CA2486446A1 - Substituted fused pyrazolecarboxylic acid arylamides and related compounds - Google Patents

Info

Publication number

CA2486446A1

CA2486446A1 CA002486446A CA2486446A CA2486446A1 CA 2486446 A1 CA2486446 A1 CA 2486446A1 CA 002486446 A CA002486446 A CA 002486446A CA 2486446 A CA2486446 A CA 2486446A CA 2486446 A1 CA2486446 A1 CA 2486446A1

Authority

CA

Canada

Prior art keywords

alkyl

hydrogen

compound

amino

straight

Prior art date

2002-02-07

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 302
• KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 title abstract description 14
• 102000027484 GABAA receptors Human genes 0.000 claims abstract description 59
• 108091008681 GABAA receptors Proteins 0.000 claims abstract description 59
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
• 208000019901 Anxiety disease Diseases 0.000 claims abstract description 14
• 230000036506 anxiety Effects 0.000 claims abstract description 11
• 208000019116 sleep disease Diseases 0.000 claims abstract description 11
• 239000003814 drug Substances 0.000 claims abstract description 10
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 7
• 230000015654 memory Effects 0.000 claims abstract 3
• 229910052739 hydrogen Inorganic materials 0.000 claims description 241
• 239000001257 hydrogen Substances 0.000 claims description 241
• 125000000217 alkyl group Chemical group 0.000 claims description 233
• -1 cyano, nitro, amino Chemical group 0.000 claims description 143
• 229910052736 halogen Inorganic materials 0.000 claims description 95
• 150000002367 halogens Chemical class 0.000 claims description 94
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 82
• 150000003839 salts Chemical class 0.000 claims description 69
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 66
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 58
• 229910052760 oxygen Inorganic materials 0.000 claims description 49
• 125000003545 alkoxy group Chemical group 0.000 claims description 47
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 46
• 125000004432 carbon atom Chemical group C* 0.000 claims description 46
• 239000001301 oxygen Substances 0.000 claims description 46
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 44
• 125000000623 heterocyclic group Chemical group 0.000 claims description 44
• 238000000034 method Methods 0.000 claims description 42
• 125000002837 carbocyclic group Chemical group 0.000 claims description 41
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 36
• 239000000203 mixture Substances 0.000 claims description 35
• 229910052799 carbon Inorganic materials 0.000 claims description 28
• 125000001072 heteroaryl group Chemical group 0.000 claims description 28
• 229910052757 nitrogen Inorganic materials 0.000 claims description 28
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
• 125000004076 pyridyl group Chemical group 0.000 claims description 27
• 125000003118 aryl group Chemical group 0.000 claims description 25
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 24
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 23
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
• 230000000694 effects Effects 0.000 claims description 22
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 21
• 229910052717 sulfur Inorganic materials 0.000 claims description 21
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 19
• 125000001188 haloalkyl group Chemical group 0.000 claims description 19
• 125000001544 thienyl group Chemical group 0.000 claims description 19
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 18
• 239000011593 sulfur Substances 0.000 claims description 18
• 125000003342 alkenyl group Chemical group 0.000 claims description 17
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 17
• 125000002883 imidazolyl group Chemical group 0.000 claims description 17
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 17
• 125000000304 alkynyl group Chemical group 0.000 claims description 16
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 16
• 125000003282 alkyl amino group Chemical group 0.000 claims description 15
