SK9399A3 - Substituted triazolo-pyridazine derivatives as ligands for gaba receptors - Google Patents

Info

Publication number

SK9399A3

SK9399A3 SK93-99A SK9399A SK9399A3 SK 9399 A3 SK9399 A3 SK 9399A3 SK 9399 A SK9399 A SK 9399A SK 9399 A3 SK9399 A3 SK 9399A3

Authority

SK

Slovakia

Prior art keywords

triazolo

phenyl

ylmethoxy

methyl

pyridazine

Prior art date

1996-07-25

Links

• Espacenet
• Global Dossier
• Discuss

• CBHTTYDJRXOHHL-UHFFFAOYSA-N 2h-triazolo[4,5-c]pyridazine Chemical class N1=NC=CC2=C1N=NN2 CBHTTYDJRXOHHL-UHFFFAOYSA-N 0.000 title claims description 20
• 102000005915 GABA Receptors Human genes 0.000 title claims description 5
• 108010005551 GABA Receptors Proteins 0.000 title claims description 5
• 239000003446 ligand Substances 0.000 title abstract 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 31
• 108091008681 GABAA receptors Proteins 0.000 claims abstract description 12
• 102000027484 GABAA receptors Human genes 0.000 claims abstract description 11
• 208000019901 Anxiety disease Diseases 0.000 claims abstract description 10
• 230000002265 prevention Effects 0.000 claims abstract description 10
• 206010010904 Convulsion Diseases 0.000 claims abstract description 8
• 230000036506 anxiety Effects 0.000 claims abstract description 5
• 150000001875 compounds Chemical class 0.000 claims description 677
• -1 pyridin-2-ylmethoxy Chemical group 0.000 claims description 548
• 238000002360 preparation method Methods 0.000 claims description 323
• 125000004432 carbon atom Chemical group C* 0.000 claims description 129
• 239000000203 mixture Substances 0.000 claims description 125
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 96
• 238000000034 method Methods 0.000 claims description 92
• 125000000217 alkyl group Chemical group 0.000 claims description 50
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 38
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
• 229910052739 hydrogen Inorganic materials 0.000 claims description 32
• 150000003839 salts Chemical class 0.000 claims description 31
• 102000005962 receptors Human genes 0.000 claims description 28
• 108020003175 receptors Proteins 0.000 claims description 28
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
• 125000004076 pyridyl group Chemical group 0.000 claims description 25
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
• 239000000126 substance Substances 0.000 claims description 23
• 229910052757 nitrogen Inorganic materials 0.000 claims description 22
• LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 21
• 125000000335 thiazolyl group Chemical group 0.000 claims description 21
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 20
• XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 20
• 230000027455 binding Effects 0.000 claims description 20
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 19
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 17
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 17
• 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 16
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
• 239000000651 prodrug Substances 0.000 claims description 15
• 229940002612 prodrug Drugs 0.000 claims description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
• 125000001072 heteroaryl group Chemical group 0.000 claims description 14
• 125000003118 aryl group Chemical group 0.000 claims description 13
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 12
• 239000001257 hydrogen Substances 0.000 claims description 12
• 230000004044 response Effects 0.000 claims description 12
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 11
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 11
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 10
• 239000002243 precursor Substances 0.000 claims description 10
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 9
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
• 230000001624 sedative effect Effects 0.000 claims description 9
• 238000012360 testing method Methods 0.000 claims description 9
• 125000001544 thienyl group Chemical group 0.000 claims description 9
• 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 8
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 claims description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
• SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 8
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
• 239000004480 active ingredient Substances 0.000 claims description 7
• 239000002249 anxiolytic agent Substances 0.000 claims description 7
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 7
• 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 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000002541 furyl group Chemical group 0.000 claims description 7
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims description 7
• 238000003153 stable transfection Methods 0.000 claims description 7
• SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 6
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 6
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
• 229940049706 benzodiazepine Drugs 0.000 claims description 6
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 6
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• AAFRVZSZEIHNAI-UHFFFAOYSA-N 3,7-diphenyl-6-(1h-1,2,4-triazol-5-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1C=NNC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 AAFRVZSZEIHNAI-UHFFFAOYSA-N 0.000 claims description 4
• WOLTXCLEGCMVNA-UHFFFAOYSA-N 3,7-diphenyl-6-(pyrazin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1N=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 WOLTXCLEGCMVNA-UHFFFAOYSA-N 0.000 claims description 4
• LYGWGPHLTGKDDZ-UHFFFAOYSA-N 3,7-diphenyl-6-[(1-propyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CCCN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 LYGWGPHLTGKDDZ-UHFFFAOYSA-N 0.000 claims description 4
• NCBOIASFLNJMTE-UHFFFAOYSA-N 3-phenyl-7-piperidin-1-yl-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1N1CCCCC1 NCBOIASFLNJMTE-UHFFFAOYSA-N 0.000 claims description 4
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
• GCVRJJZTGPVPAD-UHFFFAOYSA-N 6-[(3-methylimidazol-4-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 GCVRJJZTGPVPAD-UHFFFAOYSA-N 0.000 claims description 4
• VXVLSQVFRWSMKF-UHFFFAOYSA-N 6-[(6-methylpyridin-2-yl)methoxy]-3-phenyl-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound CC1=CC=CC(COC=2C3=CC=CC=C3C3=NN=C(N3N=2)C=2C=CC=CC=2)=N1 VXVLSQVFRWSMKF-UHFFFAOYSA-N 0.000 claims description 4
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 4
• 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 4
• 239000003054 catalyst Substances 0.000 claims description 4
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
• 229910001961 silver nitrate Inorganic materials 0.000 claims description 4
• KDAYAFGPNTXUCS-UHFFFAOYSA-N 2-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-4-methyl-1,3-thiazole Chemical compound CC1=CSC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 KDAYAFGPNTXUCS-UHFFFAOYSA-N 0.000 claims description 3
• STZAMPDZKQQFBF-UHFFFAOYSA-N 2-[(7-cyclobutyl-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxy]acetonitrile Chemical compound N#CCOC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1CCC1 STZAMPDZKQQFBF-UHFFFAOYSA-N 0.000 claims description 3
