JP6609253B2 - シアノチオフェン誘導体 - Google Patents
シアノチオフェン誘導体 Download PDFInfo
- Publication number
- JP6609253B2 JP6609253B2 JP2016540227A JP2016540227A JP6609253B2 JP 6609253 B2 JP6609253 B2 JP 6609253B2 JP 2016540227 A JP2016540227 A JP 2016540227A JP 2016540227 A JP2016540227 A JP 2016540227A JP 6609253 B2 JP6609253 B2 JP 6609253B2
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- compound
- mixture
- group
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical class N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 416
- -1 cyano, carboxy carbonyl Chemical group 0.000 claims description 235
- 125000000217 alkyl group Chemical group 0.000 claims description 133
- 125000001424 substituent group Chemical group 0.000 claims description 74
- 125000003545 alkoxy group Chemical group 0.000 claims description 52
- 150000003839 salts Chemical class 0.000 claims description 47
- 125000002947 alkylene group Chemical group 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 32
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 29
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
- 125000002252 acyl group Chemical group 0.000 claims description 21
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 19
- 206010047700 Vomiting Diseases 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 229940034982 antineoplastic agent Drugs 0.000 claims description 17
- 239000002246 antineoplastic agent Substances 0.000 claims description 17
- 125000004423 acyloxy group Chemical group 0.000 claims description 15
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 14
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 13
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 12
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000003431 oxalo group Chemical group 0.000 claims description 8
- 125000004755 (C2-C7) acylamino group Chemical group 0.000 claims description 7
- 229910005965 SO 2 Inorganic materials 0.000 claims description 7
- 125000005195 alkyl amino carbonyloxy group Chemical group 0.000 claims description 7
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 7
- 230000027455 binding Effects 0.000 claims description 6
- 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 5
- 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 230000006315 carbonylation Effects 0.000 claims description 2
- 238000005810 carbonylation reaction Methods 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 795
- 239000000203 mixture Substances 0.000 description 314
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 291
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 225
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 216
- 239000011541 reaction mixture Substances 0.000 description 214
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 209
- 230000002829 reductive effect Effects 0.000 description 204
- 239000000243 solution Substances 0.000 description 188
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 178
- 238000006243 chemical reaction Methods 0.000 description 164
- 239000012442 inert solvent Substances 0.000 description 158
- 238000000034 method Methods 0.000 description 144
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 134
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 129
- 239000012044 organic layer Substances 0.000 description 127
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 109
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 106
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 103
- 239000012043 crude product Substances 0.000 description 101
- 238000010898 silica gel chromatography Methods 0.000 description 101
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 99
- 230000008569 process Effects 0.000 description 98
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 90
- 239000002904 solvent Substances 0.000 description 84
- 239000002994 raw material Substances 0.000 description 83
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 81
- 230000035484 reaction time Effects 0.000 description 80
- 238000010992 reflux Methods 0.000 description 80
- 239000012156 elution solvent Substances 0.000 description 77
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 68
- 239000002585 base Substances 0.000 description 66
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 60
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 57
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- 239000012046 mixed solvent Substances 0.000 description 47
- 239000012298 atmosphere Substances 0.000 description 46
- 238000001816 cooling Methods 0.000 description 44
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 43
- 229920006395 saturated elastomer Polymers 0.000 description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 36
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 34
- 235000017557 sodium bicarbonate Nutrition 0.000 description 34
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 34
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 239000003480 eluent Substances 0.000 description 32
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 29
- 239000007789 gas Substances 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- 229910052786 argon Inorganic materials 0.000 description 24
- 239000003795 chemical substances by application Substances 0.000 description 24
- 239000000725 suspension Substances 0.000 description 23
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 21
- 238000004519 manufacturing process Methods 0.000 description 21
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 20
- 239000002253 acid Substances 0.000 description 20
- 150000001412 amines Chemical class 0.000 description 20
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 20
