin-2-yl)oxy-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-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])C1=CC=C(C#N)C=N1 DCFPBZKCAUNHAQ-IPLXSBJHSA-N 0.000 description 1
• FPWQNTIGWQPACU-UJHHCITNSA-N tert-butyl (1s,2s,4r,5r)-5-[2-[(5-acetamido-1,3,4-thiadiazol-2-yl)sulfonylamino]-2-oxoethoxy]-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-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)NS(=O)(=O)C1=NN=C(NC(C)=O)S1 FPWQNTIGWQPACU-UJHHCITNSA-N 0.000 description 1
• HYPKHZYANLMKRK-HPCHECBXSA-N tert-butyl (1s,2s,4r,5s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-hydroxy-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@@H](O)C[C@@]1(C2)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N HYPKHZYANLMKRK-HPCHECBXSA-N 0.000 description 1
• NKJRCCLVXWMRNW-WPWOAKCXSA-N tert-butyl (1s,2s,4s,5r)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-7-fluoro-5-hydroxy-3-azabicyclo[2.2.1]heptane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])[C@H](O)C[C@@]1(C2F)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N NKJRCCLVXWMRNW-WPWOAKCXSA-N 0.000 description 1
• WRBDZIUMICOISG-WCBJTDJXSA-N tert-butyl (1s,2s,4s,5r,6s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5,6-dihydroxy-3-azabicyclo[2.2.2]octane-3-carboxylate Chemical compound O=C([C@H]1N([C@@]2([H])CC[C@@]1([C@@H]([C@@H]2O)O)[H])C(=O)OC(C)(C)C)N1CCC[C@H]1C#N WRBDZIUMICOISG-WCBJTDJXSA-N 0.000 description 1
• YYYYXTLGXNPXQH-AHDPXTMNSA-N tert-butyl (1s,3s,4s,5r)-3-[(2s)-2-cyanopyrrolidine-1-carbonyl]-5-hydroxy-2-azabicyclo[2.2.2]octane-2-carboxylate Chemical compound O=C([C@@H]1[C@]2([H])CC[C@@](C[C@H]2O)(N1C(=O)OC(C)(C)C)[H])N1CCC[C@H]1C#N YYYYXTLGXNPXQH-AHDPXTMNSA-N 0.000 description 1
• LBTOAJUJKXBURJ-HOAMVYINSA-N tert-butyl (2s)-2-[(2s)-2-carbamoylpyrrolidine-1-carbonyl]-3-azabicyclo[2.2.2]octane-3-carboxylate Chemical compound O=C([C@@H]1C2CCC(CC2)N1C(=O)OC(C)(C)C)N1CCC[C@H]1C(N)=O LBTOAJUJKXBURJ-HOAMVYINSA-N 0.000 description 1
• ONRZRWMBAAJZBF-WUCCLRPBSA-N tert-butyl (2s)-2-[(2s)-2-cyanopyrrolidine-1-carbonyl]-3-azabicyclo[2.2.2]octane-3-carboxylate Chemical compound O=C([C@@H]1C2CCC(CC2)N1C(=O)OC(C)(C)C)N1CCC[C@H]1C#N ONRZRWMBAAJZBF-WUCCLRPBSA-N 0.000 description 1
• ARRKIGJMYZVIAL-UHFFFAOYSA-N tert-butyl n-(1-benzyl-4-methylpiperidin-4-yl)carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)(C)CCN1CC1=CC=CC=C1 ARRKIGJMYZVIAL-UHFFFAOYSA-N 0.000 description 1
• PQZMMLCDNPHTGT-UHFFFAOYSA-N tert-butyl n-(4-methyl-1-pyrazin-2-ylpiperidin-4-yl)carbamate Chemical compound C1CC(NC(=O)OC(C)(C)C)(C)CCN1C1=CN=CC=N1 PQZMMLCDNPHTGT-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
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• OVRJVKCZJCNSOW-UHFFFAOYSA-N thian-4-one Chemical compound O=C1CCSCC1 OVRJVKCZJCNSOW-UHFFFAOYSA-N 0.000 description 1
• 125000000335 thiazolyl 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
• 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
• DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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