• DHVVPBUFVXPPMP-UHFFFAOYSA-N 3,7-diphenyl-6-(pyridazin-3-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C=CN=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 DHVVPBUFVXPPMP-UHFFFAOYSA-N 0.000 claims description 3
• RCAREXJZVVHPHV-UHFFFAOYSA-N 3,7-diphenyl-6-(pyrimidin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1C=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 RCAREXJZVVHPHV-UHFFFAOYSA-N 0.000 claims description 3
• UFULYACRJFODBY-UHFFFAOYSA-N 3-(2-fluorophenyl)-7-(1-methylcyclobutyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2(C)CCC2)=NN2C1=NN=C2C1=CC=CC=C1F UFULYACRJFODBY-UHFFFAOYSA-N 0.000 claims description 3
• MEVOCWHZYRHURQ-UHFFFAOYSA-N 3-(3-fluorophenyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-7-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=C(F)C=CC=2)C=2C=CC=CC=2)=N1 MEVOCWHZYRHURQ-UHFFFAOYSA-N 0.000 claims description 3
• IKZGGLQQGAJSRM-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-7-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC(F)=CC=2)C=2C=CC=CC=2)=N1 IKZGGLQQGAJSRM-UHFFFAOYSA-N 0.000 claims description 3
• UHJNPZTZEYIENC-UHFFFAOYSA-N 3-(4-methylphenyl)-7-phenyl-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C1=CC(C)=CC=C1C1=NN=C2N1N=C(OCC=1N=CC=CC=1)C(C=1C=CC=CC=1)=C2 UHJNPZTZEYIENC-UHFFFAOYSA-N 0.000 claims description 3
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
• DURXAJILKOQSQM-UHFFFAOYSA-N 3-phenyl-6-(pyridin-2-ylmethoxy)-7-thiophen-3-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C=1C=CSC=1 DURXAJILKOQSQM-UHFFFAOYSA-N 0.000 claims description 3
• JQSZTNICLOUIPD-UHFFFAOYSA-N 4-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-1,3-thiazole Chemical compound C=1SC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 JQSZTNICLOUIPD-UHFFFAOYSA-N 0.000 claims description 3
• AAWHSIIPXWKJNS-UHFFFAOYSA-N 4-[3-phenyl-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazin-7-yl]thiomorpholine Chemical compound C=1C=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1N1CCSCC1 AAWHSIIPXWKJNS-UHFFFAOYSA-N 0.000 claims description 3
• SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims description 3
• KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 3
• NZNJEHSFNBLNFP-UHFFFAOYSA-N 5-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-3-methyl-1,2,4-oxadiazole Chemical compound CC1=NOC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 NZNJEHSFNBLNFP-UHFFFAOYSA-N 0.000 claims description 3
• MDTDCBJLYUNWJT-UHFFFAOYSA-N 6-[(1-benzyl-1,2,4-triazol-3-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N1=CN(CC=2C=CC=CC=2)N=C1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 MDTDCBJLYUNWJT-UHFFFAOYSA-N 0.000 claims description 3
• SSQNGBXFKQFNSC-UHFFFAOYSA-N 6-[(1-methylimidazol-4-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SSQNGBXFKQFNSC-UHFFFAOYSA-N 0.000 claims description 3
• FLWIFTLBIHIEOW-UHFFFAOYSA-N 6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-7-thiophen-3-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2=CSC=C2)=NN2C1=NN=C2 FLWIFTLBIHIEOW-UHFFFAOYSA-N 0.000 claims description 3
• HOCBROYEBQFDGA-UHFFFAOYSA-N 7-cyclobutyl-3-phenyl-6-prop-2-ynoxy-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C#CCOC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1CCC1 HOCBROYEBQFDGA-UHFFFAOYSA-N 0.000 claims description 3
• RJTIKEAHSDDBFU-UHFFFAOYSA-N 7-cyclobutyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C2CCC2)=N1 RJTIKEAHSDDBFU-UHFFFAOYSA-N 0.000 claims description 3
• XXDJXHYFDGGRRZ-UHFFFAOYSA-N 7-cyclohexyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C2CCCCC2)=N1 XXDJXHYFDGGRRZ-UHFFFAOYSA-N 0.000 claims description 3
• OWBOIJAKHRNFNM-UHFFFAOYSA-N 7-cyclopentyl-3-(2-fluorophenyl)-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound FC1=CC=CC=C1C1=NN=C2N1N=C(OCC=1N=CC=CC=1)C(C1CCCC1)=C2 OWBOIJAKHRNFNM-UHFFFAOYSA-N 0.000 claims description 3
• KWRCOLOBBLMFAP-UHFFFAOYSA-N 7-cyclopentyl-3-phenyl-6-(1h-1,2,4-triazol-5-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1C=NNC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1CCCC1 KWRCOLOBBLMFAP-UHFFFAOYSA-N 0.000 claims description 3
• GXQDLUZEKJYFQO-UHFFFAOYSA-N 7-cyclopentyl-6-(pyridin-2-ylmethoxy)-3-thiophen-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C=CC=NC=1COC1=NN2C(C=3SC=CC=3)=NN=C2C=C1C1CCCC1 GXQDLUZEKJYFQO-UHFFFAOYSA-N 0.000 claims description 3
• SJKIGZBTHJVWLJ-UHFFFAOYSA-N 7-ethyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(OCC3=NN(C)C=N3)C(CC)=CC2=NN=C1C1=CC=CC=C1 SJKIGZBTHJVWLJ-UHFFFAOYSA-N 0.000 claims description 3
• VCVVCYCZRJIVRB-UHFFFAOYSA-N 7-methoxy-8,8-dimethyl-3-phenyl-6-pyridin-2-yl-9,10-dihydro-7H-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound CC1(C(C=2C(=NN3C(C2CC1)=NN=C3C3=CC=CC=C3)C3=NC=CC=C3)OC)C VCVVCYCZRJIVRB-UHFFFAOYSA-N 0.000 claims description 3
• ZNDFCLQAPKFMIN-UHFFFAOYSA-N 7-methoxy-8-methyl-3-phenyl-6-pyridin-2-yl-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound CC1C(C=2C(=NN3C(C2CC1)=NN=C3C3=CC=CC=C3)C3=NC=CC=C3)OC ZNDFCLQAPKFMIN-UHFFFAOYSA-N 0.000 claims description 3
• JFVXMYNPAGVOIJ-UHFFFAOYSA-N 8-methoxy-7-methyl-3-phenyl-6-pyridin-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1N=C2C(OC)=C(C)C(C=3N=CC=CC=3)=NN2C=1C1=CC=CC=C1 JFVXMYNPAGVOIJ-UHFFFAOYSA-N 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
• 125000004254 isoquinolin-1-yl group Chemical group [H]C1=C([H])C2=C([H])C([H])=C([H])C([H])=C2C(*)=N1 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 239000001294 propane Substances 0.000 claims description 3
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 3
• 229910052723 transition metal Inorganic materials 0.000 claims description 3
• 150000003624 transition metals Chemical class 0.000 claims description 3
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 2
• MMDIHJNGUCQPFF-UHFFFAOYSA-N 2-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-5-methyl-1,3-thiazole Chemical compound S1C(C)=CN=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 MMDIHJNGUCQPFF-UHFFFAOYSA-N 0.000 claims description 2
• GIUNTDNEYLMTBV-UHFFFAOYSA-N 2-[3-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-1,2,4-triazol-1-yl]acetonitrile Chemical compound N#CCN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 GIUNTDNEYLMTBV-UHFFFAOYSA-N 0.000 claims description 2
• PCWJWLZHLADFLD-UHFFFAOYSA-N 3-(2-fluorophenyl)-7-(1-methylcyclobutyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C(=CC=CC=2)F)C2(C)CCC2)=N1 PCWJWLZHLADFLD-UHFFFAOYSA-N 0.000 claims description 2
• KQYHETYQOIUNLY-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-7-thiophen-3-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2=CSC=C2)=NN2C1=NN=C2C1=CC=C(F)C=C1 KQYHETYQOIUNLY-UHFFFAOYSA-N 0.000 claims description 2
• CRFYXSJVEFOVJZ-UHFFFAOYSA-N 3-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-5-methyl-1,2-oxazole Chemical compound O1C(C)=CC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 CRFYXSJVEFOVJZ-UHFFFAOYSA-N 0.000 claims description 2
• CVEFWTCFIHIONX-UHFFFAOYSA-N 4,5,7,8-tetrazatetracyclo[9.2.2.02,10.03,7]pentadeca-1,3,5,8,10,12-hexaene Chemical compound N1=CC2=C(C=C3)CCC3=C2C2=NN=CN21 CVEFWTCFIHIONX-UHFFFAOYSA-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
• LDIXKOVZSSLYMJ-UHFFFAOYSA-N 6-[(1-ethylimidazol-2-yl)methoxy]-3-(4-methylphenyl)-7-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CCN1C=CN=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=C(C)C=C1 LDIXKOVZSSLYMJ-UHFFFAOYSA-N 0.000 claims description 2
