NO323514B1 - Nye spiroforbindelser, fremgangsmate for fremstilling av slike, samt nevnte spiroforbindelser for medisinsk bruk. - Google Patents

Info

Publication number

NO323514B1

NO323514B1 NO20020814A NO20020814A NO323514B1 NO 323514 B1 NO323514 B1 NO 323514B1 NO 20020814 A NO20020814 A NO 20020814A NO 20020814 A NO20020814 A NO 20020814A NO 323514 B1 NO323514 B1 NO 323514B1

Authority

NO

Norway

Prior art keywords

carboxamide

phenyl

oxo

trans

alkyl

Prior art date

1999-08-20

Links

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• 238000002360 preparation method Methods 0.000 title claims description 104
• 238000000034 method Methods 0.000 title claims description 43
• 230000008569 process Effects 0.000 title description 8
• 150000003413 spiro compounds Chemical class 0.000 title description 3
• -1 C 1 -C 6 alkoxy Chemical group 0.000 claims description 271
• 150000001875 compounds Chemical class 0.000 claims description 265
• 125000003003 spiro group Chemical group 0.000 claims description 113
• 229910052736 halogen Inorganic materials 0.000 claims description 88
• 125000001424 substituent group Chemical group 0.000 claims description 72
• 150000002367 halogens Chemical class 0.000 claims description 69
• 125000000217 alkyl group Chemical group 0.000 claims description 48
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
• 125000005843 halogen group Chemical group 0.000 claims description 46
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 42
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 39
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 38
• 125000001072 heteroaryl group Chemical group 0.000 claims description 36
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 32
• 125000002883 imidazolyl group Chemical group 0.000 claims description 32
• 125000004076 pyridyl group Chemical group 0.000 claims description 30
• 125000005493 quinolyl group Chemical group 0.000 claims description 30
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
• 150000003857 carboxamides Chemical class 0.000 claims description 29
• 229910052757 nitrogen Inorganic materials 0.000 claims description 28
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 24
• 125000006239 protecting group Chemical group 0.000 claims description 22
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 19
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 19
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 19
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 19
• 125000000335 thiazolyl group Chemical group 0.000 claims description 19
• 229910052720 vanadium Inorganic materials 0.000 claims description 18
• 125000002971 oxazolyl group Chemical group 0.000 claims description 17
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 17
• 125000001589 carboacyl group Chemical group 0.000 claims description 16
• 150000003839 salts Chemical class 0.000 claims description 16
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 15
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 14
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 14
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 13
• 125000003545 alkoxy group Chemical group 0.000 claims description 13
• 125000002947 alkylene group Chemical group 0.000 claims description 13
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
• 150000002148 esters Chemical class 0.000 claims description 13
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 125000004590 pyridopyridyl group Chemical group N1=C(C=CC2=C1C=CC=N2)* 0.000 claims description 13
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 13
• 125000004306 triazinyl group Chemical group 0.000 claims description 13
• 125000001425 triazolyl group Chemical group 0.000 claims description 13
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
• 229910052760 oxygen Inorganic materials 0.000 claims description 12
• 239000001301 oxygen Substances 0.000 claims description 12
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 12
• 238000011282 treatment Methods 0.000 claims description 12
• 150000001408 amides Chemical class 0.000 claims description 11
• 229910052727 yttrium Inorganic materials 0.000 claims description 10
• 208000008589 Obesity Diseases 0.000 claims description 9
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
• 239000001257 hydrogen Substances 0.000 claims description 9
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 235000020824 obesity Nutrition 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 208000032841 Bulimia Diseases 0.000 claims description 7
• 206010006550 Bulimia nervosa Diseases 0.000 claims description 7
• 206010012601 diabetes mellitus Diseases 0.000 claims description 7
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 6
• BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims description 6
• 238000003379 elimination reaction Methods 0.000 claims description 6
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 5
• 125000003342 alkenyl group Chemical group 0.000 claims description 5
• 230000008030 elimination Effects 0.000 claims description 5
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 4
• 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 claims description 4
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
• FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 229950004889 piperamide Drugs 0.000 claims description 3
• 229910052721 tungsten Inorganic materials 0.000 claims description 3
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
• PANHPCJYUHDCRL-UHFFFAOYSA-N 3-oxo-n-(5-phenylpyrazin-2-yl)spiro[2h-isoindole-1,4'-piperidine]-1'-carboxamide Chemical compound C1CC2(C3=CC=CC=C3C(=O)N2)CCN1C(=O)NC(N=C1)=CN=C1C1=CC=CC=C1 PANHPCJYUHDCRL-UHFFFAOYSA-N 0.000 claims description 2
• RMAMQNKLHRDEKZ-UHFFFAOYSA-N 3-oxo-n-(5-phenylpyrazin-2-yl)spiro[4h-isochromene-1,4'-piperidine]-1'-carboxamide Chemical compound C1CC2(C3=CC=CC=C3CC(=O)O2)CCN1C(=O)NC(N=C1)=CN=C1C1=CC=CC=C1 RMAMQNKLHRDEKZ-UHFFFAOYSA-N 0.000 claims description 2
