HRP970173A2 - Arylamino fused pyridines and pyrimidines - Google Patents

Info

Publication number

HRP970173A2

HRP970173A2 HR60/039,124A HRP970173A HRP970173A2 HR P970173 A2 HRP970173 A2 HR P970173A2 HR P970173 A HRP970173 A HR P970173A HR P970173 A2 HRP970173 A2 HR P970173A2

Authority

HR

Croatia

Prior art keywords

alkyl

cycloalkyl

occurrence

haloalkyl

cor7

Prior art date

1996-03-27

Links

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• 150000003230 pyrimidines Chemical class 0.000 title claims description 7
• 150000003222 pyridines Chemical class 0.000 title description 3
• 125000001769 aryl amino group Chemical group 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 195
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 95
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 89
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 89
• 125000005843 halogen group Chemical group 0.000 claims description 74
• 125000003118 aryl group Chemical group 0.000 claims description 66
• 229910052739 hydrogen Inorganic materials 0.000 claims description 62
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 61
• 125000001072 heteroaryl group Chemical group 0.000 claims description 60
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 55
• -1 p-methylbenzyl Chemical group 0.000 claims description 55
• 125000001424 substituent group Chemical group 0.000 claims description 55
• 239000000203 mixture Substances 0.000 claims description 50
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 44
• 238000000034 method Methods 0.000 claims description 44
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 44
• 229910052799 carbon Inorganic materials 0.000 claims description 38
• 238000006243 chemical reaction Methods 0.000 claims description 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 33
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 30
• 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims description 29
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 27
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 27
• 229910052727 yttrium Inorganic materials 0.000 claims description 24
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 22
• XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims description 21
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 19
• 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 19
• 125000004076 pyridyl group Chemical group 0.000 claims description 19
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 18
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 18
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 18
• 239000002904 solvent Substances 0.000 claims description 18
• 125000000623 heterocyclic group Chemical group 0.000 claims description 17
• 150000003839 salts Chemical group 0.000 claims description 16
• 229920006395 saturated elastomer Polymers 0.000 claims description 16
• 125000002541 furyl group Chemical group 0.000 claims description 15
• 125000002883 imidazolyl group Chemical group 0.000 claims description 15
• 125000001041 indolyl group Chemical group 0.000 claims description 15
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
• 125000001624 naphthyl group Chemical group 0.000 claims description 15
• 125000002971 oxazolyl group Chemical group 0.000 claims description 15
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 15
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 15
• 125000000335 thiazolyl group Chemical group 0.000 claims description 15
• 125000001544 thienyl group Chemical group 0.000 claims description 15
• 125000004306 triazinyl group Chemical group 0.000 claims description 15
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 14
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 14
• 239000002769 corticotropin releasing factor antagonist Substances 0.000 claims description 14
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 13
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 13
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 13
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 13
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 13
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 13
• 229940122010 Corticotropin releasing factor antagonist Drugs 0.000 claims description 12
• 241000124008 Mammalia Species 0.000 claims description 11
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 239000000651 prodrug Chemical group 0.000 claims description 11
• 229940002612 prodrug Drugs 0.000 claims description 11
• 208000019901 Anxiety disease Diseases 0.000 claims description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 9
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 9
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 9
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 9
• 125000001425 triazolyl group Chemical group 0.000 claims description 9
• 125000005233 alkylalcohol group Chemical group 0.000 claims description 8
