ES2883831T3 - Compuestos antagonistas del receptor D3 de dopamina - Google Patents

Info

Publication number

ES2883831T3

ES2883831T3 ES15790229T ES15790229T ES2883831T3 ES 2883831 T3 ES2883831 T3 ES 2883831T3 ES 15790229 T ES15790229 T ES 15790229T ES 15790229 T ES15790229 T ES 15790229T ES 2883831 T3 ES2883831 T3 ES 2883831T3

Authority

ES

Spain

Prior art keywords

methyl

azaspiro

phenyl

triazol

sulfanyl

Prior art date

2014-10-31

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

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 293
• 229940088353 Dopamine D3 receptor antagonist Drugs 0.000 title description 2
• 239000002300 dopamine 3 receptor blocking agent Substances 0.000 title description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 235
• -1 cyano, hydroxyl Chemical group 0.000 claims abstract description 153
• 150000003839 salts Chemical class 0.000 claims abstract description 100
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 58
• 125000001424 substituent group Chemical group 0.000 claims abstract description 39
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 34
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 34
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
• 239000001257 hydrogen Substances 0.000 claims abstract description 28
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 26
• 150000002367 halogens Chemical class 0.000 claims abstract description 26
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 24
• 125000004076 pyridyl group Chemical group 0.000 claims abstract description 20
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 19
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 17
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 16
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 13
• 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 8
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims abstract description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 7
• 125000004429 atom Chemical group 0.000 claims abstract description 6
• 239000001301 oxygen Substances 0.000 claims abstract description 6
• 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims abstract description 5
• 235000010290 biphenyl Nutrition 0.000 claims abstract description 4
• 239000004305 biphenyl Substances 0.000 claims abstract description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
• 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 136
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 132
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 116
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 59
• RNOVGJWJVRESAA-UHFFFAOYSA-N 4-fluoro-2-(trifluoromethyl)phenol Chemical group OC1=CC=C(F)C=C1C(F)(F)F RNOVGJWJVRESAA-UHFFFAOYSA-N 0.000 claims description 38
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 31
• 208000011117 substance-related disease Diseases 0.000 claims description 25
• 229910052727 yttrium Inorganic materials 0.000 claims description 19
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 16
• 208000028017 Psychotic disease Diseases 0.000 claims description 15
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 15
• 201000009032 substance abuse Diseases 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 14
• 229910052721 tungsten Inorganic materials 0.000 claims description 13
• ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 12
• 201000000980 schizophrenia Diseases 0.000 claims description 11
• 229940079593 drug Drugs 0.000 claims description 10
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 10
• 231100000736 substance abuse Toxicity 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
• AAPXNHMQKBDDJN-GCJKJVERSA-N 4-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-phenyl-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-oxazole Chemical compound CN1C(=NN=C1C1=C(N=CO1)C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=CC=C2)CC1 AAPXNHMQKBDDJN-GCJKJVERSA-N 0.000 claims description 8
• XRDPJIJIWYVCKW-GCJKJVERSA-N 5-[5-[3-[(2R,3S)-2-(4-fluorophenyl)-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole Chemical compound FC1=CC=C(C=C1)[C@H]1C[C@@]11CN(CC1)CCCSC1=NN=C(N1C)C1=C(N=CO1)C XRDPJIJIWYVCKW-GCJKJVERSA-N 0.000 claims description 8
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 8
• 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 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 125000002971 oxazolyl group Chemical group 0.000 claims description 8
• JGGOHKJHMHHQML-OFNKIYASSA-N (2R,3S)-2-(4-fluorophenyl)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-5-azaspiro[2.4]heptane Chemical compound FC1=CC=C(C=C1)[C@H]1C[C@@]11CN(CC1)CCCSC1=NN=C(N1C)C=1C=NC=CC=1 JGGOHKJHMHHQML-OFNKIYASSA-N 0.000 claims description 7
• CTRVTEOXKBMCKO-QPPBQGQZSA-N (2R,3S)-5-[3-[(5-cyclohexyl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound C1(CCCCC1)C=1N(C(=NN=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C CTRVTEOXKBMCKO-QPPBQGQZSA-N 0.000 claims description 7
• 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 7
• 206010013663 drug dependence Diseases 0.000 claims description 7
• 125000005843 halogen group Chemical group 0.000 claims description 7
• BACQHWSKKKMEGV-BWKNWUBXSA-N 1-[4-[5-[3-[(2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]ethanone Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@H]1C[C@@]11CN(CC1)CCCSC=1N(C(=NN=1)C1CCN(CC1)C(C)=O)C BACQHWSKKKMEGV-BWKNWUBXSA-N 0.000 claims description 6
• JVGDBVAGMMZAGB-YKSBVNFPSA-N 1-methyl-4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridin-2-one Chemical compound CN1C(C=C(C=C1)C1=NN=C(N1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)=O JVGDBVAGMMZAGB-YKSBVNFPSA-N 0.000 claims description 6
• BMDSVLIJPPCGHQ-DVECYGJZSA-N 4-[5-[3-[(2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-1-methylpyridin-2-one Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@H]1C[C@@]11CN(CC1)CCCSC=1N(C(=NN=1)C1=CC(N(C=C1)C)=O)C BMDSVLIJPPCGHQ-DVECYGJZSA-N 0.000 claims description 6
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 6
• 208000018737 Parkinson disease Diseases 0.000 claims description 6
• 230000005764 inhibitory process Effects 0.000 claims description 6
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
• 125000001425 triazolyl group Chemical group 0.000 claims description 6
• MRFLPGUUAPCTFB-RDGATRHJSA-N (2R,3S)-5-[3-[[5-(2,6-dimethylpyridin-3-yl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CC1=NC(=CC=C1C=1N(C(=NN=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C)C MRFLPGUUAPCTFB-RDGATRHJSA-N 0.000 claims description 5
• DOTLHOVQYVFUDB-YKSBVNFPSA-N (2R,3S)-5-[3-[[5-(2-methoxypyridin-3-yl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound COC1=NC=CC=C1C=1N(C(=NN=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C DOTLHOVQYVFUDB-YKSBVNFPSA-N 0.000 claims description 5
• XNMSLJNWIPSTJD-KNQAVFIVSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]morpholine Chemical compound CN1C(=NN=C1N1CCOCC1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 XNMSLJNWIPSTJD-KNQAVFIVSA-N 0.000 claims description 5
• PQHIRTDXFUZNBI-DVECYGJZSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C=1C=CC(=NC=1)C(=O)N PQHIRTDXFUZNBI-DVECYGJZSA-N 0.000 claims description 5
• 208000030814 Eating disease Diseases 0.000 claims description 5
• 201000001880 Sexual dysfunction Diseases 0.000 claims description 5
• 235000014632 disordered eating Nutrition 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• 231100000872 sexual dysfunction Toxicity 0.000 claims description 5
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 4
• IQKUCRAAVAKXAF-CEJRHITASA-N (2R,3S)-5-[3-[[4-methyl-5-(8-oxabicyclo[3.2.1]octan-3-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1CC2CCC(C1)O2)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 IQKUCRAAVAKXAF-CEJRHITASA-N 0.000 claims description 4
• PPLSEYBUMZWQHS-OFNKIYASSA-N (2R,3S)-5-[3-[[4-methyl-5-(oxan-4-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1CCOCC1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 PPLSEYBUMZWQHS-OFNKIYASSA-N 0.000 claims description 4
• BKKDXLNOKQPSKN-RDGATRHJSA-N 1-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-1-yl]ethanone Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1CCN(CC1)C(C)=O BKKDXLNOKQPSKN-RDGATRHJSA-N 0.000 claims description 4
• IHJPCMRDCZSJMC-KCWPFWIISA-N 3-methoxy-1-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-1-yl]propan-1-one Chemical compound COCCC(=O)N1CCC(CC1)C1=NN=C(N1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 IHJPCMRDCZSJMC-KCWPFWIISA-N 0.000 claims description 4
• YYUNOOUJRWVVBW-XXBNENTESA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1H-pyridin-2-one Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C=1C=CC(NC=1)=O YYUNOOUJRWVVBW-XXBNENTESA-N 0.000 claims description 4
• 229960003920 cocaine Drugs 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• 229960002715 nicotine Drugs 0.000 claims description 4
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• GPDZHKOGLHALQL-GCJKJVERSA-N (2R,3S)-5-[3-[(4-methyl-5-pyrazin-2-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=NC=CN=C1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 GPDZHKOGLHALQL-GCJKJVERSA-N 0.000 claims description 3
• ZDHMFNGMBGJLNF-OFNKIYASSA-N (2R,3S)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C=1C=NC=CC=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 ZDHMFNGMBGJLNF-OFNKIYASSA-N 0.000 claims description 3
• KIDLIVLNXRZSJP-KNQAVFIVSA-N (2R,3S)-5-[3-[[4-methyl-5-(1-methylpyrazol-4-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C=1C=NN(C=1)C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 KIDLIVLNXRZSJP-KNQAVFIVSA-N 0.000 claims description 3
• BADZIIJBCNPURN-GCJKJVERSA-N (2R,3S)-5-[3-[[4-methyl-5-(2-methylpyrazol-3-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=CC=NN1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 BADZIIJBCNPURN-GCJKJVERSA-N 0.000 claims description 3
• WSVPKQPBMGHTOP-XXBNENTESA-N (2R,3S)-5-[3-[[4-methyl-5-(3-methylpyrazin-2-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=NC=CN=C1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 WSVPKQPBMGHTOP-XXBNENTESA-N 0.000 claims description 3
• DRMNJQDZXRGJRN-YKSBVNFPSA-N 1-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridin-2-one Chemical compound CN1C(C=CC(=C1)C1=NN=C(N1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)=O DRMNJQDZXRGJRN-YKSBVNFPSA-N 0.000 claims description 3
• NIFGQHGFOUMQJN-KCWPFWIISA-N 2-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]phenyl]-1,3-oxazole Chemical compound CN1C(=NN=C1C1=CC=C(C=C1)C=1OC=CN=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 NIFGQHGFOUMQJN-KCWPFWIISA-N 0.000 claims description 3
• XUTJSHVGYIHURB-BWKNWUBXSA-N 3-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]benzamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C=1C=C(C(=O)N)C=CC=1 XUTJSHVGYIHURB-BWKNWUBXSA-N 0.000 claims description 3
• TXEGIIUTZDNUKA-GCJKJVERSA-N 3-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,2-oxazole Chemical compound CN1C(=NN=C1C1=CC(=NO1)C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 TXEGIIUTZDNUKA-GCJKJVERSA-N 0.000 claims description 3
• DGRHJZMAQQIHDX-BWKNWUBXSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]benzamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC=C(C(=O)N)C=C1 DGRHJZMAQQIHDX-BWKNWUBXSA-N 0.000 claims description 3
• ITIATPRLDJMYTO-RDGATRHJSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]benzonitrile Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC=C(C#N)C=C1 ITIATPRLDJMYTO-RDGATRHJSA-N 0.000 claims description 3
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
• 208000019901 Anxiety disease Diseases 0.000 claims description 3
• 208000028698 Cognitive impairment Diseases 0.000 claims description 3
• 208000024254 Delusional disease Diseases 0.000 claims description 3
• AQQXAAJKFUHAHW-CLOONOSVSA-N N-methyl-6-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound CNC(=O)C1=NC(=CC=C1)C1=NN=C(N1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 AQQXAAJKFUHAHW-CLOONOSVSA-N 0.000 claims description 3
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 3
• 230000036506 anxiety Effects 0.000 claims description 3
• 208000010877 cognitive disease Diseases 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 230000000142 dyskinetic effect Effects 0.000 claims description 3
• 230000030135 gastric motility Effects 0.000 claims description 3
• 239000003176 neuroleptic agent Substances 0.000 claims description 3
• 208000002851 paranoid schizophrenia Diseases 0.000 claims description 3
• ACKJXZGTUCARLB-KNQAVFIVSA-N (2R,3S)-5-[3-[(4-methyl-5-pyridazin-4-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=CN=NC=C1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 ACKJXZGTUCARLB-KNQAVFIVSA-N 0.000 claims description 2
• MJUZYNLBBPDZMI-QPPBQGQZSA-N (2R,3S)-5-[3-[[4-methyl-5-(2-methylpyridin-3-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C=1C(=NC=CC=1)C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 MJUZYNLBBPDZMI-QPPBQGQZSA-N 0.000 claims description 2