• 239000002660 neuropeptide Y receptor antagonist Substances 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 24
• 239000004480 active ingredient Substances 0.000 claims 2
• 238000006467 substitution reaction Methods 0.000 claims 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• 229940119154 Neuropeptide Y receptor antagonist Drugs 0.000 claims 1
• 125000004430 oxygen atom Chemical group O* 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 279
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 127
• 238000002844 melting Methods 0.000 description 104
• 230000008018 melting Effects 0.000 description 104
• 239000000203 mixture Substances 0.000 description 83
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 82
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
• 239000000243 solution Substances 0.000 description 74
• 239000011541 reaction mixture Substances 0.000 description 72
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
• 239000013078 crystal Substances 0.000 description 58
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
• 238000006243 chemical reaction Methods 0.000 description 50
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
• 239000012044 organic layer Substances 0.000 description 44
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 41
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
• 101710151321 Melanostatin Proteins 0.000 description 39
• 102100028427 Pro-neuropeptide Y Human genes 0.000 description 39
• 239000011734 sodium Substances 0.000 description 36
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 35
• URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 34
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• 238000004440 column chromatography Methods 0.000 description 33
• 239000000741 silica gel Substances 0.000 description 32
• 229910002027 silica gel Inorganic materials 0.000 description 32
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
• 239000002904 solvent Substances 0.000 description 29
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 25
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 25
• 239000002585 base Substances 0.000 description 22
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
• 238000001914 filtration Methods 0.000 description 20
• 238000001816 cooling Methods 0.000 description 19
• 239000007787 solid Substances 0.000 description 19
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
• 230000035484 reaction time Effects 0.000 description 18
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
• 239000012442 inert solvent Substances 0.000 description 16
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
• 229920006395 saturated elastomer Polymers 0.000 description 16
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 15
• 125000004043 oxo group Chemical group O=* 0.000 description 15
• 230000000694 effects Effects 0.000 description 14
• 238000004519 manufacturing process Methods 0.000 description 14
• 235000017557 sodium bicarbonate Nutrition 0.000 description 14
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
• RBKHNGHPZZZJCI-UHFFFAOYSA-N (4-aminophenyl)-phenylmethanone Chemical compound C1=CC(N)=CC=C1C(=O)C1=CC=CC=C1 RBKHNGHPZZZJCI-UHFFFAOYSA-N 0.000 description 13
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
• 239000003814 drug Substances 0.000 description 13
• 235000002639 sodium chloride Nutrition 0.000 description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
• 239000003795 chemical substances by application Substances 0.000 description 11
• 238000007796 conventional method Methods 0.000 description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
• 102000005962 receptors Human genes 0.000 description 11
• 108020003175 receptors Proteins 0.000 description 11
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 10
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
• 239000007832 Na2SO4 Substances 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 238000009835 boiling Methods 0.000 description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
• 239000003960 organic solvent Substances 0.000 description 9
• REKAGYBALLGJMY-UHFFFAOYSA-N phenyl n-(5-phenylpyrazin-2-yl)carbamate Chemical compound C=1C=CC=CC=1OC(=O)NC(N=C1)=CN=C1C1=CC=CC=C1 REKAGYBALLGJMY-UHFFFAOYSA-N 0.000 description 9
• 229910052938 sodium sulfate Inorganic materials 0.000 description 9
• 235000011152 sodium sulphate Nutrition 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• 238000004458 analytical method Methods 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• KYVVLBCWPRONOU-UHFFFAOYSA-N ethene hexane Chemical compound C=C.CCCCCC KYVVLBCWPRONOU-UHFFFAOYSA-N 0.000 description 8
• 230000000144 pharmacologic effect Effects 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 208000019901 Anxiety disease Diseases 0.000 description 7
• 208000002193 Pain Diseases 0.000 description 7
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 7
• 230000036506 anxiety Effects 0.000 description 7
• 230000027455 binding Effects 0.000 description 7
• 229940125773 compound 10 Drugs 0.000 description 7
• 229940079593 drug Drugs 0.000 description 7
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 7
• 239000010410 layer Substances 0.000 description 7
• 230000001404 mediated effect Effects 0.000 description 7
• KDTFRJFLHWHGBS-UHFFFAOYSA-N phenyl n-(4-benzoylphenyl)carbamate Chemical compound C=1C=CC=CC=1OC(=O)NC(C=C1)=CC=C1C(=O)C1=CC=CC=C1 KDTFRJFLHWHGBS-UHFFFAOYSA-N 0.000 description 7
• 235000011181 potassium carbonates Nutrition 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 210000003169 central nervous system Anatomy 0.000 description 6
• 235000015165 citric acid Nutrition 0.000 description 6
• 201000010099 disease Diseases 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 239000005556 hormone Substances 0.000 description 6
• 229940088597 hormone Drugs 0.000 description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 238000000634 powder X-ray diffraction Methods 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
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