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 20
- 229910052739 hydrogen Inorganic materials 0.000 description 20
- 239000001257 hydrogen Substances 0.000 description 20
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 20
- 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 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 18
- 238000007327 hydrogenolysis reaction Methods 0.000 description 18
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 17
- 239000003054 catalyst Substances 0.000 description 17
- 230000008859 change Effects 0.000 description 17
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 17
- 238000005903 acid hydrolysis reaction Methods 0.000 description 16
- 239000003638 chemical reducing agent Substances 0.000 description 16
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical class CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 16
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 15
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
- 230000002378 acidificating effect Effects 0.000 description 15
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 14
- 229910000024 caesium carbonate Inorganic materials 0.000 description 14
- 238000005859 coupling reaction Methods 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- ATALOFNDEOCMKK-OITMNORJSA-N aprepitant Chemical compound O([C@@H]([C@@H]1C=2C=CC(F)=CC=2)O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1CC1=NNC(=O)N1 ATALOFNDEOCMKK-OITMNORJSA-N 0.000 description 12
- 229960001372 aprepitant Drugs 0.000 description 12
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 12
- 238000010531 catalytic reduction reaction Methods 0.000 description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 11
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 10
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 10
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
- 239000000654 additive Substances 0.000 description 10
- BLEBFDYUDVZRFG-UHFFFAOYSA-N dichloromethane;propan-2-ol Chemical compound ClCCl.CC(C)O BLEBFDYUDVZRFG-UHFFFAOYSA-N 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 239000012279 sodium borohydride Substances 0.000 description 10
- 229910000033 sodium borohydride Inorganic materials 0.000 description 10
- 229910000029 sodium carbonate Inorganic materials 0.000 description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
- 229910052801 chlorine Inorganic materials 0.000 description 9
- 125000001309 chloro group Chemical group Cl* 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 229910052740 iodine Inorganic materials 0.000 description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 8
- 150000001336 alkenes Chemical class 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 239000011259 mixed solution Substances 0.000 description 8
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 8
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 125000003944 tolyl group Chemical group 0.000 description 8
- 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 8
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 150000001728 carbonyl compounds Chemical class 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- 239000012448 Lithium borohydride Substances 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- DSVGQVZAZSZEEX-UHFFFAOYSA-N [C].[Pt] Chemical compound [C].[Pt] DSVGQVZAZSZEEX-UHFFFAOYSA-N 0.000 description 6
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 230000000069 prophylactic effect Effects 0.000 description 6
- 235000009518 sodium iodide Nutrition 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- 150000008065 acid anhydrides Chemical class 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 239000003513 alkali Substances 0.000 description 5
- 150000001350 alkyl halides Chemical class 0.000 description 5
- 238000005576 amination reaction Methods 0.000 description 5
- 238000006482 condensation reaction Methods 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000008406 drug-drug interaction Effects 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 5
- UKJFVOWPUXSBOM-UHFFFAOYSA-N hexane;oxolane Chemical compound C1CCOC1.CCCCCC UKJFVOWPUXSBOM-UHFFFAOYSA-N 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 5
- 230000003449 preventive effect Effects 0.000 description 5
- 230000008673 vomiting Effects 0.000 description 5
- PKDPUENCROCRCH-UHFFFAOYSA-N 1-piperazin-1-ylethanone Chemical compound CC(=O)N1CCNCC1 PKDPUENCROCRCH-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
- 239000012346 acetyl chloride Substances 0.000 description 4
- 150000001345 alkine derivatives Chemical class 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 4
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 4
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 4
- 235000011056 potassium acetate Nutrition 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000002464 receptor antagonist Substances 0.000 description 4
- 229940044551 receptor antagonist Drugs 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 229940076279 serotonin Drugs 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
- HVHZEKKZMFRULH-UHFFFAOYSA-N 2,6-ditert-butyl-4-methylpyridine Chemical compound CC1=CC(C(C)(C)C)=NC(C(C)(C)C)=C1 HVHZEKKZMFRULH-UHFFFAOYSA-N 0.000 description 3
- TUJWGDXCTRWVDC-UHFFFAOYSA-N 2-diethoxyphosphorylethyl acetate Chemical compound CCOP(=O)(OCC)CCOC(C)=O TUJWGDXCTRWVDC-UHFFFAOYSA-N 0.000 description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- 102100024304 Protachykinin-1 Human genes 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 239000002111 antiemetic agent Substances 0.000 description 3