• RBJIRQAVFUSFOC-YKSBVNFPSA-N (2R,3S)-5-[3-[[4-methyl-5-(3-methylpyridin-2-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=NC=CC=C1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 RBJIRQAVFUSFOC-YKSBVNFPSA-N 0.000 claims description 2
• ZXFZECKVGJDLHN-IRPSRAIASA-N (2R,3S)-5-[3-[[4-methyl-5-(6-phenoxypyridin-3-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C=1C=NC(=CC=1)OC1=CC=CC=C1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 ZXFZECKVGJDLHN-IRPSRAIASA-N 0.000 claims description 2
• DVUOLXOWKHDIAV-XXBNENTESA-N (2R,3S)-5-[3-[[4-methyl-5-[2-(trifluoromethyl)pyridin-3-yl]-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C=1C(=NC=CC=1)C(F)(F)F)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 DVUOLXOWKHDIAV-XXBNENTESA-N 0.000 claims description 2
• YGYAGUWNTSRVJU-BVAGGSTKSA-N (2R,3S)-5-[3-[[4-methyl-5-[4-(1,2,4-triazol-4-yl)phenyl]-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=CC=C(C=C1)N1C=NN=C1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 YGYAGUWNTSRVJU-BVAGGSTKSA-N 0.000 claims description 2
• HMTJKRFRBLRBNL-BVAGGSTKSA-N 1-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]phenyl]ethanone Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC=C(C=C1)C(C)=O HMTJKRFRBLRBNL-BVAGGSTKSA-N 0.000 claims description 2
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 2
• GVNGVHIMGMRLJR-GJZUVCINSA-N 2-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]phenyl]-1,3,4-oxadiazole Chemical compound CN1C(=NN=C1C1=CC=C(C=C1)C=1OC=NN=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 GVNGVHIMGMRLJR-GJZUVCINSA-N 0.000 claims description 2
• HZISGJVOPZSKRZ-QPPBQGQZSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]benzenesulfonamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC=C(C=C1)S(=O)(=O)N HZISGJVOPZSKRZ-QPPBQGQZSA-N 0.000 claims description 2
• LGSHURNTQKZWCE-QPPBQGQZSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carbonitrile Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC(=NC=C1)C#N LGSHURNTQKZWCE-QPPBQGQZSA-N 0.000 claims description 2
• YSWRGUATAJTXLZ-DVECYGJZSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC(=NC=C1)C(=O)N YSWRGUATAJTXLZ-DVECYGJZSA-N 0.000 claims description 2
• KDMBMLINAPXLCW-UZLBHIALSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]thiadiazole Chemical compound CN1C(=NN=C1C=1N=NSC=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 KDMBMLINAPXLCW-UZLBHIALSA-N 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• NFIANDWIUXYLJZ-GCJKJVERSA-N 4-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-thiazole Chemical compound CN1C(=NN=C1C1=C(N=CS1)C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 NFIANDWIUXYLJZ-GCJKJVERSA-N 0.000 claims description 2
• YEXWXZVNQKZBGQ-UTKZUKDTSA-N 4-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]thiadiazole Chemical compound CN1C(=NN=C1C1=C(N=NS1)C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 YEXWXZVNQKZBGQ-UTKZUKDTSA-N 0.000 claims description 2
• IDNOJRMZJBFBHO-RLWLMLJZSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-2-pyridin-3-yl-1,3-oxazole Chemical compound CN1C(=NN=C1C1=CN=C(O1)C=1C=NC=CC=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 IDNOJRMZJBFBHO-RLWLMLJZSA-N 0.000 claims description 2
• HRCUUSWFFWLUTD-PNYWAOBFSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-2-one Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1CCC(NC1)=O HRCUUSWFFWLUTD-PNYWAOBFSA-N 0.000 claims description 2
• LMYXDMLXVWZVJJ-QPPBQGQZSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carbonitrile Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C=1C=CC(=NC=1)C#N LMYXDMLXVWZVJJ-QPPBQGQZSA-N 0.000 claims description 2
• JVZGREXNJZVCNO-YKSBVNFPSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-3-carboxamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C=1C=C(C=NC=1)C(=O)N JVZGREXNJZVCNO-YKSBVNFPSA-N 0.000 claims description 2
• CCKIRENVCMGNMA-KCWPFWIISA-N 5-methyl-3-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]phenyl]-1,2,4-oxadiazole Chemical compound CN1C(=NN=C1C1=CC=C(C=C1)C1=NOC(=N1)C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 CCKIRENVCMGNMA-KCWPFWIISA-N 0.000 claims description 2
• DDNNHDCWWVGYRK-DVECYGJZSA-N 6-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-3-carboxamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC=C(C=N1)C(=O)N DDNNHDCWWVGYRK-DVECYGJZSA-N 0.000 claims description 2
• IXZSNEAXRLARHF-KOSHJBKYSA-N 6-[5-[3-[(2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]pyridine-3-carboxamide Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@H]1C[C@@]11CN(CC1)CCCSC=1N(C(=NN=1)C1=CC=C(C=N1)C(=O)N)C IXZSNEAXRLARHF-KOSHJBKYSA-N 0.000 claims description 2
• WEEBXSDEOQNZPK-NLFFAJNJSA-N 6-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound CC1=C(C=CC(=N1)C(=O)N)C1=NN=C(N1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 WEEBXSDEOQNZPK-NLFFAJNJSA-N 0.000 claims description 2
• 208000024827 Alzheimer disease Diseases 0.000 claims description 2
• 208000000044 Amnesia Diseases 0.000 claims description 2
• 208000031091 Amnestic disease Diseases 0.000 claims description 2
• 206010003805 Autism Diseases 0.000 claims description 2
• 208000020706 Autistic disease Diseases 0.000 claims description 2
• 208000017164 Chronobiology disease Diseases 0.000 claims description 2
• 206010012289 Dementia Diseases 0.000 claims description 2
• 208000001613 Gambling Diseases 0.000 claims description 2
• GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 claims description 2
• 206010026749 Mania Diseases 0.000 claims description 2
• 208000026139 Memory disease Diseases 0.000 claims description 2
• 208000016285 Movement disease Diseases 0.000 claims description 2
• 208000027099 Paranoid disease Diseases 0.000 claims description 2
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 2
• 206010034010 Parkinsonism Diseases 0.000 claims description 2
• 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 2
• 208000012886 Vertigo Diseases 0.000 claims description 2
• 206010047700 Vomiting Diseases 0.000 claims description 2
• 230000016571 aggressive behavior Effects 0.000 claims description 2
• 230000006986 amnesia Effects 0.000 claims description 2
• 229940049706 benzodiazepine Drugs 0.000 claims description 2
• 229960002069 diamorphine Drugs 0.000 claims description 2
• 208000024714 major depressive disease Diseases 0.000 claims description 2
• 230000000701 neuroleptic effect Effects 0.000 claims description 2
• 229940127240 opiate Drugs 0.000 claims description 2
• 206010036596 premature ejaculation Diseases 0.000 claims description 2
• 208000022610 schizoaffective disease Diseases 0.000 claims description 2
• 208000019116 sleep disease Diseases 0.000 claims description 2
• 229940124530 sulfonamide Drugs 0.000 claims description 2
• 150000003456 sulfonamides Chemical class 0.000 claims description 2
• 231100000889 vertigo Toxicity 0.000 claims description 2
• IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims 5
• 229910006074 SO2NH2 Inorganic materials 0.000 claims 2
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims 1
• NMEPMLDUQJFQOK-KCWPFWIISA-N 2-[3-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]phenyl]-1,3-oxazole Chemical compound CN1C(=NN=C1C1=CC(=CC=C1)C=1OC=CN=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 NMEPMLDUQJFQOK-KCWPFWIISA-N 0.000 claims 1
• BCTUVZJFJIFLND-GJZUVCINSA-N 2-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]phenyl]acetamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC=C(C=C1)CC(=O)N BCTUVZJFJIFLND-GJZUVCINSA-N 0.000 claims 1
• VUGZGZOSCLESTN-BVAGGSTKSA-N 2-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]phenyl]acetonitrile Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC=C(C=C1)CC#N VUGZGZOSCLESTN-BVAGGSTKSA-N 0.000 claims 1
• YMMKVLDFUKHZTJ-UTKZUKDTSA-N 2-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-thiazole Chemical compound CN1C(=NN=C1C=1SC=CN=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 YMMKVLDFUKHZTJ-UTKZUKDTSA-N 0.000 claims 1
• OLSWHYGQZCEOFP-BWKNWUBXSA-N 3-methyl-6-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-[1,2,4]triazolo[4,3-a]pyridine Chemical compound CN1C(=NN=C1C=1C=CC=2N(C=1)C(=NN=2)C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 OLSWHYGQZCEOFP-BWKNWUBXSA-N 0.000 claims 1
• MNAFRWGRFIBAQX-GCJKJVERSA-N 4-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-oxazole Chemical compound CN1C(=NN=C1C1=C(N=CO1)C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 MNAFRWGRFIBAQX-GCJKJVERSA-N 0.000 claims 1
• MYWIEDWDJCLOLH-XXBNENTESA-N 4-methyl-5-[4-methyl-5-[4-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]butyl]-1,2,4-triazol-3-yl]-1,3-oxazole Chemical compound CN1C(=NN=C1C1=C(N=CO1)C)CCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 MYWIEDWDJCLOLH-XXBNENTESA-N 0.000 claims 1
• TXOPCODJELQURT-KOSHJBKYSA-N 5-[5-[3-[(2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@H]1C[C@@]11CN(CC1)CCCSC=1N(C(=NN=1)C=1C=CC(=NC=1)C(=O)N)C TXOPCODJELQURT-KOSHJBKYSA-N 0.000 claims 1
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims 1
• MYBFGSHZAXDGJK-DVECYGJZSA-N 7-[5-[3-[(2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-[1,2,4]triazolo[4,3-a]pyridine Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@H]1C[C@@]11CN(CC1)CCCSC1=NN=C(N1C)C1=CC=2N(C=C1)C=NN=2 MYBFGSHZAXDGJK-DVECYGJZSA-N 0.000 claims 1
• MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
• IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 claims 1
• 208000020685 sleep-wake disease Diseases 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 295
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 237
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 207
• 239000000243 solution Substances 0.000 description 200
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 193
• 239000000203 mixture Substances 0.000 description 181
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 158
• 238000002360 preparation method Methods 0.000 description 142
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 135
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 125
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 115
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 107
• 238000005481 NMR spectroscopy Methods 0.000 description 101
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 101
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 101
• 238000005160 1H NMR spectroscopy Methods 0.000 description 96
• 239000002904 solvent Substances 0.000 description 95
• 229910000029 sodium carbonate Inorganic materials 0.000 description 82
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
• 235000017550 sodium carbonate Nutrition 0.000 description 79
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
• 239000007787 solid Substances 0.000 description 67
• 238000002347 injection Methods 0.000 description 62
• 239000007924 injection Substances 0.000 description 62
• 239000012071 phase Substances 0.000 description 62
• 230000002829 reductive effect Effects 0.000 description 57
• 238000000034 method Methods 0.000 description 55
• 230000014759 maintenance of location Effects 0.000 description 54
• 239000011541 reaction mixture Substances 0.000 description 50
• 208000035475 disorder Diseases 0.000 description 49
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 40
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 38
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 34
• 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 34
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
• 239000003480 eluent Substances 0.000 description 33
• 238000006243 chemical reaction Methods 0.000 description 32
• 238000001514 detection method Methods 0.000 description 31
• 238000004237 preparative chromatography Methods 0.000 description 31
• 239000012044 organic layer Substances 0.000 description 30
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
• 239000013058 crude material Substances 0.000 description 27
• 239000012074 organic phase Substances 0.000 description 26
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 24
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 23
• 239000003921 oil Substances 0.000 description 23
• 235000019198 oils Nutrition 0.000 description 23
• 239000002244 precipitate Substances 0.000 description 23
• 239000000741 silica gel Substances 0.000 description 23
• 229910002027 silica gel Inorganic materials 0.000 description 23
• QCZWAZSRPCRGMC-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole Chemical compound N1=COC(C=2N(C(SCCCCl)=NN=2)C)=C1C QCZWAZSRPCRGMC-UHFFFAOYSA-N 0.000 description 22
• 125000000217 alkyl group Chemical group 0.000 description 22
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 22
• 238000004296 chiral HPLC Methods 0.000 description 22
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 22
• 239000000725 suspension Substances 0.000 description 22
• LPROBZJLXVUDMD-NEPJUHHUSA-N (2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound FC(C1=CC=C(C=C1)[C@H]1C[C@@]11CNCC1)(F)F LPROBZJLXVUDMD-NEPJUHHUSA-N 0.000 description 21
• 238000012545 processing Methods 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
• 238000005406 washing Methods 0.000 description 20
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
• 239000000377 silicon dioxide Substances 0.000 description 19
