SK45898A3 - Pharmaceutically active quinazoline compounds - Google Patents

Info

Publication number

SK45898A3

SK45898A3 SK458-98A SK45898A SK45898A3 SK 45898 A3 SK45898 A3 SK 45898A3 SK 45898 A SK45898 A SK 45898A SK 45898 A3 SK45898 A3 SK 45898A3

Authority

SK

Slovakia

Prior art keywords

compound

formula

alkyl

prepared

group

Prior art date

1995-10-17

Links

• Espacenet
• Global Dossier
• Discuss

• 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 295
• -1 nitro, hydroxymethyl Chemical group 0.000 claims abstract description 146
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 80
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 67
• 239000001257 hydrogen Substances 0.000 claims abstract description 59
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 49
• 125000003118 aryl group Chemical group 0.000 claims abstract description 39
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 38
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 35
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 33
• 150000003839 salts Chemical class 0.000 claims abstract description 32
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 31
• 150000002367 halogens Chemical class 0.000 claims abstract description 30
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 27
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 26
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 25
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 23
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 23
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 20
• 150000002431 hydrogen Chemical class 0.000 claims abstract description 19
• 238000011282 treatment Methods 0.000 claims abstract description 17
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 15
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
• 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 12
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract description 11
• 239000003814 drug Substances 0.000 claims abstract description 7
• 208000027866 inflammatory disease Diseases 0.000 claims abstract 2
• 238000000034 method Methods 0.000 claims description 91
• 238000006243 chemical reaction Methods 0.000 claims description 27
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 23
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 16
• 125000001424 substituent group Chemical group 0.000 claims description 13
• 238000003786 synthesis reaction Methods 0.000 claims description 12
• 230000015572 biosynthetic process Effects 0.000 claims description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 10
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 10
• 239000002253 acid Substances 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 238000011321 prophylaxis Methods 0.000 claims description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
• 201000010099 disease Diseases 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 229910052727 yttrium Inorganic materials 0.000 claims description 8
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 230000004968 inflammatory condition Effects 0.000 claims description 6
• 230000005764 inhibitory process Effects 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
• 150000001412 amines Chemical class 0.000 claims description 5
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
• 125000003386 piperidinyl group Chemical group 0.000 claims description 5
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
• 229910021529 ammonia Inorganic materials 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• 125000002541 furyl group Chemical group 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 125000001624 naphthyl group Chemical group 0.000 claims description 4
• 125000004043 oxo group Chemical group O=* 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• 125000003277 amino group Chemical group 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 230000002255 enzymatic effect Effects 0.000 claims description 3
• 238000005886 esterification reaction Methods 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
• 239000001301 oxygen Substances 0.000 claims description 3
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 claims description 2
• 230000002152 alkylating effect Effects 0.000 claims description 2
• 125000004429 atom Chemical group 0.000 claims description 2
• 125000004965 chloroalkyl group Chemical group 0.000 claims description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
• 230000032050 esterification Effects 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 2
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 2
• 125000000335 thiazolyl group Chemical group 0.000 claims description 2
• 238000006392 deoxygenation reaction Methods 0.000 claims 1
• 208000035475 disorder Diseases 0.000 claims 1
• 239000000546 pharmaceutical excipient Substances 0.000 claims 1
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
• 239000000047 product Substances 0.000 description 186
• 238000002844 melting Methods 0.000 description 165
• 230000008018 melting Effects 0.000 description 165
• 239000000543 intermediate Substances 0.000 description 119
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 113
• 239000007787 solid Substances 0.000 description 112
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
• 238000005481 NMR spectroscopy Methods 0.000 description 94
• 239000013078 crystal Substances 0.000 description 93
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 84
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 83
• 239000000243 solution Substances 0.000 description 83
• 239000000203 mixture Substances 0.000 description 73
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 66
• 125000003003 spiro group Chemical group 0.000 description 56
• 239000000843 powder Substances 0.000 description 52
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
• WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
• 229910052938 sodium sulfate Inorganic materials 0.000 description 32
• 235000011152 sodium sulphate Nutrition 0.000 description 32
• 239000003921 oil Substances 0.000 description 27
• 235000019198 oils Nutrition 0.000 description 27
• 239000002904 solvent Substances 0.000 description 26
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 20
• 239000000460 chlorine Substances 0.000 description 20
• 238000003818 flash chromatography Methods 0.000 description 20
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 238000000354 decomposition reaction Methods 0.000 description 17
• 239000006260 foam Substances 0.000 description 17
• 210000004027 cell Anatomy 0.000 description 16
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• 239000012442 inert solvent Substances 0.000 description 14
• 239000012230 colorless oil Substances 0.000 description 13
• 239000011521 glass Substances 0.000 description 13
• 239000000741 silica gel Substances 0.000 description 13
• 229910002027 silica gel Inorganic materials 0.000 description 13
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• 239000012267 brine Substances 0.000 description 11
• SVDVENGLRIRJNL-UHFFFAOYSA-N 2-amino-6-fluorobenzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=C(N)C=CC=C1F SVDVENGLRIRJNL-UHFFFAOYSA-N 0.000 description 10
• IUSQOUNNWVPUSZ-UHFFFAOYSA-N 2-aminobenzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=CC=CC=C1N IUSQOUNNWVPUSZ-UHFFFAOYSA-N 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 230000000694 effects Effects 0.000 description 9
• LUBGFMZTGFXIIN-UHFFFAOYSA-N ethyl 4-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)CC1 LUBGFMZTGFXIIN-UHFFFAOYSA-N 0.000 description 9
• 239000000284 extract Substances 0.000 description 9
• RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 8
• HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• LULMFXBDFDUVHI-UHFFFAOYSA-N 2-(methylamino)benzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.CNC1=CC=CC=C1C(N)=N LULMFXBDFDUVHI-UHFFFAOYSA-N 0.000 description 7
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• 108090000790 Enzymes Proteins 0.000 description 7
• 102000004190 Enzymes Human genes 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 238000001704 evaporation Methods 0.000 description 7
• 230000008020 evaporation Effects 0.000 description 7
• 235000015097 nutrients Nutrition 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• 239000000376 reactant Substances 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 238000001914 filtration Methods 0.000 description 6
• 230000001965 increasing effect Effects 0.000 description 6
• 150000002576 ketones Chemical class 0.000 description 6
• VRJHQPZVIGNGMX-UHFFFAOYSA-N piperidine-4-one Natural products O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 6
• 238000005406 washing Methods 0.000 description 6
• GFDHRKOVNQEVGF-UHFFFAOYSA-N 2-amino-6-chlorobenzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=C(N)C=CC=C1Cl GFDHRKOVNQEVGF-UHFFFAOYSA-N 0.000 description 5
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 229960002173 citrulline Drugs 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• JQJLUWQYAYGAPQ-UHFFFAOYSA-N 2-amino-6-hydroxybenzenecarboximidamide dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=C(N)C=CC=C1O JQJLUWQYAYGAPQ-UHFFFAOYSA-N 0.000 description 4
• VWSSAMDUZQSVND-UHFFFAOYSA-N 2-amino-6-methoxybenzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.COC1=CC=CC(N)=C1C(N)=N VWSSAMDUZQSVND-UHFFFAOYSA-N 0.000 description 4
• HVVYJQCEYFYXGQ-UHFFFAOYSA-N 4-(1,4-dioxa-8-azaspiro[4.5]decane-8-carbonyl)benzonitrile Chemical compound C=1C=C(C#N)C=CC=1C(=O)N(CC1)CCC21OCCO2 HVVYJQCEYFYXGQ-UHFFFAOYSA-N 0.000 description 4
• CISZXTDYAMELHB-UHFFFAOYSA-N Cl.N1C2(N=C(C3=CC=CC=C13)N)CCNCC2 Chemical compound Cl.N1C2(N=C(C3=CC=CC=C13)N)CCNCC2 CISZXTDYAMELHB-UHFFFAOYSA-N 0.000 description 4