- XGGTZCKQRWXCHW-WMTVXVAQSA-N casopitant Chemical compound C1([C@H]2C[C@H](CCN2C(=O)N(C)[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)N2CCN(CC2)C(C)=O)=CC=C(F)C=C1C XGGTZCKQRWXCHW-WMTVXVAQSA-N 0.000 description 3
- 229960003778 casopitant Drugs 0.000 description 3
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 3
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 3
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 description 3
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 3
- JIWAALDUIFCBLV-UHFFFAOYSA-N oxoosmium Chemical compound [Os]=O JIWAALDUIFCBLV-UHFFFAOYSA-N 0.000 description 3
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- SRJOCJYGOFTFLH-UHFFFAOYSA-M piperidine-4-carboxylate Chemical compound [O-]C(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-M 0.000 description 3
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
- NJORMFNJZLXLCN-UHFFFAOYSA-N tert-butyl 4-(2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate Chemical compound CCOC(=O)C=C1CCN(C(=O)OC(C)(C)C)CC1 NJORMFNJZLXLCN-UHFFFAOYSA-N 0.000 description 3
- PMLBUVZPRKXMOX-UHFFFAOYSA-N tert-butyl 4-oxoazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(=O)CC1 PMLBUVZPRKXMOX-UHFFFAOYSA-N 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 229910052720 vanadium Inorganic materials 0.000 description 3
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 3
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 2
- XPNMCDYOYIKVGB-CONSDPRKSA-N (2s,3s)-2-benzhydryl-n-[(2-methoxy-5-propan-2-ylphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine Chemical compound COC1=CC=C(C(C)C)C=C1CN[C@@H]1[C@H](C(C=2C=CC=CC=2)C=2C=CC=CC=2)N2CCC1CC2 XPNMCDYOYIKVGB-CONSDPRKSA-N 0.000 description 2
- XILNRORTJVDYRH-HKUYNNGSSA-N (2s,3s)-n-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenylpiperidin-3-amine Chemical compound C1([C@@H]2NCCC[C@@H]2NCC2=CC(=CC=C2OC)N2C(=NN=N2)C(F)(F)F)=CC=CC=C1 XILNRORTJVDYRH-HKUYNNGSSA-N 0.000 description 2
- IQMLIVUHMSIOQP-UHFFFAOYSA-N (4-fluoro-2-methylphenyl)boronic acid Chemical compound CC1=CC(F)=CC=C1B(O)O IQMLIVUHMSIOQP-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 2
- PMDHIMMPXRSDML-UHFFFAOYSA-N 2-methylpyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC=N1 PMDHIMMPXRSDML-UHFFFAOYSA-N 0.000 description 2
- UYTPDZISLVQNTP-UHFFFAOYSA-N 2-piperidin-4-ylethyl acetate Chemical compound CC(=O)OCCC1CCNCC1 UYTPDZISLVQNTP-UHFFFAOYSA-N 0.000 description 2
- OGPXXRPXGBEGKN-VEIFNGETSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CC[C@H](C3)N)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F.Cl Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CC[C@H](C3)N)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F.Cl OGPXXRPXGBEGKN-VEIFNGETSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 2
- 108010000543 Cytochrome P-450 CYP2C9 Proteins 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 2
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 2
- 102100029358 Cytochrome P450 2C9 Human genes 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 208000031649 Postoperative Nausea and Vomiting Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 101800003906 Substance P Proteins 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- VZOVOHRDLOYBJX-UHFFFAOYSA-N benzyl 4-oxopiperidine-1-carboxylate Chemical compound C1CC(=O)CCN1C(=O)OCC1=CC=CC=C1 VZOVOHRDLOYBJX-UHFFFAOYSA-N 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 description 2
- NZNMSOFKMUBTKW-UHFFFAOYSA-M cyclohexanecarboxylate Chemical compound [O-]C(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-M 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- IHSUFLCKRIHFGY-UHFFFAOYSA-N ethyl 2-piperidin-4-ylacetate Chemical compound CCOC(=O)CC1CCNCC1 IHSUFLCKRIHFGY-UHFFFAOYSA-N 0.000 description 2
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 229950000331 ezlopitant Drugs 0.000 description 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000006138 lithiation reaction Methods 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 2
- AEZHUDXZHNLVKG-UHFFFAOYSA-N methyl 2-(4-oxocyclohexyl)acetate Chemical compound COC(=O)CC1CCC(=O)CC1 AEZHUDXZHNLVKG-UHFFFAOYSA-N 0.000 description 2
- ZQWPRMPSCMSAJU-UHFFFAOYSA-N methyl cyclohexanecarboxylate Chemical compound COC(=O)C1CCCCC1 ZQWPRMPSCMSAJU-UHFFFAOYSA-N 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- HDCCJUCOIKLZNM-ZCFIWIBFSA-N n-[(3r)-pyrrolidin-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1CCNC1 HDCCJUCOIKLZNM-ZCFIWIBFSA-N 0.000 description 2
- SFMJNHNUOVADRW-UHFFFAOYSA-N n-[5-[9-[4-(methanesulfonamido)phenyl]-2-oxobenzo[h][1,6]naphthyridin-1-yl]-2-methylphenyl]prop-2-enamide Chemical compound C1=C(NC(=O)C=C)C(C)=CC=C1N1C(=O)C=CC2=C1C1=CC(C=3C=CC(NS(C)(=O)=O)=CC=3)=CC=C1N=C2 SFMJNHNUOVADRW-UHFFFAOYSA-N 0.000 description 2
- WAXQNWCZJDTGBU-UHFFFAOYSA-N netupitant Chemical compound C=1N=C(N2CCN(C)CC2)C=C(C=2C(=CC=CC=2)C)C=1N(C)C(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WAXQNWCZJDTGBU-UHFFFAOYSA-N 0.000 description 2
- 229960005163 netupitant Drugs 0.000 description 2
- BYEVBITUADOIGY-UHFFFAOYSA-N nonanoic acid ethyl ester Natural products CCCCCCCCC(=O)OCC BYEVBITUADOIGY-UHFFFAOYSA-N 0.000 description 2
- 238000006772 olefination reaction Methods 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 2
- IIKFXOLJMNWWCH-UHFFFAOYSA-N piperidine-1,4-dicarboxylic acid Chemical compound OC(=O)C1CCN(C(O)=O)CC1 IIKFXOLJMNWWCH-UHFFFAOYSA-N 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
- NSILYQWHARROMG-UHFFFAOYSA-N tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC(CO)C1 NSILYQWHARROMG-UHFFFAOYSA-N 0.000 description 2