• PTVZQOAHCSKAAS-UHFFFAOYSA-N 4-methyl-3-thiosemicarbazide Chemical compound CNC(=S)NN PTVZQOAHCSKAAS-UHFFFAOYSA-N 0.000 description 18
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
• 238000010992 reflux Methods 0.000 description 18
• 229910052938 sodium sulfate Inorganic materials 0.000 description 18
• 235000011152 sodium sulphate Nutrition 0.000 description 18
• 238000003756 stirring Methods 0.000 description 18
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
• 239000007864 aqueous solution Substances 0.000 description 17
• 239000012267 brine Substances 0.000 description 17
• MVILWLLYYQVYNH-UHFFFAOYSA-N pyridine-2-carboxamide Chemical compound NC(=O)C1=CC=CC=N1.NC(=O)C1=CC=CC=N1 MVILWLLYYQVYNH-UHFFFAOYSA-N 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
• 238000011282 treatment Methods 0.000 description 16
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• 229910000027 potassium carbonate Inorganic materials 0.000 description 15
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 14
• GGRDOXUBAWRZIN-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-1H-pyridin-2-one Chemical compound ClCCCSC=1N(C(=NN=1)C=1C=CC(NC=1)=O)C GGRDOXUBAWRZIN-UHFFFAOYSA-N 0.000 description 14
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
• 125000003545 alkoxy group Chemical group 0.000 description 14
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• 238000001704 evaporation Methods 0.000 description 13
• 230000008020 evaporation Effects 0.000 description 13
• WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
• 235000015320 potassium carbonate Nutrition 0.000 description 13
• 229940002612 prodrug Drugs 0.000 description 13
• 239000000651 prodrug Substances 0.000 description 13
• 229920006395 saturated elastomer Polymers 0.000 description 13
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• 229960003638 dopamine Drugs 0.000 description 12
• 239000000543 intermediate Substances 0.000 description 12
• 238000012799 strong cation exchange Methods 0.000 description 12
• 102000015554 Dopamine receptor Human genes 0.000 description 11
• 108050004812 Dopamine receptor Proteins 0.000 description 11
• 239000002253 acid Substances 0.000 description 11
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 11
• 239000000126 substance Substances 0.000 description 11
• 108090000525 Dopamine D3 Receptors Proteins 0.000 description 10
• 102000004073 Dopamine D3 Receptors Human genes 0.000 description 10
• MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 10
• 239000008346 aqueous phase Substances 0.000 description 10
• 125000002619 bicyclic group Chemical group 0.000 description 10
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 10
• 102000005962 receptors Human genes 0.000 description 10
• 108020003175 receptors Proteins 0.000 description 10
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 9
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 9
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
• 238000007792 addition Methods 0.000 description 9
• 150000001299 aldehydes Chemical class 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 229910052799 carbon Inorganic materials 0.000 description 9
• 238000010511 deprotection reaction Methods 0.000 description 9
• 230000008569 process Effects 0.000 description 9
• 125000006239 protecting group Chemical group 0.000 description 9
• NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical class C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 8
• 241000124008 Mammalia Species 0.000 description 8
• 125000003118 aryl group Chemical group 0.000 description 8
• 235000019253 formic acid Nutrition 0.000 description 8
• 231100000566 intoxication Toxicity 0.000 description 8
• 230000035987 intoxication Effects 0.000 description 8
• LJWBNVJHNKSJSU-XXBNENTESA-N (2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-[3-[[4-methyl-5-(oxan-4-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-5-azaspiro[2.4]heptane Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@H]1C[C@@]11CN(CC1)CCCSC1=NN=C(N1C)C1CCOCC1 LJWBNVJHNKSJSU-XXBNENTESA-N 0.000 description 7
• 239000003638 chemical reducing agent Substances 0.000 description 7
• 239000006260 foam Substances 0.000 description 7
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 7
• 235000017557 sodium bicarbonate Nutrition 0.000 description 7
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
• BISDORAEHNGDRY-OFNKIYASSA-N (2R,3S)-5-[3-[(4-methyl-5-piperidin-4-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1CCNCC1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 BISDORAEHNGDRY-OFNKIYASSA-N 0.000 description 6
• CTRVTEOXKBMCKO-XUZZJYLKSA-N (2S,3R)-5-[3-[(5-cyclohexyl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound C1(CCCCC1)C=1N(C(=NN=1)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C CTRVTEOXKBMCKO-XUZZJYLKSA-N 0.000 description 6
• OGHZHVONWMXUPW-UHFFFAOYSA-N 1-benzyl-3-methylidenepyrrolidine-2,5-dione Chemical compound O=C1C(=C)CC(=O)N1CC1=CC=CC=C1 OGHZHVONWMXUPW-UHFFFAOYSA-N 0.000 description 6
• OZLMWITUNBVEPK-UHFFFAOYSA-N 3-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]pyridine Chemical compound CN1C(SCCCCl)=NN=C1C1=CC=CN=C1 OZLMWITUNBVEPK-UHFFFAOYSA-N 0.000 description 6
• NQITUZDGXBAHQQ-UHFFFAOYSA-N 4-methyl-3-(4-methyl-1,3-oxazol-5-yl)-1h-1,2,4-triazole-5-thione Chemical compound N1=COC(C=2N(C(=S)NN=2)C)=C1C NQITUZDGXBAHQQ-UHFFFAOYSA-N 0.000 description 6
• 239000007832 Na2SO4 Substances 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 6
• 239000002249 anxiolytic agent Substances 0.000 description 6
• 230000000949 anxiolytic effect Effects 0.000 description 6
• 238000005984 hydrogenation reaction Methods 0.000 description 6
• 230000000147 hypnotic effect Effects 0.000 description 6
• 239000003607 modifier Substances 0.000 description 6
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 6
• 239000000932 sedative agent Substances 0.000 description 6
• 230000001624 sedative effect Effects 0.000 description 6
• 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 6
• OEFQLZIOQVHTKX-UHFFFAOYSA-N tert-butyl 4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]piperidine-1-carboxylate Chemical compound ClCCCSC=1N(C(=NN=1)C1CCN(CC1)C(=O)OC(C)(C)C)C OEFQLZIOQVHTKX-UHFFFAOYSA-N 0.000 description 6
• AWRRTDZQIOHQEP-PWSUYJOCSA-N (2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@H]1C[C@@]11CNCC1 AWRRTDZQIOHQEP-PWSUYJOCSA-N 0.000 description 5
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 5
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
• STGRGBWQBVWJJK-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-6-methylpyridine-2-carboxamide Chemical compound ClCCCSC=1N(C(=NN=1)C=1C=CC(=NC=1C)C(=O)N)C STGRGBWQBVWJJK-UHFFFAOYSA-N 0.000 description 5
• ZIQDGXNDXRMRPM-HTAPYJJXSA-N 5-[5-[3-[(2R,3R)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@@H]1C[C@]11CN(CC1)CCCSC1=NN=C(N1C)C1=C(N=CO1)C ZIQDGXNDXRMRPM-HTAPYJJXSA-N 0.000 description 5
• GMUAEZGQWYAELO-UHFFFAOYSA-N 6-cyano-2-methylpyridine-3-carboxylic acid Chemical compound C(#N)C1=CC=C(C(=N1)C)C(=O)O GMUAEZGQWYAELO-UHFFFAOYSA-N 0.000 description 5
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 210000004556 brain Anatomy 0.000 description 5
• 229960001948 caffeine Drugs 0.000 description 5
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 5
• 150000001721 carbon Chemical group 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 206010007776 catatonia Diseases 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 239000012141 concentrate Substances 0.000 description 5
• 235000008504 concentrate Nutrition 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• 150000007857 hydrazones Chemical class 0.000 description 5
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• IYZFQXRWZSKMLS-UHFFFAOYSA-N methyl 6-(benzotriazole-1-carbonyl)pyridine-2-carboxylate Chemical compound N1(N=NC2=C1C=CC=C2)C(=O)C1=CC=CC(=N1)C(=O)OC IYZFQXRWZSKMLS-UHFFFAOYSA-N 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 235000009518 sodium iodide Nutrition 0.000 description 5
• 239000012453 solvate Substances 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• 125000000335 thiazolyl group Chemical group 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• IKSPSLCLHNNQFS-WMZHIEFXSA-N (2R,3R)-2-(2,4-difluorophenyl)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-5-azaspiro[2.4]heptane Chemical compound FC1=C(C=CC(=C1)F)[C@@H]1C[C@]11CN(CC1)CCCSC1=NN=C(N1C)C=1C=NC=CC=1 IKSPSLCLHNNQFS-WMZHIEFXSA-N 0.000 description 4
• JZCCFPRFOOIKRY-WMZHIEFXSA-N (2R,3R)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-5-azaspiro[2.4]heptane Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@@H]1C[C@]11CN(CC1)CCCSC1=NN=C(N1C)C=1C=NC=CC=1 JZCCFPRFOOIKRY-WMZHIEFXSA-N 0.000 description 4
• IKSPSLCLHNNQFS-XXBNENTESA-N (2S,3S)-2-(2,4-difluorophenyl)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-5-azaspiro[2.4]heptane Chemical compound FC1=C(C=CC(=C1)F)[C@H]1C[C@@]11CN(CC1)CCCSC1=NN=C(N1C)C=1C=NC=CC=1 IKSPSLCLHNNQFS-XXBNENTESA-N 0.000 description 4
• JZCCFPRFOOIKRY-XXBNENTESA-N (2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-5-azaspiro[2.4]heptane Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@H]1C[C@@]11CN(CC1)CCCSC1=NN=C(N1C)C=1C=NC=CC=1 JZCCFPRFOOIKRY-XXBNENTESA-N 0.000 description 4
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 4
• FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 4
• WMMGJGPLJVAJQR-UHFFFAOYSA-N 3-(3-chloropropylsulfanyl)-4-methyl-5-(oxan-4-yl)-1,2,4-triazole Chemical compound CN1C(SCCCCl)=NN=C1C1CCOCC1 WMMGJGPLJVAJQR-UHFFFAOYSA-N 0.000 description 4
• GVCBLUCHEDAJMU-UHFFFAOYSA-N 3-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-2-methylpyridine Chemical compound CC1=NC=CC=C1C1=NN=C(SCCCCl)N1C GVCBLUCHEDAJMU-UHFFFAOYSA-N 0.000 description 4
• BRSAYQMINJJVBB-UHFFFAOYSA-N 4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-1-methylpyridin-2-one Chemical compound ClCCCSC=1N(C(=NN=1)C1=CC(N(C=C1)C)=O)C BRSAYQMINJJVBB-UHFFFAOYSA-N 0.000 description 4
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
• ZIXUNDOOBLSXPE-UHFFFAOYSA-N 4-methyl-1,3-oxazole-5-carboxylic acid Chemical compound CC=1N=COC=1C(O)=O ZIXUNDOOBLSXPE-UHFFFAOYSA-N 0.000 description 4
• IPTIQOGHHNCAFD-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound ClCCCSC=1N(C(=NN=1)C=1C=CC(=NC=1)C(=O)N)C IPTIQOGHHNCAFD-UHFFFAOYSA-N 0.000 description 4
• XRDPJIJIWYVCKW-PGRDOPGGSA-N 5-[5-[3-[(2S,3R)-2-(4-fluorophenyl)-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole Chemical compound CN1C(SCCCN2CC[C@@]3(C[C@H]3C3=CC=C(F)C=C3)C2)=NN=C1C1=C(C)N=CO1 XRDPJIJIWYVCKW-PGRDOPGGSA-N 0.000 description 4
• ZIQDGXNDXRMRPM-VGSWGCGISA-N 5-[5-[3-[(2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@H]1C[C@@]11CN(CC1)CCCSC1=NN=C(N1C)C1=C(N=CO1)C ZIQDGXNDXRMRPM-VGSWGCGISA-N 0.000 description 4
• HOXWESKAHYABGO-UHFFFAOYSA-N 5-azaspiro[2.4]heptane Chemical class C1CC11CNCC1 HOXWESKAHYABGO-UHFFFAOYSA-N 0.000 description 4
• TWEMPJMORRYYGZ-UHFFFAOYSA-N 5-methyl-6-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyridine-2-carbonitrile Chemical compound CC=1C=CC(=NC=1C1=NN=C(N1C)S)C#N TWEMPJMORRYYGZ-UHFFFAOYSA-N 0.000 description 4
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
• FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 4
• 241000218236 Cannabis Species 0.000 description 4
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
• 235000002637 Nicotiana tabacum Nutrition 0.000 description 4
• 235000019270 ammonium chloride Nutrition 0.000 description 4
• 235000011114 ammonium hydroxide Nutrition 0.000 description 4
• 230000008485 antagonism Effects 0.000 description 4
• 230000009286 beneficial effect Effects 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• 239000012230 colorless oil Substances 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 235000019788 craving Nutrition 0.000 description 4
• GKZLRXXOLCFQEN-KCWPFWIISA-N cyclopropyl-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-1-yl]methanone Chemical compound C1(CC1)C(=O)N1CCC(CC1)C=1N(C(=NN=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C GKZLRXXOLCFQEN-KCWPFWIISA-N 0.000 description 4
• 150000008049 diazo compounds Chemical class 0.000 description 4
• 239000006196 drop Substances 0.000 description 4
• UTLLKYPKASRAIG-UHFFFAOYSA-N ethyl 2-pyridin-3-yl-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC(C=2C=NC=CC=2)=N1 UTLLKYPKASRAIG-UHFFFAOYSA-N 0.000 description 4
• MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• 239000000380 hallucinogen Substances 0.000 description 4
• 150000003949 imides Chemical class 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• 239000012280 lithium aluminium hydride Substances 0.000 description 4
• WAVOCBHUAXDNLE-UHFFFAOYSA-N n,n'-dimethylhex-5-enimidamide;hydrochloride Chemical compound Cl.CNC(=NC)CCCC=C WAVOCBHUAXDNLE-UHFFFAOYSA-N 0.000 description 4
• JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 4
• 229950010883 phencyclidine Drugs 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 238000006722 reduction reaction Methods 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 4
• CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 4