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
• 206010061218 Inflammation Diseases 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• 150000001299 aldehydes Chemical class 0.000 description 4
• 150000001350 alkyl halides Chemical class 0.000 description 4
• 238000005804 alkylation reaction Methods 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• JXHYCCGOZUGBFD-UHFFFAOYSA-N benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC=C1 JXHYCCGOZUGBFD-UHFFFAOYSA-N 0.000 description 4
• 230000004054 inflammatory process Effects 0.000 description 4
• 230000007935 neutral effect Effects 0.000 description 4
• YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
• 239000002798 polar solvent Substances 0.000 description 4
• 229920001467 poly(styrenesulfonates) Polymers 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 4
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
• RBVYKSQOMAYZNS-UHFFFAOYSA-N 2-amino-3,6-difluorobenzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=C(F)C=CC(F)=C1N RBVYKSQOMAYZNS-UHFFFAOYSA-N 0.000 description 3
• BIHSCOBKWIMEDK-UHFFFAOYSA-N 2-amino-4,6-difluorobenzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=C(N)C=C(F)C=C1F BIHSCOBKWIMEDK-UHFFFAOYSA-N 0.000 description 3
• NNYCWCOJMARORO-UHFFFAOYSA-N 2-fluoro-6-(methylamino)benzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.CNC1=CC=CC(F)=C1C(N)=N NNYCWCOJMARORO-UHFFFAOYSA-N 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 201000004624 Dermatitis Diseases 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
• 229930064664 L-arginine Natural products 0.000 description 3
• 235000014852 L-arginine Nutrition 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• 239000007868 Raney catalyst Substances 0.000 description 3
• 229910000564 Raney nickel Inorganic materials 0.000 description 3
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
• 206010040070 Septic Shock Diseases 0.000 description 3
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
• 239000003377 acid catalyst Substances 0.000 description 3
• 150000001263 acyl chlorides Chemical class 0.000 description 3
• 239000002168 alkylating agent Substances 0.000 description 3
• 229940100198 alkylating agent Drugs 0.000 description 3
• 150000001408 amides Chemical class 0.000 description 3
• 235000019270 ammonium chloride Nutrition 0.000 description 3
• 125000003710 aryl alkyl group Chemical group 0.000 description 3
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 238000003776 cleavage reaction Methods 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 239000003480 eluent Substances 0.000 description 3
• 239000002158 endotoxin Substances 0.000 description 3
• DQYGBMLEVQLDQC-UHFFFAOYSA-N ethyl 3-oxopyrrolidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)C1 DQYGBMLEVQLDQC-UHFFFAOYSA-N 0.000 description 3
• 125000004494 ethyl ester group Chemical group 0.000 description 3
• CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 3
• 230000002496 gastric effect Effects 0.000 description 3
• 150000004678 hydrides Chemical class 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
• CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 3
• 229920006008 lipopolysaccharide Polymers 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
• CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 3
• 230000007017 scission Effects 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• 238000001665 trituration Methods 0.000 description 3
• KSLQOJHYMGLPBA-UHFFFAOYSA-N 1'-benzylspiro[1h-quinazoline-2,3'-piperidine]-4-amine;dihydrochloride Chemical compound Cl.Cl.N1C2=CC=CC=C2C(N)=NC1(C1)CCCN1CC1=CC=CC=C1 KSLQOJHYMGLPBA-UHFFFAOYSA-N 0.000 description 2
• ZGTFNNUASMWGTM-UHFFFAOYSA-N 1,3-thiazole-2-carbaldehyde Chemical compound O=CC1=NC=CS1 ZGTFNNUASMWGTM-UHFFFAOYSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• NZAXGZYPZGEVBD-UHFFFAOYSA-N 1-benzoylpiperidin-4-one Chemical compound C=1C=CC=CC=1C(=O)N1CCC(=O)CC1 NZAXGZYPZGEVBD-UHFFFAOYSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• QFKFRNQYQIIOLE-UHFFFAOYSA-N 2-[2-(1,3-dioxolan-2-yl)phenyl]ethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCC1=CC=CC=C1C1OCCO1 QFKFRNQYQIIOLE-UHFFFAOYSA-N 0.000 description 2
• UIKILNQFWZSCKW-UHFFFAOYSA-N 2-[2-(2-azidoethyl)phenyl]-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=CC=C1CCN=[N+]=[N-] UIKILNQFWZSCKW-UHFFFAOYSA-N 0.000 description 2
• VQSOLJQLCZGNAM-UHFFFAOYSA-N 2-amino-3,6-difluorobenzenecarboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=C(F)C=CC(F)=C1N VQSOLJQLCZGNAM-UHFFFAOYSA-N 0.000 description 2
• YBONLHDOTOQJBG-UHFFFAOYSA-N 2-amino-3-chloro-6-fluoro-n'-hydroxybenzenecarboximidamide Chemical compound ON=C(N)C1=C(F)C=CC(Cl)=C1N YBONLHDOTOQJBG-UHFFFAOYSA-N 0.000 description 2
• AXIBHVDUEBFKDM-UHFFFAOYSA-N 2-amino-3-chloro-6-fluorobenzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.NC(=N)C1=C(F)C=CC(Cl)=C1N AXIBHVDUEBFKDM-UHFFFAOYSA-N 0.000 description 2
• ACQUVZGWVRNLBS-UHFFFAOYSA-N 2-amino-6-methylsulfanylbenzenecarboximidamide;dihydrochloride Chemical compound Cl.Cl.CSC1=CC=CC(N)=C1C(N)=N ACQUVZGWVRNLBS-UHFFFAOYSA-N 0.000 description 2
• CFZHYRNQLHEHJS-UHFFFAOYSA-N 2-amino-n'-hydroxybenzenecarboximidamide Chemical compound ON=C(N)C1=CC=CC=C1N CFZHYRNQLHEHJS-UHFFFAOYSA-N 0.000 description 2
• UIVBEDXMYPINIM-UHFFFAOYSA-N 2-aminobenzenecarboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=CC=CC=C1N UIVBEDXMYPINIM-UHFFFAOYSA-N 0.000 description 2
• HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical compound NC1=CC=CC=C1C#N HLCPWBZNUKCSBN-UHFFFAOYSA-N 0.000 description 2
• CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 2
• HFKZZEDGXXYRDW-UHFFFAOYSA-N 3-chloro-2,6-difluorobenzaldehyde Chemical compound FC1=CC=C(Cl)C(F)=C1C=O HFKZZEDGXXYRDW-UHFFFAOYSA-N 0.000 description 2
• QYALCKFGISNFMJ-UHFFFAOYSA-N 3-chloro-2,6-difluorobenzonitrile Chemical compound FC1=CC=C(Cl)C(F)=C1C#N QYALCKFGISNFMJ-UHFFFAOYSA-N 0.000 description 2
• IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 2
• CZUGFKJYCPYHHV-UHFFFAOYSA-N 3-methylthiopropanol Chemical compound CSCCCO CZUGFKJYCPYHHV-UHFFFAOYSA-N 0.000 description 2
• GFLPSABXBDCMCN-UHFFFAOYSA-N 4,4-diethoxybutan-1-amine Chemical compound CCOC(OCC)CCCN GFLPSABXBDCMCN-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• HXHGULXINZUGJX-UHFFFAOYSA-N 4-chlorobutanol Chemical compound OCCCCCl HXHGULXINZUGJX-UHFFFAOYSA-N 0.000 description 2
• RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-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
• 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 2
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
• KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 2
• 239000004475 Arginine Substances 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
• 239000005977 Ethylene Substances 0.000 description 2
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
• GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 2
• 235000010469 Glycine max Nutrition 0.000 description 2
• 244000068988 Glycine max Species 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 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 2
• AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• 229930182816 L-glutamine Natural products 0.000 description 2
• MRAUNPAHJZDYCK-BYPYZUCNSA-N L-nitroarginine Chemical compound OC(=O)[C@@H](N)CCCNC(=N)N[N+]([O-])=O MRAUNPAHJZDYCK-BYPYZUCNSA-N 0.000 description 2
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
• 206010033645 Pancreatitis Diseases 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 239000005708 Sodium hypochlorite Substances 0.000 description 2
• 229920004890 Triton X-100 Polymers 0.000 description 2
• 239000013504 Triton X-100 Substances 0.000 description 2
• 229940122618 Trypsin inhibitor Drugs 0.000 description 2
• 101710162629 Trypsin inhibitor Proteins 0.000 description 2
• XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 2
• 150000001241 acetals Chemical class 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 125000005256 alkoxyacyl group Chemical group 0.000 description 2
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 235000011114 ammonium hydroxide Nutrition 0.000 description 2
• APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 2
• 229960003942 amphotericin b Drugs 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 229940088710 antibiotic agent Drugs 0.000 description 2
• 206010003246 arthritis Diseases 0.000 description 2
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 2
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• 239000001569 carbon dioxide Substances 0.000 description 2
• 229910002092 carbon dioxide Inorganic materials 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 238000006555 catalytic reaction Methods 0.000 description 2
• 239000013592 cell lysate Substances 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• INVYSLWXPIEDIQ-UHFFFAOYSA-N cyclobutanecarbaldehyde Chemical compound O=CC1CCC1 INVYSLWXPIEDIQ-UHFFFAOYSA-N 0.000 description 2
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
• JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• PRHIVMLJGOBNIE-UHFFFAOYSA-N diazonio-[2-[2-(1,3-dioxolan-2-yl)phenyl]ethyl]azanide Chemical compound [N-]=[N+]=NCCC1=CC=CC=C1C1OCCO1 PRHIVMLJGOBNIE-UHFFFAOYSA-N 0.000 description 2
• 101150042537 dld1 gene Proteins 0.000 description 2
• 229940088679 drug related substance Drugs 0.000 description 2
• FFMIXGDALDXDJU-UHFFFAOYSA-N ethene;1-(thiophene-2-carbonyl)piperidin-4-one Chemical group C=C.C=1C=CSC=1C(=O)N1CCC(=O)CC1 FFMIXGDALDXDJU-UHFFFAOYSA-N 0.000 description 2
• BMVJPNDAUATLHS-UHFFFAOYSA-N ethene;2-methyl-4-(4-oxopiperidine-1-carbonyl)benzonitrile Chemical group C=C.C1=C(C#N)C(C)=CC(C(=O)N2CCC(=O)CC2)=C1 BMVJPNDAUATLHS-UHFFFAOYSA-N 0.000 description 2