- DQQJBEAXSOOCPG-SSDOTTSWSA-N tert-butyl n-[(3r)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCNC1 DQQJBEAXSOOCPG-SSDOTTSWSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 150000003577 thiophenes Chemical class 0.000 description 2
- 150000003606 tin compounds Chemical class 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 2
- 229950005485 vofopitant Drugs 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 1
- SBBYBXSFWOLDDG-JLTOFOAXSA-N (2s)-n-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-(4-fluoro-2-methylphenyl)-n-methylpiperazine-1-carboxamide Chemical compound C1([C@H]2CNCCN2C(=O)N(C)[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=CC=C(F)C=C1C SBBYBXSFWOLDDG-JLTOFOAXSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- NOLMGELTBIIGOL-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]dec-7-en-8-yl trifluoromethanesulfonate Chemical compound C1CC(OS(=O)(=O)C(F)(F)F)=CCC21OCCO2 NOLMGELTBIIGOL-UHFFFAOYSA-N 0.000 description 1
- VKRKCBWIVLSRBJ-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-8-one Chemical compound C1CC(=O)CCC21OCCO2 VKRKCBWIVLSRBJ-UHFFFAOYSA-N 0.000 description 1
- YIWGJFPJRAEKMK-UHFFFAOYSA-N 1-(2H-benzotriazol-5-yl)-3-methyl-8-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carbonyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione Chemical compound CN1C(=O)N(c2ccc3n[nH]nc3c2)C2(CCN(CC2)C(=O)c2cnc(NCc3cccc(OC(F)(F)F)c3)nc2)C1=O YIWGJFPJRAEKMK-UHFFFAOYSA-N 0.000 description 1
- IUAFKLWCODTXIO-UHFFFAOYSA-N 1-(4-prop-2-ynylpiperazin-1-yl)ethanone Chemical compound CC(=O)N1CCN(CC#C)CC1 IUAFKLWCODTXIO-UHFFFAOYSA-N 0.000 description 1
- RZQHJTNUKFLYEA-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]azepane-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCCC(C(O)=O)CC1 RZQHJTNUKFLYEA-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
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 1
- BRXKHIPPSTYCKO-MRVPVSSYSA-N 1-o-tert-butyl 2-o-methyl (2r)-piperazine-1,2-dicarboxylate Chemical compound COC(=O)[C@H]1CNCCN1C(=O)OC(C)(C)C BRXKHIPPSTYCKO-MRVPVSSYSA-N 0.000 description 1
- BRXKHIPPSTYCKO-UHFFFAOYSA-N 1-o-tert-butyl 2-o-methyl piperazine-1,2-dicarboxylate Chemical compound COC(=O)C1CNCCN1C(=O)OC(C)(C)C BRXKHIPPSTYCKO-UHFFFAOYSA-N 0.000 description 1
- YCXCRFGBFZTUSU-UHFFFAOYSA-N 1-o-tert-butyl 3-o-ethyl piperidine-1,3-dicarboxylate Chemical compound CCOC(=O)C1CCCN(C(=O)OC(C)(C)C)C1 YCXCRFGBFZTUSU-UHFFFAOYSA-N 0.000 description 1
- LYYJQMCPEHXOEW-UHFFFAOYSA-N 1-o-tert-butyl 3-o-methyl piperidine-1,3-dicarboxylate Chemical compound COC(=O)C1CCCN(C(=O)OC(C)(C)C)C1 LYYJQMCPEHXOEW-UHFFFAOYSA-N 0.000 description 1
- BGYFVOHWJYYBER-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl azepane-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCCN(C(=O)OC(C)(C)C)CC1 BGYFVOHWJYYBER-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- ZKMZMDVFKFXHKK-UHFFFAOYSA-N 2,3,4,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-6-one;hydrochloride Chemical compound Cl.C1NCCN2C(=O)CCC21 ZKMZMDVFKFXHKK-UHFFFAOYSA-N 0.000 description 1
- JCHWHOHZZYWUMP-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C(CC1)=CCC21OCCO2 JCHWHOHZZYWUMP-UHFFFAOYSA-N 0.000 description 1
- TXUGEISFHODXQL-UHFFFAOYSA-N 2-(1,4-dioxaspiro[4.5]decan-8-yl)ethanol Chemical compound C1CC(CCO)CCC21OCCO2 TXUGEISFHODXQL-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- ORLKRFYFNMCQIG-UHFFFAOYSA-N 2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoic acid Chemical compound OC(=O)C(C)(C)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 ORLKRFYFNMCQIG-UHFFFAOYSA-N 0.000 description 1
- CUHRIRXNRTVEOH-UHFFFAOYSA-N 2-aminoacetic acid;chloroethane Chemical compound CCCl.NCC(O)=O CUHRIRXNRTVEOH-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- QNDPJPULQTYCSY-UHFFFAOYSA-N 3-(1,4-dioxaspiro[4.5]decan-8-yl)propanoic acid Chemical compound OC(=O)CCC1CCC2(CC1)OCCO2 QNDPJPULQTYCSY-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- XJLDYKIEURAVBW-UHFFFAOYSA-N 3-decanone Chemical compound CCCCCCCC(=O)CC XJLDYKIEURAVBW-UHFFFAOYSA-N 0.000 description 1
- HTNUUDFQRYBJPH-UHFFFAOYSA-N 3-methoxypropanehydrazide Chemical compound COCCC(=O)NN HTNUUDFQRYBJPH-UHFFFAOYSA-N 0.000 description 1
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 description 1
- TTWDSNLYYKPTCC-UHFFFAOYSA-N 4-(2-ethoxy-2-oxoethylidene)-3-methylpiperidine-1-carboxylic acid Chemical class C(C)OC(=O)C=C1C(CN(CC1)C(=O)O)C TTWDSNLYYKPTCC-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- MPAQGNXNNJFYRB-UHFFFAOYSA-N 6-azaspiro[2.5]octane-2,6-dicarboxylic acid Chemical compound OC(=O)C1CC11CCN(C(O)=O)CC1 MPAQGNXNNJFYRB-UHFFFAOYSA-N 0.000 description 1
- NVZWMJWMTWOVNJ-UHFFFAOYSA-N 6-azaspiro[3.4]octane Chemical compound C1CCC21CNCC2 NVZWMJWMTWOVNJ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- MOVWIWCHDAQELU-UHFFFAOYSA-N C(C)Cl.COCC1(CNCCC1)C(=O)O Chemical compound C(C)Cl.COCC1(CNCCC1)C(=O)O MOVWIWCHDAQELU-UHFFFAOYSA-N 0.000 description 1
- UJWAIQJBXVJKBJ-UHFFFAOYSA-N C1CNCCC1CCN=C=O Chemical compound C1CNCCC1CCN=C=O UJWAIQJBXVJKBJ-UHFFFAOYSA-N 0.000 description 1
- PAGKYQOBMNJMKC-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3(CCN(CC3)C)O)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3(CCN(CC3)C)O)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F PAGKYQOBMNJMKC-UHFFFAOYSA-N 0.000 description 1
- VRGFARZPRFHDEX-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3(CCN(CC3)CC(=O)O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3(CCN(CC3)CC(=O)O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F VRGFARZPRFHDEX-UHFFFAOYSA-N 0.000 description 1
- SGYALVDFLWPJFK-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3(CCN(CC3)CC4=NNC(=O)N4)O)C#N)N(C)C(=O)C(C)(C)C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3(CCN(CC3)CC4=NNC(=O)N4)O)C#N)N(C)C(=O)C(C)(C)C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F SGYALVDFLWPJFK-UHFFFAOYSA-N 0.000 description 1
