NZ523951A - Phenoxybenzylamine derivatives as selective serotonin re-uptake inhibitors - Google Patents

Info

Publication number

NZ523951A

NZ523951A NZ523951A NZ52395101A NZ523951A NZ 523951 A NZ523951 A NZ 523951A NZ 523951 A NZ523951 A NZ 523951A NZ 52395101 A NZ52395101 A NZ 52395101A NZ 523951 A NZ523951 A NZ 523951A

Authority

NZ

New Zealand

Prior art keywords

compound

methyl

mhz

compounds

formula

Prior art date

2000-08-31

Links

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• 230000000697 serotonin reuptake Effects 0.000 title claims description 14
• 239000003112 inhibitor Substances 0.000 title description 11
• YXMXAXHPRPWBJB-UHFFFAOYSA-N n-phenoxy-1-phenylmethanamine Chemical class C=1C=CC=CC=1CNOC1=CC=CC=C1 YXMXAXHPRPWBJB-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 270
• 150000003839 salts Chemical class 0.000 claims abstract description 40
• 238000000034 method Methods 0.000 claims abstract description 37
• 239000012453 solvate Substances 0.000 claims abstract description 25
• 238000011282 treatment Methods 0.000 claims abstract description 23
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
• 208000035475 disorder Diseases 0.000 claims abstract description 15
• 239000003814 drug Substances 0.000 claims abstract description 11
• 238000004519 manufacturing process Methods 0.000 claims abstract description 10
• 230000002265 prevention Effects 0.000 claims abstract description 9
• 230000008569 process Effects 0.000 claims abstract description 9
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims abstract description 8
• 201000009032 substance abuse Diseases 0.000 claims abstract description 8
• 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 7
• 208000028173 post-traumatic stress disease Diseases 0.000 claims abstract description 7
• 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 7
• 231100000736 substance abuse Toxicity 0.000 claims abstract description 7
• 208000011117 substance-related disease Diseases 0.000 claims abstract description 7
• 101710164184 Synaptic vesicular amine transporter Proteins 0.000 claims abstract description 6
• 102100034333 Synaptic vesicular amine transporter Human genes 0.000 claims abstract description 6
• 230000033228 biological regulation Effects 0.000 claims abstract description 6
• 238000002360 preparation method Methods 0.000 claims description 113
• 238000006243 chemical reaction Methods 0.000 claims description 82
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 76
• 229910052739 hydrogen Inorganic materials 0.000 claims description 74
• 239000001257 hydrogen Substances 0.000 claims description 65
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 55
• 239000002904 solvent Substances 0.000 claims description 55
• -1 methoxyethyl Chemical group 0.000 claims description 42
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 37
• 229910052757 nitrogen Inorganic materials 0.000 claims description 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
• 150000001412 amines Chemical class 0.000 claims description 21
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
• 125000000623 heterocyclic group Chemical group 0.000 claims description 16
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
• 229910052760 oxygen Inorganic materials 0.000 claims description 15
• 125000000217 alkyl group Chemical group 0.000 claims description 14
• 239000003638 chemical reducing agent Substances 0.000 claims description 14
• 239000012442 inert solvent Substances 0.000 claims description 14
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 14
• 230000002411 adverse Effects 0.000 claims description 13
• 125000005842 heteroatom Chemical group 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 12
• 206010036596 premature ejaculation Diseases 0.000 claims description 12
• 239000003795 chemical substances by application Substances 0.000 claims description 11
• 229910052736 halogen Inorganic materials 0.000 claims description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
• 150000002367 halogens Chemical class 0.000 claims description 10
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 9
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 9
• 125000003118 aryl group Chemical group 0.000 claims description 9
• 125000002883 imidazolyl group Chemical group 0.000 claims description 9
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 9
• 229920006395 saturated elastomer Polymers 0.000 claims description 9
• 125000001425 triazolyl group Chemical group 0.000 claims description 9
• 229910052731 fluorine Inorganic materials 0.000 claims description 8
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 7
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 7
• 125000004429 atom Chemical group 0.000 claims description 7
• XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 7
• 238000005859 coupling reaction Methods 0.000 claims description 7
• YKUFJPGUCDDEEY-UHFFFAOYSA-N 4-(2,3-dihydro-1-benzothiophen-5-yloxy)-3-(methylaminomethyl)benzamide Chemical compound CNCC1=CC(C(N)=O)=CC=C1OC1=CC=C(SCC2)C2=C1 YKUFJPGUCDDEEY-UHFFFAOYSA-N 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 125000004432 carbon atom Chemical group C* 0.000 claims description 6
• 229960003638 dopamine Drugs 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 150000004678 hydrides Chemical class 0.000 claims description 6
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 6
• JCNJJQOCZPBSDY-UHFFFAOYSA-N 3-(methylaminomethyl)-4-(3-methyl-4-methylsulfanylphenoxy)benzamide Chemical compound CNCC1=CC(C(N)=O)=CC=C1OC1=CC=C(SC)C(C)=C1 JCNJJQOCZPBSDY-UHFFFAOYSA-N 0.000 claims description 5
• SLWDKAHRQIGZDY-UHFFFAOYSA-N 3-(methylaminomethyl)-4-quinolin-6-yloxybenzenesulfonamide Chemical compound CNCC1=CC(S(N)(=O)=O)=CC=C1OC1=CC=C(N=CC=C2)C2=C1 SLWDKAHRQIGZDY-UHFFFAOYSA-N 0.000 claims description 5
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 5
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 5
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
• 230000008878 coupling Effects 0.000 claims description 5
• 238000010168 coupling process Methods 0.000 claims description 5
• 239000011737 fluorine Substances 0.000 claims description 5
• 238000002955 isolation Methods 0.000 claims description 5