• 230000036506 anxiety Effects 0.000 claims description 8
• 229940079593 drug Drugs 0.000 claims description 8
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 7
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 7
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
• 208000019022 Mood disease Diseases 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 150000008064 anhydrides Chemical class 0.000 claims description 6
• 201000010099 disease Diseases 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 150000001412 amines Chemical class 0.000 claims description 5
• 150000004982 aromatic amines Chemical class 0.000 claims description 5
• 208000024891 symptom Diseases 0.000 claims description 5
• 208000011580 syndromic disease Diseases 0.000 claims description 5
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
• 208000030814 Eating disease Diseases 0.000 claims description 4
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 4
• 125000001246 bromo group Chemical group Br* 0.000 claims description 4
• 239000003638 chemical reducing agent Substances 0.000 claims description 4
• 235000014632 disordered eating Nutrition 0.000 claims description 4
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 3
• 208000024827 Alzheimer disease Diseases 0.000 claims description 3
• 206010048327 Supranuclear palsy Diseases 0.000 claims description 3
• 229910052801 chlorine Inorganic materials 0.000 claims description 3
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 claims description 3
• 230000001629 suppression Effects 0.000 claims description 3
• ABTLZAVJDRUDNG-UHFFFAOYSA-N 4,6-dihydroxy-5-nitropyrimidine Chemical compound OC=1N=CNC(=O)C=1[N+]([O-])=O ABTLZAVJDRUDNG-UHFFFAOYSA-N 0.000 claims description 2
• 208000000103 Anorexia Nervosa Diseases 0.000 claims description 2
• 206010005052 Bladder irritation Diseases 0.000 claims description 2
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
• 206010013663 drug dependence Diseases 0.000 claims description 2
• 230000035558 fertility Effects 0.000 claims description 2
• 210000005095 gastrointestinal system Anatomy 0.000 claims description 2
• 125000001188 haloalkyl group Chemical group 0.000 claims description 2
• 210000000987 immune system Anatomy 0.000 claims description 2
• 208000027866 inflammatory disease Diseases 0.000 claims description 2
• 230000008569 process Effects 0.000 claims description 2
• 208000011117 substance-related disease Diseases 0.000 claims description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 2
• 235000019000 fluorine Nutrition 0.000 claims 2
• 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 345
• 239000000047 product Substances 0.000 description 183
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 177
• 239000007787 solid Substances 0.000 description 139
• 235000019439 ethyl acetate Nutrition 0.000 description 132
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 118
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• 239000011541 reaction mixture Substances 0.000 description 85
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 82
• 238000000921 elemental analysis Methods 0.000 description 71
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 66
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 65
• 239000000741 silica gel Substances 0.000 description 55
• 229910002027 silica gel Inorganic materials 0.000 description 55
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 49
• 238000004587 chromatography analysis Methods 0.000 description 43
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
• 239000000284 extract Substances 0.000 description 36
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
• 239000000243 solution Substances 0.000 description 32
• 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 31
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
• 102100021752 Corticoliberin Human genes 0.000 description 27
• 239000012267 brine Substances 0.000 description 27
• 239000012264 purified product Substances 0.000 description 27
• 238000010992 reflux Methods 0.000 description 27
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
• 229910000104 sodium hydride Inorganic materials 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• 239000003921 oil Substances 0.000 description 24
• 235000019198 oils Nutrition 0.000 description 24
• 239000012044 organic layer Substances 0.000 description 24
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 20
• 239000012312 sodium hydride Substances 0.000 description 20
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 18
• 239000012230 colorless oil Substances 0.000 description 17
• 239000010410 layer Substances 0.000 description 17
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• 229960000583 acetic acid Drugs 0.000 description 15
• 238000003818 flash chromatography Methods 0.000 description 15
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
• 229910019213 POCl3 Inorganic materials 0.000 description 14