- GZRIEWLYRAIDRG-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3(CCNCC3)O)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3(CCNCC3)O)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F GZRIEWLYRAIDRG-UHFFFAOYSA-N 0.000 description 1
- SRQVMSUYBZVKKK-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3=CCC(CC3)CC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3=CCC(CC3)CC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F SRQVMSUYBZVKKK-UHFFFAOYSA-N 0.000 description 1
- VKYSYIUXNMWQJE-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3=CCC(CC3)OC(=O)C)C#N)CNCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3=CCC(CC3)OC(=O)C)C#N)CNCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F VKYSYIUXNMWQJE-UHFFFAOYSA-N 0.000 description 1
- FVEOLPPTQICFAS-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3=CCC4(CC3)OCCO4)C#N)N(C)C(=O)C(C)(C)C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3=CCC4(CC3)OCCO4)C#N)N(C)C(=O)C(C)(C)C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F FVEOLPPTQICFAS-UHFFFAOYSA-N 0.000 description 1
- GUJJRQXHQKTWDT-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3CCC(=O)CC3)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3CCC(=O)CC3)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F GUJJRQXHQKTWDT-UHFFFAOYSA-N 0.000 description 1
- FDVJDVAIELFECQ-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3CCC(CC3)CC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3CCC(CC3)CC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F FDVJDVAIELFECQ-UHFFFAOYSA-N 0.000 description 1
- VAKCAMMDWLRWKQ-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3CCC(CC3)CCO)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3CCC(CC3)CCO)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F VAKCAMMDWLRWKQ-UHFFFAOYSA-N 0.000 description 1
- VZGYXARUUCUPQS-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3CCNCC3)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)C3CCNCC3)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F VZGYXARUUCUPQS-UHFFFAOYSA-N 0.000 description 1
- FIMRJXHQPYMYMH-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CC3(CCN(CC3)C(=O)C)C(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CC3(CCN(CC3)C(=O)C)C(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F FIMRJXHQPYMYMH-UHFFFAOYSA-N 0.000 description 1
- WFDMEMBBQMMUGP-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(=O)CC3)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(=O)CC3)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F WFDMEMBBQMMUGP-UHFFFAOYSA-N 0.000 description 1
- ULLLOCAMVRUPTO-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)CC(=O)N)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)CC(=O)N)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F ULLLOCAMVRUPTO-UHFFFAOYSA-N 0.000 description 1
- IFHNUCUTNLFYJT-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)CC(=O)NS(=O)(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)CC(=O)NS(=O)(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F IFHNUCUTNLFYJT-UHFFFAOYSA-N 0.000 description 1
- BYACRDIFFPVYKC-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)CN)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F.Cl Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)CN)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F.Cl BYACRDIFFPVYKC-UHFFFAOYSA-N 0.000 description 1
- ZVXPJYGARGZFJJ-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)CNC(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)CNC(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F ZVXPJYGARGZFJJ-UHFFFAOYSA-N 0.000 description 1
- NRHCAPZETXGOIO-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)O)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCC(CC3)O)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F NRHCAPZETXGOIO-UHFFFAOYSA-N 0.000 description 1
- DJPFGKCIIOLACW-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCN(CC3)CCCC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCN(CC3)CCCC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F DJPFGKCIIOLACW-UHFFFAOYSA-N 0.000 description 1
- FAJLGNZGQJXOPT-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCN(CC3CO)C(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCN(CC3CO)C(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F FAJLGNZGQJXOPT-UHFFFAOYSA-N 0.000 description 1
- JDOFIXZGSDUHGU-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCNCC3)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F.Cl Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCNCC3)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F.Cl JDOFIXZGSDUHGU-UHFFFAOYSA-N 0.000 description 1
- AYOFSIYAGUWTPB-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCNCC3CO)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F.Cl Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)CN3CCNCC3CO)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F.Cl AYOFSIYAGUWTPB-UHFFFAOYSA-N 0.000 description 1
- AQHMCOZYNLGRRX-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(C(C3)(C)C)CC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(C(C3)(C)C)CC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F AQHMCOZYNLGRRX-UHFFFAOYSA-N 0.000 description 1
- CIQUHPJAILNILO-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(C(C3)OC)CC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(C(C3)OC)CC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F CIQUHPJAILNILO-UHFFFAOYSA-N 0.000 description 1
- DQCWMUZBWZOEJE-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(CC3)CC(=O)N)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(CC3)CC(=O)N)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F DQCWMUZBWZOEJE-UHFFFAOYSA-N 0.000 description 1