• 239000012259 ether extract Substances 0.000 description 2
• DXAVFRMBJHJZSB-UHFFFAOYSA-N ethyl 2-formylpyrrole-1-carboxylate Chemical compound CCOC(=O)N1C=CC=C1C=O DXAVFRMBJHJZSB-UHFFFAOYSA-N 0.000 description 2
• DJRNGEMHPLQJRB-UHFFFAOYSA-N ethyl 3-formylpyrrole-1-carboxylate Chemical compound CCOC(=O)N1C=CC(C=O)=C1 DJRNGEMHPLQJRB-UHFFFAOYSA-N 0.000 description 2
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000012091 fetal bovine serum Substances 0.000 description 2
• 239000011768 flavin mononucleotide Substances 0.000 description 2
• FVTCRASFADXXNN-SCRDCRAPSA-N flavin mononucleotide Chemical compound OP(=O)(O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-SCRDCRAPSA-N 0.000 description 2
• 229940013640 flavin mononucleotide Drugs 0.000 description 2
• FVTCRASFADXXNN-UHFFFAOYSA-N flavin mononucleotide Natural products OP(=O)(O)OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O FVTCRASFADXXNN-UHFFFAOYSA-N 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• KCBFAIDPMHIZBJ-UHFFFAOYSA-N imidazol-1-yl(1h-pyrrol-2-yl)methanone Chemical compound C1=CN=CN1C(=O)C1=CC=CN1 KCBFAIDPMHIZBJ-UHFFFAOYSA-N 0.000 description 2
• 150000002460 imidazoles Chemical class 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 108700027921 interferon tau Proteins 0.000 description 2
• YPJRHEKCFKOVRT-UHFFFAOYSA-N lerociclib Chemical compound C1CN(C(C)C)CCN1C(C=N1)=CC=C1NC1=NC=C(C=C2N3C4(CCCCC4)CNC2=O)C3=N1 YPJRHEKCFKOVRT-UHFFFAOYSA-N 0.000 description 2
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
• 108010052968 leupeptin Proteins 0.000 description 2
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 2
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 2
• 239000006166 lysate Substances 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• ILOWHTHPQMGHBX-UHFFFAOYSA-N n-(2-cyanophenyl)-2,2,2-trifluoro-n-methylacetamide Chemical compound FC(F)(F)C(=O)N(C)C1=CC=CC=C1C#N ILOWHTHPQMGHBX-UHFFFAOYSA-N 0.000 description 2
• MIVMEDNHXXVPBX-UHFFFAOYSA-N n-(2-cyanophenyl)-2,2,2-trifluoroacetamide Chemical compound FC(F)(F)C(=O)NC1=CC=CC=C1C#N MIVMEDNHXXVPBX-UHFFFAOYSA-N 0.000 description 2
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
• 201000008482 osteoarthritis Diseases 0.000 description 2
• ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
• 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• 229940056360 penicillin g Drugs 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 230000002797 proteolythic effect Effects 0.000 description 2
• 235000019231 riboflavin-5'-phosphate Nutrition 0.000 description 2
• SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 2
• FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 description 2
• 229960004617 sapropterin Drugs 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 238000003345 scintillation counting Methods 0.000 description 2
• 238000007790 scraping Methods 0.000 description 2
• 239000002002 slurry Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• 125000004665 trialkylsilyl group Chemical group 0.000 description 2
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
• 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 2
• GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 2
• 239000002753 trypsin inhibitor Substances 0.000 description 2
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
• ANEHDMUVENGPFC-UHFFFAOYSA-N (4'-amino-5'-fluoro-1'-methylspiro[piperidine-4,2'-quinazoline]-1-yl)-thiophen-2-ylmethanone hydrochloride Chemical compound Cl.CN1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CS1 ANEHDMUVENGPFC-UHFFFAOYSA-N 0.000 description 1
• MRVAVHIQSORMPZ-UHFFFAOYSA-N (4-amino-5,7-difluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-thiophen-2-ylmethanone hydrochloride Chemical compound Cl.N1C2=CC(F)=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CS1 MRVAVHIQSORMPZ-UHFFFAOYSA-N 0.000 description 1
• UKEFENWFCNROPH-UHFFFAOYSA-N (4-amino-5,8-difluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-(4-chlorophenyl)methanone hydrochloride Chemical compound Cl.N1C2=C(F)C=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1 UKEFENWFCNROPH-UHFFFAOYSA-N 0.000 description 1
• OBYCIUJQELKQLJ-UHFFFAOYSA-N (4-amino-5,8-difluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-thiophen-2-ylmethanone;hydrochloride Chemical compound Cl.N1C2=C(F)C=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CS1 OBYCIUJQELKQLJ-UHFFFAOYSA-N 0.000 description 1
• YRVVEPAHZIKAOA-UHFFFAOYSA-N (4-amino-5-chlorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(furan-2-yl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC(Cl)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CO1 YRVVEPAHZIKAOA-UHFFFAOYSA-N 0.000 description 1
• BXCTVJOFXRKMNO-UHFFFAOYSA-N (4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-(1,3-thiazol-5-yl)methanone hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CN=CS1 BXCTVJOFXRKMNO-UHFFFAOYSA-N 0.000 description 1
• RHZVCLBQXRFEQW-UHFFFAOYSA-N (4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-(3,4-dichlorophenyl)methanone hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C(Cl)=C1 RHZVCLBQXRFEQW-UHFFFAOYSA-N 0.000 description 1
• USSSAYUXGLWYTP-UHFFFAOYSA-N (4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-(4-methylsulfonylphenyl)methanone hydrochloride Chemical compound Cl.C1=CC(S(=O)(=O)C)=CC=C1C(=O)N1CCC2(N=C(N)C3=C(F)C=CC=C3N2)CC1 USSSAYUXGLWYTP-UHFFFAOYSA-N 0.000 description 1
• IFLQEFCSPJLNAD-UHFFFAOYSA-N (4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-(5-bromothiophen-2-yl)methanone hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Br)S1 IFLQEFCSPJLNAD-UHFFFAOYSA-N 0.000 description 1
• IYXGQRDNZXGLCI-UHFFFAOYSA-N (4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-(5-ethylthiophen-2-yl)methanone hydrochloride Chemical compound Cl.S1C(CC)=CC=C1C(=O)N1CCC2(N=C(N)C3=C(F)C=CC=C3N2)CC1 IYXGQRDNZXGLCI-UHFFFAOYSA-N 0.000 description 1
• LEAYQKLHZHBLBO-UHFFFAOYSA-N (4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-(6-chloropyridin-3-yl)methanone hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)N=C1 LEAYQKLHZHBLBO-UHFFFAOYSA-N 0.000 description 1
• SOAMRAUSDWRXKC-UHFFFAOYSA-N (4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-[4-(trifluoromethoxy)phenyl]methanone hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(OC(F)(F)F)C=C1 SOAMRAUSDWRXKC-UHFFFAOYSA-N 0.000 description 1
• MSAKLSAMGBDCEM-UHFFFAOYSA-N (4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-phenylmethanone hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CC=C1 MSAKLSAMGBDCEM-UHFFFAOYSA-N 0.000 description 1
• MINONABDZAFTQA-UHFFFAOYSA-N (4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-pyridin-4-ylmethanone hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=NC=C1 MINONABDZAFTQA-UHFFFAOYSA-N 0.000 description 1
• QKBCCJAYLAFFET-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(2-fluorophenyl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CC=C1F QKBCCJAYLAFFET-UHFFFAOYSA-N 0.000 description 1
• AWPBMAMMGZVMRD-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-bromophenyl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Br)C=C1 AWPBMAMMGZVMRD-UHFFFAOYSA-N 0.000 description 1
• HMQBWDTZTRADGV-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-chloro-3-iodophenyl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C(I)=C1 HMQBWDTZTRADGV-UHFFFAOYSA-N 0.000 description 1
• DKPXEKKTMRIAGO-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-ethylphenyl)methanone;hydrochloride Chemical compound Cl.C1=CC(CC)=CC=C1C(=O)N1CCC2(N=C(N)C3=C(F)C=CC=C3N2)CC1 DKPXEKKTMRIAGO-UHFFFAOYSA-N 0.000 description 1
• KQGTWBNBZKMOJH-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-ethynylphenyl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(C#C)C=C1 KQGTWBNBZKMOJH-UHFFFAOYSA-N 0.000 description 1
• UNIHNTBTGDDQTA-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-propylphenyl)methanone;hydrochloride Chemical compound Cl.C1=CC(CCC)=CC=C1C(=O)N1CCC2(N=C(N)C3=C(F)C=CC=C3N2)CC1 UNIHNTBTGDDQTA-UHFFFAOYSA-N 0.000 description 1
• FPJZQSMHXMCEOJ-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(5-methylpyrazin-2-yl)methanone;hydrochloride Chemical compound Cl.C1=NC(C)=CN=C1C(=O)N1CCC2(N=C(N)C3=C(F)C=CC=C3N2)CC1 FPJZQSMHXMCEOJ-UHFFFAOYSA-N 0.000 description 1
• NUFQPRBLTLCULX-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(furan-2-yl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CO1 NUFQPRBLTLCULX-UHFFFAOYSA-N 0.000 description 1
• QYHFVJPJACEIAX-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-[2-(3-bromothiophen-2-yl)-1,3-thiazol-5-yl]methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C(S1)=CN=C1C=1SC=CC=1Br QYHFVJPJACEIAX-UHFFFAOYSA-N 0.000 description 1
• PNSCNODZRJIJGG-UHFFFAOYSA-N (4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-thiophen-2-ylmethanone;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CS1 PNSCNODZRJIJGG-UHFFFAOYSA-N 0.000 description 1
• CFRVZBDQSSPFJZ-UHFFFAOYSA-N (4-amino-5-hydroxyspiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-(4-bromophenyl)methanone hydrochloride Chemical compound Cl.NC1=NC2(CCN(CC2)C(=O)c2ccc(Br)cc2)Nc2cccc(O)c12 CFRVZBDQSSPFJZ-UHFFFAOYSA-N 0.000 description 1
• LQXLJUGOORLLQP-UHFFFAOYSA-N (4-aminophenyl)-(4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)methanone;dihydrochloride Chemical compound Cl.Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(N)C=C1 LQXLJUGOORLLQP-UHFFFAOYSA-N 0.000 description 1
• PRVOECGNSVPPKA-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(2-methylphenyl)methanone;hydrochloride Chemical compound Cl.CC1=CC=CC=C1C(=O)N1CCC2(N=C(N)C3=CC=CC=C3N2)CC1 PRVOECGNSVPPKA-UHFFFAOYSA-N 0.000 description 1