• PHYHYDJDDHSJHT-UHFFFAOYSA-N 7-(1-methylcyclopentyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C2(C)CCCC2)=N1 PHYHYDJDDHSJHT-UHFFFAOYSA-N 0.000 claims description 2
• KNMAFBOMLOGQPL-UHFFFAOYSA-N 7-(1-methylcyclopentyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2(C)CCCC2)=NN2C1=NN=C2C1=CC=CC=C1 KNMAFBOMLOGQPL-UHFFFAOYSA-N 0.000 claims description 2
• KRNIZJFCJNEAMC-UHFFFAOYSA-N 7-(1-methylcyclopropyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C2(C)CC2)=N1 KRNIZJFCJNEAMC-UHFFFAOYSA-N 0.000 claims description 2
• XPMNJDCXQMPCIO-UHFFFAOYSA-N 7-(5-chlorothiophen-2-yl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C=2SC(Cl)=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 XPMNJDCXQMPCIO-UHFFFAOYSA-N 0.000 claims description 2
• OHSIIKNYYFSTJF-UHFFFAOYSA-N 7-cyclopentyl-3-(2-fluorophenyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C(=CC=CC=2)F)C2CCCC2)=N1 OHSIIKNYYFSTJF-UHFFFAOYSA-N 0.000 claims description 2
• NAPZJLJMVTYFBO-UHFFFAOYSA-N 7-cyclopentyl-3-(4-methoxyphenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C1=CC(OC)=CC=C1C1=NN=C2N1N=C(OCC=1N(N=CN=1)C)C(C1CCCC1)=C2 NAPZJLJMVTYFBO-UHFFFAOYSA-N 0.000 claims description 2
• IUDSPISXHWGEOI-UHFFFAOYSA-N 7-cyclopentyl-3-phenyl-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1CCCC1 IUDSPISXHWGEOI-UHFFFAOYSA-N 0.000 claims description 2
• VVJSGHJWLDLMMJ-UHFFFAOYSA-N 7-cyclopentyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2SC=CC=2)C2CCCC2)=N1 VVJSGHJWLDLMMJ-UHFFFAOYSA-N 0.000 claims description 2
• BWXDDFASLOAGES-UHFFFAOYSA-N 7-cyclopentyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-pyridin-4-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2CCCC2)=NN2C1=NN=C2C1=CC=NC=C1 BWXDDFASLOAGES-UHFFFAOYSA-N 0.000 claims description 2
• MEPCRBQODHCLEP-UHFFFAOYSA-N 7-ethyl-8-methoxy-3-phenyl-6-pyridin-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(C=3N=CC=CC=3)C(CC)=C(OC)C2=NN=C1C1=CC=CC=C1 MEPCRBQODHCLEP-UHFFFAOYSA-N 0.000 claims description 2
• GKNLPIGLRWAOGQ-UHFFFAOYSA-N 7-methoxy-3-phenyl-6-pyridin-2-yl-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound COC1CCCC(C2=NN=3)=C1C(C=1N=CC=CC=1)=NN2C=3C1=CC=CC=C1 GKNLPIGLRWAOGQ-UHFFFAOYSA-N 0.000 claims description 2
• XCTVOZPAIUDJLQ-UHFFFAOYSA-N 7-tert-butyl-3-(2-fluorophenyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C(=CC=CC=2)F)C(C)(C)C)=N1 XCTVOZPAIUDJLQ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000004526 pyridazin-2-yl group Chemical group N1N(C=CC=C1)* 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• VNAOXTIBJQHVRM-UHFFFAOYSA-N 2-[3-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-1,2,4-triazol-1-yl]-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 VNAOXTIBJQHVRM-UHFFFAOYSA-N 0.000 claims 1
• MYJSELOFPLYFEG-UHFFFAOYSA-N 3,7-diphenyl-6-(pyrimidin-4-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C=NC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 MYJSELOFPLYFEG-UHFFFAOYSA-N 0.000 claims 1
• KCSTVGDYVKXIJT-UHFFFAOYSA-N 3,7-diphenyl-6-[[1-(2-pyrrolidin-1-ylethyl)-1,2,4-triazol-3-yl]methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C1CCCN1CCN(N=1)C=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 KCSTVGDYVKXIJT-UHFFFAOYSA-N 0.000 claims 1
• MCASNKXBBBTTOS-UHFFFAOYSA-N 3-(2-fluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-7-thiophen-3-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2=CSC=C2)=NN2C1=NN=C2C1=CC=CC=C1F MCASNKXBBBTTOS-UHFFFAOYSA-N 0.000 claims 1
• SIYUIIGNHRAJJA-UHFFFAOYSA-N 6-(1h-benzimidazol-2-ylmethoxy)-3-(2,4-difluorophenyl)-7-(1-methylcyclopentyl)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C2=NN=C(C=3C(=CC(F)=CC=3)F)N2N=C(OCC=2NC3=CC=CC=C3N=2)C=1C1(C)CCCC1 SIYUIIGNHRAJJA-UHFFFAOYSA-N 0.000 claims 1
• ZQTRFFPESLNLHA-UHFFFAOYSA-N 6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-7-pyrrolidin-1-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)N2CCCC2)=NN2C1=NN=C2C1=CC=CC=C1 ZQTRFFPESLNLHA-UHFFFAOYSA-N 0.000 claims 1
• CFOOYYMKAMEJBL-UHFFFAOYSA-N 7-(1-methylcyclobutyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2(C)CCC2)=NN2C1=NN=C2C1=CC=CC=C1 CFOOYYMKAMEJBL-UHFFFAOYSA-N 0.000 claims 1
• YMQOGAWQHTZWAL-UHFFFAOYSA-N 7-(1-methylcyclopropyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2(C)CC2)=NN2C1=NN=C2C1=CC=CC=C1 YMQOGAWQHTZWAL-UHFFFAOYSA-N 0.000 claims 1
• FPKLVZXGBZJJNX-UHFFFAOYSA-N 7-cyclopentyl-3-(2,4-difluorophenyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C(=CC(F)=CC=2)F)C2CCCC2)=N1 FPKLVZXGBZJJNX-UHFFFAOYSA-N 0.000 claims 1
• SXFKAOHJTVSOPJ-UHFFFAOYSA-N 7-cyclopentyl-3-(2,4-difluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2CCCC2)=NN2C1=NN=C2C1=CC=C(F)C=C1F SXFKAOHJTVSOPJ-UHFFFAOYSA-N 0.000 claims 1
• DVIJGLIEZLXACB-UHFFFAOYSA-N 7-cyclopentyl-3-(2-fluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2CCCC2)=NN2C1=NN=C2C1=CC=CC=C1F DVIJGLIEZLXACB-UHFFFAOYSA-N 0.000 claims 1
• PRWJSLUUGOBAFN-UHFFFAOYSA-N 7-cyclopentyl-3-(furan-2-yl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2OC=CC=2)C2CCCC2)=N1 PRWJSLUUGOBAFN-UHFFFAOYSA-N 0.000 claims 1
• NKRMWVWOOQBTCY-UHFFFAOYSA-N 7-cyclopentyl-3-(furan-2-yl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2CCCC2)=NN2C1=NN=C2C1=CC=CO1 NKRMWVWOOQBTCY-UHFFFAOYSA-N 0.000 claims 1
• HBZNQGWSCQNEBB-UHFFFAOYSA-N 7-cyclopentyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2CCCC2)=NN2C1=NN=C2C1=CC=CS1 HBZNQGWSCQNEBB-UHFFFAOYSA-N 0.000 claims 1
• YEIFFGBURLJKHG-UHFFFAOYSA-N 8-methyl-7-(1-methylcyclobutyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1N2C(C=3C=CC=CC=3)=NN=C2C(C)=C(C2(C)CCC2)C=1OCC1=NC=NN1C YEIFFGBURLJKHG-UHFFFAOYSA-N 0.000 claims 1
• 230000000949 anxiolytic effect Effects 0.000 claims 1
• 239000004305 biphenyl Substances 0.000 claims 1
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group 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 1
• 230000001939 inductive effect Effects 0.000 claims 1
• 238000012216 screening Methods 0.000 claims 1
• YRACHDVMKITFAZ-UHFFFAOYSA-N [1,2,4]triazolo[4,3-b]pyridazine Chemical class C1=CC=NN2C=NN=C21 YRACHDVMKITFAZ-UHFFFAOYSA-N 0.000 abstract description 25
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
• 210000003169 central nervous system Anatomy 0.000 abstract description 3
• 230000036461 convulsion Effects 0.000 abstract description 2
• 125000005415 substituted alkoxy group Chemical group 0.000 abstract 1
• 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 330
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 257
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 225
• 239000011541 reaction mixture Substances 0.000 description 152
• 238000005481 NMR spectroscopy Methods 0.000 description 150
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 137
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 131
• 238000005160 1H NMR spectroscopy Methods 0.000 description 124
• 238000011156 evaluation Methods 0.000 description 117
• 239000000243 solution Substances 0.000 description 116
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 94
• 235000019439 ethyl acetate Nutrition 0.000 description 88
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 83
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
• SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 69
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 62
• 239000007787 solid Substances 0.000 description 58