- HLELCYKECSRXOS-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(CC3)CC(=O)NS(=O)(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(CC3)CC(=O)NS(=O)(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F HLELCYKECSRXOS-UHFFFAOYSA-N 0.000 description 1
- HQEHPFIVFYACEW-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(CC3)NCC(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(CC3)NCC(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F HQEHPFIVFYACEW-UHFFFAOYSA-N 0.000 description 1
- AQPANYQZANMCKJ-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(CC3)OCCC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCC(CC3)OCCC(=O)O)C#N)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F AQPANYQZANMCKJ-UHFFFAOYSA-N 0.000 description 1
- GOWBVJSCZBDXCU-UHFFFAOYSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCN(CC3)C(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CCN(CC3)C(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F GOWBVJSCZBDXCU-UHFFFAOYSA-N 0.000 description 1
- QDABBBXWBRNWPY-JOCHJYFZSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CC[C@H](C3)NC(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CC[C@H](C3)NC(=O)C)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F QDABBBXWBRNWPY-JOCHJYFZSA-N 0.000 description 1
- BBRRPKCQYJCOFA-HSZRJFAPSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CC[C@H](C3)NC(=O)C4CC4)C#N)NCC(=O)C(C)(C)C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CC[C@H](C3)NC(=O)C4CC4)C#N)NCC(=O)C(C)(C)C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F BBRRPKCQYJCOFA-HSZRJFAPSA-N 0.000 description 1
- LIIWFATZMCLREL-HSZRJFAPSA-N CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CC[C@H](C3)NC(=O)CCOC)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F Chemical compound CC1=C(C=CC(=C1)F)C2=C(C(=C(S2)N3CC[C@H](C3)NC(=O)CCOC)C#N)N(C)C(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F LIIWFATZMCLREL-HSZRJFAPSA-N 0.000 description 1
- XLDMKOLEDPTFEX-UHFFFAOYSA-N CC1CN(CCC1CC(=O)O)C2=C(C(=C(S2)C3=C(C=C(C=C3)F)C)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)C#N Chemical compound CC1CN(CCC1CC(=O)O)C2=C(C(=C(S2)C3=C(C=C(C=C3)F)C)NCC(=O)C(C)(C)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)C#N XLDMKOLEDPTFEX-UHFFFAOYSA-N 0.000 description 1
- WDTMKQDPIFLZON-UHFFFAOYSA-N CCC(CCCCC(=O)OCC)C(=O)OC(C)(C)C Chemical compound CCC(CCCCC(=O)OCC)C(=O)OC(C)(C)C WDTMKQDPIFLZON-UHFFFAOYSA-N 0.000 description 1
- YEUNTQQFKFOGQP-UHFFFAOYSA-N CCOC(=O)C1C2CCNCC12 Chemical compound CCOC(=O)C1C2CCNCC12 YEUNTQQFKFOGQP-UHFFFAOYSA-N 0.000 description 1
- RCDOGVJAFIAVBV-UHFFFAOYSA-N CCOC(=O)CC1CCCN(CC1)C(=O)OC(C)(C)C Chemical compound CCOC(=O)CC1CCCN(CC1)C(=O)OC(C)(C)C RCDOGVJAFIAVBV-UHFFFAOYSA-N 0.000 description 1
- IWFRJQJLDXUKBC-UHFFFAOYSA-N CCOC(=O)c1c(sc(Br)c1C#N)-c1ccccc1C Chemical compound CCOC(=O)c1c(sc(Br)c1C#N)-c1ccccc1C IWFRJQJLDXUKBC-UHFFFAOYSA-N 0.000 description 1
- OBDIEFWOWBPECT-UHFFFAOYSA-N CCOC(=O)c1c(sc(N)c1C#N)-c1ccccc1C Chemical compound CCOC(=O)c1c(sc(N)c1C#N)-c1ccccc1C OBDIEFWOWBPECT-UHFFFAOYSA-N 0.000 description 1
- FWLVCFWBKMBDPD-UHFFFAOYSA-N CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(Br)c1C#N)-c1ccccc1C Chemical compound CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(Br)c1C#N)-c1ccccc1C FWLVCFWBKMBDPD-UHFFFAOYSA-N 0.000 description 1
- BBYQFLKESONAKA-UHFFFAOYSA-N CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(C=C)c1C#N)-c1ccccc1C Chemical compound CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(C=C)c1C#N)-c1ccccc1C BBYQFLKESONAKA-UHFFFAOYSA-N 0.000 description 1
- WFGJAXPIBUJCNB-UHFFFAOYSA-N CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(C=O)c1C#N)-c1ccc(F)cc1C Chemical compound CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(C=O)c1C#N)-c1ccc(F)cc1C WFGJAXPIBUJCNB-UHFFFAOYSA-N 0.000 description 1
- ZKZJTRQJNDVHIY-UHFFFAOYSA-N CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(C=O)c1C#N)-c1ccccc1C Chemical compound CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(C=O)c1C#N)-c1ccccc1C ZKZJTRQJNDVHIY-UHFFFAOYSA-N 0.000 description 1
- SILAIJSXCLNOII-UHFFFAOYSA-N CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(CCl)c1C#N)-c1ccc(F)cc1C Chemical compound CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(CCl)c1C#N)-c1ccc(F)cc1C SILAIJSXCLNOII-UHFFFAOYSA-N 0.000 description 1
- FBTCHWGEBGBINJ-UHFFFAOYSA-N CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(CN2CCN3C(CCC3=O)C2)c1C#N)-c1ccc(F)cc1C Chemical compound CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(CN2CCN3C(CCC3=O)C2)c1C#N)-c1ccc(F)cc1C FBTCHWGEBGBINJ-UHFFFAOYSA-N 0.000 description 1
- KKTCVICIVSUJTM-UHFFFAOYSA-N CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(CO)c1C#N)-c1ccc(F)cc1C Chemical compound CN(C(=O)C(C)(C)c1cc(cc(c1)C(F)(F)F)C(F)(F)F)c1c(sc(CO)c1C#N)-c1ccc(F)cc1C KKTCVICIVSUJTM-UHFFFAOYSA-N 0.000 description 1
- ISGDQKXBYIDBQO-UHFFFAOYSA-N COC(C1CCNCC1)C(=O)OC Chemical compound COC(C1CCNCC1)C(=O)OC ISGDQKXBYIDBQO-UHFFFAOYSA-N 0.000 description 1
- HSHJJUVXCNUUKH-UHFFFAOYSA-N COCC1(CCCN(C1)C(=O)O)C(=O)O Chemical compound COCC1(CCCN(C1)C(=O)O)C(=O)O HSHJJUVXCNUUKH-UHFFFAOYSA-N 0.000 description 1
- PVPGQPRVKBUZFR-UHFFFAOYSA-N Cc1cc(F)ccc1-c1sc(Br)c(C#N)c1C(O)=O Chemical compound Cc1cc(F)ccc1-c1sc(Br)c(C#N)c1C(O)=O PVPGQPRVKBUZFR-UHFFFAOYSA-N 0.000 description 1
- UUQPJVCDOWWXOM-UHFFFAOYSA-N Cc1cc(F)ccc1-c1sc(Br)c(C#N)c1N Chemical compound Cc1cc(F)ccc1-c1sc(Br)c(C#N)c1N UUQPJVCDOWWXOM-UHFFFAOYSA-N 0.000 description 1
- PZIPYYQJEGSCLB-UHFFFAOYSA-N Cc1ccccc1-c1sc(Br)c(C#N)c1C(O)=O Chemical compound Cc1ccccc1-c1sc(Br)c(C#N)c1C(O)=O PZIPYYQJEGSCLB-UHFFFAOYSA-N 0.000 description 1