• GFRLBZKQPXEXHL-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(3-methylphenyl)methanone;hydrochloride Chemical compound Cl.CC1=CC=CC(C(=O)N2CCC3(CC2)N=C(N)C2=CC=CC=C2N3)=C1 GFRLBZKQPXEXHL-UHFFFAOYSA-N 0.000 description 1
• CZMLCPXLIWEOKG-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(3-nitrophenyl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CC([N+]([O-])=O)=C1 CZMLCPXLIWEOKG-UHFFFAOYSA-N 0.000 description 1
• NICQNKRDGQUWRB-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-chlorophenyl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(Cl)C=C1 NICQNKRDGQUWRB-UHFFFAOYSA-N 0.000 description 1
• LVAHVXTZJVRTDH-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-fluorophenyl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(F)C=C1 LVAHVXTZJVRTDH-UHFFFAOYSA-N 0.000 description 1
• OJYGCDDUDTYZJK-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-iodophenyl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(I)C=C1 OJYGCDDUDTYZJK-UHFFFAOYSA-N 0.000 description 1
• OFVJTFBOACDKIB-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-methylsulfonylphenyl)methanone;hydrochloride Chemical compound Cl.C1=CC(S(=O)(=O)C)=CC=C1C(=O)N1CCC2(N=C(N)C3=CC=CC=C3N2)CC1 OFVJTFBOACDKIB-UHFFFAOYSA-N 0.000 description 1
• ULAQPOPJZVJKDJ-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-(4-nitrophenyl)methanone;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C([N+]([O-])=O)C=C1 ULAQPOPJZVJKDJ-UHFFFAOYSA-N 0.000 description 1
• OKUPULZTNZGNPI-UHFFFAOYSA-N (4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-phenylmethanone;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=CC=C1 OKUPULZTNZGNPI-UHFFFAOYSA-N 0.000 description 1
• KZSVLGZQVQBKPG-UHFFFAOYSA-N (5-bromo-2-methoxyphenyl)methyl 4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-carboxylate;hydrochloride Chemical compound Cl.COC1=CC=C(Br)C=C1COC(=O)N1CCC2(N=C(N)C3=C(F)C=CC=C3N2)CC1 KZSVLGZQVQBKPG-UHFFFAOYSA-N 0.000 description 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
• ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• WLOGPUQXSPOPPX-UHFFFAOYSA-N 1'-(1,3-thiazol-2-yl)spiro[1h-quinazoline-2,4'-piperidine]-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C1=NC=CS1 WLOGPUQXSPOPPX-UHFFFAOYSA-N 0.000 description 1
• RJAIKKPEXPGRPN-UHFFFAOYSA-N 1'-benzylspiro[1h-quinazoline-2,4'-piperidine]-4-amine;dihydrochloride Chemical compound Cl.Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1CC1=CC=CC=C1 RJAIKKPEXPGRPN-UHFFFAOYSA-N 0.000 description 1
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
• AZNIVJFAQUVTMB-UHFFFAOYSA-N 1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(N)=NCNC2=C1 AZNIVJFAQUVTMB-UHFFFAOYSA-N 0.000 description 1
• MXWLGIKDBLPODE-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decan-8-yl(imidazol-1-yl)methanone Chemical compound C1=CN=CN1C(=O)N(CC1)CCC21OCCO2 MXWLGIKDBLPODE-UHFFFAOYSA-N 0.000 description 1
• APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
• LUOSNGFOANFUES-UHFFFAOYSA-N 1-(2,2,2-trifluoroacetyl)piperidin-4-one Chemical compound FC(F)(F)C(=O)N1CCC(=O)CC1 LUOSNGFOANFUES-UHFFFAOYSA-N 0.000 description 1
• LGTFCISIMRHJBA-UHFFFAOYSA-N 1-(3,4-dichlorobenzoyl)piperidin-4-one;ethene Chemical group C=C.C1=C(Cl)C(Cl)=CC=C1C(=O)N1CCC(=O)CC1 LGTFCISIMRHJBA-UHFFFAOYSA-N 0.000 description 1
• FTJMRVIAQKBBIZ-UHFFFAOYSA-N 1-(3,5-difluorobenzoyl)piperidin-4-one;ethene Chemical group C=C.FC1=CC(F)=CC(C(=O)N2CCC(=O)CC2)=C1 FTJMRVIAQKBBIZ-UHFFFAOYSA-N 0.000 description 1
• PPWDBBJQQHEYRQ-UHFFFAOYSA-N 1-(3,5-dimethylbenzoyl)piperidin-4-one;ethene Chemical group C=C.CC1=CC(C)=CC(C(=O)N2CCC(=O)CC2)=C1 PPWDBBJQQHEYRQ-UHFFFAOYSA-N 0.000 description 1
• XJFISKVECQZGEK-UHFFFAOYSA-N 1-(3-amino-4-chlorobenzoyl)piperidin-4-one;ethene Chemical group C=C.C1=C(Cl)C(N)=CC(C(=O)N2CCC(=O)CC2)=C1 XJFISKVECQZGEK-UHFFFAOYSA-N 0.000 description 1
• QLAGPCJUAFNZGR-UHFFFAOYSA-N 1-(3-hydroxypropyl)pyridin-2-one Chemical compound OCCCN1C=CC=CC1=O QLAGPCJUAFNZGR-UHFFFAOYSA-N 0.000 description 1
• CCGLGBUBMNMCFX-UHFFFAOYSA-N 1-(4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-2,2,2-trifluoroethanone hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCN(C(=O)C(F)(F)F)CC2 CCGLGBUBMNMCFX-UHFFFAOYSA-N 0.000 description 1
• KMNGGRLOJNAJQL-UHFFFAOYSA-N 1-(4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-yl)-4-phenoxybutan-1-one hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)CCCOC1=CC=CC=C1 KMNGGRLOJNAJQL-UHFFFAOYSA-N 0.000 description 1
• QZNXKDFTHUFLNM-UHFFFAOYSA-N 1-(4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)-2-[2-(trifluoromethyl)phenyl]ethanone;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)CC1=CC=CC=C1C(F)(F)F QZNXKDFTHUFLNM-UHFFFAOYSA-N 0.000 description 1
• BSJQHSXKBRPGOU-UHFFFAOYSA-N 1-(4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-yl)ethanone Chemical compound C1CN(C(=O)C)CCC21N=C(N)C1=CC=CC=C1N2 BSJQHSXKBRPGOU-UHFFFAOYSA-N 0.000 description 1
• FPIHRDBYFKFSHO-UHFFFAOYSA-N 1-(4-bromothiophene-2-carbonyl)piperidin-4-one;ethene Chemical group C=C.BrC1=CSC(C(=O)N2CCC(=O)CC2)=C1 FPIHRDBYFKFSHO-UHFFFAOYSA-N 0.000 description 1
• MJTPROAINGEUJW-UHFFFAOYSA-N 1-(4-chloro-3-iodobenzoyl)piperidin-4-one;ethene Chemical group C=C.C1=C(I)C(Cl)=CC=C1C(=O)N1CCC(=O)CC1 MJTPROAINGEUJW-UHFFFAOYSA-N 0.000 description 1
• SYWXLNAOEXIDMG-UHFFFAOYSA-N 1-(4-methylbenzoyl)piperidin-4-one Chemical compound C1=CC(C)=CC=C1C(=O)N1CCC(=O)CC1 SYWXLNAOEXIDMG-UHFFFAOYSA-N 0.000 description 1
• BXFUYAKJRYAMHR-UHFFFAOYSA-N 1-(4-nitrophenyl)sulfonylpiperidin-4-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)N1CCC(=O)CC1 BXFUYAKJRYAMHR-UHFFFAOYSA-N 0.000 description 1
• XPZKIQJFJIQTKY-UHFFFAOYSA-N 1-(5-bromofuran-2-carbonyl)piperidin-4-one Chemical compound O1C(Br)=CC=C1C(=O)N1CCC(=O)CC1 XPZKIQJFJIQTKY-UHFFFAOYSA-N 0.000 description 1
• RWQSSMKWXNLSKW-UHFFFAOYSA-N 1-(5-chlorothiophene-2-carbonyl)piperidin-4-one;ethene Chemical group C=C.S1C(Cl)=CC=C1C(=O)N1CCC(=O)CC1 RWQSSMKWXNLSKW-UHFFFAOYSA-N 0.000 description 1
• WMDDQPGCUBZMFH-UHFFFAOYSA-N 1-(6-bromopyridine-3-carbonyl)piperidin-4-one;ethene Chemical group C=C.C1=NC(Br)=CC=C1C(=O)N1CCC(=O)CC1 WMDDQPGCUBZMFH-UHFFFAOYSA-N 0.000 description 1
• ULHKIMBKWYCESD-UHFFFAOYSA-N 1-(6-chloropyridine-3-carbonyl)piperidin-4-one;ethene Chemical group C=C.C1=NC(Cl)=CC=C1C(=O)N1CCC(=O)CC1 ULHKIMBKWYCESD-UHFFFAOYSA-N 0.000 description 1
• VCQPLTXOXQMUQJ-UHFFFAOYSA-N 1-(imidazole-1-carbonyl)piperidin-4-one Chemical compound C1=CN=CN1C(=O)N1CCC(=O)CC1 VCQPLTXOXQMUQJ-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• XAGZJIQIVXSURR-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]piperidin-2-one Chemical group C1=CC(C(F)(F)F)=CC=C1N1C(=O)CCCC1 XAGZJIQIVXSURR-UHFFFAOYSA-N 0.000 description 1
• NNFOVLFUGLWWCL-UHFFFAOYSA-N 1-acetylpiperidin-4-one Chemical compound CC(=O)N1CCC(=O)CC1 NNFOVLFUGLWWCL-UHFFFAOYSA-N 0.000 description 1
• WLEXMRPHAFXLKR-UHFFFAOYSA-N 1-benzofuran-2-ylmethyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC11CCN(C(=O)OCC=2OC3=CC=CC=C3C=2)CC1 WLEXMRPHAFXLKR-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
• BMYPHGUYQSUCGQ-UHFFFAOYSA-N 1-butanoylpiperidin-4-one Chemical compound CCCC(=O)N1CCC(=O)CC1 BMYPHGUYQSUCGQ-UHFFFAOYSA-N 0.000 description 1
• AJCSNHQKXUSMMY-UHFFFAOYSA-N 1-chloro-2,4-difluorobenzene Chemical compound FC1=CC=C(Cl)C(F)=C1 AJCSNHQKXUSMMY-UHFFFAOYSA-N 0.000 description 1
• GMUALAZMCZEAIJ-UHFFFAOYSA-N 1-methyl-2-phenyl-2h-quinazolin-4-amine;hydrochloride Chemical compound Cl.N1=C(N)C2=CC=CC=C2N(C)C1C1=CC=CC=C1 GMUALAZMCZEAIJ-UHFFFAOYSA-N 0.000 description 1
• XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
• QRFWMHKJQDJVGR-UHFFFAOYSA-N 2,2,2-trifluoroethyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCN(C(=O)OCC(F)(F)F)CC2 QRFWMHKJQDJVGR-UHFFFAOYSA-N 0.000 description 1
• QUJSMOIAFOKMIB-UHFFFAOYSA-N 2,2-dimethyl-1h-quinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(N)=NC(C)(C)NC2=C1 QUJSMOIAFOKMIB-UHFFFAOYSA-N 0.000 description 1
• YWTXHALVWAISPR-UHFFFAOYSA-N 2,3,6-trifluorobenzonitrile Chemical compound FC1=CC=C(F)C(C#N)=C1F YWTXHALVWAISPR-UHFFFAOYSA-N 0.000 description 1
• QMIGEDXMDGEZSR-UHFFFAOYSA-N 2,5-dimethoxyoxolane-3-carbaldehyde Chemical compound COC1CC(C=O)C(OC)O1 QMIGEDXMDGEZSR-UHFFFAOYSA-N 0.000 description 1
• ZYDGHQSJZAFMLU-UHFFFAOYSA-N 2,6-dinitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=CC([N+]([O-])=O)=C1C#N ZYDGHQSJZAFMLU-UHFFFAOYSA-N 0.000 description 1
• DWJVYJNRLHHBEW-UHFFFAOYSA-N 2-(1h-imidazol-2-yl)-1,2-dihydroquinazolin-4-amine;dihydrochloride Chemical compound Cl.Cl.N1C2=CC=CC=C2C(N)=NC1C1=NC=CN1 DWJVYJNRLHHBEW-UHFFFAOYSA-N 0.000 description 1
• KTHWGYGTFXLGSX-UHFFFAOYSA-N 2-(2-ethenylphenyl)-1,3-dioxolane Chemical compound C=CC1=CC=CC=C1C1OCCO1 KTHWGYGTFXLGSX-UHFFFAOYSA-N 0.000 description 1
• MWIWCNXRWWSIKQ-UHFFFAOYSA-N 2-(2-nitrophenyl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=CC=C1[N+]([O-])=O MWIWCNXRWWSIKQ-UHFFFAOYSA-N 0.000 description 1
• ZSHKKTPHGJDGBG-UHFFFAOYSA-N 2-(2-trimethylsilylethynyl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(N)=NC(C#C[Si](C)(C)C)NC2=C1 ZSHKKTPHGJDGBG-UHFFFAOYSA-N 0.000 description 1
• SNIRZZNDHWRYSX-UHFFFAOYSA-N 2-(3-aminopropyl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(N)=NC(CCCN)NC2=C1 SNIRZZNDHWRYSX-UHFFFAOYSA-N 0.000 description 1
• NDPRJLVNQGWVRR-UHFFFAOYSA-N 2-(4-amino-5-fluoro-1,2-dihydroquinazolin-2-yl)phenol;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1=CC=CC=C1O NDPRJLVNQGWVRR-UHFFFAOYSA-N 0.000 description 1
• ANNJWZPZPOMJFC-UHFFFAOYSA-N 2-(4-nitrophenyl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=C([N+]([O-])=O)C=C1 ANNJWZPZPOMJFC-UHFFFAOYSA-N 0.000 description 1
• ILPFVYFBRQEFPB-UHFFFAOYSA-N 2-(5-nitrothiophen-2-yl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=C([N+]([O-])=O)S1 ILPFVYFBRQEFPB-UHFFFAOYSA-N 0.000 description 1