• 239000000047 product Substances 0.000 description 52
• 238000002156 mixing Methods 0.000 description 42
• 238000000926 separation method Methods 0.000 description 42
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
• 239000008346 aqueous phase Substances 0.000 description 39
• 239000000284 extract Substances 0.000 description 39
• WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 37
• 239000012074 organic phase Substances 0.000 description 36
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
• 238000003756 stirring Methods 0.000 description 35
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 34
• 239000012299 nitrogen atmosphere Substances 0.000 description 34
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 31
• 235000019341 magnesium sulphate Nutrition 0.000 description 31
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 30
• 239000012312 sodium hydride Substances 0.000 description 30
• 229910000104 sodium hydride Inorganic materials 0.000 description 30
• 229910052938 sodium sulfate Inorganic materials 0.000 description 30
• 235000011152 sodium sulphate Nutrition 0.000 description 30
• 239000000741 silica gel Substances 0.000 description 29
• 229910002027 silica gel Inorganic materials 0.000 description 29
• 239000003480 eluent Substances 0.000 description 27
• 229920006395 saturated elastomer Polymers 0.000 description 27
• 238000010992 reflux Methods 0.000 description 26
• 239000010410 layer Substances 0.000 description 25
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• JVJPJKLSGUJUJK-UHFFFAOYSA-N [1,2,4]triazolo[3,4-a]phthalazine Chemical class C1=CC=C2C=NN3C=NN=C3C2=C1 JVJPJKLSGUJUJK-UHFFFAOYSA-N 0.000 description 24
• 238000010898 silica gel chromatography Methods 0.000 description 24
• 210000004027 cell Anatomy 0.000 description 23
• WEDYTSQNYJKOPC-UHFFFAOYSA-N (1-methyl-1,2,4-triazol-3-yl)methanol Chemical compound CN1C=NC(CO)=N1 WEDYTSQNYJKOPC-UHFFFAOYSA-N 0.000 description 22
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
• 125000001424 substituent group Chemical group 0.000 description 22
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
• 238000001914 filtration Methods 0.000 description 21
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
• JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 20
• 238000003818 flash chromatography Methods 0.000 description 20
• 238000004949 mass spectrometry Methods 0.000 description 20
• 239000012044 organic layer Substances 0.000 description 19
• 239000002904 solvent Substances 0.000 description 19
• 238000006243 chemical reaction Methods 0.000 description 18
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 18
• 238000002844 melting Methods 0.000 description 18
• 230000008018 melting Effects 0.000 description 18
• 239000012267 brine Substances 0.000 description 17
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 16
• ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 16
• QUAQZVSGXQVIEP-UHFFFAOYSA-N (2-methyl-1,2,4-triazol-3-yl)methanol Chemical compound CN1N=CN=C1CO QUAQZVSGXQVIEP-UHFFFAOYSA-N 0.000 description 15
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• 239000002253 acid Substances 0.000 description 14
• 239000000460 chlorine Substances 0.000 description 14
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
• 238000004128 high performance liquid chromatography Methods 0.000 description 13
• 239000004533 oil dispersion Substances 0.000 description 13
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
• 229910052801 chlorine Inorganic materials 0.000 description 12
• SOGBOGBTIKMGFS-UHFFFAOYSA-N thiophene-2-carbohydrazide Chemical compound NNC(=O)C1=CC=CS1 SOGBOGBTIKMGFS-UHFFFAOYSA-N 0.000 description 12
• CVKOOKPNCVYHNY-UHFFFAOYSA-N 3-(bromomethyl)benzonitrile Chemical compound BrCC1=CC=CC(C#N)=C1 CVKOOKPNCVYHNY-UHFFFAOYSA-N 0.000 description 11
• 229910052736 halogen Inorganic materials 0.000 description 11
• 150000002367 halogens Chemical class 0.000 description 11
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 235000019198 oils Nutrition 0.000 description 11
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
• 235000017557 sodium bicarbonate Nutrition 0.000 description 11
• 239000011780 sodium chloride Substances 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 10
• 238000001816 cooling Methods 0.000 description 10
• 125000006513 pyridinyl methyl group Chemical group 0.000 description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 238000004587 chromatography analysis Methods 0.000 description 9
• VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 239000008096 xylene Substances 0.000 description 9
• 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 8
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
• QFTQDUMQGBKEHW-UHFFFAOYSA-N dilithium;dioxido(pyridin-4-yl)borane Chemical compound [Li+].[Li+].[O-]B([O-])C1=CC=NC=C1 QFTQDUMQGBKEHW-UHFFFAOYSA-N 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 238000000746 purification Methods 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 7
• 239000006185 dispersion Substances 0.000 description 7
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 7
• 239000012071 phase Substances 0.000 description 7
• 125000003386 piperidinyl group Chemical group 0.000 description 7
• 238000001953 recrystallisation Methods 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• 238000004809 thin layer chromatography Methods 0.000 description 7
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 239000000556 agonist Substances 0.000 description 6
• 125000003545 alkoxy group Chemical group 0.000 description 6
• 235000011114 ammonium hydroxide Nutrition 0.000 description 6
• 125000004093 cyano group Chemical group *C#N 0.000 description 6
• 238000001035 drying Methods 0.000 description 6
• 238000001704 evaporation Methods 0.000 description 6
• 238000000605 extraction Methods 0.000 description 6
• 125000005843 halogen group Chemical group 0.000 description 6
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
• 239000000543 intermediate Substances 0.000 description 6
• 229910000029 sodium carbonate Inorganic materials 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 6
• 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 6
• 239000003039 volatile agent Substances 0.000 description 6
• 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 5
• GCZGQVRHZLOCDD-UHFFFAOYSA-N 1-methylcyclobutane-1-carboxylic acid Chemical compound OC(=O)C1(C)CCC1 GCZGQVRHZLOCDD-UHFFFAOYSA-N 0.000 description 5
• YJCCKQQVXNNAAR-UHFFFAOYSA-N 2-fluorobenzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1F YJCCKQQVXNNAAR-UHFFFAOYSA-N 0.000 description 5
• RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 5
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 5
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 230000008020 evaporation Effects 0.000 description 5
• 125000001188 haloalkyl group Chemical group 0.000 description 5
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
• 125000002757 morpholinyl group Chemical group 0.000 description 5
• 125000006542 morpholinylalkyl group Chemical group 0.000 description 5
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
• 239000000377 silicon dioxide Substances 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 5