• FFCDNTCSZVWUHJ-OFNKIYASSA-N (2R,3S)-5-[3-[[4-methyl-5-(oxan-4-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-phenyl-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1CCOCC1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=CC=C2)CC1 FFCDNTCSZVWUHJ-OFNKIYASSA-N 0.000 description 3
• JGGOHKJHMHHQML-NZQKXSOJSA-N (2S,3R)-2-(4-fluorophenyl)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-5-azaspiro[2.4]heptane Chemical compound FC1=CC=C(C=C1)[C@@H]1C[C@]11CN(CC1)CCCSC1=NN=C(N1C)C=1C=NC=CC=1 JGGOHKJHMHHQML-NZQKXSOJSA-N 0.000 description 3
• PPLSEYBUMZWQHS-NZQKXSOJSA-N (2S,3R)-5-[3-[[4-methyl-5-(oxan-4-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1CCOCC1)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 PPLSEYBUMZWQHS-NZQKXSOJSA-N 0.000 description 3
• DTWXQPNQLDOYHA-UHFFFAOYSA-N (4-fluorophenyl)methylidenehydrazine Chemical compound NN=CC1=CC=C(F)C=C1 DTWXQPNQLDOYHA-UHFFFAOYSA-N 0.000 description 3
• MZJYQXPULRLGCA-UHFFFAOYSA-N 1,1-dichlorocyclopropane Chemical compound ClC1(Cl)CC1 MZJYQXPULRLGCA-UHFFFAOYSA-N 0.000 description 3
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
• BCTIQMZKHMPOPO-UHFFFAOYSA-N 1-[4-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)piperidin-1-yl]ethanone Chemical compound CN1C(=NN=C1S)C1CCN(CC1)C(C)=O BCTIQMZKHMPOPO-UHFFFAOYSA-N 0.000 description 3
• ITOQQHRQNOLRDU-UHFFFAOYSA-N 1-[4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]ethanone Chemical compound ClCCCSC=1N(C(=NN=1)C1CCN(CC1)C(C)=O)C ITOQQHRQNOLRDU-UHFFFAOYSA-N 0.000 description 3
• OMMZSDGGKVRGGP-UHFFFAOYSA-N 1-methylsulfonylbenzotriazole Chemical compound C1=CC=C2N(S(=O)(=O)C)N=NC2=C1 OMMZSDGGKVRGGP-UHFFFAOYSA-N 0.000 description 3
• PLARMKHRAUIKNQ-UHFFFAOYSA-N 2-[4-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)phenyl]acetonitrile Chemical compound CN1C(=NN=C1S)C1=CC=C(C=C1)CC#N PLARMKHRAUIKNQ-UHFFFAOYSA-N 0.000 description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
• RITCSTBZUHHKIO-UHFFFAOYSA-N 3-(3-chloropropylsulfanyl)-5-cyclohexyl-4-methyl-1,2,4-triazole Chemical compound ClCCCSC1=NN=C(N1C)C1CCCCC1 RITCSTBZUHHKIO-UHFFFAOYSA-N 0.000 description 3
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
• VMJMQACRJQLQPM-UHFFFAOYSA-N 3-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-1H-pyridin-2-one Chemical compound ClCCCSC=1N(C(=NN=1)C=1C(NC=CC=1)=O)C VMJMQACRJQLQPM-UHFFFAOYSA-N 0.000 description 3
• KYNXOUQMCPMERR-UHFFFAOYSA-N 4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-1H-pyridin-2-one Chemical compound ClCCCSC=1N(C(=NN=1)C1=CC(NC=C1)=O)C KYNXOUQMCPMERR-UHFFFAOYSA-N 0.000 description 3
• LWJRKKCQLNJMOK-UHFFFAOYSA-N 4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]pyridine Chemical compound CN1C(SCCCCl)=NN=C1C1=CC=NC=C1 LWJRKKCQLNJMOK-UHFFFAOYSA-N 0.000 description 3
• MYMAGULLKUMKDT-UHFFFAOYSA-N 4-methyl-1,3-oxazole-5-carbohydrazide Chemical compound CC=1N=COC=1C(=O)NN MYMAGULLKUMKDT-UHFFFAOYSA-N 0.000 description 3
• HJAFSBLBCXOUSZ-UHFFFAOYSA-N 4-methyl-3-(oxan-4-yl)-1h-1,2,4-triazole-5-thione Chemical compound N1C(=S)N(C)C(C2CCOCC2)=N1 HJAFSBLBCXOUSZ-UHFFFAOYSA-N 0.000 description 3
• QPVMMPSZLYYSJC-UHFFFAOYSA-N 4-methyl-3-(oxan-4-yl)-5-pent-4-enyl-1,2,4-triazole Chemical compound CN1C(CCCC=C)=NN=C1C1CCOCC1 QPVMMPSZLYYSJC-UHFFFAOYSA-N 0.000 description 3
• GMKPTESLNAMLHU-UHFFFAOYSA-N 5-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyrazine-2-carboxamide Chemical compound CN1C(=NN=C1S)C=1N=CC(=NC=1)C(=O)N GMKPTESLNAMLHU-UHFFFAOYSA-N 0.000 description 3
• SYOGDSCBCPOGGO-UHFFFAOYSA-N 6-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyridine-3-carbonitrile Chemical compound CN1C(=NN=C1S)C1=CC=C(C=N1)C#N SYOGDSCBCPOGGO-UHFFFAOYSA-N 0.000 description 3
• CEMRUUXIKYWBGD-UHFFFAOYSA-N 6-(dimethylcarbamoyl)pyridine-2-carboxylic acid Chemical compound CN(C)C(=O)C1=CC=CC(C(O)=O)=N1 CEMRUUXIKYWBGD-UHFFFAOYSA-N 0.000 description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
• 239000004229 Alkannin Substances 0.000 description 3
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• KXFOUVDJLTZHFJ-UHFFFAOYSA-N CNC(=O)C1=CC=CC(=N1)C(=O)OC Chemical compound CNC(=O)C1=CC=CC(=N1)C(=O)OC KXFOUVDJLTZHFJ-UHFFFAOYSA-N 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
• 102000006441 Dopamine Plasma Membrane Transport Proteins Human genes 0.000 description 3
• 108010044266 Dopamine Plasma Membrane Transport Proteins Proteins 0.000 description 3
• 206010013654 Drug abuse Diseases 0.000 description 3
• YIPUQDPKROUMQD-UHFFFAOYSA-N FC1=C(C=CC(=C1)F)C=NN Chemical compound FC1=C(C=CC(=C1)F)C=NN YIPUQDPKROUMQD-UHFFFAOYSA-N 0.000 description 3
• FWYUQLQGEFVVKE-UHFFFAOYSA-N FC1=CC(=C(C=C1)C=NN)C(F)(F)F Chemical compound FC1=CC(=C(C=C1)C=NN)C(F)(F)F FWYUQLQGEFVVKE-UHFFFAOYSA-N 0.000 description 3
• 239000004214 Fast Green FCF Substances 0.000 description 3
• 239000004230 Fast Yellow AB Substances 0.000 description 3
• 101000632319 Homo sapiens Septin-7 Proteins 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• QDBPUGDJXGIOJW-HFYIJGDASA-N N-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]cyclohexyl]acetamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1CCC(CC1)NC(C)=O QDBPUGDJXGIOJW-HFYIJGDASA-N 0.000 description 3
• QDBPUGDJXGIOJW-VJLZBEPXSA-N N-[4-[4-methyl-5-[3-[(2S,3R)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]cyclohexyl]acetamide Chemical compound CN1C(=NN=C1SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1CCC(CC1)NC(C)=O QDBPUGDJXGIOJW-VJLZBEPXSA-N 0.000 description 3
• YTXKYITUGXWMMS-UHFFFAOYSA-N NN=CC1=CC(Cl)=CC(Cl)=C1 Chemical compound NN=CC1=CC(Cl)=CC(Cl)=C1 YTXKYITUGXWMMS-UHFFFAOYSA-N 0.000 description 3
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 3
• 244000061176 Nicotiana tabacum Species 0.000 description 3
• 208000026251 Opioid-Related disease Diseases 0.000 description 3
• 208000002193 Pain Diseases 0.000 description 3
• 102100027981 Septin-7 Human genes 0.000 description 3
• NSOMTUYKANPMLJ-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]methylidenehydrazine Chemical compound NN=CC1=CC=CC=C1C(F)(F)F NSOMTUYKANPMLJ-UHFFFAOYSA-N 0.000 description 3
• PGAHUJGUYJGSDA-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]methylidenehydrazine Chemical compound NN=CC1=CC=C(C(F)(F)F)C=C1 PGAHUJGUYJGSDA-UHFFFAOYSA-N 0.000 description 3
• PSBUFIIECWRZIW-UHFFFAOYSA-N [6-(trifluoromethyl)pyridin-3-yl]methylidenehydrazine Chemical compound C(=NN)C=1C=CC(=NC=1)C(F)(F)F PSBUFIIECWRZIW-UHFFFAOYSA-N 0.000 description 3
• 235000011054 acetic acid Nutrition 0.000 description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
• 239000000443 aerosol Substances 0.000 description 3
• 235000019232 alkannin Nutrition 0.000 description 3
• 239000000164 antipsychotic agent Substances 0.000 description 3
• 239000003125 aqueous solvent Substances 0.000 description 3
• CRKDNNLDFYKBEE-UHFFFAOYSA-N benzylidenehydrazine Chemical compound NN=CC1=CC=CC=C1 CRKDNNLDFYKBEE-UHFFFAOYSA-N 0.000 description 3
• 239000004109 brown FK Substances 0.000 description 3
• 235000012713 brown FK Nutrition 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 235000019241 carbon black Nutrition 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• DQGTTXDDKDMEHB-UHFFFAOYSA-N dimethyl pyrazine-2,5-dicarboxylate Chemical compound COC(=O)C1=CN=C(C(=O)OC)C=N1 DQGTTXDDKDMEHB-UHFFFAOYSA-N 0.000 description 3
• 201000010099 disease Diseases 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• 150000002148 esters Chemical class 0.000 description 3
• QTQNOBVKWYIKMP-UHFFFAOYSA-N ethyl 2-methyl-1-oxidopyridin-1-ium-3-carboxylate Chemical compound CCOC(=O)C1=CC=C[N+]([O-])=C1C QTQNOBVKWYIKMP-UHFFFAOYSA-N 0.000 description 3
• LRHOQESOANTRMH-UHFFFAOYSA-N ethyl 6-cyano-2-methylpyridine-3-carboxylate Chemical compound C(#N)C1=CC=C(C(=N1)C)C(=O)OCC LRHOQESOANTRMH-UHFFFAOYSA-N 0.000 description 3
• 235000019240 fast green FCF Nutrition 0.000 description 3
• 235000019233 fast yellow AB Nutrition 0.000 description 3
• 235000019256 formaldehyde Nutrition 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 125000002541 furyl group Chemical group 0.000 description 3
• 235000010193 gold Nutrition 0.000 description 3
• 239000004333 gold (food color) Substances 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 238000011065 in-situ storage Methods 0.000 description 3
• 229910052740 iodine Inorganic materials 0.000 description 3
• 239000011630 iodine Substances 0.000 description 3
• 125000001786 isothiazolyl group Chemical group 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 239000007937 lozenge Substances 0.000 description 3
• 238000004519 manufacturing process Methods 0.000 description 3
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 3
• PKFNYIJQJRDTKG-UHFFFAOYSA-N methyl 3-(1,3-oxazol-2-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C=2OC=CN=2)=C1 PKFNYIJQJRDTKG-UHFFFAOYSA-N 0.000 description 3
• JKNYFEXHKRIDTA-UHFFFAOYSA-N methyl 3-(2,2-dimethoxyethylcarbamoyl)benzoate Chemical compound COC(OC)CNC(=O)C1=CC=CC(C(=O)OC)=C1 JKNYFEXHKRIDTA-UHFFFAOYSA-N 0.000 description 3
• QEJUPLJEEGHOSO-UHFFFAOYSA-N methyl 4-(benzylamino)cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OC)CCC1NCC1=CC=CC=C1 QEJUPLJEEGHOSO-UHFFFAOYSA-N 0.000 description 3
• BLYKGTCYDJZLFB-UHFFFAOYSA-N methyl 4-oxocyclohexane-1-carboxylate Chemical compound COC(=O)C1CCC(=O)CC1 BLYKGTCYDJZLFB-UHFFFAOYSA-N 0.000 description 3
• XIDIMHCCDGNIFC-UHFFFAOYSA-N methyl 6-(dimethylcarbamoyl)pyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(C(=O)N(C)C)=N1 XIDIMHCCDGNIFC-UHFFFAOYSA-N 0.000 description 3
• HSIMZVAOBIGDIM-UHFFFAOYSA-N methyl 6-carbamoylpyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(C(N)=O)=N1 HSIMZVAOBIGDIM-UHFFFAOYSA-N 0.000 description 3
• WSSXMHWFUBRWDR-UHFFFAOYSA-N methyl 6-cyano-3-methylpyridine-2-carboxylate Chemical compound C(#N)C1=CC=C(C(=N1)C(=O)OC)C WSSXMHWFUBRWDR-UHFFFAOYSA-N 0.000 description 3
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
• 125000002950 monocyclic group Chemical group 0.000 description 3
• 239000012452 mother liquor Substances 0.000 description 3
• 210000002569 neuron Anatomy 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
• 239000003960 organic solvent Substances 0.000 description 3
• 239000007800 oxidant agent Substances 0.000 description 3
• 208000020016 psychiatric disease Diseases 0.000 description 3
• 125000003226 pyrazolyl group Chemical group 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 125000000168 pyrrolyl group Chemical group 0.000 description 3
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 239000004173 sunset yellow FCF Substances 0.000 description 3
• 235000012751 sunset yellow FCF Nutrition 0.000 description 3
• KCGGPGMJJFCCAA-UHFFFAOYSA-N tert-butyl 3-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)azetidine-1-carboxylate Chemical compound CN1C(=NN=C1S)C1CN(C1)C(=O)OC(C)(C)C KCGGPGMJJFCCAA-UHFFFAOYSA-N 0.000 description 3
• NKFMQMVGMYAMBF-UHFFFAOYSA-N tert-butyl 4-(4-methyl-5-sulfanylidene-1h-1,2,4-triazol-3-yl)piperidine-1-carboxylate Chemical compound N1C(=S)N(C)C(C2CCN(CC2)C(=O)OC(C)(C)C)=N1 NKFMQMVGMYAMBF-UHFFFAOYSA-N 0.000 description 3
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
• 125000001544 thienyl group Chemical group 0.000 description 3
• 239000004408 titanium dioxide Substances 0.000 description 3
• 235000010215 titanium dioxide Nutrition 0.000 description 3
• 239000004108 vegetable carbon Substances 0.000 description 3
• 235000012712 vegetable carbon Nutrition 0.000 description 3
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 2
• 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 2
• LJWBNVJHNKSJSU-WMZHIEFXSA-N (2R,3R)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-[3-[[4-methyl-5-(oxan-4-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-5-azaspiro[2.4]heptane Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@@H]1C[C@]11CN(CC1)CCCSC1=NN=C(N1C)C1CCOCC1 LJWBNVJHNKSJSU-WMZHIEFXSA-N 0.000 description 2
• AWRRTDZQIOHQEP-CMPLNLGQSA-N (2R,3R)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@@H]1C[C@]11CNCC1 AWRRTDZQIOHQEP-CMPLNLGQSA-N 0.000 description 2
• MQLQYYUFSOPSJL-UNAPJJAOSA-N (2R,3S)-5-[3-[[4-methyl-5-[2-(trifluoromethyl)pyridin-3-yl]-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane dihydrochloride Chemical compound Cl.Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1-c1cccnc1C(F)(F)F MQLQYYUFSOPSJL-UNAPJJAOSA-N 0.000 description 2
• LPROBZJLXVUDMD-NWDGAFQWSA-N (2S,3R)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound FC(C1=CC=C(C=C1)[C@@H]1C[C@]11CNCC1)(F)F LPROBZJLXVUDMD-NWDGAFQWSA-N 0.000 description 2
• ZDHMFNGMBGJLNF-NZQKXSOJSA-N (2S,3R)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C=1C=NC=CC=1)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 ZDHMFNGMBGJLNF-NZQKXSOJSA-N 0.000 description 2
• IQKUCRAAVAKXAF-SNJVWJBVSA-N (2S,3R)-5-[3-[[4-methyl-5-(8-oxabicyclo[3.2.1]octan-3-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1CC2CCC(C1)O2)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 IQKUCRAAVAKXAF-SNJVWJBVSA-N 0.000 description 2
• FFCDNTCSZVWUHJ-NZQKXSOJSA-N (2S,3R)-5-[3-[[4-methyl-5-(oxan-4-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-phenyl-5-azaspiro[2.4]heptane Chemical compound CN1C(SCCCN2CC[C@@]3(C[C@H]3C3=CC=CC=C3)C2)=NN=C1C1CCOCC1 FFCDNTCSZVWUHJ-NZQKXSOJSA-N 0.000 description 2
• MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 2
• ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 2
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 2
• APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 2
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 2
• GNVATANRVUMZDM-UHFFFAOYSA-N 1-[[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-1,2,4-triazol-3-yl]sulfanyl]-3-[2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propan-2-ol Chemical compound CN1C(=NN=C1C1=C(N=CO1)C)SCC(CN1CC2(CC2C2=CC=C(C=C2)C(F)(F)F)CC1)O GNVATANRVUMZDM-UHFFFAOYSA-N 0.000 description 2
• IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 2
• AWSNADYOKQXJRZ-BTNBVRMJSA-N 1-methyl-4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-2-one Chemical compound CN1C(CC(CC1)C1=NN=C(N1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)=O AWSNADYOKQXJRZ-BTNBVRMJSA-N 0.000 description 2
• WNLIXJOZDGVRJG-UHFFFAOYSA-N 1-phenylmethoxycarbonylimidazo[4,5-b]pyridine-5-carboxylic acid Chemical compound C(C1=CC=CC=C1)OC(=O)N1C=NC2=NC(=CC=C21)C(=O)O WNLIXJOZDGVRJG-UHFFFAOYSA-N 0.000 description 2
• IDPMMNTWQRVEML-UHFFFAOYSA-N 2-[3-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]phenyl]-1,3-oxazole Chemical compound ClCCCSC1=NN=C(N1C)C1=CC(=CC=C1)C=1OC=CN=1 IDPMMNTWQRVEML-UHFFFAOYSA-N 0.000 description 2
• GHFGGNNNLTWKEN-UHFFFAOYSA-N 2-[4-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)phenyl]acetamide Chemical compound CN1C(=NN=C1S)C1=CC=C(C=C1)CC(=O)N GHFGGNNNLTWKEN-UHFFFAOYSA-N 0.000 description 2
• MGUWSXALEQFAOZ-UHFFFAOYSA-N 2-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]pyridine Chemical compound CN1C(SCCCCl)=NN=C1C1=CC=CC=N1 MGUWSXALEQFAOZ-UHFFFAOYSA-N 0.000 description 2
• MAFJOMAYYKSZOS-UHFFFAOYSA-N 2-methoxycarbonylpyridine-4-carboxylic acid Chemical compound COC(=O)C1=CC(C(O)=O)=CC=N1 MAFJOMAYYKSZOS-UHFFFAOYSA-N 0.000 description 2
• NIXXXNOOBQYVOB-UHFFFAOYSA-N 3-(1H-imidazo[4,5-b]pyridin-5-yl)-4-methyl-1H-1,2,4-triazole-5-thione Chemical compound N1C=NC2=NC(=CC=C21)C=1N(C(=NN=1)S)C NIXXXNOOBQYVOB-UHFFFAOYSA-N 0.000 description 2
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 2
• GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 2
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 2
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 2
• SRVXSISGYBMIHR-UHFFFAOYSA-N 3-[3-[3-(2-amino-2-oxoethyl)phenyl]-5-chlorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid Chemical compound S1C(C)=CN=C1C(CC(O)=O)C1=CC(Cl)=CC(C=2C=C(CC(N)=O)C=CC=2)=C1 SRVXSISGYBMIHR-UHFFFAOYSA-N 0.000 description 2
• XMWDJTUUMHJBRG-GZAZMHIXSA-N 3-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1H-pyridin-2-one hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1-c1ccc[nH]c1=O XMWDJTUUMHJBRG-GZAZMHIXSA-N 0.000 description 2
• LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
• NSWZKCPOERCLNH-UHFFFAOYSA-N 4-(1,3-oxazol-2-yl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=NC=CO1 NSWZKCPOERCLNH-UHFFFAOYSA-N 0.000 description 2
• MRSILKKIKHKEQZ-UHFFFAOYSA-N 4-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyridine-2-carbonitrile Chemical compound CN1C(=NN=C1S)C1=CC(=NC=C1)C#N MRSILKKIKHKEQZ-UHFFFAOYSA-N 0.000 description 2
• KXMRDHPZQHAXML-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1CCC(C(O)=O)CC1 KXMRDHPZQHAXML-UHFFFAOYSA-N 0.000 description 2
• YFCIFWOJYYFDQP-PTWZRHHISA-N 4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide Chemical compound CNC[C@@H](NC(=O)c1ccc(cc1F)-c1nc(cnc1N)[C@H]1CC[C@H](O)[C@@H](F)C1)c1cc(F)cc(Br)c1 YFCIFWOJYYFDQP-PTWZRHHISA-N 0.000 description 2
• ZGTXSHRFCAXYNP-UHFFFAOYSA-N 4-[4-methyl-5-(oxan-4-yl)-1,2,4-triazol-3-yl]butanal Chemical compound CN1C(CCCC=O)=NN=C1C1CCOCC1 ZGTXSHRFCAXYNP-UHFFFAOYSA-N 0.000 description 2
• ARSLLTCMIOZESX-PNYWAOBFSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-2-one Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1CC(NCC1)=O ARSLLTCMIOZESX-PNYWAOBFSA-N 0.000 description 2
• XNMSLJNWIPSTJD-SIKLNZKXSA-N 4-[4-methyl-5-[3-[(2S,3R)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]morpholine Chemical compound CN1C(=NN=C1N1CCOCC1)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 XNMSLJNWIPSTJD-SIKLNZKXSA-N 0.000 description 2
• WCKCEHUUMCYDGR-UHFFFAOYSA-N 4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]morpholine Chemical compound ClCCCSC=1N(C(=NN=1)N1CCOCC1)C WCKCEHUUMCYDGR-UHFFFAOYSA-N 0.000 description 2
• XBFIJSPGWWUAPE-FWUDBZNBSA-N 4-[5-[3-[(2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-1-methylpyridin-2-one hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3F)C(F)(F)F)C2)nnc1-c1ccn(C)c(=O)c1 XBFIJSPGWWUAPE-FWUDBZNBSA-N 0.000 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 description 2
• LYURAHWBLCUAND-UHFFFAOYSA-N 4-carbamoylpyridine-2-carboxylic acid Chemical compound NC(=O)C1=CC=NC(C(O)=O)=C1 LYURAHWBLCUAND-UHFFFAOYSA-N 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• RQPGGRBSYQWYQW-UHFFFAOYSA-N 4-methyl-3-[3-(1,3-oxazol-2-yl)phenyl]-1H-1,2,4-triazole-5-thione Chemical compound CN1C(=NN=C1C1=CC(=CC=C1)C=1OC=CN=1)S RQPGGRBSYQWYQW-UHFFFAOYSA-N 0.000 description 2
• NDIKYSYWQURBJB-VNJAQMQMSA-N 4-methyl-5-[4-methyl-5-[3-[(2S,3R)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-oxazole hydrochloride Chemical compound Cl.Cc1ncoc1-c1nnc(SCCCN2CC[C@@]3(C[C@H]3c3ccc(cc3)C(F)(F)F)C2)n1C NDIKYSYWQURBJB-VNJAQMQMSA-N 0.000 description 2
• KVKJBMULEWEFNA-UHFFFAOYSA-N 5-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyridine-2-carbonitrile Chemical compound CN1C(=NN=C1S)C=1C=CC(=NC=1)C#N KVKJBMULEWEFNA-UHFFFAOYSA-N 0.000 description 2
• JINYWWDQIYCOSB-UHFFFAOYSA-N 5-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyridine-2-carboxamide Chemical compound CN1C(=NN=C1S)C=1C=CC(=NC=1)C(=O)N JINYWWDQIYCOSB-UHFFFAOYSA-N 0.000 description 2
• AAZJGIHLRBTBEB-UHFFFAOYSA-N 5-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyridine-3-carboxamide Chemical compound CN1C(=NN=C1S)C=1C=C(C=NC=1)C(=O)N AAZJGIHLRBTBEB-UHFFFAOYSA-N 0.000 description 2
• IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 2
• NHELUCTUUFRFHY-QTVLPVNYSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-2-one hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1C1CCC(=O)NC1 NHELUCTUUFRFHY-QTVLPVNYSA-N 0.000 description 2
• FALMNTGGMASRSO-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-6-methylpyridine-2-carboxylic acid Chemical compound ClCCCSC=1N(C(=NN=1)C=1C=CC(=NC=1C)C(=O)O)C FALMNTGGMASRSO-UHFFFAOYSA-N 0.000 description 2
• XIHOJUYAGODVFH-HTAPYJJXSA-N 5-[5-[3-[(2R,3R)-2-(2,4-difluorophenyl)-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole Chemical compound FC1=C(C=CC(=C1)F)[C@@H]1C[C@]11CN(CC1)CCCSC1=NN=C(N1C)C1=C(N=CO1)C XIHOJUYAGODVFH-HTAPYJJXSA-N 0.000 description 2
• UNOMGZZFCMNBCN-UHFFFAOYSA-N 5-azaspiro[2.5]octane Chemical class C1CC11CNCCC1 UNOMGZZFCMNBCN-UHFFFAOYSA-N 0.000 description 2
• SRIRTFSQYOUBGL-UHFFFAOYSA-N 5-carbamoylpyridine-3-carboxylic acid Chemical compound NC(=O)C1=CN=CC(C(O)=O)=C1 SRIRTFSQYOUBGL-UHFFFAOYSA-N 0.000 description 2
• NHTJPSWLHXHXSA-UHFFFAOYSA-N 5-methoxycarbonylpyrazine-2-carboxylic acid Chemical compound COC(=O)C1=CN=C(C(O)=O)C=N1 NHTJPSWLHXHXSA-UHFFFAOYSA-N 0.000 description 2
• GUXKBDHITFXEJG-UHFFFAOYSA-N 5-methoxycarbonylpyridine-3-carboxylic acid Chemical compound COC(=O)C1=CN=CC(C(O)=O)=C1 GUXKBDHITFXEJG-UHFFFAOYSA-N 0.000 description 2
• VKHIOWQNHRMQSF-CLOONOSVSA-N 5-methyl-6-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound CC=1C=CC(=NC=1C1=NN=C(N1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C(=O)N VKHIOWQNHRMQSF-CLOONOSVSA-N 0.000 description 2
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 2
• OMYIFQWNOTZYKT-UHFFFAOYSA-N 6-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyridine-3-carboxamide Chemical compound CN1C(=NN=C1S)C1=CC=C(C=N1)C(=O)N OMYIFQWNOTZYKT-UHFFFAOYSA-N 0.000 description 2
• NPBRDFPBRHOBAK-UHFFFAOYSA-N 6-(methylcarbamoyl)pyridine-2-carboxylic acid Chemical compound CNC(=O)C1=CC=CC(C(O)=O)=N1 NPBRDFPBRHOBAK-UHFFFAOYSA-N 0.000 description 2
• IDDNHZRBMURCQV-UHFFFAOYSA-N 6-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-1H-pyridin-2-one Chemical compound ClCCCSC=1N(C(=NN=1)C1=CC=CC(N1)=O)C IDDNHZRBMURCQV-UHFFFAOYSA-N 0.000 description 2
• GIBPTWPJEVCTGR-UHFFFAOYSA-N 6-azaspiro[2.5]octane Chemical class C1CC11CCNCC1 GIBPTWPJEVCTGR-UHFFFAOYSA-N 0.000 description 2
• NVZWMJWMTWOVNJ-UHFFFAOYSA-N 6-azaspiro[3.4]octane Chemical class C1CCC21CNCC2 NVZWMJWMTWOVNJ-UHFFFAOYSA-N 0.000 description 2
• MUTVEWJASOPKGU-UHFFFAOYSA-N 6-carbamoylpyridine-2-carboxylic acid Chemical compound NC(=O)C1=CC=CC(C(O)=O)=N1 MUTVEWJASOPKGU-UHFFFAOYSA-N 0.000 description 2
• WMHSQCDPPJRWIL-UHFFFAOYSA-N 6-cyanopyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(C#N)N=C1 WMHSQCDPPJRWIL-UHFFFAOYSA-N 0.000 description 2
• VWIOMFMPIVMLIR-UHFFFAOYSA-N 6-methoxycarbonylpyridine-2-carboxylic acid Chemical compound COC(=O)C1=CC=CC(C(O)=O)=N1 VWIOMFMPIVMLIR-UHFFFAOYSA-N 0.000 description 2
• 125000003627 8 membered carbocyclic group Chemical group 0.000 description 2
• 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 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 208000007848 Alcoholism Diseases 0.000 description 2
• 241000937413 Axia Species 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 101150049660 DRD2 gene Proteins 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 2
• 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
• 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• 230000005526 G1 to G0 transition Effects 0.000 description 2
• 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
• 239000004233 Indanthrene blue RS Substances 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 208000003863 Marijuana Abuse Diseases 0.000 description 2
• BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
• 102000010909 Monoamine Oxidase Human genes 0.000 description 2
• 108010062431 Monoamine oxidase Proteins 0.000 description 2
• URGSEMBRCTUTHV-IBVKSMDESA-N N,N-dimethyl-6-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound CN(C(=O)C1=NC(=CC=C1)C1=NN=C(N1C)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C URGSEMBRCTUTHV-IBVKSMDESA-N 0.000 description 2
• ULMHMJAEGZPQRY-UHFFFAOYSA-N N-(tert-butoxycarbonyl)piperidin-2-one Chemical compound CC(C)(C)OC(=O)N1CCCCC1=O ULMHMJAEGZPQRY-UHFFFAOYSA-N 0.000 description 2
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 2
• VFEXIMIXXMBLTJ-KFKMBJRHSA-N N-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]cyclohexyl]acetamide hydrochloride Chemical compound Cl.CC(=O)NC1CCC(CC1)c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)n1C VFEXIMIXXMBLTJ-KFKMBJRHSA-N 0.000 description 2
• 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 2
• ZIMOOJPJWDBGGB-UHFFFAOYSA-N NC(=O)C1=CN=C(C=N1)C(O)=O Chemical compound NC(=O)C1=CN=C(C=N1)C(O)=O ZIMOOJPJWDBGGB-UHFFFAOYSA-N 0.000 description 2
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 2
• 208000005374 Poisoning Diseases 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 239000004237 Ponceau 6R Substances 0.000 description 2
• 239000004236 Ponceau SX Substances 0.000 description 2
• 239000004231 Riboflavin-5-Sodium Phosphate Substances 0.000 description 2
• 208000027674 Schizophrenia Spectrum and Other Psychotic disease Diseases 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• 238000007239 Wittig reaction Methods 0.000 description 2
• 239000004234 Yellow 2G Substances 0.000 description 2
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
• 239000004479 aerosol dispenser Substances 0.000 description 2
• 208000028505 alcohol-related disease Diseases 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• 239000004191 allura red AC Substances 0.000 description 2
• 235000012741 allura red AC Nutrition 0.000 description 2
• 239000004411 aluminium Substances 0.000 description 2
• 235000010210 aluminium Nutrition 0.000 description 2
• 239000004178 amaranth Substances 0.000 description 2
• 235000012735 amaranth Nutrition 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 150000001450 anions Chemical class 0.000 description 2
• 239000004410 anthocyanin Substances 0.000 description 2
• 235000010208 anthocyanin Nutrition 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 2
• 239000004176 azorubin Substances 0.000 description 2
• 235000012733 azorubine Nutrition 0.000 description 2
• 239000011324 bead Substances 0.000 description 2
• 239000001654 beetroot red Substances 0.000 description 2
• 235000012677 beetroot red Nutrition 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical class BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
• 230000027455 binding Effects 0.000 description 2
• 239000004126 brilliant black BN Substances 0.000 description 2
• 235000012709 brilliant black BN Nutrition 0.000 description 2
• 239000004161 brilliant blue FCF Substances 0.000 description 2
• 235000012745 brilliant blue FCF Nutrition 0.000 description 2
• 239000001678 brown HT Substances 0.000 description 2