• RNLCVZJLIXXGSG-UHFFFAOYSA-N 2-(furan-2-yl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=CO1 RNLCVZJLIXXGSG-UHFFFAOYSA-N 0.000 description 1
• RIFWQEWZSJJUMD-UHFFFAOYSA-N 2-(furan-2-yl)-5-methylsulfanyl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1=C(N)C=2C(SC)=CC=CC=2NC1C1=CC=CO1 RIFWQEWZSJJUMD-UHFFFAOYSA-N 0.000 description 1
• SHIBMGQAICRHTE-UHFFFAOYSA-N 2-(methylamino)benzonitrile Chemical compound CNC1=CC=CC=C1C#N SHIBMGQAICRHTE-UHFFFAOYSA-N 0.000 description 1
• ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 1
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
• ZZHHWYQWOMLYSB-UHFFFAOYSA-N 2-[2-(1,3-dioxolan-2-yl)phenyl]ethanol Chemical compound OCCC1=CC=CC=C1C1OCCO1 ZZHHWYQWOMLYSB-UHFFFAOYSA-N 0.000 description 1
• IYRQMILIVVVQOB-UHFFFAOYSA-N 2-[2-(2-aminoethyl)phenyl]-1,2-dihydroquinazolin-4-amine;dihydrochloride Chemical compound Cl.Cl.NCCC1=CC=CC=C1C1N=C(N)C2=CC=CC=C2N1 IYRQMILIVVVQOB-UHFFFAOYSA-N 0.000 description 1
• YGYPTJIFRUJAEE-UHFFFAOYSA-N 2-[4-(dimethylamino)phenyl]-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC(N(C)C)=CC=C1C1N=C(N)C2=CC=CC=C2N1 YGYPTJIFRUJAEE-UHFFFAOYSA-N 0.000 description 1
• IEMMBWWQXVXBEU-UHFFFAOYSA-N 2-acetylfuran Chemical compound CC(=O)C1=CC=CO1 IEMMBWWQXVXBEU-UHFFFAOYSA-N 0.000 description 1
• TVPHVSHQKCRVLD-UHFFFAOYSA-N 2-amino-3,6-difluoro-n'-hydroxybenzenecarboximidamide Chemical compound ON=C(N)C1=C(F)C=CC(F)=C1N TVPHVSHQKCRVLD-UHFFFAOYSA-N 0.000 description 1
• ZPQFHGOBMGGBEP-UHFFFAOYSA-N 2-amino-3,6-difluorobenzonitrile Chemical compound NC1=C(F)C=CC(F)=C1C#N ZPQFHGOBMGGBEP-UHFFFAOYSA-N 0.000 description 1
• GTEZSHJBMRWRIG-UHFFFAOYSA-N 2-amino-3-[4-(naphthalene-2-carbonyloxy)phenyl]propanoic acid Chemical group C1=CC(CC(N)C(O)=O)=CC=C1OC(=O)C1=CC=C(C=CC=C2)C2=C1 GTEZSHJBMRWRIG-UHFFFAOYSA-N 0.000 description 1
• LNLPSPHZNBXYIR-UHFFFAOYSA-N 2-amino-3-chloro-6-fluorobenzamide;dihydrochloride Chemical compound Cl.Cl.NC(=O)C1=C(F)C=CC(Cl)=C1N LNLPSPHZNBXYIR-UHFFFAOYSA-N 0.000 description 1
• JMLLGMVTOGELLM-UHFFFAOYSA-N 2-amino-3-chloro-6-fluorobenzonitrile Chemical compound NC1=C(Cl)C=CC(F)=C1C#N JMLLGMVTOGELLM-UHFFFAOYSA-N 0.000 description 1
• XGRYXBCBZPBCHC-UHFFFAOYSA-N 2-amino-4,6-difluoro-n'-hydroxybenzenecarboximidamide Chemical compound ON=C(N)C1=C(N)C=C(F)C=C1F XGRYXBCBZPBCHC-UHFFFAOYSA-N 0.000 description 1
• NLUJKZOGZQXBJB-UHFFFAOYSA-N 2-amino-4,6-difluorobenzonitrile Chemical compound NC1=CC(F)=CC(F)=C1C#N NLUJKZOGZQXBJB-UHFFFAOYSA-N 0.000 description 1
• GCSGBUKZCUBGCY-UHFFFAOYSA-N 2-amino-6-chloro-n'-hydroxybenzenecarboximidamide Chemical compound ON=C(N)C1=C(N)C=CC=C1Cl GCSGBUKZCUBGCY-UHFFFAOYSA-N 0.000 description 1
• GKZDQAPUZKNVRK-UHFFFAOYSA-N 2-amino-6-fluoro-n'-hydroxybenzenecarboximidamide Chemical compound ON=C(N)C1=C(N)C=CC=C1F GKZDQAPUZKNVRK-UHFFFAOYSA-N 0.000 description 1
• FGLHGYFETAMVPK-UHFFFAOYSA-N 2-amino-6-fluorobenzenecarboximidamide Chemical compound NC(=N)C1=C(N)C=CC=C1F FGLHGYFETAMVPK-UHFFFAOYSA-N 0.000 description 1
• VOHYSMFZEKLXPB-UHFFFAOYSA-N 2-amino-6-fluorobenzenecarboximidamide;hydrochloride Chemical compound Cl.NC(=N)C1=C(N)C=CC=C1F VOHYSMFZEKLXPB-UHFFFAOYSA-N 0.000 description 1
• RZMZBLMYASOCDB-UHFFFAOYSA-N 2-amino-6-methylsulfanylbenzonitrile Chemical compound CSC1=CC=CC(N)=C1C#N RZMZBLMYASOCDB-UHFFFAOYSA-N 0.000 description 1
• NQRWSXVAHJPYER-UHFFFAOYSA-N 2-amino-n'-hydroxy-6-methoxybenzenecarboximidamide Chemical compound COC1=CC=CC(N)=C1C(N)=NO NQRWSXVAHJPYER-UHFFFAOYSA-N 0.000 description 1
• ZGQCYUUCSFNWJW-UHFFFAOYSA-N 2-anthracen-9-yl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(C3N=C(C4=CC=CC=C4N3)N)=C(C=CC=C3)C3=CC2=C1 ZGQCYUUCSFNWJW-UHFFFAOYSA-N 0.000 description 1
• RXNZFHIEDZEUQM-UHFFFAOYSA-N 2-bromo-1,3-thiazole Chemical compound BrC1=NC=CS1 RXNZFHIEDZEUQM-UHFFFAOYSA-N 0.000 description 1
• PGMMKKMEEBXRRU-UHFFFAOYSA-N 2-cyanoethyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCN(C(=O)OCCC#N)CC2 PGMMKKMEEBXRRU-UHFFFAOYSA-N 0.000 description 1
• WTZVZCJSBZWSOU-UHFFFAOYSA-N 2-cyclobutyl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1CCC1 WTZVZCJSBZWSOU-UHFFFAOYSA-N 0.000 description 1
• PMQJDOSIKPJMDS-UHFFFAOYSA-N 2-cyclobutyl-5-fluoro-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1CCC1 PMQJDOSIKPJMDS-UHFFFAOYSA-N 0.000 description 1
• BBBNDGFQQYIKBZ-UHFFFAOYSA-N 2-cyclopentyl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1CCCC1 BBBNDGFQQYIKBZ-UHFFFAOYSA-N 0.000 description 1
• POADPHDQYVODHT-UHFFFAOYSA-N 2-cyclopropyl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1CC1 POADPHDQYVODHT-UHFFFAOYSA-N 0.000 description 1
• ZUJZCZUFRBURBT-UHFFFAOYSA-N 2-cyclopropyl-1-methyl-2h-quinazolin-4-amine;hydrochloride Chemical compound Cl.N1=C(N)C2=CC=CC=C2N(C)C1C1CC1 ZUJZCZUFRBURBT-UHFFFAOYSA-N 0.000 description 1
• DHEJIZSVHGOKMJ-UHFFFAOYSA-N 2-ethenylbenzaldehyde Chemical compound C=CC1=CC=CC=C1C=O DHEJIZSVHGOKMJ-UHFFFAOYSA-N 0.000 description 1
• WOKWNFYLABPWII-UHFFFAOYSA-N 2-ethyl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(N)=NC(CC)NC2=C1 WOKWNFYLABPWII-UHFFFAOYSA-N 0.000 description 1
• PFKPYMQEFMFASQ-UHFFFAOYSA-N 2-ethyl-2-methyl-1h-quinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(N)=NC(CC)(C)NC2=C1 PFKPYMQEFMFASQ-UHFFFAOYSA-N 0.000 description 1
• NEXVNWWOFFGQHL-UHFFFAOYSA-N 2-ethynyl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(N)=NC(C#C)NC2=C1 NEXVNWWOFFGQHL-UHFFFAOYSA-N 0.000 description 1
• UUAAIYMRUCNNQG-UHFFFAOYSA-N 2-fluoro-6-(methylamino)benzenecarboximidamide Chemical compound CNC1=CC=CC(F)=C1C(N)=N UUAAIYMRUCNNQG-UHFFFAOYSA-N 0.000 description 1
• JTLHDMJPZWFPGO-UHFFFAOYSA-N 2-fluoro-6-(methylamino)benzenecarboximidamide;hydrochloride Chemical compound Cl.CNC1=CC=CC(F)=C1C(N)=N JTLHDMJPZWFPGO-UHFFFAOYSA-N 0.000 description 1
• HORADRWTTKWYNT-UHFFFAOYSA-N 2-fluoro-6-(methylamino)benzonitrile Chemical compound CNC1=CC=CC(F)=C1C#N HORADRWTTKWYNT-UHFFFAOYSA-N 0.000 description 1
• 102100027324 2-hydroxyacyl-CoA lyase 1 Human genes 0.000 description 1
• NFFGRBSJCKAODP-UHFFFAOYSA-N 2-methoxyethyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.C1CN(C(=O)OCCOC)CCC21N=C(N)C1=C(F)C=CC=C1N2 NFFGRBSJCKAODP-UHFFFAOYSA-N 0.000 description 1
• NDYYWMXJZWHRLZ-UHFFFAOYSA-N 2-methoxyethyl carbonochloridate Chemical compound COCCOC(Cl)=O NDYYWMXJZWHRLZ-UHFFFAOYSA-N 0.000 description 1
• QNGXWLFGIOYGQK-UHFFFAOYSA-N 2-methyl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2C(N)=NC(C)NC2=C1 QNGXWLFGIOYGQK-UHFFFAOYSA-N 0.000 description 1
• YILCKRZMMXEGGG-UHFFFAOYSA-N 2-methyl-2-phenyl-1h-quinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(C)C1=CC=CC=C1 YILCKRZMMXEGGG-UHFFFAOYSA-N 0.000 description 1
• AFXKCBFBGDUFAM-UHFFFAOYSA-N 2-methylpropan-2-amine;hydrofluoride Chemical compound [F-].CC(C)(C)[NH3+] AFXKCBFBGDUFAM-UHFFFAOYSA-N 0.000 description 1
• USPSGCJLBSEJID-UHFFFAOYSA-N 2-methylpropyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.C1CN(C(=O)OCC(C)C)CCC21N=C(N)C1=C(F)C=CC=C1N2 USPSGCJLBSEJID-UHFFFAOYSA-N 0.000 description 1
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
• CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
• QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
• VSGXFFOERLMJRI-UHFFFAOYSA-N 2-phenoxyethyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)OCCOC1=CC=CC=C1 VSGXFFOERLMJRI-UHFFFAOYSA-N 0.000 description 1
• BQIIJRYMENPCOV-UHFFFAOYSA-N 2-phenyl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=CC=C1 BQIIJRYMENPCOV-UHFFFAOYSA-N 0.000 description 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• KNMKDTWDWOXVSB-UHFFFAOYSA-N 2-pyridin-4-yl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=NC=C1 KNMKDTWDWOXVSB-UHFFFAOYSA-N 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• APCKJOUUUYJOMR-UHFFFAOYSA-N 2-thiophen-2-yl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=CS1 APCKJOUUUYJOMR-UHFFFAOYSA-N 0.000 description 1
• PXXMSHBZYAOHBD-UHFFFAOYSA-N 3,3-diethoxypropan-1-amine Chemical compound CCOC(CCN)OCC PXXMSHBZYAOHBD-UHFFFAOYSA-N 0.000 description 1
• GZLPFEYTAAXJCP-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-sulfonyl chloride Chemical compound CC1=NOC(C)=C1S(Cl)(=O)=O GZLPFEYTAAXJCP-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 1
• UEKIYSWVVBBXGS-UHFFFAOYSA-N 3-chloropropyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCN(C(=O)OCCCCl)CC2 UEKIYSWVVBBXGS-UHFFFAOYSA-N 0.000 description 1
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
• ZHFWJCUKKDMFIV-UHFFFAOYSA-N 3-methyl-5-(trichloromethyl)-1,2,4-oxadiazole Chemical compound CC1=NOC(C(Cl)(Cl)Cl)=N1 ZHFWJCUKKDMFIV-UHFFFAOYSA-N 0.000 description 1
• OLFGNTRKVIXJKP-UHFFFAOYSA-N 3-phenoxypropyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)OCCCOC1=CC=CC=C1 OLFGNTRKVIXJKP-UHFFFAOYSA-N 0.000 description 1
• BRPBYEIDAAOJRK-UHFFFAOYSA-N 3-phenylpropyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)OCCCC1=CC=CC=C1 BRPBYEIDAAOJRK-UHFFFAOYSA-N 0.000 description 1
• BQFZLZCBCSKUPL-UHFFFAOYSA-N 3-thiophen-2-ylpropan-1-ol Chemical compound OCCCC1=CC=CS1 BQFZLZCBCSKUPL-UHFFFAOYSA-N 0.000 description 1
• LJRWLSKYGWLYIM-UHFFFAOYSA-N 3-trimethylsilylprop-2-ynal Chemical compound C[Si](C)(C)C#CC=O LJRWLSKYGWLYIM-UHFFFAOYSA-N 0.000 description 1
• MIMOLENYMISASI-UHFFFAOYSA-N 4,4,4-trifluorobutyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCN(C(=O)OCCCC(F)(F)F)CC2 MIMOLENYMISASI-UHFFFAOYSA-N 0.000 description 1
• PXHLRVFDFIDDMJ-UHFFFAOYSA-N 4-(4-amino-1,2-dihydroquinazolin-2-yl)benzonitrile;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=C(C#N)C=C1 PXHLRVFDFIDDMJ-UHFFFAOYSA-N 0.000 description 1
• BMNWAFMQHVJQEZ-UHFFFAOYSA-N 4-(4-amino-5,8-difluorospiro[1h-quinazoline-2,4'-piperidine]-1'-carbonyl)benzonitrile;hydrochloride Chemical compound Cl.N1C2=C(F)C=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(C#N)C=C1 BMNWAFMQHVJQEZ-UHFFFAOYSA-N 0.000 description 1