- AWJFVGPAAVHQEK-UHFFFAOYSA-N Cc1ccccc1-c1sc(Br)c(C#N)c1N Chemical compound Cc1ccccc1-c1sc(Br)c(C#N)c1N AWJFVGPAAVHQEK-UHFFFAOYSA-N 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- PLLGTQKTDBBUQX-UHFFFAOYSA-N ClCC=1NCNN1 Chemical compound ClCC=1NCNN1 PLLGTQKTDBBUQX-UHFFFAOYSA-N 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 101000831616 Homo sapiens Protachykinin-1 Proteins 0.000 description 1
- 206010020853 Hypertonic bladder Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
- VCUFZILGIRCDQQ-KRWDZBQOSA-N N-[[(5S)-2-oxo-3-(2-oxo-3H-1,3-benzoxazol-6-yl)-1,3-oxazolidin-5-yl]methyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C1O[C@H](CN1C1=CC2=C(NC(O2)=O)C=C1)CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F VCUFZILGIRCDQQ-KRWDZBQOSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- JAWMENYCRQKKJY-UHFFFAOYSA-N [3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-ylmethyl)-1-oxa-2,8-diazaspiro[4.5]dec-2-en-8-yl]-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]methanone Chemical compound N1N=NC=2CN(CCC=21)CC1=NOC2(C1)CCN(CC2)C(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F JAWMENYCRQKKJY-UHFFFAOYSA-N 0.000 description 1
- FKCBLVCOSCZFHV-UHFFFAOYSA-N acetonitrile;ethanol Chemical compound CCO.CC#N FKCBLVCOSCZFHV-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000003818 area postrema Anatomy 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- WFTRLIZPJMFJER-UHFFFAOYSA-N azepan-1-ium-4-one;chloride Chemical compound Cl.O=C1CCCNCC1 WFTRLIZPJMFJER-UHFFFAOYSA-N 0.000 description 1
- GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 108091008690 chemoreceptors Proteins 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- QMMLUKRVXWXKSI-UHFFFAOYSA-J dichloromethane;titanium(4+);tetrachloride Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ti+4].ClCCl QMMLUKRVXWXKSI-UHFFFAOYSA-J 0.000 description 1
- LXCYSACZTOKNNS-UHFFFAOYSA-N diethoxy(oxo)phosphanium Chemical compound CCO[P+](=O)OCC LXCYSACZTOKNNS-UHFFFAOYSA-N 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- FFDGPVCHZBVARC-UHFFFAOYSA-N dimethylaminoacetic acid Natural products CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- XIWBSOUNZWSFKU-SSDOTTSWSA-N ethyl (3r)-piperidine-3-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCNC1 XIWBSOUNZWSFKU-SSDOTTSWSA-N 0.000 description 1
- JUSOQWCRQRDWKL-UHFFFAOYSA-N ethyl 1-prop-2-ynylpiperidine-4-carboxylate Chemical compound CCOC(=O)C1CCN(CC#C)CC1 JUSOQWCRQRDWKL-UHFFFAOYSA-N 0.000 description 1
- OWZFULPEVHKEKS-UHFFFAOYSA-N ethyl 2-chloro-2-oxoacetate Chemical compound CCOC(=O)C(Cl)=O OWZFULPEVHKEKS-UHFFFAOYSA-N 0.000 description 1
- BPDUMABHEZKFFT-UHFFFAOYSA-N ethyl 2-methylpiperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNC(C)C1 BPDUMABHEZKFFT-UHFFFAOYSA-N 0.000 description 1
- WOMYMRWGDVTGQI-UHFFFAOYSA-N ethyl 2-methylpyridine-4-carboxylate Chemical compound CCOC(=O)C1=CC=NC(C)=C1 WOMYMRWGDVTGQI-UHFFFAOYSA-N 0.000 description 1
- VAYPMPDBKBYGSQ-UHFFFAOYSA-N ethyl 2-piperidin-4-ylideneacetate Chemical compound CCOC(=O)C=C1CCNCC1 VAYPMPDBKBYGSQ-UHFFFAOYSA-N 0.000 description 1
- KBQUFOYZOQRUEW-UHFFFAOYSA-N ethyl 2-piperidin-4-ylpropanoate Chemical compound CCOC(=O)C(C)C1CCNCC1 KBQUFOYZOQRUEW-UHFFFAOYSA-N 0.000 description 1
- LNANFKKPVLUIBX-UHFFFAOYSA-N ethyl 3-methylpiperidine-3-carboxylate Chemical compound CCOC(=O)C1(C)CCCNC1 LNANFKKPVLUIBX-UHFFFAOYSA-N 0.000 description 1
- ZREZDODZGZVRBD-UHFFFAOYSA-N ethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylate Chemical compound C1C(C(=O)OCC)CCC(B2OC(C)(C)C(C)(C)O2)=C1 ZREZDODZGZVRBD-UHFFFAOYSA-N 0.000 description 1
- FKPYEDFRKMRJBL-UHFFFAOYSA-N ethyl 4-(trifluoromethylsulfonyloxy)cyclohex-3-ene-1-carboxylate Chemical compound CCOC(=O)C1CCC(OS(=O)(=O)C(F)(F)F)=CC1 FKPYEDFRKMRJBL-UHFFFAOYSA-N 0.000 description 1
- JNKKSNLOKAEBOJ-UHFFFAOYSA-N ethyl 5-amino-2-bromo-4-cyanothiophene-3-carboxylate Chemical compound CCOC(=O)C1=C(Br)SC(N)=C1C#N JNKKSNLOKAEBOJ-UHFFFAOYSA-N 0.000 description 1
- QWMPXTNXXREMCK-UHFFFAOYSA-N ethyl 5-oxopyrrolidine-3-carboxylate Chemical compound CCOC(=O)C1CNC(=O)C1 QWMPXTNXXREMCK-UHFFFAOYSA-N 0.000 description 1
- AFOQFPZDCLCIBL-UHFFFAOYSA-N ethyl azepane-4-carboxylate Chemical compound CCOC(=O)C1CCCNCC1 AFOQFPZDCLCIBL-UHFFFAOYSA-N 0.000 description 1
- YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 description 1
- YSPVHAUJXLGZHP-UHFFFAOYSA-N ethyl piperidine-1-carboxylate Chemical compound CCOC(=O)N1CCCCC1 YSPVHAUJXLGZHP-UHFFFAOYSA-N 0.000 description 1
- XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 210000004055 fourth ventricle Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- YMRAMAYADDQJIS-UHFFFAOYSA-N methyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-piperidin-4-ylacetate Chemical compound CC(C)(C)OC(=O)NC(C(=O)OC)C1CCNCC1 YMRAMAYADDQJIS-UHFFFAOYSA-N 0.000 description 1
- SIGOIUCRXKUEIG-UHFFFAOYSA-N methyl 2-dimethoxyphosphorylacetate Chemical compound COC(=O)CP(=O)(OC)OC SIGOIUCRXKUEIG-UHFFFAOYSA-N 0.000 description 1
- BPFXEXBNHJUTCF-UHFFFAOYSA-N methyl 4-methoxypiperidine-4-carboxylate Chemical compound COC(=O)C1(OC)CCNCC1 BPFXEXBNHJUTCF-UHFFFAOYSA-N 0.000 description 1
- DLZVZNAPRCRXEG-UHFFFAOYSA-N methyl 4-oxobutanoate Chemical compound COC(=O)CCC=O DLZVZNAPRCRXEG-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 201000003152 motion sickness Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 229910000487 osmium oxide Inorganic materials 0.000 description 1
- 208000020629 overactive bladder Diseases 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 150000008301 phosphite esters Chemical class 0.000 description 1