• 235000012670 brown HT Nutrition 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 239000004106 carminic acid Substances 0.000 description 2
• 235000012730 carminic acid Nutrition 0.000 description 2
• 230000003197 catalytic effect Effects 0.000 description 2
• 150000001768 cations Chemical class 0.000 description 2
• 235000010980 cellulose Nutrition 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 239000001752 chlorophylls and chlorophyllins Substances 0.000 description 2
• 235000012698 chlorophylls and chlorophyllins Nutrition 0.000 description 2
• 239000001679 citrus red 2 Substances 0.000 description 2
• 235000013986 citrus red 2 Nutrition 0.000 description 2
• 239000004121 copper complexes of chlorophylls and chlorophyllins Substances 0.000 description 2
• 235000012700 copper complexes of chlorophylls and chlorophyllins Nutrition 0.000 description 2
• 239000004148 curcumin Substances 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 150000005690 diesters Chemical class 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 230000001544 dysphoric effect Effects 0.000 description 2
• 239000004174 erythrosine Substances 0.000 description 2
• 235000012732 erythrosine Nutrition 0.000 description 2
• TZORNSWZUZDUCU-UHFFFAOYSA-N ethyl 2-methylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC=CN=C1C TZORNSWZUZDUCU-UHFFFAOYSA-N 0.000 description 2
• 238000001914 filtration Methods 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 239000007903 gelatin capsule Substances 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• 239000004120 green S Substances 0.000 description 2
• 235000012701 green S Nutrition 0.000 description 2
• UNAQSRLBVVDYGP-UHFFFAOYSA-N hex-5-enenitrile Chemical compound C=CCCCC#N UNAQSRLBVVDYGP-UHFFFAOYSA-N 0.000 description 2
• 235000019239 indanthrene blue RS Nutrition 0.000 description 2
• 239000004179 indigotine Substances 0.000 description 2
• 235000012738 indigotine Nutrition 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 239000004407 iron oxides and hydroxides Substances 0.000 description 2
• 235000010213 iron oxides and hydroxides Nutrition 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
• 239000004335 litholrubine BK Substances 0.000 description 2
• 235000010187 litholrubine BK Nutrition 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 238000012423 maintenance Methods 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• IYFCPKFXJHLORW-UHFFFAOYSA-N methyl 3-(2-oxoethylcarbamoyl)benzoate Chemical compound COC(=O)C1=CC=CC(C(=O)NCC=O)=C1 IYFCPKFXJHLORW-UHFFFAOYSA-N 0.000 description 2
• YSRBMUMDFAGAAD-UHFFFAOYSA-N methyl 3-methyl-1-oxidopyridin-1-ium-2-carboxylate Chemical compound COC(=O)C1=C(C)C=CC=[N+]1[O-] YSRBMUMDFAGAAD-UHFFFAOYSA-N 0.000 description 2
• RKOQMDUDKCMVFW-UHFFFAOYSA-N methyl 4-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylate Chemical compound COC(=O)C1CCC(NC(=O)OC(C)(C)C)CC1 RKOQMDUDKCMVFW-UHFFFAOYSA-N 0.000 description 2
• FFKGMXGWLOPOAO-UHFFFAOYSA-N methyl 4-aminocyclohexane-1-carboxylate Chemical compound COC(=O)C1CCC(N)CC1 FFKGMXGWLOPOAO-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• SRAXAXHQMCQHSH-UHFFFAOYSA-N n-benzyl-2-chloroacetamide Chemical compound ClCC(=O)NCC1=CC=CC=C1 SRAXAXHQMCQHSH-UHFFFAOYSA-N 0.000 description 2
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• UBBSHXCLOFHQHW-UHFFFAOYSA-N oxane-4-carbohydrazide Chemical compound NNC(=O)C1CCOCC1 UBBSHXCLOFHQHW-UHFFFAOYSA-N 0.000 description 2
• 238000005949 ozonolysis reaction Methods 0.000 description 2
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
• 239000004177 patent blue V Substances 0.000 description 2
• 235000012736 patent blue V Nutrition 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 231100000572 poisoning Toxicity 0.000 description 2
• 230000000607 poisoning effect Effects 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000004175 ponceau 4R Substances 0.000 description 2
• 235000012731 ponceau 4R Nutrition 0.000 description 2
• 235000019238 ponceau 6R Nutrition 0.000 description 2
• 235000019237 ponceau SX Nutrition 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 230000001242 postsynaptic effect Effects 0.000 description 2
• 235000011181 potassium carbonates Nutrition 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 210000005215 presynaptic neuron Anatomy 0.000 description 2
• 239000003380 propellant Substances 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 239000004172 quinoline yellow Substances 0.000 description 2
• 235000012752 quinoline yellow Nutrition 0.000 description 2
• 239000002287 radioligand Substances 0.000 description 2
• 229940044551 receptor antagonist Drugs 0.000 description 2
• 239000002464 receptor antagonist Substances 0.000 description 2
• 239000004180 red 2G Substances 0.000 description 2
• 235000012739 red 2G Nutrition 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 239000002151 riboflavin Substances 0.000 description 2
• 235000019192 riboflavin Nutrition 0.000 description 2
• 235000019234 riboflavin-5-sodium phosphate Nutrition 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• 239000004248 saffron Substances 0.000 description 2
• 235000013974 saffron Nutrition 0.000 description 2
• XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 2
• 239000004332 silver Substances 0.000 description 2
• 235000010191 silver Nutrition 0.000 description 2
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 239000001648 tannin Substances 0.000 description 2
• 235000018553 tannin Nutrition 0.000 description 2
• 239000004149 tartrazine Substances 0.000 description 2
• 235000012756 tartrazine Nutrition 0.000 description 2
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• YJVQHMCAELMPFG-UHFFFAOYSA-N tert-butyl 1H-imidazo[4,5-b]pyridine-5-carboxylate Chemical compound N1C=NC2=NC(=CC=C21)C(=O)OC(C)(C)C YJVQHMCAELMPFG-UHFFFAOYSA-N 0.000 description 2
• GPNPKYIEFVVKJV-UHFFFAOYSA-N tert-butyl 3-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]azetidine-1-carboxylate Chemical compound ClCCCSC=1N(C(=NN=1)C1CN(C1)C(=O)OC(C)(C)C)C GPNPKYIEFVVKJV-UHFFFAOYSA-N 0.000 description 2
• DSPKFTKFUCSZMM-LXFBAYGMSA-N tert-butyl 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidine-1-carboxylate Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1CCN(CC1)C(=O)OC(C)(C)C DSPKFTKFUCSZMM-LXFBAYGMSA-N 0.000 description 2
• VUZSTQJBWQCOIP-UHFFFAOYSA-N tert-butyl N-[4-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)cyclohexyl]carbamate Chemical compound CN1C(=NN=C1S)C1CCC(CC1)NC(OC(C)(C)C)=O VUZSTQJBWQCOIP-UHFFFAOYSA-N 0.000 description 2
• QJTBFAYOONJPNN-UHFFFAOYSA-N tert-butyl N-[4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]cyclohexyl]carbamate Chemical compound ClCCCSC=1N(C(=NN=1)C1CCC(CC1)NC(OC(C)(C)C)=O)C QJTBFAYOONJPNN-UHFFFAOYSA-N 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• 235000019235 yellow 2G Nutrition 0.000 description 2
• MPZCQSMGJZWATG-YJKXCHRFSA-N (2R,3R)-2-(2,4-difluorophenyl)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-5-azaspiro[2.4]heptane dihydrochloride Chemical compound Cl.Cl.Cn1c(SCCCN2CC[C@@]3(C[C@H]3c3ccc(F)cc3F)C2)nnc1-c1cccnc1 MPZCQSMGJZWATG-YJKXCHRFSA-N 0.000 description 1
• GXOYNBTVJDTLKB-GBXCKJPGSA-N (2R,3R)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-[4-[4-methyl-5-(oxan-4-yl)-1,2,4-triazol-3-yl]butyl]-5-azaspiro[2.4]heptane Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@@H]1C[C@]11CN(CC1)CCCCC1=NN=C(N1C)C1CCOCC1 GXOYNBTVJDTLKB-GBXCKJPGSA-N 0.000 description 1
• OIYCSJHRTCYWDE-QPBMFBNESA-N (2R,3S)-2-(4-fluorophenyl)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-5-azaspiro[2.4]heptane dihydrochloride Chemical compound Cl.Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(F)cc3)C2)nnc1-c1cccnc1 OIYCSJHRTCYWDE-QPBMFBNESA-N 0.000 description 1
• JPWLTBCERFJSPC-MOPGFXCFSA-N (2R,3S)-5-(4-methylphenyl)sulfonyl-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CC1=CC=C(C=C1)S(=O)(=O)N1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 JPWLTBCERFJSPC-MOPGFXCFSA-N 0.000 description 1
• DRWIXNVECBQZQQ-QPBMFBNESA-N (2R,3S)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane dihydrochloride Chemical compound Cl.Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1-c1cccnc1 DRWIXNVECBQZQQ-QPBMFBNESA-N 0.000 description 1
• LDARTYSGUXXZNF-WKDBURHASA-N (2R,3S)-5-[3-[(5-cyclohexyl-4-methyl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1C1CCCCC1 LDARTYSGUXXZNF-WKDBURHASA-N 0.000 description 1
• VOQSYGZGARDKHD-ZCTICWJUSA-N (2R,3S)-5-[3-[[4-methyl-5-(2-methylpyridin-3-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane dihydrochloride Chemical compound Cl.Cl.Cc1ncccc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)n1C VOQSYGZGARDKHD-ZCTICWJUSA-N 0.000 description 1
• VOMFPLMIPVEXFG-BWBOJHCNSA-N (2R,3S)-5-[3-[[4-methyl-5-(3-methylpyridin-2-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane dihydrochloride Chemical compound Cl.Cl.Cc1cccnc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)n1C VOMFPLMIPVEXFG-BWBOJHCNSA-N 0.000 description 1
• VDNXNGGDIUEYIL-PBOJDWPOSA-N (2R,3S)-5-[3-[[4-methyl-5-(8-oxabicyclo[3.2.1]octan-3-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1C1CC2CCC(C1)O2 VDNXNGGDIUEYIL-PBOJDWPOSA-N 0.000 description 1
• IWCSEKQLVZIHPU-BWKNWUBXSA-N (2R,3S)-5-[3-[[4-methyl-5-[4-(2H-tetrazol-5-yl)phenyl]-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=CC=C(C=C1)C1=NN=NN1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 IWCSEKQLVZIHPU-BWKNWUBXSA-N 0.000 description 1
• GPDZHKOGLHALQL-PGRDOPGGSA-N (2S,3R)-5-[3-[(4-methyl-5-pyrazin-2-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=NC=CN=C1)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 GPDZHKOGLHALQL-PGRDOPGGSA-N 0.000 description 1
• ACKJXZGTUCARLB-SIKLNZKXSA-N (2S,3R)-5-[3-[(4-methyl-5-pyridazin-4-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=CN=NC=C1)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 ACKJXZGTUCARLB-SIKLNZKXSA-N 0.000 description 1
• KIDLIVLNXRZSJP-SIKLNZKXSA-N (2S,3R)-5-[3-[[4-methyl-5-(1-methylpyrazol-4-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C=1C=NN(C=1)C)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 KIDLIVLNXRZSJP-SIKLNZKXSA-N 0.000 description 1
• BADZIIJBCNPURN-PGRDOPGGSA-N (2S,3R)-5-[3-[[4-methyl-5-(2-methylpyrazol-3-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=CC=NN1C)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 BADZIIJBCNPURN-PGRDOPGGSA-N 0.000 description 1
• WSVPKQPBMGHTOP-WMZHIEFXSA-N (2S,3R)-5-[3-[[4-methyl-5-(3-methylpyrazin-2-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C1=NC=CN=C1C)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 WSVPKQPBMGHTOP-WMZHIEFXSA-N 0.000 description 1
• DOMQFIFVDIAOOT-ROUUACIJSA-N (2S,3R)-N-[4-(2,6-dimethoxyphenyl)-5-(5-methylpyridin-3-yl)-1,2,4-triazol-3-yl]-3-(5-methylpyrimidin-2-yl)butane-2-sulfonamide Chemical compound COC1=C(C(=CC=C1)OC)N1C(=NN=C1C=1C=NC=C(C=1)C)NS(=O)(=O)[C@@H](C)[C@H](C)C1=NC=C(C=N1)C DOMQFIFVDIAOOT-ROUUACIJSA-N 0.000 description 1
• MPZCQSMGJZWATG-UNAPJJAOSA-N (2S,3S)-2-(2,4-difluorophenyl)-5-[3-[(4-methyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]propyl]-5-azaspiro[2.4]heptane dihydrochloride Chemical compound Cl.Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(F)cc3F)C2)nnc1-c1cccnc1 MPZCQSMGJZWATG-UNAPJJAOSA-N 0.000 description 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
• UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical group CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• WORJRXHJTUTINR-UHFFFAOYSA-N 1,4-dioxane;hydron;chloride Chemical compound Cl.C1COCCO1 WORJRXHJTUTINR-UHFFFAOYSA-N 0.000 description 1
• 150000000094 1,4-dioxanes Chemical class 0.000 description 1
• MJUVRTYWUMPBTR-MRXNPFEDSA-N 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-n-[1-[(2r)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide Chemical compound FC=1C=C2N(C[C@@H](O)CO)C(C(C)(CO)C)=CC2=CC=1NC(=O)C1(C=2C=C3OC(F)(F)OC3=CC=2)CC1 MJUVRTYWUMPBTR-MRXNPFEDSA-N 0.000 description 1
• NCADHSLPNSTDMJ-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]azetidine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CC(C(O)=O)C1 NCADHSLPNSTDMJ-UHFFFAOYSA-N 0.000 description 1
• XBRXHKVRMSRUIF-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]imidazo[4,5-b]pyridine-5-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)N1C=NC2=NC(=CC=C21)C(=O)O XBRXHKVRMSRUIF-UHFFFAOYSA-N 0.000 description 1
• JWOHBPPVVDQMKB-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C(O)=O)CC1 JWOHBPPVVDQMKB-UHFFFAOYSA-N 0.000 description 1
• JSWRFEXRUMWDHM-OEAUSWNVSA-N 1-[4-[5-[3-[(2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]piperidin-1-yl]ethanone hydrochloride Chemical compound Cl.CC(=O)N1CCC(CC1)c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3F)C(F)(F)F)C2)n1C JSWRFEXRUMWDHM-OEAUSWNVSA-N 0.000 description 1
• TVDCSPSRGSLXOV-UHFFFAOYSA-N 1-bromo-3-chloropropan-2-ol Chemical compound ClCC(O)CBr TVDCSPSRGSLXOV-UHFFFAOYSA-N 0.000 description 1
• NIDSRGCVYOEDFW-UHFFFAOYSA-N 1-bromo-4-chlorobutane Chemical compound ClCCCCBr NIDSRGCVYOEDFW-UHFFFAOYSA-N 0.000 description 1
• CGGIRFQQHXXJJP-UHFFFAOYSA-N 1-chloro-3-[[4-methyl-5-(4-methyl-1,3-oxazol-5-yl)-1,2,4-triazol-3-yl]sulfanyl]propan-2-ol Chemical compound ClCC(CSC1=NN=C(N1C)C1=C(N=CO1)C)O CGGIRFQQHXXJJP-UHFFFAOYSA-N 0.000 description 1