• 230000027455 binding Effects 0.000 claims description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
• 210000004027 cell Anatomy 0.000 claims description 14
• 125000006413 ring segment Chemical group 0.000 claims description 14
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 13
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 13
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
• 125000006165 cyclic alkyl group Chemical group 0.000 claims description 12
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 125000001424 substituent group Chemical group 0.000 claims description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 125000002541 furyl group Chemical group 0.000 claims description 11
• 125000003107 substituted aryl group Chemical group 0.000 claims description 11
• 210000003169 central nervous system Anatomy 0.000 claims description 10
• 125000002971 oxazolyl group Chemical group 0.000 claims description 10
• 125000003386 piperidinyl group Chemical group 0.000 claims description 10
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
• 241001465754 Metazoa Species 0.000 claims description 9
• 238000000338 in vitro Methods 0.000 claims description 9
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 9
• 229920006395 saturated elastomer Polymers 0.000 claims description 9
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 8
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• 125000002757 morpholinyl group Chemical group 0.000 claims description 8
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 8
• 125000000335 thiazolyl group Chemical group 0.000 claims description 8
• 210000001519 tissue Anatomy 0.000 claims description 8
• 125000001425 triazolyl group Chemical group 0.000 claims description 8
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 7
• 125000002393 azetidinyl group Chemical group 0.000 claims description 7
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
• 125000004193 piperazinyl group Chemical group 0.000 claims description 7
• 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 6
• 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 6
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
• 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 6
• 238000000211 autoradiogram Methods 0.000 claims description 6
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
• 125000004043 oxo group Chemical group O=* 0.000 claims description 6
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 6
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
• 239000003795 chemical substances by application Substances 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000005843 halogen group Chemical group 0.000 claims description 5
• MPSSQPWYDKLRTB-UHFFFAOYSA-N n-[6-[3-(diethylamino)propoxy]pyridin-3-yl]-4-oxo-1,5,6,7-tetrahydroindazole-3-carboxamide Chemical compound C1=NC(OCCCN(CC)CC)=CC=C1NC(=O)C1=NNC2=C1C(=O)CCC2 MPSSQPWYDKLRTB-UHFFFAOYSA-N 0.000 claims description 5
• 125000001624 naphthyl group Chemical group 0.000 claims description 5
• 230000003389 potentiating effect Effects 0.000 claims description 5
• 239000006188 syrup Substances 0.000 claims description 5
• 235000020357 syrup Nutrition 0.000 claims description 5
• MDTUWBLTRPRXBX-UHFFFAOYSA-N 1,2,4-triazol-3-one Chemical compound O=C1N=CN=N1 MDTUWBLTRPRXBX-UHFFFAOYSA-N 0.000 claims description 4
• 230000007831 electrophysiology Effects 0.000 claims description 4
• 238000002001 electrophysiology Methods 0.000 claims description 4
• 238000001727 in vivo Methods 0.000 claims description 4
• 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
• 230000004075 alteration Effects 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 239000002775 capsule Substances 0.000 claims description 3
• 230000008859 change Effects 0.000 claims description 3
• 239000012530 fluid Substances 0.000 claims description 3
• RCOONRVHELRGKW-UHFFFAOYSA-N n-[6-[3-(diethylamino)propoxy]pyridin-3-yl]-1,4,5,6-tetrahydropyrazolo[3,4-e]indazole-8-carboxamide Chemical compound C1=NC(OCCCN(CC)CC)=CC=C1NC(=O)C1=NNC2=C1C1=NNC=C1CC2 RCOONRVHELRGKW-UHFFFAOYSA-N 0.000 claims description 3