• IDFPQEHZYBXIFO-GFCCVEGCSA-N (R)-(4-fluoro-2-propylphenyl)-(1H-imidazol-2-yl)methanol Chemical compound CCCc1cc(F)ccc1[C@@H](O)c1ncc[nH]1 IDFPQEHZYBXIFO-GFCCVEGCSA-N 0.000 description 4
• MNIBBVOEXUQHFF-UHFFFAOYSA-N 1-methylcyclopentanecarboxylic acid Chemical compound OC(=O)C1(C)CCCC1 MNIBBVOEXUQHFF-UHFFFAOYSA-N 0.000 description 4
• REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 4
• ROYHWGZNGMXQEU-UHFFFAOYSA-N 3,6-dichloro-4-methylpyridazine Chemical compound CC1=CC(Cl)=NN=C1Cl ROYHWGZNGMXQEU-UHFFFAOYSA-N 0.000 description 4
• BMASTHFFAMGJKZ-UHFFFAOYSA-N 4-bromo-1,2-dihydropyridazine-3,6-dione Chemical compound BrC1=CC(=O)NNC1=O BMASTHFFAMGJKZ-UHFFFAOYSA-N 0.000 description 4
• 108090000862 Ion Channels Proteins 0.000 description 4
• 102000004310 Ion Channels Human genes 0.000 description 4
• 241000700159 Rattus Species 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-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
• 150000001412 amines Chemical class 0.000 description 4
• 229910021529 ammonia Inorganic materials 0.000 description 4
• 230000000049 anti-anxiety effect Effects 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• HDEZVVJUPXSHAN-UHFFFAOYSA-N bicyclo[2.2.2]oct-2-ene-2,3-dicarboxylic acid Chemical compound C1CC2C(C(=O)O)=C(C(O)=O)C1CC2 HDEZVVJUPXSHAN-UHFFFAOYSA-N 0.000 description 4
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 238000011049 filling Methods 0.000 description 4
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 125000006431 methyl cyclopropyl group Chemical group 0.000 description 4
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 4
• 239000008363 phosphate buffer Substances 0.000 description 4
• 239000002953 phosphate buffered saline Substances 0.000 description 4
• 239000006187 pill Substances 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000012279 sodium borohydride Substances 0.000 description 4
• 229910000033 sodium borohydride Inorganic materials 0.000 description 4
• XXKNPBDPZLPLFF-UHFFFAOYSA-N tert-butyl naphthalene-1-carboxylate Chemical compound C1=CC=C2C(C(=O)OC(C)(C)C)=CC=CC2=C1 XXKNPBDPZLPLFF-UHFFFAOYSA-N 0.000 description 4
• MJXVQODBCVNJOV-UHFFFAOYSA-N tert-butyl-dimethyl-[(2-propyl-1,2,4-triazol-3-yl)methoxy]silane Chemical compound CCCN1N=CN=C1CO[Si](C)(C)C(C)(C)C MJXVQODBCVNJOV-UHFFFAOYSA-N 0.000 description 4
• QSXOMCULJQCHDG-UHFFFAOYSA-N tert-butyl-dimethyl-[(3-methylimidazol-4-yl)methoxy]silane Chemical compound CN1C=NC=C1CO[Si](C)(C)C(C)(C)C QSXOMCULJQCHDG-UHFFFAOYSA-N 0.000 description 4
• ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 4
• 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 3
• SUXYJBSEDDEAMK-UHFFFAOYSA-N (6-chloro-5-morpholin-4-ylpyridazin-3-yl)hydrazine Chemical compound N1=NC(NN)=CC(N2CCOCC2)=C1Cl SUXYJBSEDDEAMK-UHFFFAOYSA-N 0.000 description 3
• ZRNXOHYTSIFSDP-UHFFFAOYSA-N (6-methylpyridin-2-yl)methyl acetate Chemical compound CC(=O)OCC1=CC=CC(C)=N1 ZRNXOHYTSIFSDP-UHFFFAOYSA-N 0.000 description 3
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 3
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 3
• MSFVEEFXECBJPG-UHFFFAOYSA-N 2-(chloromethyl)pyrimidine Chemical compound ClCC1=NC=CC=N1 MSFVEEFXECBJPG-UHFFFAOYSA-N 0.000 description 3
• 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• FTIXDMFAYOIIQM-UHFFFAOYSA-N 3,6-dichloro-4-(furan-2-yl)pyridazine Chemical compound N1=NC(Cl)=CC(C=2OC=CC=2)=C1Cl FTIXDMFAYOIIQM-UHFFFAOYSA-N 0.000 description 3
• GUSWJGOYDXFJSI-UHFFFAOYSA-N 3,6-dichloropyridazine Chemical compound ClC1=CC=C(Cl)N=N1 GUSWJGOYDXFJSI-UHFFFAOYSA-N 0.000 description 3
• DQPAAFTXZFHSMD-UHFFFAOYSA-N 3,7-diphenyl-6-(pyrimidin-5-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1N=CN=CC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 DQPAAFTXZFHSMD-UHFFFAOYSA-N 0.000 description 3
• GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 3
• 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 3
• TWCGCUQPXQOQCA-UHFFFAOYSA-N 3-(chloromethyl)pyridazine Chemical compound ClCC1=CC=CN=N1 TWCGCUQPXQOQCA-UHFFFAOYSA-N 0.000 description 3
• UIVXXFYJRYVRKJ-UHFFFAOYSA-N 4-fluorobenzohydrazide Chemical compound NNC(=O)C1=CC=C(F)C=C1 UIVXXFYJRYVRKJ-UHFFFAOYSA-N 0.000 description 3
• PPPCEAMFCKQRHG-UHFFFAOYSA-N 5-(bromomethyl)pyrimidine Chemical compound BrCC1=CN=CN=C1 PPPCEAMFCKQRHG-UHFFFAOYSA-N 0.000 description 3
• NAHDCPURDJHFAG-UHFFFAOYSA-N 6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-7-phenyl-3-thiophen-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2SC=CC=2)C=2C=CC=CC=2)=N1 NAHDCPURDJHFAG-UHFFFAOYSA-N 0.000 description 3
• MGIHNTDQHRDPQF-UHFFFAOYSA-N 6-[(5-methyl-1h-1,2,4-triazol-3-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CC1=NNC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 MGIHNTDQHRDPQF-UHFFFAOYSA-N 0.000 description 3
• JLVBSBMJQUMAMW-UHFFFAOYSA-N 6-methyl-2-pyridinemethanol Chemical compound CC1=CC=CC(CO)=N1 JLVBSBMJQUMAMW-UHFFFAOYSA-N 0.000 description 3
• QUDANIBRZAJEHA-UHFFFAOYSA-N 7-(furan-2-yl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C=2OC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 QUDANIBRZAJEHA-UHFFFAOYSA-N 0.000 description 3
• YLPHFEFMBAMSKS-UHFFFAOYSA-N 7-cyclohexyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2CCCCC2)=NN2C1=NN=C2C1=CC=CC=C1 YLPHFEFMBAMSKS-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 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 3
• QHBMBQBPMXVQFL-UHFFFAOYSA-N C=1C=CC=NC=1COC(C=1CNCCC=1C1=NN=2)=NN1C=2C1=CC=CC=C1 Chemical compound C=1C=CC=NC=1COC(C=1CNCCC=1C1=NN=2)=NN1C=2C1=CC=CC=C1 QHBMBQBPMXVQFL-UHFFFAOYSA-N 0.000 description 3
• NYWJEAMQXNWJJW-UHFFFAOYSA-N CN1N=CN=C1C(O)C1=NN(C=N1)C Chemical compound CN1N=CN=C1C(O)C1=NN(C=N1)C NYWJEAMQXNWJJW-UHFFFAOYSA-N 0.000 description 3
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• ZQKHRAXLCGDJDL-UHFFFAOYSA-N [1-(2-trimethylsilylethoxymethyl)imidazol-2-yl]methanol Chemical compound C[Si](C)(C)CCOCN1C=CN=C1CO ZQKHRAXLCGDJDL-UHFFFAOYSA-N 0.000 description 3
• 125000004103 aminoalkyl group Chemical group 0.000 description 3
• 235000019270 ammonium chloride Nutrition 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• 238000009835 boiling Methods 0.000 description 3
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000012230 colorless oil Substances 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 125000004802 cyanophenyl group Chemical group 0.000 description 3
• TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 description 3
• 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 3
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 3
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
• SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 description 3
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
• DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 3
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
• 229960004381 flumazenil Drugs 0.000 description 3
• 239000012442 inert solvent Substances 0.000 description 3
• 230000009871 nonspecific binding Effects 0.000 description 3
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 3
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
• 238000002953 preparative HPLC Methods 0.000 description 3
• LFCWHDGQCWJKCG-UHFFFAOYSA-N pyrazin-2-ylmethanol Chemical compound OCC1=CN=CC=N1 LFCWHDGQCWJKCG-UHFFFAOYSA-N 0.000 description 3
• 125000003373 pyrazinyl group Chemical group 0.000 description 3
• 125000002098 pyridazinyl group Chemical group 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 3