• ZSTHADWLZNALCH-UHFFFAOYSA-N 4-(4-amino-5-fluoro-1,2-dihydroquinazolin-2-yl)phenol;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1=CC=C(O)C=C1 ZSTHADWLZNALCH-UHFFFAOYSA-N 0.000 description 1
• RRTQTSDPLHXDQM-UHFFFAOYSA-N 4-(4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carbonyl)-2-fluorobenzonitrile hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)C1=CC=C(C#N)C(F)=C1 RRTQTSDPLHXDQM-UHFFFAOYSA-N 0.000 description 1
• UANVYWDCFHWOCK-UHFFFAOYSA-N 4-(4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carbonyl)-2-methylbenzonitrile hydrochloride Chemical compound Cl.C1=C(C#N)C(C)=CC(C(=O)N2CCC3(CC2)N=C(N)C2=C(F)C=CC=C2N3)=C1 UANVYWDCFHWOCK-UHFFFAOYSA-N 0.000 description 1
• YVGHBFYUNDEJAC-UHFFFAOYSA-N 4-(4-amino-5-hydroxyspiro[1H-quinazoline-2,4'-piperidine]-1'-carbonyl)benzonitrile hydrochloride Chemical compound Cl.NC1=NC2(CCN(CC2)C(=O)c2ccc(cc2)C#N)Nc2cccc(O)c12 YVGHBFYUNDEJAC-UHFFFAOYSA-N 0.000 description 1
• BVXXBNLCTCXYRF-UHFFFAOYSA-N 4-(4-amino-5-methoxyspiro[1h-quinazoline-2,4'-piperidine]-1'-carbonyl)benzonitrile;hydrochloride Chemical compound Cl.N1=C(N)C=2C(OC)=CC=CC=2NC1(CC1)CCN1C(=O)C1=CC=C(C#N)C=C1 BVXXBNLCTCXYRF-UHFFFAOYSA-N 0.000 description 1
• XXZRHCIVQAGULW-UHFFFAOYSA-N 4-(4-oxopiperidine-1-carbothioyl)benzonitrile Chemical compound C1CC(=O)CCN1C(=S)C1=CC=C(C#N)C=C1 XXZRHCIVQAGULW-UHFFFAOYSA-N 0.000 description 1
• BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 1
• BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
• 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 description 1
• VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
• YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 1
• XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• GOXLYYFBMIXPDI-UHFFFAOYSA-N 4-amino-n-ethyl-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-carboxamide;hydrochloride Chemical compound Cl.C1CN(C(=O)NCC)CCC21N=C(N)C1=C(F)C=CC=C1N2 GOXLYYFBMIXPDI-UHFFFAOYSA-N 0.000 description 1
• LPEBMDFRIKYFCF-UHFFFAOYSA-N 4-bromo-2-methylbenzonitrile Chemical compound CC1=CC(Br)=CC=C1C#N LPEBMDFRIKYFCF-UHFFFAOYSA-N 0.000 description 1
• 125000002672 4-bromobenzoyl group Chemical group BrC1=CC=C(C(=O)*)C=C1 0.000 description 1
• 125000000242 4-chlorobenzoyl group Chemical group ClC1=CC=C(C(=O)*)C=C1 0.000 description 1
• KKKWDVKSJWHJFX-UHFFFAOYSA-N 4-chlorobutyl 4'-amino-5'-fluoro-1'-methylspiro[piperidine-4,2'-quinazoline]-1-carboxylate hydrochloride Chemical compound Cl.CN1C2=CC=CC(F)=C2C(N)=NC11CCN(C(=O)OCCCCCl)CC1 KKKWDVKSJWHJFX-UHFFFAOYSA-N 0.000 description 1
• GIKYUODUYGVGBS-UHFFFAOYSA-N 4-chlorobutyl 4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-carboxylate;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCN(C(=O)OCCCCCl)CC2 GIKYUODUYGVGBS-UHFFFAOYSA-N 0.000 description 1
• ZWKNDLMYSLLMRF-UHFFFAOYSA-N 4-cyano-3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C(F)=C1 ZWKNDLMYSLLMRF-UHFFFAOYSA-N 0.000 description 1
• LTRYUAZFLOGRLJ-UHFFFAOYSA-N 4-cyano-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1C#N LTRYUAZFLOGRLJ-UHFFFAOYSA-N 0.000 description 1
• WZWIQYMTQZCSKI-UHFFFAOYSA-N 4-cyanobenzaldehyde Chemical compound O=CC1=CC=C(C#N)C=C1 WZWIQYMTQZCSKI-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• NQUVCRCCRXRJCK-UHFFFAOYSA-N 4-methylbenzoyl chloride Chemical compound CC1=CC=C(C(Cl)=O)C=C1 NQUVCRCCRXRJCK-UHFFFAOYSA-N 0.000 description 1
• QRVYABWJVXXOTN-UHFFFAOYSA-N 4-methylsulfanylbenzaldehyde Chemical compound CSC1=CC=C(C=O)C=C1 QRVYABWJVXXOTN-UHFFFAOYSA-N 0.000 description 1
• JSNDPQMTXGDMIM-UHFFFAOYSA-N 4-nitro-1,2-benzoxazol-3-amine Chemical compound C1=CC([N+]([O-])=O)=C2C(N)=NOC2=C1 JSNDPQMTXGDMIM-UHFFFAOYSA-N 0.000 description 1
• BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
• JXRGUPLJCCDGKG-UHFFFAOYSA-N 4-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(S(Cl)(=O)=O)C=C1 JXRGUPLJCCDGKG-UHFFFAOYSA-N 0.000 description 1
• XBWWFWSWYNQMRK-UHFFFAOYSA-N 4-phenylbutyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)OCCCCC1=CC=CC=C1 XBWWFWSWYNQMRK-UHFFFAOYSA-N 0.000 description 1
• FYYLSCWWCHQDFX-UHFFFAOYSA-N 4-thiophen-2-ylbutan-1-ol Chemical compound OCCCCC1=CC=CS1 FYYLSCWWCHQDFX-UHFFFAOYSA-N 0.000 description 1
• NTSNKFYZLVZBHJ-UHFFFAOYSA-N 5'-fluoro-1'-[2-(4-methyl-1,3-thiazol-5-yl)ethyl]spiro[piperidine-4,2'-quinazoline]-4'-amine Chemical compound CC=1N=CSC=1CCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 NTSNKFYZLVZBHJ-UHFFFAOYSA-N 0.000 description 1
• OPEBPPZVBMNRAQ-UHFFFAOYSA-N 5-(4-oxopiperidine-1-carbonyl)pyridine-2-carbonitrile Chemical compound C=1C=C(C#N)N=CC=1C(=O)N1CCC(=O)CC1 OPEBPPZVBMNRAQ-UHFFFAOYSA-N 0.000 description 1
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
• YVTQHZDUDUCGRD-UHFFFAOYSA-N 5-bromofuran-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Br)O1 YVTQHZDUDUCGRD-UHFFFAOYSA-N 0.000 description 1
• VKTOGECFSAMVRU-UHFFFAOYSA-N 5-chloro-2-(furan-2-yl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(Cl)=C2C(N)=NC1C1=CC=CO1 VKTOGECFSAMVRU-UHFFFAOYSA-N 0.000 description 1
• HSTNXMSRIXLOOZ-UHFFFAOYSA-N 5-chloro-2-thiophen-2-yl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(Cl)=C2C(N)=NC1C1=CC=CS1 HSTNXMSRIXLOOZ-UHFFFAOYSA-N 0.000 description 1
• VSMKBHCHBLJYRJ-UHFFFAOYSA-N 5-fluoro-2-(1,3-thiazol-2-yl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1=NC=CS1 VSMKBHCHBLJYRJ-UHFFFAOYSA-N 0.000 description 1
• RQPPXXJEROKIBK-UHFFFAOYSA-N 5-fluoro-2-(4-fluorophenyl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1=CC=C(F)C=C1 RQPPXXJEROKIBK-UHFFFAOYSA-N 0.000 description 1
• DSBLALDYLSSGHN-UHFFFAOYSA-N 5-fluoro-2-(4-methoxyphenyl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1N=C(N)C2=C(F)C=CC=C2N1 DSBLALDYLSSGHN-UHFFFAOYSA-N 0.000 description 1
• AVTDLSZGEFEUTD-UHFFFAOYSA-N 5-fluoro-2-(4-methylsulfanylphenyl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC(SC)=CC=C1C1N=C(N)C2=C(F)C=CC=C2N1 AVTDLSZGEFEUTD-UHFFFAOYSA-N 0.000 description 1
• JWGLFQXBMLBLMD-UHFFFAOYSA-N 5-fluoro-2-(furan-2-yl)-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1=CC=CO1 JWGLFQXBMLBLMD-UHFFFAOYSA-N 0.000 description 1
• IKCBFJLMJWRTHU-UHFFFAOYSA-N 5-fluoro-2-[2-(trifluoromethyl)phenyl]-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1=CC=CC=C1C(F)(F)F IKCBFJLMJWRTHU-UHFFFAOYSA-N 0.000 description 1
• YMAOBXPWOZUFSL-UHFFFAOYSA-N 5-fluoro-2-[4-(trifluoromethyl)phenyl]-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1=CC=C(C(F)(F)F)C=C1 YMAOBXPWOZUFSL-UHFFFAOYSA-N 0.000 description 1
• MCJFJOGLHPANJV-UHFFFAOYSA-N 5-fluoro-2-phenyl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1=CC=CC=C1 MCJFJOGLHPANJV-UHFFFAOYSA-N 0.000 description 1
• STTFYTRPQVNDQA-UHFFFAOYSA-N 5-fluoro-2-propan-2-yl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.C1=CC(F)=C2C(N)=NC(C(C)C)NC2=C1 STTFYTRPQVNDQA-UHFFFAOYSA-N 0.000 description 1
• NEBMCWKEDXNGOF-UHFFFAOYSA-N 5-fluoro-2-thiophen-2-yl-1,2-dihydroquinazolin-4-amine;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1C1=CC=CS1 NEBMCWKEDXNGOF-UHFFFAOYSA-N 0.000 description 1
• BWQKVQOXURJROY-UHFFFAOYSA-N 5-fluorospiro[1h-quinazoline-2,3'-azetidine]-4-amine Chemical compound N1C2=CC=CC(F)=C2C(N)=NC21CNC2 BWQKVQOXURJROY-UHFFFAOYSA-N 0.000 description 1
• XOTLDQOUNJEZHK-UHFFFAOYSA-N 5-fluorospiro[1h-quinazoline-2,4'-piperidine]-4-amine;dihydrochloride Chemical compound Cl.Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCNCC2 XOTLDQOUNJEZHK-UHFFFAOYSA-N 0.000 description 1
• CHTSWZNXEKOLPM-UHFFFAOYSA-N 5-nitrothiophene-2-carbaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)S1 CHTSWZNXEKOLPM-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• GOGZSIPEPYNIHK-UHFFFAOYSA-N 6-chlorohexyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCN(C(=O)OCCCCCCCl)CC2 GOGZSIPEPYNIHK-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 208000035939 Alveolitis allergic Diseases 0.000 description 1
• 241000272517 Anseriformes Species 0.000 description 1
• 108010039627 Aprotinin Proteins 0.000 description 1
• 208000004300 Atrophic Gastritis Diseases 0.000 description 1
• 208000031729 Bacteremia Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• JQJGKAAYRCKQDZ-UHFFFAOYSA-N C(C)N(C1=CC=CC=C1)CCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 Chemical compound C(C)N(C1=CC=CC=C1)CCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 JQJGKAAYRCKQDZ-UHFFFAOYSA-N 0.000 description 1
• SVKBIXXTHZVXJA-UHFFFAOYSA-N C(C1=CC=CC=C1)(NNC)=NO Chemical compound C(C1=CC=CC=C1)(NNC)=NO SVKBIXXTHZVXJA-UHFFFAOYSA-N 0.000 description 1
• WSUGKXIMMBAJLL-UHFFFAOYSA-N C1(=CC=CC=C1)SCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 Chemical compound C1(=CC=CC=C1)SCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 WSUGKXIMMBAJLL-UHFFFAOYSA-N 0.000 description 1
• GSUOSBNMGDBJOZ-UHFFFAOYSA-N C=C.BrC1=C(SC=C1)C(=O)C1C(CCNC1)=O Chemical group C=C.BrC1=C(SC=C1)C(=O)C1C(CCNC1)=O GSUOSBNMGDBJOZ-UHFFFAOYSA-N 0.000 description 1
• WEMSECNEMGNLDE-UHFFFAOYSA-N C=C.CC1(N=C(OC1)C1=CC=C(C(=O)N2CCC(CC2)=O)C=C1)C Chemical group C=C.CC1(N=C(OC1)C1=CC=C(C(=O)N2CCC(CC2)=O)C=C1)C WEMSECNEMGNLDE-UHFFFAOYSA-N 0.000 description 1
• OYJAQIANJBUGMD-UHFFFAOYSA-N C=C.N1=NC(=CC=C1)C(=O)N1CCC(CC1)=O Chemical group C=C.N1=NC(=CC=C1)C(=O)N1CCC(CC1)=O OYJAQIANJBUGMD-UHFFFAOYSA-N 0.000 description 1
• IQOPZHHXBZYENW-UHFFFAOYSA-N C=C.N1C(=CC=C1)C(=O)N1CCC(CC1)=O Chemical group C=C.N1C(=CC=C1)C(=O)N1CCC(CC1)=O IQOPZHHXBZYENW-UHFFFAOYSA-N 0.000 description 1
• UENQKGYRJCQLLY-UHFFFAOYSA-N C=C.[N+](=O)([O-])C=1C=C(C(=O)N2CCC(CC2)=O)C=CC1 Chemical group C=C.[N+](=O)([O-])C=1C=C(C(=O)N2CCC(CC2)=O)C=CC1 UENQKGYRJCQLLY-UHFFFAOYSA-N 0.000 description 1
• JWFWJYFDTHGTTH-UHFFFAOYSA-N CS(=O)(=O)CCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 Chemical compound CS(=O)(=O)CCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 JWFWJYFDTHGTTH-UHFFFAOYSA-N 0.000 description 1