• INKQEZWTEKQNAN-UHFFFAOYSA-N n-[6-[3-(diethylamino)propoxy]pyridin-3-yl]-2-methyl-6,7-dihydro-5h-pyrazolo[3,4-h]quinazoline-9-carboxamide Chemical compound C1=NC(OCCCN(CC)CC)=CC=C1NC(=O)C1=NNC2=C1C1=NC(C)=NC=C1CC2 INKQEZWTEKQNAN-UHFFFAOYSA-N 0.000 claims description 3
• MEEPOBWLULRNOL-UHFFFAOYSA-N n-[6-[3-(diethylamino)propoxy]pyridin-3-yl]-6,7-dihydro-5h-pyrazolo[3,4-h]quinazoline-9-carboxamide Chemical compound C1=NC(OCCCN(CC)CC)=CC=C1NC(=O)C1=NNC2=C1C1=NC=NC=C1CC2 MEEPOBWLULRNOL-UHFFFAOYSA-N 0.000 claims description 3
• FXDDFCGQANIZOT-UHFFFAOYSA-N n-[6-[3-(diethylamino)propoxy]pyridin-3-yl]-6,7-dihydro-5h-pyrazolo[3,4-h]quinoline-9-carboxamide Chemical compound C1=NC(OCCCN(CC)CC)=CC=C1NC(=O)C1=NNC2=C1C1=NC=CC=C1CC2 FXDDFCGQANIZOT-UHFFFAOYSA-N 0.000 claims description 3
• 239000006187 pill Substances 0.000 claims description 3
• 230000006403 short-term memory Effects 0.000 claims description 3
• 208000020685 sleep-wake disease Diseases 0.000 claims description 3
• 125000004306 triazinyl group Chemical group 0.000 claims description 3
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
• 239000000443 aerosol Substances 0.000 claims description 2
• 239000006071 cream Substances 0.000 claims description 2
• 238000001514 detection method Methods 0.000 claims description 2
• 238000005259 measurement Methods 0.000 claims description 2
• NTMRIZLYBYXRDQ-UHFFFAOYSA-N n-[1-[3-(azetidin-1-yl)propyl]pyrazol-3-yl]-5,6,7,8-tetrahydropyrazolo[2,3]cyclohepta[2,4-b]pyridine-10-carboxamide Chemical compound N=1NC=2CCCC3=CC=CN=C3C=2C=1C(=O)NC(=N1)C=CN1CCCN1CCC1 NTMRIZLYBYXRDQ-UHFFFAOYSA-N 0.000 claims description 2
• FBAPDXMFBUMOBP-UHFFFAOYSA-N n-phenyl-5,6,7,8-tetrahydropyrazolo[2,3]cyclohepta[2,4-b]pyridine-10-carboxamide Chemical compound N=1NC=2CCCC3=CC=CN=C3C=2C=1C(=O)NC1=CC=CC=C1 FBAPDXMFBUMOBP-UHFFFAOYSA-N 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 23
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 15
• 229910006074 SO2NH2 Inorganic materials 0.000 claims 6
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 2
• YMEHWISYYMKMFO-WOMRJYOTSA-N methyl N-[(12E,15S)-15-[(4S)-4-(3-chlorophenyl)-2-oxopiperidin-1-yl]-9-oxo-8,17,19-triazatricyclo[14.2.1.02,7]nonadeca-1(18),2(7),3,5,12,16-hexaen-5-yl]carbamate Chemical group COC(=O)Nc1ccc2-c3cnc([nH]3)[C@H](C\C=C\CCC(=O)Nc2c1)N1CC[C@@H](CC1=O)c1cccc(Cl)c1 YMEHWISYYMKMFO-WOMRJYOTSA-N 0.000 claims 2
• 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 1
• 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims 1
• 230000006399 behavior Effects 0.000 claims 1
• 210000001124 body fluid Anatomy 0.000 claims 1
• 239000010839 body fluid Substances 0.000 claims 1
• 210000004958 brain cell Anatomy 0.000 claims 1
• 210000001175 cerebrospinal fluid Anatomy 0.000 claims 1
• 230000003834 intracellular effect Effects 0.000 claims 1
• 210000002569 neuron Anatomy 0.000 claims 1
• 230000002285 radioactive effect Effects 0.000 claims 1
• 230000001225 therapeutic effect Effects 0.000 claims 1
• 229940049706 benzodiazepine Drugs 0.000 abstract description 24
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 abstract description 20
• 102000005962 receptors Human genes 0.000 abstract description 17
• 108020003175 receptors Proteins 0.000 abstract description 17
• 239000000523 sample Substances 0.000 abstract description 15
• 239000000556 agonist Substances 0.000 abstract description 14
• 238000003786 synthesis reaction Methods 0.000 abstract description 10
• 229940079593 drug Drugs 0.000 abstract description 9
• 230000015572 biosynthetic process Effects 0.000 abstract description 8
• 239000005557 antagonist Substances 0.000 abstract description 7
• 239000000651 prodrug Substances 0.000 abstract description 5
• 229940002612 prodrug Drugs 0.000 abstract description 5
• 210000004556 brain Anatomy 0.000 abstract description 4
• 239000000543 intermediate Substances 0.000 abstract description 4
• RCTBACSGXPVNOF-UHFFFAOYSA-N 5,6,7,8-tetrahydropyrazolo[2,3]cyclohepta[2,4-b]pyridine-10-carboxylic acid Chemical compound C1CCC2=CC=CN=C2C2=C1NN=C2C(=O)O RCTBACSGXPVNOF-UHFFFAOYSA-N 0.000 abstract description 3