• DKKUSUXSDPJUSI-UFZJIDKFSA-N 1-methyl-4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridin-2-one hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1-c1ccn(C)c(=O)c1 DKKUSUXSDPJUSI-UFZJIDKFSA-N 0.000 description 1
• LNNUOCXOGAGPSZ-UFZJIDKFSA-N 1-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridin-2-one hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1-c1ccc(=O)n(C)c1 LNNUOCXOGAGPSZ-UFZJIDKFSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• NRVIZYWYHXROKA-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyridine-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=NC2=N1 NRVIZYWYHXROKA-UHFFFAOYSA-N 0.000 description 1
• QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
• WCGPCBACLBHDCI-UHFFFAOYSA-N 2,4-difluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(F)=C1 WCGPCBACLBHDCI-UHFFFAOYSA-N 0.000 description 1
• ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 1
• PGNPMTAEFDKCKN-BWKNWUBXSA-N 2-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]benzamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=C(C(=O)N)C=CC=C1 PGNPMTAEFDKCKN-BWKNWUBXSA-N 0.000 description 1
• YMMKVLDFUKHZTJ-LAUBAEHRSA-N 2-[4-methyl-5-[3-[(2S,3R)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-thiazole Chemical compound CN1C(=NN=C1C=1SC=CN=1)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 YMMKVLDFUKHZTJ-LAUBAEHRSA-N 0.000 description 1
• FUEBNGXWVTUNNZ-UHFFFAOYSA-N 2-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-3-methylpyridine Chemical compound ClCCCSC=1N(C(=NN=1)C1=NC=CC=C1C)C FUEBNGXWVTUNNZ-UHFFFAOYSA-N 0.000 description 1
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
• RIEKUXDEDZHANI-UHFFFAOYSA-N 2-carbamoylpyridine-4-carboxylic acid Chemical compound NC(=O)C1=CC(C(O)=O)=CC=N1 RIEKUXDEDZHANI-UHFFFAOYSA-N 0.000 description 1
• MPSVJNPESHZCIB-UHFFFAOYSA-N 2-cyanopyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(C#N)=C1 MPSVJNPESHZCIB-UHFFFAOYSA-N 0.000 description 1
• KFEHNXLFIGPWNB-UHFFFAOYSA-N 2-fluoro-4-(trifluoromethyl)benzaldehyde Chemical compound FC1=CC(C(F)(F)F)=CC=C1C=O KFEHNXLFIGPWNB-UHFFFAOYSA-N 0.000 description 1
• CASRSOJWLARCRX-UHFFFAOYSA-N 3,5-dichlorobenzaldehyde Chemical compound ClC1=CC(Cl)=CC(C=O)=C1 CASRSOJWLARCRX-UHFFFAOYSA-N 0.000 description 1
• IMAITKPPSLYKDS-UHFFFAOYSA-N 3-(1,3-oxazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2OC=CN=2)=C1 IMAITKPPSLYKDS-UHFFFAOYSA-N 0.000 description 1
• ZXWWKJQUEJPGPJ-UHFFFAOYSA-N 3-(2-fluoropyridin-3-yl)-4-methyl-1H-1,2,4-triazole-5-thione Chemical compound FC1=NC=CC=C1C=1N(C(=NN=1)S)C ZXWWKJQUEJPGPJ-UHFFFAOYSA-N 0.000 description 1
• DYFVISXQTYSCOG-UHFFFAOYSA-N 3-(3-chloropropylsulfanyl)-4-methyl-5-(8-oxabicyclo[3.2.1]octan-3-yl)-1,2,4-triazole Chemical compound ClCCCSC1=NN=C(N1C)C1CC2CCC(C1)O2 DYFVISXQTYSCOG-UHFFFAOYSA-N 0.000 description 1
• YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
• ZKYFBZLLGWGMBS-XXBNENTESA-N 3-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1H-pyridin-2-one Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C=1C(NC=CC=1)=O ZKYFBZLLGWGMBS-XXBNENTESA-N 0.000 description 1
• WASDZRRTJAQSFA-UHFFFAOYSA-N 3-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-2,6-dimethylpyridine Chemical compound ClCCCSC=1N(C(=NN=1)C=1C(=NC(=CC=1)C)C)C WASDZRRTJAQSFA-UHFFFAOYSA-N 0.000 description 1
• JUXCJIJVFUQCPC-UHFFFAOYSA-N 3-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-2-(trifluoromethyl)pyridine Chemical compound ClCCCSC=1N(C(=NN=1)C=1C(=NC=CC=1)C(F)(F)F)C JUXCJIJVFUQCPC-UHFFFAOYSA-N 0.000 description 1
• HTFCFZTUXIFCBY-UHFFFAOYSA-N 3-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-2-methoxypyridine Chemical compound ClCCCSC=1N(C(=NN=1)C=1C(=NC=CC=1)OC)C HTFCFZTUXIFCBY-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
• GTYRFVGHYNRSKT-UHFFFAOYSA-N 3-benzylpyrrole-2,5-dione Chemical compound O=C1NC(=O)C(CC=2C=CC=CC=2)=C1 GTYRFVGHYNRSKT-UHFFFAOYSA-N 0.000 description 1
• JCGXQZJXWOVCST-VFFVIGNKSA-N 3-methoxy-1-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-1-yl]propan-1-one hydrochloride Chemical compound Cl.COCCC(=O)N1CCC(CC1)c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)n1C JCGXQZJXWOVCST-VFFVIGNKSA-N 0.000 description 1
• WMZNGTSLFSJHMZ-UHFFFAOYSA-N 3-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=CC(C(O)=O)=C1 WMZNGTSLFSJHMZ-UHFFFAOYSA-N 0.000 description 1
• HTNUUDFQRYBJPH-UHFFFAOYSA-N 3-methoxypropanehydrazide Chemical compound COCCC(=O)NN HTNUUDFQRYBJPH-UHFFFAOYSA-N 0.000 description 1
• TXEGIIUTZDNUKA-PGRDOPGGSA-N 3-methyl-5-[4-methyl-5-[3-[(2S,3R)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,2-oxazole Chemical compound CN1C(=NN=C1C1=CC(=NO1)C)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 TXEGIIUTZDNUKA-PGRDOPGGSA-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
• GCYLRAAXDONHQQ-UHFFFAOYSA-N 4-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyridine-2-carboxamide Chemical compound CN1C(=NN=C1S)C1=CC(=NC=C1)C(=O)N GCYLRAAXDONHQQ-UHFFFAOYSA-N 0.000 description 1
• RSGBXCFAYHOKQZ-UHFFFAOYSA-N 4-(cyanomethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(CC#N)C=C1 RSGBXCFAYHOKQZ-UHFFFAOYSA-N 0.000 description 1
• BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
• VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
• ZBANATRLWYFNTQ-GVWAYPJCSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]morpholine hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1N1CCOCC1 ZBANATRLWYFNTQ-GVWAYPJCSA-N 0.000 description 1
• AXPQNGNDUAAQRH-QTVLPVNYSA-N 4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-2-one hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1C1CCNC(=O)C1 AXPQNGNDUAAQRH-QTVLPVNYSA-N 0.000 description 1
• XTBZISSXSHQVSO-UHFFFAOYSA-N 4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-1-methylpiperidin-2-one Chemical compound ClCCCSC=1N(C(=NN=1)C1CC(N(CC1)C)=O)C XTBZISSXSHQVSO-UHFFFAOYSA-N 0.000 description 1
• URFMTBQGGFADPK-UHFFFAOYSA-N 4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]piperidin-2-one Chemical compound ClCCCSC=1N(C(=NN=1)C1CC(NCC1)=O)C URFMTBQGGFADPK-UHFFFAOYSA-N 0.000 description 1
• SNZKCVJAXZSPCW-UHFFFAOYSA-N 4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]pyridine-2-carbonitrile Chemical compound ClCCCSC=1N(C(=NN=1)C1=CC(=NC=C1)C#N)C SNZKCVJAXZSPCW-UHFFFAOYSA-N 0.000 description 1
• NXHZAJXHHRXNJO-UHFFFAOYSA-N 4-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound ClCCCSC=1N(C(=NN=1)C1=CC(=NC=C1)C(=O)N)C NXHZAJXHHRXNJO-UHFFFAOYSA-N 0.000 description 1
• XYWIPYBIIRTJMM-IBGZPJMESA-N 4-[[(2S)-2-[4-[5-chloro-2-[4-(trifluoromethyl)triazol-1-yl]phenyl]-5-methoxy-2-oxopyridin-1-yl]butanoyl]amino]-2-fluorobenzamide Chemical compound CC[C@H](N1C=C(OC)C(=CC1=O)C1=C(C=CC(Cl)=C1)N1C=C(N=N1)C(F)(F)F)C(=O)NC1=CC(F)=C(C=C1)C(N)=O XYWIPYBIIRTJMM-IBGZPJMESA-N 0.000 description 1
• JDDQECMBPWVIRU-UHFFFAOYSA-N 4-azaspiro[2.4]heptane Chemical compound C1CC11NCCC1 JDDQECMBPWVIRU-UHFFFAOYSA-N 0.000 description 1
• VAYDZIKCDHPPKD-UHFFFAOYSA-N 4-azaspiro[2.4]heptane;hydrochloride Chemical compound Cl.C1CC11NCCC1 VAYDZIKCDHPPKD-UHFFFAOYSA-N 0.000 description 1
• JMHSCWJIDIKGNZ-UHFFFAOYSA-N 4-carbamoylbenzoic acid Chemical compound NC(=O)C1=CC=C(C(O)=O)C=C1 JMHSCWJIDIKGNZ-UHFFFAOYSA-N 0.000 description 1
• NONOHEMDNFTKCZ-UHFFFAOYSA-N 4-fluoro-2-(trifluoromethyl)benzaldehyde Chemical compound FC1=CC=C(C=O)C(C(F)(F)F)=C1 NONOHEMDNFTKCZ-UHFFFAOYSA-N 0.000 description 1
• UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
• BRQOCRJSLFBJEA-UHFFFAOYSA-N 4-methyl-5-(4-methyl-5-pent-4-enyl-1,2,4-triazol-3-yl)-1,3-oxazole Chemical compound N1=COC(C=2N(C(CCCC=C)=NN=2)C)=C1C BRQOCRJSLFBJEA-UHFFFAOYSA-N 0.000 description 1
• NDIKYSYWQURBJB-MYXGOWFTSA-N 4-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-oxazole hydrochloride Chemical compound Cl.Cc1ncoc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)n1C NDIKYSYWQURBJB-MYXGOWFTSA-N 0.000 description 1
• BDWGMLHCTFNAOZ-MYXGOWFTSA-N 4-methyl-5-[4-methyl-5-[3-[(2R,3S)-2-phenyl-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-oxazole hydrochloride Chemical compound Cl.Cc1ncoc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccccc3)C2)n1C BDWGMLHCTFNAOZ-MYXGOWFTSA-N 0.000 description 1
• NFIANDWIUXYLJZ-PGRDOPGGSA-N 4-methyl-5-[4-methyl-5-[3-[(2S,3R)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-thiazole Chemical compound CN1C(=NN=C1C1=C(N=CS1)C)SCCCN1C[C@]2(C[C@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 NFIANDWIUXYLJZ-PGRDOPGGSA-N 0.000 description 1
• AAPXNHMQKBDDJN-PGRDOPGGSA-N 4-methyl-5-[4-methyl-5-[3-[(2S,3R)-2-phenyl-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1,3-oxazole Chemical compound CN1C(SCCCN2CC[C@@]3(C[C@H]3C3=CC=CC=C3)C2)=NN=C1C1=C(C)N=CO1 AAPXNHMQKBDDJN-PGRDOPGGSA-N 0.000 description 1
• OWLXUYGCLDGHJJ-UHFFFAOYSA-N 4-oxocyclohexanecarboxylic acid Chemical compound OC(=O)C1CCC(=O)CC1 OWLXUYGCLDGHJJ-UHFFFAOYSA-N 0.000 description 1
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
• KIDLIVLNXRZSJP-UHFFFAOYSA-N 5-[3-[[4-methyl-5-(1-methylpyrazol-4-yl)-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptane Chemical compound CN1C(=NN=C1C=1C=NN(C=1)C)SCCCN1CC2(CC2C2=CC=C(C=C2)C(F)(F)F)CC1 KIDLIVLNXRZSJP-UHFFFAOYSA-N 0.000 description 1
• KMLVPTIJPYAULP-KOSHJBKYSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-1H-imidazo[4,5-b]pyridine Chemical compound N1C=NC2=NC(=CC=C21)C=1N(C(=NN=1)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C KMLVPTIJPYAULP-KOSHJBKYSA-N 0.000 description 1
• REOIANOERYLQGC-HXOBKFHXSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyrazine-2-carboxamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C=1N=CC(=NC=1)C(=O)N REOIANOERYLQGC-HXOBKFHXSA-N 0.000 description 1
• VBAHHNZBILDQIH-ZCTICWJUSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carbonitrile dihydrochloride Chemical compound Cl.Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1-c1ccc(nc1)C#N VBAHHNZBILDQIH-ZCTICWJUSA-N 0.000 description 1
• FSHUHBLZJXALFQ-SRQVPYBOSA-N 5-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carboxamide dihydrochloride Chemical compound Cl.Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1-c1ccc(nc1)C(N)=O FSHUHBLZJXALFQ-SRQVPYBOSA-N 0.000 description 1
• FOLYXAZAZJLWIN-UHFFFAOYSA-N 5-[5-(2-chloroethylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole Chemical compound CN1C(SCCCl)=NN=C1C1=C(C)N=CO1 FOLYXAZAZJLWIN-UHFFFAOYSA-N 0.000 description 1
• HIFXSTYPFANQMX-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-1-methylpyridin-2-one Chemical compound ClCCCSC=1N(C(=NN=1)C=1C=CC(N(C=1)C)=O)C HIFXSTYPFANQMX-UHFFFAOYSA-N 0.000 description 1
• FSNPGNWRDLLLLF-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]-2-methylpyridine Chemical compound C1=NC(C)=CC=C1C1=NN=C(SCCCCl)N1C FSNPGNWRDLLLLF-UHFFFAOYSA-N 0.000 description 1
• JCYPFJSDILFUTQ-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]piperidin-2-one Chemical compound ClCCCSC=1N(C(=NN=1)C1CCC(NC1)=O)C JCYPFJSDILFUTQ-UHFFFAOYSA-N 0.000 description 1
• IVFKAAIJLNUGCM-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]pyridine-2-carbonitrile Chemical compound ClCCCSC=1N(C(=NN=1)C=1C=CC(=NC=1)C#N)C IVFKAAIJLNUGCM-UHFFFAOYSA-N 0.000 description 1
• ZVRHXYHNVBAMMP-UHFFFAOYSA-N 5-[5-(3-chloropropylsulfanyl)-4-methyl-1,2,4-triazol-3-yl]pyridine-3-carboxamide Chemical compound ClCCCSC=1N(C(=NN=1)C=1C=C(C=NC=1)C(=O)N)C ZVRHXYHNVBAMMP-UHFFFAOYSA-N 0.000 description 1
• TXOPCODJELQURT-MHECFPHRSA-N 5-[5-[3-[(2R,3R)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)[C@@H]1C[C@]11CN(CC1)CCCSC=1N(C(=NN=1)C=1C=CC(=NC=1)C(=O)N)C TXOPCODJELQURT-MHECFPHRSA-N 0.000 description 1
• AHMAFHOXASLFCL-MYXGOWFTSA-N 5-[5-[3-[(2R,3S)-2-(4-fluorophenyl)-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole hydrochloride Chemical compound Cl.Cc1ncoc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(F)cc3)C2)n1C AHMAFHOXASLFCL-MYXGOWFTSA-N 0.000 description 1
• XIHOJUYAGODVFH-VGSWGCGISA-N 5-[5-[3-[(2S,3S)-2-(2,4-difluorophenyl)-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole Chemical compound CN1C(SCCCN2CC[C@]3(C[C@@H]3C3=C(F)C=C(F)C=C3)C2)=NN=C1C1=C(C)N=CO1 XIHOJUYAGODVFH-VGSWGCGISA-N 0.000 description 1
• LVMBQHRBJHASKT-YITVUBHWSA-N 5-[5-[3-[(2S,3S)-2-[2-fluoro-4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-4-methyl-1,2,4-triazol-3-yl]-4-methyl-1,3-oxazole hydrochloride Chemical compound Cl.Cc1ncoc1-c1nnc(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3F)C(F)(F)F)C2)n1C LVMBQHRBJHASKT-YITVUBHWSA-N 0.000 description 1
• HRLVPHGCEGTVLK-UHFFFAOYSA-N 5-cyanopyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(C#N)C=N1 HRLVPHGCEGTVLK-UHFFFAOYSA-N 0.000 description 1
• PUMHSXJEGULOAA-UHFFFAOYSA-N 5-methyl-6-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)pyridine-2-carboxamide Chemical compound CC=1C=CC(=NC=1C1=NN=C(N1C)S)C(=O)N PUMHSXJEGULOAA-UHFFFAOYSA-N 0.000 description 1
• IKHSNNZHMXUISD-UHFFFAOYSA-N 6-(4-methyl-5-sulfanylidene-1H-1,2,4-triazol-3-yl)-1H-pyridin-2-one Chemical compound CN1C(=NN=C1S)C1=CC=CC(N1)=O IKHSNNZHMXUISD-UHFFFAOYSA-N 0.000 description 1
• MRPAGRCGPAXOGS-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carbaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=N1 MRPAGRCGPAXOGS-UHFFFAOYSA-N 0.000 description 1