• 239000000376 reactant Substances 0.000 description 3
• 239000002002 slurry Substances 0.000 description 3
• 235000017281 sodium acetate Nutrition 0.000 description 3
• OCYGMRNKWAZEGT-UHFFFAOYSA-N tert-butyl-dimethyl-[(1-methylimidazol-4-yl)methoxy]silane Chemical compound CN1C=NC(CO[Si](C)(C)C(C)(C)C)=C1 OCYGMRNKWAZEGT-UHFFFAOYSA-N 0.000 description 3
• 125000001425 triazolyl group Chemical group 0.000 description 3
• QYEQHVNOKQUFFM-UHFFFAOYSA-N (1-ethylimidazol-2-yl)methanol Chemical compound CCN1C=CN=C1CO QYEQHVNOKQUFFM-UHFFFAOYSA-N 0.000 description 2
• NLEAEGDBKRBJAP-UHFFFAOYSA-N (1-methylimidazol-4-yl)methanol Chemical compound CN1C=NC(CO)=C1 NLEAEGDBKRBJAP-UHFFFAOYSA-N 0.000 description 2
• VPUXNLAGWDWLEN-UHFFFAOYSA-N (1-propyl-1,2,4-triazol-3-yl)methanol Chemical compound CCCN1C=NC(CO)=N1 VPUXNLAGWDWLEN-UHFFFAOYSA-N 0.000 description 2
• QLAGECZOQRFYJG-UHFFFAOYSA-N (3-ethoxypyridin-2-yl)methanol Chemical compound CCOC1=CC=CN=C1CO QLAGECZOQRFYJG-UHFFFAOYSA-N 0.000 description 2
• ACDAPUOXXWLLSC-UHFFFAOYSA-N (3-methylpyridin-2-yl)methanol Chemical compound CC1=CC=CN=C1CO ACDAPUOXXWLLSC-UHFFFAOYSA-N 0.000 description 2
• CQMPPPAHJBQCOY-UHFFFAOYSA-N (4-methyl-1,3-thiazol-2-yl)methanol Chemical compound CC1=CSC(CO)=N1 CQMPPPAHJBQCOY-UHFFFAOYSA-N 0.000 description 2
• JFCLNCVCDFUJPO-UHFFFAOYSA-N (5-chlorothiophen-2-yl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)S1 JFCLNCVCDFUJPO-UHFFFAOYSA-N 0.000 description 2
• BWKAOFJDCPNWEC-UHFFFAOYSA-N (5-methyl-1,3-thiazol-2-yl)methanol Chemical compound CC1=CN=C(CO)S1 BWKAOFJDCPNWEC-UHFFFAOYSA-N 0.000 description 2
• YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 2
• WQVOUANKVCYEIQ-UHFFFAOYSA-N 1,3-thiazol-4-ylmethanol Chemical compound OCC1=CSC=N1 WQVOUANKVCYEIQ-UHFFFAOYSA-N 0.000 description 2
• GGAOIBVAWZNQPD-SRZZPIQSSA-N 1-(4-amino-1,2,5-oxadiazol-3-yl)-n-[(e)-cyclohex-3-en-1-ylmethylideneamino]-5-(4-methylphenyl)triazole-4-carboxamide Chemical compound C1=CC(C)=CC=C1C1=C(C(=O)N\N=C\C2CC=CCC2)N=NN1C1=NON=C1N GGAOIBVAWZNQPD-SRZZPIQSSA-N 0.000 description 2
• MWZDIEIXRBWPLG-UHFFFAOYSA-N 1-methyl-1,2,4-triazole Chemical compound CN1C=NC=N1 MWZDIEIXRBWPLG-UHFFFAOYSA-N 0.000 description 2
• DIZKLZKLNKQFGB-UHFFFAOYSA-N 1-methylcyclopropane-1-carboxylic acid Chemical compound OC(=O)C1(C)CC1 DIZKLZKLNKQFGB-UHFFFAOYSA-N 0.000 description 2
• LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 2
• ZECOOENHOVXEDD-UHFFFAOYSA-N 151813-29-5 Chemical compound C1CC2CCC1C1=C2C(=O)OC1=O ZECOOENHOVXEDD-UHFFFAOYSA-N 0.000 description 2
• HPYNZHMRTTWQTB-UHFFFAOYSA-N 2,3-dimethylpyridine Chemical compound CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 2
• NJYBIFYEWYWYAN-UHFFFAOYSA-N 2,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1F NJYBIFYEWYWYAN-UHFFFAOYSA-N 0.000 description 2
• BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 2
• NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• UTAFVZLZZYEYDA-UHFFFAOYSA-N 2-[[4-(furan-2-ylmethyl)-5-pyrazin-2-yl-1,2,4-triazol-3-yl]sulfanylmethyl]-1h-benzimidazole Chemical compound N=1C2=CC=CC=C2NC=1CSC(N1CC=2OC=CC=2)=NN=C1C1=CN=CC=N1 UTAFVZLZZYEYDA-UHFFFAOYSA-N 0.000 description 2
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
• AAOSLLBWWRKJIR-UHFFFAOYSA-N 2-chloro-1-pyrrolidin-1-ylethanone Chemical compound ClCC(=O)N1CCCC1 AAOSLLBWWRKJIR-UHFFFAOYSA-N 0.000 description 2
• LNJMHEJAYSYZKK-UHFFFAOYSA-N 2-methylpyrimidine Chemical compound CC1=NC=CC=N1 LNJMHEJAYSYZKK-UHFFFAOYSA-N 0.000 description 2
• DIEAHNGJKNPSMQ-UHFFFAOYSA-N 2h-[1,2,4]triazolo[4,3-b]pyridazin-3-one Chemical compound C1=CC=NN2C(=O)NN=C21 DIEAHNGJKNPSMQ-UHFFFAOYSA-N 0.000 description 2
• YYESFGLDKLTUCO-UHFFFAOYSA-N 3,6-dichloro-4-cyclopentylpyridazine Chemical compound N1=NC(Cl)=CC(C2CCCC2)=C1Cl YYESFGLDKLTUCO-UHFFFAOYSA-N 0.000 description 2
• JGSDXYKPYCBWRI-UHFFFAOYSA-N 3,6-dichloro-4-piperidin-1-ylpyridazine Chemical compound N1=NC(Cl)=CC(N2CCCCC2)=C1Cl JGSDXYKPYCBWRI-UHFFFAOYSA-N 0.000 description 2
• OHEFKPDASJTVDT-UHFFFAOYSA-N 3,6-dichloro-4-pyridin-4-ylpyridazine Chemical compound N1=NC(Cl)=CC(C=2C=CN=CC=2)=C1Cl OHEFKPDASJTVDT-UHFFFAOYSA-N 0.000 description 2
• AJKPWFIRLCHFCQ-UHFFFAOYSA-N 3,7-diphenyl-5h-[1,2,4]triazolo[4,3-b]pyridazin-6-one Chemical compound O=C1NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 AJKPWFIRLCHFCQ-UHFFFAOYSA-N 0.000 description 2
• WEJVWILDQNWNJW-UHFFFAOYSA-N 3,7-diphenyl-6-(2h-triazol-4-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C1=NNN=C1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 WEJVWILDQNWNJW-UHFFFAOYSA-N 0.000 description 2
• RPXIOUYOWINDIB-UHFFFAOYSA-N 3,7-diphenyl-6-[(2-propyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CCCN1N=CN=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 RPXIOUYOWINDIB-UHFFFAOYSA-N 0.000 description 2
• GQZORSSJIAKBEJ-UHFFFAOYSA-N 3-(2-fluorophenyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-7-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C(=CC=CC=2)F)C=2C=CC=CC=2)=N1 GQZORSSJIAKBEJ-UHFFFAOYSA-N 0.000 description 2
• REJBYWVLGVSIGN-UHFFFAOYSA-N 3-(4-methylphenyl)-6-[(3-methylpyridin-2-yl)methoxy]-7-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C1=CC(C)=CC=C1C1=NN=C2N1N=C(OCC=1C(=CC=CN=1)C)C(C=1C=CC=CC=1)=C2 REJBYWVLGVSIGN-UHFFFAOYSA-N 0.000 description 2
• WPBNUNIAHANIRG-UHFFFAOYSA-N 3-(furan-3-yl)-7-methoxy-6-pyridin-2-yl-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound O1C=C(C=C1)C1=NN=C2N1N=C(C=1C(CCCC21)OC)C2=NC=CC=C2 WPBNUNIAHANIRG-UHFFFAOYSA-N 0.000 description 2
• UZOHRFHDDLPKKS-UHFFFAOYSA-N 3-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-5-methyl-1,2,4-oxadiazole Chemical compound O1C(C)=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 UZOHRFHDDLPKKS-UHFFFAOYSA-N 0.000 description 2
• JQYSPBXUNCRBJS-UHFFFAOYSA-N 3-phenyl-7-pyridin-4-yl-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=NC=C1 JQYSPBXUNCRBJS-UHFFFAOYSA-N 0.000 description 2
• QZYCWJVSPFQUQC-UHFFFAOYSA-N 3-phenylfuran-2,5-dione Chemical compound O=C1OC(=O)C(C=2C=CC=CC=2)=C1 QZYCWJVSPFQUQC-UHFFFAOYSA-N 0.000 description 2
• MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 2
• WITWOVXHOBYYMU-UHFFFAOYSA-N 4-(3,6-dichloropyridazin-4-yl)morpholine Chemical compound N1=NC(Cl)=CC(N2CCOCC2)=C1Cl WITWOVXHOBYYMU-UHFFFAOYSA-N 0.000 description 2
• AROGQTWAAJTEFR-UHFFFAOYSA-N 4-(chloromethyl)pyrimidine Chemical compound ClCC1=CC=NC=N1 AROGQTWAAJTEFR-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-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
• GSQTYKQADBTZAF-UHFFFAOYSA-N 4-[3-phenyl-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazin-7-yl]morpholine Chemical compound C=1C=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1N1CCOCC1 GSQTYKQADBTZAF-UHFFFAOYSA-N 0.000 description 2
• XAXKZIUQIROVNV-UHFFFAOYSA-N 4-bromo-3,6-dichloropyridazine Chemical compound ClC1=CC(Br)=C(Cl)N=N1 XAXKZIUQIROVNV-UHFFFAOYSA-N 0.000 description 2
• BKAWJIRCKVUVED-UHFFFAOYSA-N 5-(2-hydroxyethyl)-4-methylthiazole Chemical compound CC=1N=CSC=1CCO BKAWJIRCKVUVED-UHFFFAOYSA-N 0.000 description 2
• VJYHJBZTXOLVMU-UHFFFAOYSA-N 6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-7-propan-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(OCC3=NN(C)C=N3)C(C(C)C)=CC2=NN=C1C1=CC=CC=C1 VJYHJBZTXOLVMU-UHFFFAOYSA-N 0.000 description 2
• LHMYCKKRCBXCBI-UHFFFAOYSA-N 6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 LHMYCKKRCBXCBI-UHFFFAOYSA-N 0.000 description 2