• 230000000694 effects Effects 0.000 description 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• 108090000765 processed proteins & peptides Proteins 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• 229940024606 amino acid Drugs 0.000 description 12
• 150000001413 amino acids Chemical class 0.000 description 12
• 238000010790 dilution Methods 0.000 description 12
• 239000012895 dilution Substances 0.000 description 12
• 239000012442 inert solvent Substances 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 11
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
• 238000000605 extraction Methods 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• 238000005481 NMR spectroscopy Methods 0.000 description 10
• 239000004480 active ingredient Substances 0.000 description 10
• 229910052783 alkali metal Inorganic materials 0.000 description 10
• 239000000543 intermediate Substances 0.000 description 10
• 239000012299 nitrogen atmosphere Substances 0.000 description 9
• 235000010288 sodium nitrite Nutrition 0.000 description 9
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 229960004979 fampridine Drugs 0.000 description 8
• CLJMMQGDJNYDER-UHFFFAOYSA-N heptan-4-amine Chemical compound CCCC(N)CCC CLJMMQGDJNYDER-UHFFFAOYSA-N 0.000 description 8
• 239000003960 organic solvent Substances 0.000 description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
• 235000017557 sodium bicarbonate Nutrition 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• 239000002585 base Substances 0.000 description 7
• 210000004027 cell Anatomy 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• 239000003480 eluent Substances 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 238000007363 ring formation reaction Methods 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• 238000005160 1H NMR spectroscopy Methods 0.000 description 6
• WEMDUNBELVTSRP-UHFFFAOYSA-N 2-bromo-4-propan-2-ylaniline Chemical compound CC(C)C1=CC=C(N)C(Br)=C1 WEMDUNBELVTSRP-UHFFFAOYSA-N 0.000 description 6
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
• 229910000102 alkali metal hydride Inorganic materials 0.000 description 6
• 150000008046 alkali metal hydrides Chemical class 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 239000002024 ethyl acetate extract Substances 0.000 description 6
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 6
• 229910052742 iron Inorganic materials 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical class [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 150000003141 primary amines Chemical class 0.000 description 6
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
• 230000009466 transformation Effects 0.000 description 6
• HDXNPIRMUMFLIC-UHFFFAOYSA-N 2-bromo-4,6-dimethoxyaniline Chemical compound COC1=CC(Br)=C(N)C(OC)=C1 HDXNPIRMUMFLIC-UHFFFAOYSA-N 0.000 description 5
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 5
• 239000003513 alkali Substances 0.000 description 5
• 150000001340 alkali metals Chemical class 0.000 description 5
• 150000001408 amides Chemical class 0.000 description 5
• 230000000949 anxiolytic effect Effects 0.000 description 5
• 230000003542 behavioural effect Effects 0.000 description 5
• 229940049706 benzodiazepine Drugs 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• 238000009835 boiling Methods 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 150000004292 cyclic ethers Chemical class 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 150000002828 nitro derivatives Chemical class 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 108090000623 proteins and genes Proteins 0.000 description 5
• JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 5
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• QAFODUGVXFNLBE-UHFFFAOYSA-N 1-methoxybutan-2-amine Chemical compound CCC(N)COC QAFODUGVXFNLBE-UHFFFAOYSA-N 0.000 description 4
• VHHUWUXXXYAXQA-UHFFFAOYSA-N 2-(tritylamino)propane-1,3-diol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(NC(CO)CO)C1=CC=CC=C1 VHHUWUXXXYAXQA-UHFFFAOYSA-N 0.000 description 4
• IHGSJUGRPUIDRO-UHFFFAOYSA-N 2-chloro-4,6-dimethoxyaniline Chemical compound COC1=CC(Cl)=C(N)C(OC)=C1 IHGSJUGRPUIDRO-UHFFFAOYSA-N 0.000 description 4
• GIIGHSIIKVOWKZ-UHFFFAOYSA-N 2h-triazolo[4,5-d]pyrimidine Chemical class N1=CN=CC2=NNN=C21 GIIGHSIIKVOWKZ-UHFFFAOYSA-N 0.000 description 4
• LXOGQFQXRSVZRP-UHFFFAOYSA-N 4-chloro-6-methyl-3-nitro-1h-pyridin-2-one Chemical compound CC1=CC(Cl)=C([N+]([O-])=O)C(O)=N1 LXOGQFQXRSVZRP-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 4
• DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 4
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
• CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 230000009471 action Effects 0.000 description 4
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
• 150000001342 alkaline earth metals Chemical class 0.000 description 4
• 125000003277 amino group Chemical group 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
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