• UUWXJILVVQMLCK-UHFFFAOYSA-N CSCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 Chemical compound CSCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 UUWXJILVVQMLCK-UHFFFAOYSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• HMVXAGSYEXPIFN-UHFFFAOYSA-N Cl.C1CN(C(=O)N)CCC21N=C(N)C1=CC=CC=C1N2 Chemical compound Cl.C1CN(C(=O)N)CCC21N=C(N)C1=CC=CC=C1N2 HMVXAGSYEXPIFN-UHFFFAOYSA-N 0.000 description 1
• NRDOSHQRUYWCAY-UHFFFAOYSA-N Cl.CC1(Nc2cccc(F)c2C(N)=N1)c1ccco1 Chemical compound Cl.CC1(Nc2cccc(F)c2C(N)=N1)c1ccco1 NRDOSHQRUYWCAY-UHFFFAOYSA-N 0.000 description 1
• GBGZSNHUKJLKHI-UHFFFAOYSA-N Cl.NC1=NC2(CCN(CC2)C(=O)OC2CCCC2)Nc2cccc(F)c12 Chemical compound Cl.NC1=NC2(CCN(CC2)C(=O)OC2CCCC2)Nc2cccc(F)c12 GBGZSNHUKJLKHI-UHFFFAOYSA-N 0.000 description 1
• WZKZQZHXXWVQEI-UHFFFAOYSA-N Cl.NC1=NC2(CCN(CC2)C(=O)c2ccc(Cl)nc2)Nc2c(F)ccc(F)c12 Chemical compound Cl.NC1=NC2(CCN(CC2)C(=O)c2ccc(Cl)nc2)Nc2c(F)ccc(F)c12 WZKZQZHXXWVQEI-UHFFFAOYSA-N 0.000 description 1
• MVTLHRWLNYDXKX-UHFFFAOYSA-N Cl.NC1=NC2(CCN(CC2)C(=O)c2ccc(cc2)C#N)Nc2cccc(Cl)c12 Chemical compound Cl.NC1=NC2(CCN(CC2)C(=O)c2ccc(cc2)C#N)Nc2cccc(Cl)c12 MVTLHRWLNYDXKX-UHFFFAOYSA-N 0.000 description 1
• HQLREBMMTOOJAX-UHFFFAOYSA-N Cl.NC1=NC2(CCN(CC2)C(=O)c2cccc(N)c2)Nc2ccccc12 Chemical compound Cl.NC1=NC2(CCN(CC2)C(=O)c2cccc(N)c2)Nc2ccccc12 HQLREBMMTOOJAX-UHFFFAOYSA-N 0.000 description 1
• OGTYXNKNMYIZOO-UHFFFAOYSA-N Cl.NC1=NC2(CCN(CC2)C(=O)c2cccs2)Nc2cccc(Cl)c12 Chemical compound Cl.NC1=NC2(CCN(CC2)C(=O)c2cccs2)Nc2cccc(Cl)c12 OGTYXNKNMYIZOO-UHFFFAOYSA-N 0.000 description 1
• PTJFPXYAUYMFEZ-UHFFFAOYSA-N Cl.S1C(=NC=C1)C1NC2=CC=CC=C2C(=N1)N Chemical compound Cl.S1C(=NC=C1)C1NC2=CC=CC=C2C(=N1)N PTJFPXYAUYMFEZ-UHFFFAOYSA-N 0.000 description 1
• PCTJAEQLKCMDJX-UHFFFAOYSA-N ClC1=CC=C(OCCN2C3(N=C(C4=C(C=CC=C24)F)N)CCNCC3)C=C1 Chemical compound ClC1=CC=C(OCCN2C3(N=C(C4=C(C=CC=C24)F)N)CCNCC3)C=C1 PCTJAEQLKCMDJX-UHFFFAOYSA-N 0.000 description 1
• 208000015943 Coeliac disease Diseases 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 241000272201 Columbiformes Species 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
• 208000037487 Endotoxemia Diseases 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• 208000027445 Farmer Lung Diseases 0.000 description 1
• 208000007882 Gastritis Diseases 0.000 description 1
• 208000036495 Gastritis atrophic Diseases 0.000 description 1
• 201000005569 Gout Diseases 0.000 description 1
• 241000590002 Helicobacter pylori Species 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101001009252 Homo sapiens 2-hydroxyacyl-CoA lyase 1 Proteins 0.000 description 1
• DRAJWRKLRBNJRQ-UHFFFAOYSA-N Hydroxycarbamic acid Chemical compound ONC(O)=O DRAJWRKLRBNJRQ-UHFFFAOYSA-N 0.000 description 1
• 206010062016 Immunosuppression Diseases 0.000 description 1
• 239000003810 Jones reagent Substances 0.000 description 1
• 208000019693 Lung disease Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• NTNWOCRCBQPEKQ-YFKPBYRVSA-N N(omega)-methyl-L-arginine Chemical compound CN=C(N)NCCC[C@H](N)C(O)=O NTNWOCRCBQPEKQ-YFKPBYRVSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• FAGCRRQWCRFLFK-UHFFFAOYSA-N N1=C(C=CC=C1)CCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 Chemical compound N1=C(C=CC=C1)CCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 FAGCRRQWCRFLFK-UHFFFAOYSA-N 0.000 description 1
• UIFMUEINMFLQOH-UHFFFAOYSA-N N1=C(C=CC=C1)SCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 Chemical compound N1=C(C=CC=C1)SCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 UIFMUEINMFLQOH-UHFFFAOYSA-N 0.000 description 1
• NTNWOCRCBQPEKQ-UHFFFAOYSA-N NG-mono-methyl-L-arginine Natural products CN=C(N)NCCCC(N)C(O)=O NTNWOCRCBQPEKQ-UHFFFAOYSA-N 0.000 description 1
• 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
• 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 208000008469 Peptic Ulcer Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 108010029485 Protein Isoforms Proteins 0.000 description 1
• 102000001708 Protein Isoforms Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 208000025747 Rheumatic disease Diseases 0.000 description 1
• NWRUPSNGPWZMRW-UHFFFAOYSA-N S-ethyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carbothioate hydrochloride Chemical compound Cl.NC1=NC2(NC3=CC=CC(=C13)F)CCN(CC2)C(SCC)=O NWRUPSNGPWZMRW-UHFFFAOYSA-N 0.000 description 1
• YQZQMZBHZNUFFY-UHFFFAOYSA-N S1C(=CC=C1)CCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 Chemical compound S1C(=CC=C1)CCCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 YQZQMZBHZNUFFY-UHFFFAOYSA-N 0.000 description 1
• FPVMAKQLMGHGHN-UHFFFAOYSA-N S1C(=CC=C1)CCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 Chemical compound S1C(=CC=C1)CCN1C2(N=C(C3=C(C=CC=C13)F)N)CCNCC2 FPVMAKQLMGHGHN-UHFFFAOYSA-N 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 201000002661 Spondylitis Diseases 0.000 description 1
• 206010042496 Sunburn Diseases 0.000 description 1
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
• 206010044248 Toxic shock syndrome Diseases 0.000 description 1
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• UQIYBSYVZUNECP-UHFFFAOYSA-N [2-(4-amino-1,2-dihydroquinazolin-2-yl)phenyl]methanol;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1C1=CC=CC=C1CO UQIYBSYVZUNECP-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
• 150000008041 alkali metal carbonates Chemical class 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 150000004703 alkoxides Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 239000012080 ambient air Substances 0.000 description 1
• DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 1
• HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 1
• 210000004102 animal cell Anatomy 0.000 description 1
• YMNKUHIVVMFOFO-UHFFFAOYSA-N anthracene-9-carbaldehyde Chemical compound C1=CC=C2C(C=O)=C(C=CC=C3)C3=CC2=C1 YMNKUHIVVMFOFO-UHFFFAOYSA-N 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 208000002399 aphthous stomatitis Diseases 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 229960004405 aprotinin Drugs 0.000 description 1
• 230000002917 arthritic effect Effects 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 150000008316 benzisoxazoles Chemical class 0.000 description 1
• VLMMTGKGDOAYER-UHFFFAOYSA-N benzyl 3-oxoazetidine-1-carboxylate Chemical compound C1C(=O)CN1C(=O)OCC1=CC=CC=C1 VLMMTGKGDOAYER-UHFFFAOYSA-N 0.000 description 1
• APYSBADMUOHVGZ-UHFFFAOYSA-N benzyl 4-amino-5-fluorospiro[1h-quinazoline-2,3'-azetidine]-1'-carboxylate Chemical compound N1C2=CC=CC(F)=C2C(N)=NC1(C1)CN1C(=O)OCC1=CC=CC=C1 APYSBADMUOHVGZ-UHFFFAOYSA-N 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 206010006451 bronchitis Diseases 0.000 description 1
• 244000309464 bull Species 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
• ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
• DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• TWFZGCMQGLPBSX-UHFFFAOYSA-N carbendazim Chemical compound C1=CC=C2NC(NC(=O)OC)=NC2=C1 TWFZGCMQGLPBSX-UHFFFAOYSA-N 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 150000001728 carbonyl compounds Chemical class 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 238000005277 cation exchange chromatography Methods 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 239000012320 chlorinating reagent Substances 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 208000016644 chronic atrophic gastritis Diseases 0.000 description 1
• 238000011278 co-treatment Methods 0.000 description 1
• 201000010897 colon adenocarcinoma Diseases 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 210000000795 conjunctiva Anatomy 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• CNQZXLHXLHEYCE-UHFFFAOYSA-N cyclobutyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC1(CC1)CCN1C(=O)OC1CCC1 CNQZXLHXLHEYCE-UHFFFAOYSA-N 0.000 description 1
• VELDYOPRLMJFIK-UHFFFAOYSA-N cyclopentanecarbaldehyde Chemical compound O=CC1CCCC1 VELDYOPRLMJFIK-UHFFFAOYSA-N 0.000 description 1
• ZFQCRLNKHHXELH-UHFFFAOYSA-N cyclopentyl carbonochloridate Chemical compound ClC(=O)OC1CCCC1 ZFQCRLNKHHXELH-UHFFFAOYSA-N 0.000 description 1
• UQHKFADEQIVWID-UHFFFAOYSA-N cytokinin Natural products C1=NC=2C(NCC=C(CO)C)=NC=NC=2N1C1CC(O)C(CO)O1 UQHKFADEQIVWID-UHFFFAOYSA-N 0.000 description 1
• 239000004062 cytokinin Substances 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• QMMFVYPAHWMCMS-UHFFFAOYSA-N dimethylsulfide Substances CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 230000002183 duodenal effect Effects 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
• JVJJXFMLOQOCLY-UHFFFAOYSA-N ethene;1-(1,2-oxazole-5-carbonyl)piperidin-4-one Chemical group C=C.C=1C=NOC=1C(=O)N1CCC(=O)CC1 JVJJXFMLOQOCLY-UHFFFAOYSA-N 0.000 description 1
• BVDFLAYZQWPYID-UHFFFAOYSA-N ethene;1-(1,2-thiazole-4-carbonyl)piperidin-4-one Chemical group C=C.C1=NSC=C1C(=O)N1CCC(=O)CC1 BVDFLAYZQWPYID-UHFFFAOYSA-N 0.000 description 1
• APGAONKZPIIATI-UHFFFAOYSA-N ethene;1-(1,3-thiazole-2-carbonyl)piperidin-4-one Chemical group C=C.N=1C=CSC=1C(=O)N1CCC(=O)CC1 APGAONKZPIIATI-UHFFFAOYSA-N 0.000 description 1
• AODPQLTYXWEOCF-UHFFFAOYSA-N ethene;1-(1-methylpyrrole-2-carbonyl)piperidin-4-one Chemical group C=C.CN1C=CC=C1C(=O)N1CCC(=O)CC1 AODPQLTYXWEOCF-UHFFFAOYSA-N 0.000 description 1
• SHDMBWUMBVDZAU-UHFFFAOYSA-N ethene;1-(2-methylbenzoyl)piperidin-4-one Chemical group C=C.CC1=CC=CC=C1C(=O)N1CCC(=O)CC1 SHDMBWUMBVDZAU-UHFFFAOYSA-N 0.000 description 1
• OERRSUXBIOOMAP-UHFFFAOYSA-N ethene;1-(3-fluoro-4-methylbenzoyl)piperidin-4-one Chemical group C=C.C1=C(F)C(C)=CC=C1C(=O)N1CCC(=O)CC1 OERRSUXBIOOMAP-UHFFFAOYSA-N 0.000 description 1
• BMBYJYJXZIPXAU-UHFFFAOYSA-N ethene;1-(3-methyl-1,2,4-oxadiazol-5-yl)piperidin-4-one Chemical group C=C.CC1=NOC(N2CCC(=O)CC2)=N1 BMBYJYJXZIPXAU-UHFFFAOYSA-N 0.000 description 1