• IHINHVZKTRUFRD-UHFFFAOYSA-N 4-(2,3-dihydro-1-benzothiophen-5-yloxy)-3-[(dimethylamino)methyl]benzenesulfonamide Chemical compound CN(C)CC1=CC(S(N)(=O)=O)=CC=C1OC1=CC=C(SCC2)C2=C1 IHINHVZKTRUFRD-UHFFFAOYSA-N 0.000 claims description 4
• SNFPHAIZQSQJBE-UHFFFAOYSA-N 4-(3-chloro-4-methylsulfanylphenoxy)-3-[(dimethylamino)methyl]benzenesulfonamide Chemical compound C1=C(Cl)C(SC)=CC=C1OC1=CC=C(S(N)(=O)=O)C=C1CN(C)C SNFPHAIZQSQJBE-UHFFFAOYSA-N 0.000 claims description 4
• 229910052794 bromium Inorganic materials 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 238000011065 in-situ storage Methods 0.000 claims description 4
• 229910052740 iodine Inorganic materials 0.000 claims description 4
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 4
• 230000000966 norepinephrine reuptake Effects 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 239000011593 sulfur Chemical group 0.000 claims description 4
• 125000004434 sulfur atom Chemical group 0.000 claims description 4
• 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
• 230000002140 halogenating effect Effects 0.000 claims description 3
• 230000000802 nitrating effect Effects 0.000 claims description 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 claims description 2
• 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 2
• 239000002671 adjuvant Substances 0.000 claims description 2
• 125000002393 azetidinyl group Chemical group 0.000 claims description 2
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 2
• 125000001188 haloalkyl group Chemical group 0.000 claims description 2
• 125000005843 halogen group Chemical group 0.000 claims description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
• 230000005764 inhibitory process Effects 0.000 claims 13
• 150000002431 hydrogen Chemical group 0.000 claims 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
• 230000003389 potentiating effect Effects 0.000 claims 3
• WFSZGLDEZANSFJ-UHFFFAOYSA-N 3-[(dimethylamino)methyl]-4-quinolin-6-yloxybenzamide Chemical compound CN(C)CC1=CC(C(N)=O)=CC=C1OC1=CC=C(N=CC=C2)C2=C1 WFSZGLDEZANSFJ-UHFFFAOYSA-N 0.000 claims 2
• IRWJTTNPJDLUOM-UHFFFAOYSA-N 4-(2,3-dihydro-1,4-benzoxathiin-7-yloxy)-3-[(dimethylamino)methyl]benzamide Chemical compound CN(C)CC1=CC(C(N)=O)=CC=C1OC1=CC=C(SCCO2)C2=C1 IRWJTTNPJDLUOM-UHFFFAOYSA-N 0.000 claims 2
• QEIZOHJXMQOJAP-UHFFFAOYSA-N 4-(2,3-dihydro-1-benzothiophen-5-yloxy)-3-(methylaminomethyl)benzenesulfonamide Chemical compound CNCC1=CC(S(N)(=O)=O)=CC=C1OC1=CC=C(SCC2)C2=C1 QEIZOHJXMQOJAP-UHFFFAOYSA-N 0.000 claims 2
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 2
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims 1
• 230000006735 deficit Effects 0.000 claims 1
• 208000013403 hyperactivity Diseases 0.000 claims 1
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 abstract description 7
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 abstract description 6
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 abstract description 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 167
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 110
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 89
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 88
• 239000000203 mixture Substances 0.000 description 87
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 66
• 239000002243 precursor Substances 0.000 description 66
• 239000000243 solution Substances 0.000 description 61
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
• 235000019439 ethyl acetate Nutrition 0.000 description 43
• 239000010410 layer Substances 0.000 description 39
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 36
• 239000012044 organic layer Substances 0.000 description 36
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 28
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 27
• 239000000047 product Substances 0.000 description 27
• 239000007787 solid Substances 0.000 description 25
• 239000003921 oil Substances 0.000 description 23
• 235000019198 oils Nutrition 0.000 description 23
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
• 238000000746 purification Methods 0.000 description 22
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
• 238000003756 stirring Methods 0.000 description 20
• 238000004440 column chromatography Methods 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• 239000012267 brine Substances 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 16
• 238000010992 reflux Methods 0.000 description 15
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
• 239000002585 base Substances 0.000 description 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• 238000001816 cooling Methods 0.000 description 13
• 229910000027 potassium carbonate Inorganic materials 0.000 description 13
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
• 238000003556 assay Methods 0.000 description 11
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 11
• 239000011541 reaction mixture Substances 0.000 description 11
• 239000000284 extract Substances 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000000843 powder Substances 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• 241000282414 Homo sapiens Species 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 239000002552 dosage form Substances 0.000 description 9
• 239000006260 foam Substances 0.000 description 9
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 7
• 229920002472 Starch Polymers 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 239000000651 prodrug Substances 0.000 description 7
• 229940002612 prodrug Drugs 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 229940032147 starch Drugs 0.000 description 7
• 239000008107 starch Substances 0.000 description 7
• 235000019698 starch Nutrition 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
• 229920000858 Cyclodextrin Polymers 0.000 description 6
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 150000001299 aldehydes Chemical class 0.000 description 6
• 150000001408 amides Chemical class 0.000 description 6
• 125000004452 carbocyclyl group Chemical group 0.000 description 6
• 125000004093 cyano group Chemical group *C#N 0.000 description 6
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 229940124530 sulfonamide Drugs 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
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