• 230000004807 localization Effects 0.000 abstract description 3
• 206010015037 epilepsy Diseases 0.000 abstract description 2
• FFRVYBLGEPTAIP-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrazolo[3,4-e]indazole-8-carboxylic acid Chemical compound C1CC2=CNN=C2C2=C1NN=C2C(=O)O FFRVYBLGEPTAIP-UHFFFAOYSA-N 0.000 abstract 1
• YWTLNUUWJFOGPI-UHFFFAOYSA-N 6,7-dihydro-5h-pyrazolo[3,4-h]quinazoline-9-carboxylic acid Chemical compound C1CC2=CN=CN=C2C2=C1NN=C2C(=O)O YWTLNUUWJFOGPI-UHFFFAOYSA-N 0.000 abstract 1
• SSPQZSGBPQJKGU-UHFFFAOYSA-N 6,7-dihydro-5h-pyrazolo[3,4-h]quinoline-9-carboxylic acid Chemical compound C1CC2=CC=CN=C2C2=C1NN=C2C(=O)O SSPQZSGBPQJKGU-UHFFFAOYSA-N 0.000 abstract 1
• 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 138
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 52
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 14
• 238000005160 1H NMR spectroscopy Methods 0.000 description 14
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 14
• 238000002360 preparation method Methods 0.000 description 14
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 13
• 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 description 13
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 13
• 239000000243 solution Substances 0.000 description 13
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• 239000002904 solvent Substances 0.000 description 11
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
• 238000003556 assay Methods 0.000 description 10
• 125000004429 atom Chemical group 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 231100000252 nontoxic Toxicity 0.000 description 9
• 230000003000 nontoxic effect Effects 0.000 description 9
• 101150041968 CDC13 gene Proteins 0.000 description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 239000003446 ligand Substances 0.000 description 8
• 230000009471 action Effects 0.000 description 7
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 6
• 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• 208000010877 cognitive disease Diseases 0.000 description 6
• 208000035475 disorder Diseases 0.000 description 6
• 235000019441 ethanol Nutrition 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 239000000796 flavoring agent Substances 0.000 description 6
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
• UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 description 6
• 239000011541 reaction mixture Substances 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 6
• 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• 229910052722 tritium Inorganic materials 0.000 description 6
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 5
• JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 5
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 5
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 239000007859 condensation product Substances 0.000 description 5
• 125000004122 cyclic group Chemical group 0.000 description 5
• 235000014113 dietary fatty acids Nutrition 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 239000000194 fatty acid Substances 0.000 description 5
• 229930195729 fatty acid Natural products 0.000 description 5
• 150000004665 fatty acids Chemical class 0.000 description 5
• 235000003599 food sweetener Nutrition 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 235000019198 oils Nutrition 0.000 description 5
• 239000003755 preservative agent Substances 0.000 description 5
• 238000000159 protein binding assay Methods 0.000 description 5
• 239000000741 silica gel Substances 0.000 description 5
• 229910002027 silica gel Inorganic materials 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• 239000003981 vehicle Substances 0.000 description 5
• RRLMPLDPCKRASL-ONEGZZNKSA-N (e)-3-(dimethylamino)prop-2-enal Chemical compound CN(C)\C=C\C=O RRLMPLDPCKRASL-ONEGZZNKSA-N 0.000 description 4
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
• 239000005695 Ammonium acetate Substances 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
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