- HWYNYLXTVJYPOW-UHFFFAOYSA-N piperidine-1,3-dicarboxylic acid Chemical compound OC(=O)C1CCCN(C(O)=O)C1 HWYNYLXTVJYPOW-UHFFFAOYSA-N 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- FIVSJYGQAIEMOC-ZGNKEGEESA-N rolapitant Chemical compound C([C@@](NC1)(CO[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=2C=CC=CC=2)C[C@@]21CCC(=O)N2 FIVSJYGQAIEMOC-ZGNKEGEESA-N 0.000 description 1
- 229960001068 rolapitant Drugs 0.000 description 1
- 229960004262 romiplostim Drugs 0.000 description 1
- 108010017584 romiplostim Proteins 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 description 1
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 210000001679 solitary nucleus Anatomy 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide pyridine complex Chemical compound O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VWSBNWIPICCWAM-UHFFFAOYSA-N tert-butyl 3-methyl-4-oxopiperidine-1-carboxylate Chemical compound CC1CN(C(=O)OC(C)(C)C)CCC1=O VWSBNWIPICCWAM-UHFFFAOYSA-N 0.000 description 1
- DMPGBBUNKILXOX-UHFFFAOYSA-N tert-butyl 4-(2-ethoxy-2-oxoethyl)-3-methylpiperidine-1-carboxylate Chemical compound C(C)(C)(C)OC(=O)N1CC(C(CC1)CC(=O)OCC)C DMPGBBUNKILXOX-UHFFFAOYSA-N 0.000 description 1
- JWIXIYCYGVQYQI-UHFFFAOYSA-N tert-butyl 4-(2-ethoxy-2-oxoethylidene)azepane-1-carboxylate Chemical compound CCOC(=O)C=C1CCCN(C(=O)OC(C)(C)C)CC1 JWIXIYCYGVQYQI-UHFFFAOYSA-N 0.000 description 1
- GWIFZKJNRMQRJU-UHFFFAOYSA-N tert-butyl 4-cyanoazepane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC(C#N)CC1 GWIFZKJNRMQRJU-UHFFFAOYSA-N 0.000 description 1
- RQRMFFGCUUGYPC-UHFFFAOYSA-N tert-butyl n-(2-piperidin-4-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCC1CCNCC1 RQRMFFGCUUGYPC-UHFFFAOYSA-N 0.000 description 1
- VHYXAWLOJGIJPC-UHFFFAOYSA-N tert-butyl n-(piperidin-4-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1CCNCC1 VHYXAWLOJGIJPC-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
- 229950007305 vestipitant Drugs 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4535—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom, e.g. pizotifen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/08—Bridged systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2014160147 | 2014-08-06 | ||
JP2014160147 | 2014-08-06 | ||
PCT/JP2015/071993 WO2016021562A1 (fr) | 2014-08-06 | 2015-08-03 | Dérivé de cyanothiophène |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2016021562A1 JPWO2016021562A1 (ja) | 2017-06-15 |
JP6609253B2 true JP6609253B2 (ja) | 2019-11-20 |
Family
ID=55263827
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016540227A Expired - Fee Related JP6609253B2 (ja) | 2014-08-06 | 2015-08-03 | シアノチオフェン誘導体 |
Country Status (2)
Country | Link |
---|---|
JP (1) | JP6609253B2 (fr) |
WO (1) | WO2016021562A1 (fr) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017099049A1 (fr) * | 2015-12-07 | 2017-06-15 | キッセイ薬品工業株式会社 | Antagoniste du récepteur nk1 |
CN107011216A (zh) * | 2017-03-31 | 2017-08-04 | 泰州新威生物科技有限公司 | 一种反式‑4‑Boc‑氨基环己烷乙酸的制备方法 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JO2308B1 (en) * | 1999-05-31 | 2005-09-12 | اف. هوفمان- لاروش أيه جي | Derivatives of phenylpyrmidine |
AU2005311951A1 (en) * | 2004-12-03 | 2006-06-08 | Merck & Co., Inc. | Quinoline tachykinin receptor antagonists |
SI1928886T1 (sl) * | 2005-09-09 | 2011-08-31 | Glaxosmithkline Llc | Derivati piridina in njihova uporaba pri zdravljenju psihotiäśnih motenj |
JP2007277231A (ja) * | 2006-03-16 | 2007-10-25 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
CA2682506C (fr) * | 2007-04-20 | 2016-05-24 | F. Hoffmann-La Roche Ag | Derives de pyrrolidine comme antagonistes du recepteur nk1/nk3 double |
GB0808747D0 (en) * | 2008-05-14 | 2008-06-18 | Glaxo Wellcome Mfg Pte Ltd | Novel compounds |
USRE48334E1 (en) * | 2008-09-19 | 2020-12-01 | Takeda Pharmaceutical Company Limited | Nitrogen-containing heterocyclic compound and use of same |
WO2011054773A1 (fr) * | 2009-11-03 | 2011-05-12 | Glaxosmithkline Llc | Nouveaux composes lactame |
US8487102B2 (en) * | 2010-04-20 | 2013-07-16 | Hoffmann-La Roche Inc. | Pyrrazolopyridine compounds as dual NK1/NK3 receptor antagonists |
WO2011138916A1 (fr) * | 2010-05-07 | 2011-11-10 | 第一三共株式会社 | Composé polycyclique |
WO2015024203A1 (fr) * | 2013-08-20 | 2015-02-26 | Leo Pharma A/S | Nouveaux composés ii antagonistes du récepteur de la neurokinine 1 |
AU2014347644B2 (en) * | 2013-11-08 | 2018-06-14 | Kissei Pharmaceutical Co., Ltd. | Carboxymethyl piperidine derivative |
TWI649307B (zh) * | 2014-05-07 | 2019-02-01 | 日商橘生藥品工業股份有限公司 | Cyclohexylpyridine derivative |
-
2015
- 2015-08-03 WO PCT/JP2015/071993 patent/WO2016021562A1/fr active Application Filing
- 2015-08-03 JP JP2016540227A patent/JP6609253B2/ja not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
WO2016021562A1 (fr) | 2016-02-11 |
JPWO2016021562A1 (ja) | 2017-06-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6348891B2 (ja) | Cxcr4受容体アンタゴニスト | |
ES2905755T3 (es) | Derivados de piperidina | |
AU2007207053B2 (en) | Aryl-isoxazol-4-yl-imidazo[1,2-a]pyridine useful for the treatment of Alzheimer's disease via GABA receptors | |
JP2023508908A (ja) | フロインダゾール誘導体 | |
JP5806420B1 (ja) | カルボキシメチルピペリジン誘導体 | |
JP6609253B2 (ja) | シアノチオフェン誘導体 | |
JP5847362B1 (ja) | シクロヘキシルピリジン誘導体 | |
US10399949B2 (en) | NK1 receptor antagonist | |
TW200944530A (en) | Substituted sulfonamide derivatives |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180727 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190702 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190828 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20191001 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20191025 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6609253 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
LAPS | Cancellation because of no payment of annual fees |