• PSZSVRKFDXIKSS-UHFFFAOYSA-N ethene;1-(3-methylbenzoyl)piperidin-4-one Chemical group C=C.CC1=CC=CC(C(=O)N2CCC(=O)CC2)=C1 PSZSVRKFDXIKSS-UHFFFAOYSA-N 0.000 description 1
• OKCDPYYFSFJZGE-UHFFFAOYSA-N ethene;1-(4-ethynylbenzoyl)piperidin-4-one Chemical group C=C.C=1C=C(C#C)C=CC=1C(=O)N1CCC(=O)CC1 OKCDPYYFSFJZGE-UHFFFAOYSA-N 0.000 description 1
• OASFKJHXFGWVDM-UHFFFAOYSA-N ethene;1-(4-methoxybenzoyl)piperidin-4-one Chemical group C=C.C1=CC(OC)=CC=C1C(=O)N1CCC(=O)CC1 OASFKJHXFGWVDM-UHFFFAOYSA-N 0.000 description 1
• YPFJSPGTCIBTTM-UHFFFAOYSA-N ethene;1-(4-methoxyphenyl)sulfonylpiperidin-4-one Chemical group C=C.C1=CC(OC)=CC=C1S(=O)(=O)N1CCC(=O)CC1 YPFJSPGTCIBTTM-UHFFFAOYSA-N 0.000 description 1
• DSMOSPRVXYXXJE-UHFFFAOYSA-N ethene;1-(4-nitrobenzoyl)piperidin-4-one Chemical group C=C.C1=CC([N+](=O)[O-])=CC=C1C(=O)N1CCC(=O)CC1 DSMOSPRVXYXXJE-UHFFFAOYSA-N 0.000 description 1
• KRRTZBHSNCUTPF-UHFFFAOYSA-N ethene;1-(4-phenoxybutanoyl)piperidin-4-one Chemical group C=C.C1CC(=O)CCN1C(=O)CCCOC1=CC=CC=C1 KRRTZBHSNCUTPF-UHFFFAOYSA-N 0.000 description 1
• PKXOQXZRKSJRBN-UHFFFAOYSA-N ethene;1-(4-propylbenzoyl)piperidin-4-one Chemical group C=C.C1=CC(CCC)=CC=C1C(=O)N1CCC(=O)CC1 PKXOQXZRKSJRBN-UHFFFAOYSA-N 0.000 description 1
• CXJWAWRGZZRFME-UHFFFAOYSA-N ethene;1-(5-ethylthiophene-2-carbonyl)piperidin-4-one Chemical group C=C.S1C(CC)=CC=C1C(=O)N1CCC(=O)CC1 CXJWAWRGZZRFME-UHFFFAOYSA-N 0.000 description 1
• AYFHNVHEXNLTLH-UHFFFAOYSA-N ethene;1-(furan-2-carbonyl)piperidin-4-one Chemical group C=C.C=1C=COC=1C(=O)N1CCC(=O)CC1 AYFHNVHEXNLTLH-UHFFFAOYSA-N 0.000 description 1
• PDSNLTBSIGMLBT-UHFFFAOYSA-N ethene;1-(pyrazine-2-carbonyl)piperidin-4-one Chemical group C=C.C=1N=CC=NC=1C(=O)N1CCC(=O)CC1 PDSNLTBSIGMLBT-UHFFFAOYSA-N 0.000 description 1
• AIQKBXLIUVJLEZ-UHFFFAOYSA-N ethene;1-(pyridine-3-carbonyl)piperidin-4-one Chemical group C=C.C=1C=CN=CC=1C(=O)N1CCC(=O)CC1 AIQKBXLIUVJLEZ-UHFFFAOYSA-N 0.000 description 1
• CIKFHKSUUODVSH-UHFFFAOYSA-N ethene;1-(pyridine-4-carbonyl)piperidin-4-one Chemical group C=C.C=1C=NC=CC=1C(=O)N1CCC(=O)CC1 CIKFHKSUUODVSH-UHFFFAOYSA-N 0.000 description 1
• XDLFKQHBABRNEL-UHFFFAOYSA-N ethene;1-(quinoline-6-carbonyl)piperidin-4-one Chemical group C=C.C=1C=C2N=CC=CC2=CC=1C(=O)N1CCC(=O)CC1 XDLFKQHBABRNEL-UHFFFAOYSA-N 0.000 description 1
• KJSAOZFDDPEIJY-UHFFFAOYSA-N ethene;1-(thiadiazole-4-carbonyl)piperidin-4-one Chemical group C=C.C=1SN=NC=1C(=O)N1CCC(=O)CC1 KJSAOZFDDPEIJY-UHFFFAOYSA-N 0.000 description 1
• IITNFIUMULLYHV-UHFFFAOYSA-N ethene;1-(thiophene-3-carbonyl)piperidin-4-one Chemical group C=C.C1=CSC=C1C(=O)N1CCC(=O)CC1 IITNFIUMULLYHV-UHFFFAOYSA-N 0.000 description 1
• CEDUXMLMMXWWHA-UHFFFAOYSA-N ethene;1-[4-(1,3-thiazol-2-yl)benzoyl]piperidin-4-one Chemical group C=C.C=1C=C(C=2SC=CN=2)C=CC=1C(=O)N1CCC(=O)CC1 CEDUXMLMMXWWHA-UHFFFAOYSA-N 0.000 description 1
• SWIOXQZHVKBKET-UHFFFAOYSA-N ethene;1-[4-(thiadiazol-4-yl)benzoyl]piperidin-4-one Chemical group C=C.C=1C=C(C=2N=NSC=2)C=CC=1C(=O)N1CCC(=O)CC1 SWIOXQZHVKBKET-UHFFFAOYSA-N 0.000 description 1
• QXMSHHHPLKYZEY-UHFFFAOYSA-N ethene;1-[4-(trifluoromethyl)benzoyl]piperidin-4-one Chemical group C=C.C1=CC(C(F)(F)F)=CC=C1C(=O)N1CCC(=O)CC1 QXMSHHHPLKYZEY-UHFFFAOYSA-N 0.000 description 1
• XVXMWNSTEXGXQG-UHFFFAOYSA-N ethene;1-methylsulfonylpiperidin-4-one Chemical group C=C.CS(=O)(=O)N1CCC(=O)CC1 XVXMWNSTEXGXQG-UHFFFAOYSA-N 0.000 description 1
• MKNHREGIVSEAEZ-UHFFFAOYSA-N ethene;4-(4-oxopiperidine-1-carbonyl)benzoic acid Chemical group C=C.C1=CC(C(=O)O)=CC=C1C(=O)N1CCC(=O)CC1 MKNHREGIVSEAEZ-UHFFFAOYSA-N 0.000 description 1
• KKQINOOHMLPYSW-UHFFFAOYSA-N ethene;[4-(4-oxopiperidine-1-carbonyl)phenyl] acetate Chemical group C=C.C1=CC(OC(=O)C)=CC=C1C(=O)N1CCC(=O)CC1 KKQINOOHMLPYSW-UHFFFAOYSA-N 0.000 description 1
• PUWORZUAVYTLGN-UHFFFAOYSA-N ethene;propyl 4-oxopiperidine-1-carboxylate Chemical group C=C.CCCOC(=O)N1CCC(=O)CC1 PUWORZUAVYTLGN-UHFFFAOYSA-N 0.000 description 1
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
• LGMBPXNKYBDWEK-UHFFFAOYSA-N ethyl 2-(4-amino-1,2-dihydroquinazolin-2-yl)pyrrole-1-carboxylate;hydrochloride Chemical compound Cl.CCOC(=O)N1C=CC=C1C1N=C(N)C2=CC=CC=C2N1 LGMBPXNKYBDWEK-UHFFFAOYSA-N 0.000 description 1
• AQCCUQNJHACLSY-UHFFFAOYSA-N ethyl 3-hydroxypyrrolidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(O)C1 AQCCUQNJHACLSY-UHFFFAOYSA-N 0.000 description 1
• VWQXCLBFGRMQJC-UHFFFAOYSA-N ethyl 3-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCCC(=O)C1 VWQXCLBFGRMQJC-UHFFFAOYSA-N 0.000 description 1
• GMSQWLPSYYHCMA-UHFFFAOYSA-N ethyl 4-amino-5-fluorospiro[1h-quinazoline-2,3'-azetidine]-1'-carboxylate Chemical compound C1N(C(=O)OCC)CC21N=C(N)C1=C(F)C=CC=C1N2 GMSQWLPSYYHCMA-UHFFFAOYSA-N 0.000 description 1
• WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
• LBLQPBVEGKLIEU-UHFFFAOYSA-N ethyl n-(2,2-dimethoxyethyl)carbamate Chemical compound CCOC(=O)NCC(OC)OC LBLQPBVEGKLIEU-UHFFFAOYSA-N 0.000 description 1
• UQJINKCNWOCKBP-UHFFFAOYSA-N ethyl n-(3,3-diethoxypropyl)carbamate Chemical compound CCOC(OCC)CCNC(=O)OCC UQJINKCNWOCKBP-UHFFFAOYSA-N 0.000 description 1
• LXBPPQVMUJBPOF-UHFFFAOYSA-N ethyl n-(4,4-diethoxybutyl)carbamate Chemical compound CCOC(OCC)CCCNC(=O)OCC LXBPPQVMUJBPOF-UHFFFAOYSA-N 0.000 description 1
• 208000022195 farmer lung disease Diseases 0.000 description 1
• 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 1
• 239000011714 flavin adenine dinucleotide Substances 0.000 description 1
• VWWQXMAJTJZDQX-UYBVJOGSSA-N flavin adenine dinucleotide Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1CO[P@](O)(=O)O[P@@](O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 VWWQXMAJTJZDQX-UYBVJOGSSA-N 0.000 description 1
• 229940093632 flavin-adenine dinucleotide Drugs 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 208000007565 gingivitis Diseases 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 229940037467 helicobacter pylori Drugs 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• RIAYWTDPRLAWMC-UHFFFAOYSA-N hex-5-ynyl 4-amino-5-fluorospiro[1h-quinazoline-2,4'-piperidine]-1'-carboxylate;hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCN(C(=O)OCCCCC#C)CC2 RIAYWTDPRLAWMC-UHFFFAOYSA-N 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 230000001506 immunosuppresive effect Effects 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• NIZHERJWXFHGGU-UHFFFAOYSA-N isocyanato(trimethyl)silane Chemical compound C[Si](C)(C)N=C=O NIZHERJWXFHGGU-UHFFFAOYSA-N 0.000 description 1
• 208000018937 joint inflammation Diseases 0.000 description 1
• 231100001231 less toxic Toxicity 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 229910001507 metal halide Inorganic materials 0.000 description 1
• 150000005309 metal halides Chemical class 0.000 description 1
• HOEOMWYFJBSYSF-UHFFFAOYSA-N methyl 4-oxopiperidine-1-carboxylate Chemical compound COC(=O)N1CCC(=O)CC1 HOEOMWYFJBSYSF-UHFFFAOYSA-N 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• LCEDQNDDFOCWGG-UHFFFAOYSA-N morpholine-4-carbaldehyde Chemical compound O=CN1CCOCC1 LCEDQNDDFOCWGG-UHFFFAOYSA-N 0.000 description 1
• FJCTXRUXNHHDBP-UHFFFAOYSA-N n-(2-cyano-3-fluorophenyl)-2,2,2-trifluoro-n-methylacetamide Chemical compound FC(F)(F)C(=O)N(C)C1=CC=CC(F)=C1C#N FJCTXRUXNHHDBP-UHFFFAOYSA-N 0.000 description 1
• RFVOSBSFWBBUPY-UHFFFAOYSA-N n-(2-cyano-3-fluorophenyl)-2,2,2-trifluoroacetamide Chemical compound FC1=CC=CC(NC(=O)C(F)(F)F)=C1C#N RFVOSBSFWBBUPY-UHFFFAOYSA-N 0.000 description 1
• FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• FEPDUICSEXXGTR-UHFFFAOYSA-N pent-4-ynyl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.N1C2=CC=CC(F)=C2C(N)=NC21CCN(C(=O)OCCCC#C)CC2 FEPDUICSEXXGTR-UHFFFAOYSA-N 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• 229960005323 phenoxyethanol Drugs 0.000 description 1
• VFLAYLGDFSYTBK-UHFFFAOYSA-N phenyl 4-aminospiro[1h-quinazoline-2,4'-piperidine]-1'-carboxylate;hydrochloride Chemical compound Cl.N1C2=CC=CC=C2C(N)=NC1(CC1)CCN1C(=O)OC1=CC=CC=C1 VFLAYLGDFSYTBK-UHFFFAOYSA-N 0.000 description 1
• 125000005544 phthalimido group Chemical group 0.000 description 1
• LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 150000003138 primary alcohols Chemical class 0.000 description 1
• CPZIHAKODXKSMZ-UHFFFAOYSA-N propan-2-yl 4-amino-5-fluorospiro[1H-quinazoline-2,4'-piperidine]-1'-carboxylate hydrochloride Chemical compound Cl.C1CN(C(=O)OC(C)C)CCC21N=C(N)C1=C(F)C=CC=C1N2 CPZIHAKODXKSMZ-UHFFFAOYSA-N 0.000 description 1
• PQBPTUPEFJIEPC-UHFFFAOYSA-N propan-2-yl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)OC(=O)N1CCC(=O)CC1 PQBPTUPEFJIEPC-UHFFFAOYSA-N 0.000 description 1
• QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 230000000552 rheumatic effect Effects 0.000 description 1
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
• QCMHWZUFWLOOGI-UHFFFAOYSA-N s-ethyl chloromethanethioate Chemical compound CCSC(Cl)=O QCMHWZUFWLOOGI-UHFFFAOYSA-N 0.000 description 1
• 239000012266 salt solution Substances 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• KQQPGVCGJPTZDV-UHFFFAOYSA-N spiro[1h-quinazoline-2,4'-piperidine]-4-amine;dihydrochloride Chemical compound Cl.Cl.N1C2=CC=CC=C2C(N)=NC21CCNCC2 KQQPGVCGJPTZDV-UHFFFAOYSA-N 0.000 description 1
• 239000001119 stannous chloride Substances 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• DRDVJQOGFWAVLH-UHFFFAOYSA-N tert-butyl n-hydroxycarbamate Chemical compound CC(C)(C)OC(=O)NO DRDVJQOGFWAVLH-UHFFFAOYSA-N 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• VJCHUDDPWPQOLH-UHFFFAOYSA-N trimethyl(1,3-thiazol-2-yl)silane Chemical compound C[Si](C)(C)C1=NC=CS1 VJCHUDDPWPQOLH-UHFFFAOYSA-N 0.000 description 1
• DZJXLMSJAUYLCS-UHFFFAOYSA-N trimethyl(1,3-thiazol-2-yl)stannane Chemical compound C[Sn](C)(C)C1=NC=CS1 DZJXLMSJAUYLCS-UHFFFAOYSA-N 0.000 description 1
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
• 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1