• FZIBXGSEBVJOQF-KOSHJBKYSA-N 6-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]pyridine-2-carboxamide Chemical compound CN1C(=NN=C1SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1)C1=CC=CC(=N1)C(=O)N FZIBXGSEBVJOQF-KOSHJBKYSA-N 0.000 description 1
• YFBVTSTUGAZQFG-YKSBVNFPSA-N 7-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-[1,2,4]triazolo[4,3-a]pyridine Chemical compound CN1C(=NN=C1C1=CC=2N(C=C1)C=NN=2)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 YFBVTSTUGAZQFG-YKSBVNFPSA-N 0.000 description 1
• GYXPZSHXUOBHGQ-YKSBVNFPSA-N 8-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]-[1,2,4]triazolo[4,3-a]pyridine Chemical compound CN1C(=NN=C1C=1C=2N(C=CC=1)C=NN=2)SCCCN1C[C@@]2(C[C@@H]2C2=CC=C(C=C2)C(F)(F)F)CC1 GYXPZSHXUOBHGQ-YKSBVNFPSA-N 0.000 description 1
• ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 206010001605 Alcohol poisoning Diseases 0.000 description 1
• 208000017167 Alcohol-Induced disease Diseases 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 208000000103 Anorexia Nervosa Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000021465 Brief psychotic disease Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 206010006550 Bulimia nervosa Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• 208000000094 Chronic Pain Diseases 0.000 description 1
• LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
• 108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 208000035874 Excoriation Diseases 0.000 description 1
• CDYNJELVCDITSO-UHFFFAOYSA-N FC1=C(C=CC(=C1)C(F)(F)F)C=NN Chemical compound FC1=C(C=CC(=C1)C(F)(F)F)C=NN CDYNJELVCDITSO-UHFFFAOYSA-N 0.000 description 1
• GISRWBROCYNDME-PELMWDNLSA-N F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C Chemical compound F[C@H]1[C@H]([C@H](NC1=O)COC1=NC=CC2=CC(=C(C=C12)OC)C(=O)N)C GISRWBROCYNDME-PELMWDNLSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000014513 Hoarding disease Diseases 0.000 description 1
• 206010020710 Hyperphagia Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
• WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 239000002841 Lewis acid Substances 0.000 description 1
• 206010024419 Libido decreased Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 206010027387 Merycism Diseases 0.000 description 1
• 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 1
• 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 1
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
• FEYNFHSRETUBEM-UHFFFAOYSA-N N-[3-(1,1-difluoroethyl)phenyl]-1-(4-methoxyphenyl)-3-methyl-5-oxo-4H-pyrazole-4-carboxamide Chemical compound COc1ccc(cc1)N1N=C(C)C(C(=O)Nc2cccc(c2)C(C)(F)F)C1=O FEYNFHSRETUBEM-UHFFFAOYSA-N 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• 241000208125 Nicotiana Species 0.000 description 1
• 206010057852 Nicotine dependence Diseases 0.000 description 1
• 239000004235 Orange GGN Substances 0.000 description 1
• 239000004218 Orcein Substances 0.000 description 1
• CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 241001482237 Pica Species 0.000 description 1
• 208000006262 Psychological Sexual Dysfunctions Diseases 0.000 description 1
• 208000005793 Restless legs syndrome Diseases 0.000 description 1
• 208000011390 Rumination Syndrome Diseases 0.000 description 1
• 206010070834 Sensitisation Diseases 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 231100000643 Substance intoxication Toxicity 0.000 description 1
• 208000011963 Substance-induced psychotic disease Diseases 0.000 description 1
• 231100000393 Substance-induced psychotic disorder Toxicity 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 208000025569 Tobacco Use disease Diseases 0.000 description 1
• 206010043903 Tobacco abuse Diseases 0.000 description 1
• 208000000323 Tourette Syndrome Diseases 0.000 description 1
• 208000016620 Tourette disease Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• AYSYSOQSKKDJJY-UHFFFAOYSA-N [1,2,4]triazolo[4,3-a]pyridine Chemical compound C1=CC=CN2C=NN=C21 AYSYSOQSKKDJJY-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 238000011360 adjunctive therapy Methods 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 201000007930 alcohol dependence Diseases 0.000 description 1
• 208000025746 alcohol use disease Diseases 0.000 description 1
• 208000029650 alcohol withdrawal Diseases 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000003282 alkyl amino group Chemical group 0.000 description 1
• 150000005215 alkyl ethers Chemical class 0.000 description 1
• 125000005103 alkyl silyl group Chemical group 0.000 description 1
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 230000003042 antagnostic effect Effects 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000000561 anti-psychotic effect Effects 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 230000037007 arousal Effects 0.000 description 1
• 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 150000001557 benzodiazepines Chemical class 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
• 239000012964 benzotriazole Substances 0.000 description 1
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 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
• 150000003939 benzylamines Chemical class 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 208000022266 body dysmorphic disease Diseases 0.000 description 1
• 230000003925 brain function Effects 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 125000005998 bromoethyl group Chemical group 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• USJRLGNYCQWLPF-UHFFFAOYSA-N chlorophosphane Chemical compound ClP USJRLGNYCQWLPF-UHFFFAOYSA-N 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 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
• 238000011097 chromatography purification Methods 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002591 computed tomography Methods 0.000 description 1
• 238000011340 continuous therapy Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
• 238000005888 cyclopropanation reaction Methods 0.000 description 1
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
• RAGRDRQXLHMEIB-VFFVIGNKSA-N cyclopropyl-[4-[4-methyl-5-[3-[(2R,3S)-2-[4-(trifluoromethyl)phenyl]-5-azaspiro[2.4]heptan-5-yl]propylsulfanyl]-1,2,4-triazol-3-yl]piperidin-1-yl]methanone hydrochloride Chemical compound Cl.Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(cc3)C(F)(F)F)C2)nnc1C1CCN(CC1)C(=O)C1CC1 RAGRDRQXLHMEIB-VFFVIGNKSA-N 0.000 description 1
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 229940043237 diethanolamine Drugs 0.000 description 1
• 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
• BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
• HDTNLHHNQYBOHJ-UHFFFAOYSA-N dimethyl pyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=CN=CC(C(=O)OC)=C1 HDTNLHHNQYBOHJ-UHFFFAOYSA-N 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 125000005883 dithianyl group Chemical group 0.000 description 1
• 229940052760 dopamine agonists Drugs 0.000 description 1
• 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 230000000857 drug effect Effects 0.000 description 1
• 235000005686 eating Nutrition 0.000 description 1
• 230000020595 eating behavior Effects 0.000 description 1
• 230000006397 emotional response Effects 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000005538 encapsulation Methods 0.000 description 1
• 230000007613 environmental effect Effects 0.000 description 1
• 230000001856 erectile effect Effects 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• SGIBUKNPAQMWAP-UHFFFAOYSA-N ethyl 2-bromo-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC(Br)=N1 SGIBUKNPAQMWAP-UHFFFAOYSA-N 0.000 description 1
• RDULEYWUGKOCMR-UHFFFAOYSA-N ethyl 2-chloro-3-oxobutanoate Chemical compound CCOC(=O)C(Cl)C(C)=O RDULEYWUGKOCMR-UHFFFAOYSA-N 0.000 description 1
• FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 208000014840 female orgasmic disease Diseases 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 235000012631 food intake Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 208000011331 hallucinogen-persisting perception disease Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 208000017020 hypoactive sexual desire disease Diseases 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 201000004197 inhibited female orgasm Diseases 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 239000012948 isocyanate Substances 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 150000003951 lactams Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• MJIVRKPEXXHNJT-UHFFFAOYSA-N lutidinic acid Chemical compound OC(=O)C1=CC=NC(C(O)=O)=C1 MJIVRKPEXXHNJT-UHFFFAOYSA-N 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 238000002483 medication Methods 0.000 description 1
• 230000007721 medicinal effect Effects 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 230000004630 mental health Effects 0.000 description 1
• 210000001259 mesencephalon Anatomy 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
• NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• QWIBVYWYUVKJLX-UHFFFAOYSA-N methyl hept-6-enimidate hydrochloride Chemical compound Cl.COC(=N)CCCCC=C QWIBVYWYUVKJLX-UHFFFAOYSA-N 0.000 description 1
• CNCMVGXVKBJYNU-UHFFFAOYSA-N methyl oxane-4-carboxylate Chemical compound COC(=O)C1CCOCC1 CNCMVGXVKBJYNU-UHFFFAOYSA-N 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000008450 motivation Effects 0.000 description 1
• ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
• FMASTMURQSHELY-UHFFFAOYSA-N n-(4-fluoro-2-methylphenyl)-3-methyl-n-[(2-methyl-1h-indol-4-yl)methyl]pyridine-4-carboxamide Chemical compound C1=CC=C2NC(C)=CC2=C1CN(C=1C(=CC(F)=CC=1)C)C(=O)C1=CC=NC=C1C FMASTMURQSHELY-UHFFFAOYSA-N 0.000 description 1
• FTNFEHXDETWERN-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]-2,6-dimethyl-5-[(4-propan-2-yloxyphenyl)methyl]pyrimidin-4-amine Chemical compound C1=CC(OC(C)C)=CC=C1CC1=C(C)N=C(C)N=C1NP(=O)(N1CC1)N1CC1 FTNFEHXDETWERN-UHFFFAOYSA-N 0.000 description 1
• XHXVAJHZTIXQQD-UHFFFAOYSA-N n-[bis(aziridin-1-yl)phosphoryl]-5-[(4-butoxyphenyl)methyl]-2,6-dimethylpyrimidin-4-amine Chemical compound C1=CC(OCCCC)=CC=C1CC1=C(C)N=C(C)N=C1NP(=O)(N1CC1)N1CC1 XHXVAJHZTIXQQD-UHFFFAOYSA-N 0.000 description 1
• NNKPHNTWNILINE-UHFFFAOYSA-N n-cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxopyrazin-1-yl]benzamide Chemical compound CNCCOC1=CC=CC=C1C1(NC=2C(N(C=3C(=C(F)C=C(C=3)C(=O)NC3CC3)C)C=CN=2)=O)CC1 NNKPHNTWNILINE-UHFFFAOYSA-N 0.000 description 1
• 238000002610 neuroimaging Methods 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 235000005152 nicotinamide Nutrition 0.000 description 1
• 239000011570 nicotinamide Substances 0.000 description 1
• DFPAKSUCGFBDDF-UHFFFAOYSA-N nicotinic acid amide Natural products NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 1
• 229940005483 opioid analgesics Drugs 0.000 description 1
• 229940126701 oral medication Drugs 0.000 description 1
• 235000019236 orange GGN Nutrition 0.000 description 1
• 235000019248 orcein Nutrition 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• AVPKHOTUOHDTLW-UHFFFAOYSA-N oxane-4-carboxylic acid Chemical compound OC(=O)C1CCOCC1 AVPKHOTUOHDTLW-UHFFFAOYSA-N 0.000 description 1
• 125000005968 oxazolinyl group Chemical group 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 208000022821 personality disease Diseases 0.000 description 1
• 238000001050 pharmacotherapy Methods 0.000 description 1
• 239000003444 phase transfer catalyst Substances 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000002028 premature Effects 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000003518 presynaptic effect Effects 0.000 description 1
• 150000003140 primary amides Chemical class 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• GMIOYJQLNFNGPR-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid Chemical compound OC(=O)C1=CN=C(C(O)=O)C=N1 GMIOYJQLNFNGPR-UHFFFAOYSA-N 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000005412 pyrazyl group Chemical group 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 238000006798 ring closing metathesis reaction Methods 0.000 description 1
• 208000015212 rumination disease Diseases 0.000 description 1
• 238000006748 scratching Methods 0.000 description 1
• 230000002393 scratching effect Effects 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
• 230000008313 sensitization Effects 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000001568 sexual effect Effects 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• 238000002603 single-photon emission computed tomography Methods 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 210000003523 substantia nigra Anatomy 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
• HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000015883 synaptic transmission, dopaminergic Effects 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• 208000002271 trichotillomania Diseases 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
• 125000000725 trifluoropropyl group Chemical group [H]C([H])(*)C([H])([H])C(F)(F)F 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1