• VBIUWFXJSGIEKL-UHFFFAOYSA-N 6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-7-propan-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(OCC=3N(N=CN=3)C)C(C(C)C)=CC2=NN=C1C1=CC=CC=C1 VBIUWFXJSGIEKL-UHFFFAOYSA-N 0.000 description 2
• CXJRNDIMOTWWJA-UHFFFAOYSA-N 6-[(2-methyltetrazol-5-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 CXJRNDIMOTWWJA-UHFFFAOYSA-N 0.000 description 2
• XSEMGHQIUGDUIY-UHFFFAOYSA-N 6-[(2-methyltriazol-4-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 XSEMGHQIUGDUIY-UHFFFAOYSA-N 0.000 description 2
• LKJQVAJICVZOQT-UHFFFAOYSA-N 6-[(3-methylpyridin-2-yl)methoxy]-3-phenyl-7-piperidin-1-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CC1=CC=CN=C1COC(C(=C1)N2CCCCC2)=NN2C1=NN=C2C1=CC=CC=C1 LKJQVAJICVZOQT-UHFFFAOYSA-N 0.000 description 2
• TWYXCJWUBNYBMK-UHFFFAOYSA-N 6-[(3-methyltriazol-4-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=NC=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 TWYXCJWUBNYBMK-UHFFFAOYSA-N 0.000 description 2
• QCGHVFASTYYJNT-UHFFFAOYSA-N 6-chloro-3-phenyl-7-pyrrolidin-1-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound ClC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1N1CCCC1 QCGHVFASTYYJNT-UHFFFAOYSA-N 0.000 description 2
• HNOGCUCCQQVHCI-UHFFFAOYSA-N 6-chloro-3-phenyl-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound N=1N=C2C3=CC=CC=C3C(Cl)=NN2C=1C1=CC=CC=C1 HNOGCUCCQQVHCI-UHFFFAOYSA-N 0.000 description 2
• VPEZBSPBZSWTGR-UHFFFAOYSA-N 6-chloro-7-cyclopentyl-3-thiophen-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound ClC1=NN2C(C=3SC=CC=3)=NN=C2C=C1C1CCCC1 VPEZBSPBZSWTGR-UHFFFAOYSA-N 0.000 description 2
• XMTHRPGPSUJCCG-UHFFFAOYSA-N 7-(1-methylcyclopentyl)-6-[(3-methylpyridin-2-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CC1=CC=CN=C1COC(C(=C1)C2(C)CCCC2)=NN2C1=NN=C2C1=CC=CC=C1 XMTHRPGPSUJCCG-UHFFFAOYSA-N 0.000 description 2
• ZAQMVLKNVDYUHR-UHFFFAOYSA-N 7-(2-methylpyrrolidin-1-yl)-3-phenyl-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CC1CCCN1C(C(=NN12)OCC=3N=CC=CC=3)=CC1=NN=C2C1=CC=CC=C1 ZAQMVLKNVDYUHR-UHFFFAOYSA-N 0.000 description 2
• IJHVTPOBVZWJEU-UHFFFAOYSA-N 7-(5-chlorothiophen-2-yl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2SC(Cl)=CC=2)=N1 IJHVTPOBVZWJEU-UHFFFAOYSA-N 0.000 description 2
• VACJUKKURQMWHE-UHFFFAOYSA-N 7-cyclobutyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2CCC2)=NN2C1=NN=C2C1=CC=CC=C1 VACJUKKURQMWHE-UHFFFAOYSA-N 0.000 description 2
• FFPOLBVOCSSYCJ-UHFFFAOYSA-N 7-cyclobutyl-8-methyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1C=NN(C)C=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C(C)=C1C1CCC1 FFPOLBVOCSSYCJ-UHFFFAOYSA-N 0.000 description 2
• XPANKLKOSFBPSJ-UHFFFAOYSA-N 7-cyclopentyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C2CCCC2)=N1 XPANKLKOSFBPSJ-UHFFFAOYSA-N 0.000 description 2
• CMSKDYKEKYIJSD-UHFFFAOYSA-N 7-cyclopentyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C2CCCC2)=NN2C1=NN=C2C1=CC=CC=C1 CMSKDYKEKYIJSD-UHFFFAOYSA-N 0.000 description 2
• YIPQSMMRTUWGQF-UHFFFAOYSA-N 7-methyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(OCC3=NN(C)C=N3)C(C)=CC2=NN=C1C1=CC=CC=C1 YIPQSMMRTUWGQF-UHFFFAOYSA-N 0.000 description 2
• JBOZVRVPCHJHLD-UHFFFAOYSA-N 7-methyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(OCC=3N(N=CN=3)C)C(C)=CC2=NN=C1C1=CC=CC=C1 JBOZVRVPCHJHLD-UHFFFAOYSA-N 0.000 description 2
• CDBMINRIXDAEIM-UHFFFAOYSA-N 7-phenyl-3-thiophen-2-yl-6-(1h-1,2,4-triazol-5-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1C=NNC=1COC1=NN2C(C=3SC=CC=3)=NN=C2C=C1C1=CC=CC=C1 CDBMINRIXDAEIM-UHFFFAOYSA-N 0.000 description 2
• FPKKOCPCXRSNQZ-UHFFFAOYSA-N 7-tert-butyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C(C)(C)C)=N1 FPKKOCPCXRSNQZ-UHFFFAOYSA-N 0.000 description 2
• ZUENPPWCLKHVTK-UHFFFAOYSA-N 8-methyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1N2C(C=3C=CC=CC=3)=NN=C2C(C)=C(C=2C=CC=CC=2)C=1OCC=1N=CN(C)N=1 ZUENPPWCLKHVTK-UHFFFAOYSA-N 0.000 description 2
• XQFGDFHDKHDYQZ-UHFFFAOYSA-N 8-methyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1N2C(C=3C=CC=CC=3)=NN=C2C(C)=C(C=2C=CC=CC=2)C=1OCC1=NC=NN1C XQFGDFHDKHDYQZ-UHFFFAOYSA-N 0.000 description 2
• 208000008811 Agoraphobia Diseases 0.000 description 2
• 208000020925 Bipolar disease Diseases 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 208000020401 Depressive disease Diseases 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 102000004300 GABA-A Receptors Human genes 0.000 description 2
• 108090000839 GABA-A Receptors Proteins 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• ZIRSZAPPXDETEE-UHFFFAOYSA-N N1=CC=CC=C1.OCC1=NC=CC=C1 Chemical compound N1=CC=CC=C1.OCC1=NC=CC=C1 ZIRSZAPPXDETEE-UHFFFAOYSA-N 0.000 description 2
• KLPVTNQTQDEAAU-UHFFFAOYSA-N [3-(cyclopropylmethoxy)pyridin-2-yl]methanol Chemical compound OCC1=NC=CC=C1OCC1CC1 KLPVTNQTQDEAAU-UHFFFAOYSA-N 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 150000008064 anhydrides Chemical class 0.000 description 2
• 239000005557 antagonist Substances 0.000 description 2
• 239000012736 aqueous medium Substances 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
• 244000309464 bull Species 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 2
• 125000006402 chloropyridazinyl group Chemical group 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 125000002946 cyanobenzyl group Chemical group 0.000 description 2
• 125000000000 cycloalkoxy group Chemical group 0.000 description 2
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 2
• UBEKYGUUQKFFTI-UHFFFAOYSA-N dimethyl 2-pyrimidin-2-ylpropanedioate Chemical compound COC(=O)C(C(=O)OC)C1=NC=CC=N1 UBEKYGUUQKFFTI-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 229960002200 flunitrazepam Drugs 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 125000001207 fluorophenyl group Chemical group 0.000 description 2
• 238000005187 foaming Methods 0.000 description 2
• SKTSVWWOAIAIKI-UHFFFAOYSA-N furan-2-carbohydrazide Chemical compound NNC(=O)C1=CC=CO1 SKTSVWWOAIAIKI-UHFFFAOYSA-N 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 239000008240 homogeneous mixture Substances 0.000 description 2
• 150000002429 hydrazines Chemical class 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 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
• 239000002609 medium Substances 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 2
• 229960004738 nicotinyl alcohol Drugs 0.000 description 2
• XKLJHFLUAHKGGU-UHFFFAOYSA-N nitrous amide Chemical compound ON=N XKLJHFLUAHKGGU-UHFFFAOYSA-N 0.000 description 2
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
• 208000019906 panic disease Diseases 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• PTMBWNZJOQBTBK-UHFFFAOYSA-N pyridin-4-ylmethanol Chemical compound OCC1=CC=NC=C1 PTMBWNZJOQBTBK-UHFFFAOYSA-N 0.000 description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
• 239000000941 radioactive substance Substances 0.000 description 2
• 229940087562 sodium acetate trihydrate Drugs 0.000 description 2
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 229950009390 symclosene Drugs 0.000 description 2
• 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 2
• AWDWFKCXUYBBNR-UHFFFAOYSA-N tert-butyl-dimethyl-[(1-propyl-1,2,4-triazol-3-yl)methoxy]silane Chemical compound CCCN1C=NC(CO[Si](C)(C)C(C)(C)C)=N1 AWDWFKCXUYBBNR-UHFFFAOYSA-N 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• 125000003944 tolyl group Chemical group 0.000 description 2
• GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 2
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• SXFBQAMLJMDXOD-UHFFFAOYSA-N (+)-hydrogentartrate bitartrate salt Chemical compound OC(=O)C(O)C(O)C(O)=O.OC(=O)C(O)C(O)C(O)=O SXFBQAMLJMDXOD-UHFFFAOYSA-N 0.000 description 1
• OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
• 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 1
• OUXGHJCAIAMWRQ-UHFFFAOYSA-N (2-propyl-1,2,4-triazol-3-yl)methanol Chemical compound CCCN1N=CN=C1CO OUXGHJCAIAMWRQ-UHFFFAOYSA-N 0.000 description 1
• CMIBUZBMZCBCAT-HZPDHXFCSA-N (2r,3r)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HZPDHXFCSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 1
• PXGQMYCEAWZJJF-UHFFFAOYSA-N (3-methylimidazol-4-yl)methanol Chemical compound CN1C=NC=C1CO PXGQMYCEAWZJJF-UHFFFAOYSA-N 0.000 description 1
• DLLDJWMWMVUIDZ-UHFFFAOYSA-N (3-methyltriazol-4-yl)methanol Chemical compound CN1N=NC=C1CO DLLDJWMWMVUIDZ-UHFFFAOYSA-N 0.000 description 1
• KMOUUZVZFBCRAM-OLQVQODUSA-N (3as,7ar)-3a,4,7,7a-tetrahydro-2-benzofuran-1,3-dione Chemical compound C1C=CC[C@@H]2C(=O)OC(=O)[C@@H]21 KMOUUZVZFBCRAM-OLQVQODUSA-N 0.000 description 1
• CIFUFRVSHZKBEO-UHFFFAOYSA-N (4-methyl-1,2,4-triazol-3-yl)methanol Chemical compound CN1C=NN=C1CO CIFUFRVSHZKBEO-UHFFFAOYSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000006824 (C1-C6) dialkyl amine group Chemical group 0.000 description 1
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 description 1
• 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 1
• 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 1
• ONNHAORRUGAMFT-UHFFFAOYSA-N 1,2,3,5-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound C1=CC=CC2=CNN3CNNC3=C21 ONNHAORRUGAMFT-UHFFFAOYSA-N 0.000 description 1
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
• JNHDLNXNYPLBMJ-UHFFFAOYSA-N 1,3-thiazol-2-ylmethanol Chemical compound OCC1=NC=CS1 JNHDLNXNYPLBMJ-UHFFFAOYSA-N 0.000 description 1
• KLFNXIXNWZZRLE-UHFFFAOYSA-N 1,4-dichloro-5,6,7,8-tetrahydrophthalazine Chemical compound C1CCCC2=C1C(Cl)=NN=C2Cl KLFNXIXNWZZRLE-UHFFFAOYSA-N 0.000 description 1
• NJRZMKZSODVWLS-UHFFFAOYSA-N 1,4-dichloro-6-methyl-5,6,7,8-tetrahydrophthalazine Chemical compound N1=NC(Cl)=C2CC(C)CCC2=C1Cl NJRZMKZSODVWLS-UHFFFAOYSA-N 0.000 description 1
• VRPPBGTUTNCVED-UHFFFAOYSA-N 1,4-dichloro-7,7-dimethyl-6,8-dihydro-5h-phthalazine Chemical compound N1=NC(Cl)=C2CC(C)(C)CCC2=C1Cl VRPPBGTUTNCVED-UHFFFAOYSA-N 0.000 description 1
• RCHDLEVSZBOHOS-UHFFFAOYSA-N 1,4-dichlorobut-2-yne Chemical compound ClCC#CCCl RCHDLEVSZBOHOS-UHFFFAOYSA-N 0.000 description 1
• 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 1
• WYZRLXYOIMXEBO-UHFFFAOYSA-N 1-(1h-1,2,4-triazol-5-yl)ethanol Chemical compound CC(O)C1=NC=NN1 WYZRLXYOIMXEBO-UHFFFAOYSA-N 0.000 description 1
• ZPIHRUCXNRKJIF-UHFFFAOYSA-N 1-(2-trimethylsilylethoxymethyl)imidazole-2-carbaldehyde Chemical compound C[Si](C)(C)CCOCN1C=CN=C1C=O ZPIHRUCXNRKJIF-UHFFFAOYSA-N 0.000 description 1
• LSNWNTHKHQTQMT-UHFFFAOYSA-N 1-(chloromethyl)isoquinoline Chemical compound C1=CC=C2C(CCl)=NC=CC2=C1 LSNWNTHKHQTQMT-UHFFFAOYSA-N 0.000 description 1
• 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 1
• HNIHOFVDKWEICB-UHFFFAOYSA-N 1-fluorocyclobutane-1-carboxylic acid Chemical compound OC(=O)C1(F)CCC1 HNIHOFVDKWEICB-UHFFFAOYSA-N 0.000 description 1
• BAUWRHPMUVYFOD-UHFFFAOYSA-N 1-methylpiperidin-4-ol Chemical compound CN1CCC(O)CC1 BAUWRHPMUVYFOD-UHFFFAOYSA-N 0.000 description 1
• JWAWEQBUZOGIBZ-UHFFFAOYSA-N 1-methyltriazole Chemical compound CN1C=CN=N1 JWAWEQBUZOGIBZ-UHFFFAOYSA-N 0.000 description 1
• CUOVNMDNRAZFDH-UHFFFAOYSA-N 1-propyl-1,2,4-triazole Chemical compound CCCN1C=NC=N1 CUOVNMDNRAZFDH-UHFFFAOYSA-N 0.000 description 1
• IAJLTMBBAVVMQO-UHFFFAOYSA-N 1h-benzimidazol-2-ylmethanol Chemical compound C1=CC=C2NC(CO)=NC2=C1 IAJLTMBBAVVMQO-UHFFFAOYSA-N 0.000 description 1
• ZOMATQMEHRJKLO-UHFFFAOYSA-N 1h-imidazol-2-ylmethanol Chemical compound OCC1=NC=CN1 ZOMATQMEHRJKLO-UHFFFAOYSA-N 0.000 description 1
• VUAXHMVRKOTJKP-UHFFFAOYSA-N 2,2-dimethylbutyric acid Chemical compound CCC(C)(C)C(O)=O VUAXHMVRKOTJKP-UHFFFAOYSA-N 0.000 description 1
• IQOSUJMDLDGCKD-UHFFFAOYSA-N 2,3,5,6,7,8-hexahydrophthalazine-1,4-dione Chemical compound C1CCCC2=C1C(=O)NNC2=O IQOSUJMDLDGCKD-UHFFFAOYSA-N 0.000 description 1
• SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 1
• PTURTHBRTGJYRN-UHFFFAOYSA-N 2,3-dimethyl-1h-pyridin-4-one Chemical compound CC=1NC=CC(=O)C=1C PTURTHBRTGJYRN-UHFFFAOYSA-N 0.000 description 1
• LIDGFHXPUOJZMK-UHFFFAOYSA-N 2,6-dimethyl-1-oxidopyridin-1-ium Chemical compound CC1=CC=CC(C)=[N+]1[O-] LIDGFHXPUOJZMK-UHFFFAOYSA-N 0.000 description 1
• HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
• GFHPSQFCHUIFTO-UHFFFAOYSA-N 2-(chloromethyl)pyrazine Chemical compound ClCC1=CN=CC=N1 GFHPSQFCHUIFTO-UHFFFAOYSA-N 0.000 description 1
• DDEAEWMDOSXKBX-UHFFFAOYSA-N 2-(chloromethyl)quinoline Chemical compound C1=CC=CC2=NC(CCl)=CC=C21 DDEAEWMDOSXKBX-UHFFFAOYSA-N 0.000 description 1
• AAUVNJJBLOZTAO-UHFFFAOYSA-N 2-(chloromethyl)quinoxaline Chemical compound C1=CC=CC2=NC(CCl)=CN=C21 AAUVNJJBLOZTAO-UHFFFAOYSA-N 0.000 description 1
• KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 description 1
• 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 description 1
• MIVUDAUOXJDARR-UHFFFAOYSA-N 2-[(3,5-dinitrobenzoyl)amino]-2-phenylacetic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)NC(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 MIVUDAUOXJDARR-UHFFFAOYSA-N 0.000 description 1
• BFCPBUHHSDPXQF-UHFFFAOYSA-N 2-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxy]acetonitrile Chemical compound N#CCOC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 BFCPBUHHSDPXQF-UHFFFAOYSA-N 0.000 description 1
• YPYNGKVFEWEQPN-UHFFFAOYSA-N 2-[3-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-1,2,4-triazol-1-yl]ethanamine Chemical compound NCCN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 YPYNGKVFEWEQPN-UHFFFAOYSA-N 0.000 description 1
• IODZEPJJMFABOR-UHFFFAOYSA-N 2-[5-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-1,2,4-triazol-1-yl]acetamide Chemical compound NC(=O)CN1N=CN=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 IODZEPJJMFABOR-UHFFFAOYSA-N 0.000 description 1
• COCKXQZJSLFDBW-UHFFFAOYSA-N 2-[[5-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxymethyl]-1,2,4-triazol-1-yl]methoxy]ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCN1N=CN=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 COCKXQZJSLFDBW-UHFFFAOYSA-N 0.000 description 1
• PGFIHORVILKHIA-UHFFFAOYSA-N 2-bromopyrimidine Chemical compound BrC1=NC=CC=N1 PGFIHORVILKHIA-UHFFFAOYSA-N 0.000 description 1
• XBPPLECAZBTMMK-UHFFFAOYSA-N 2-chloro-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CCl XBPPLECAZBTMMK-UHFFFAOYSA-N 0.000 description 1
• WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
• SGTXILTYXULEQD-UHFFFAOYSA-N 2H-triazolo[4,5-f]phthalazine Chemical group N1=NC=C2C3=NNN=C3C=CC2=C1 SGTXILTYXULEQD-UHFFFAOYSA-N 0.000 description 1
• JZSAUQMXKHBZEO-UHFFFAOYSA-N 3,5-dichloropyridazine Chemical compound ClC1=CN=NC(Cl)=C1 JZSAUQMXKHBZEO-UHFFFAOYSA-N 0.000 description 1
• SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 description 1
• RUVVGCRPPJVNMC-UHFFFAOYSA-N 3,6-dichloro-4,5-dimethylpyridazine Chemical compound CC1=C(C)C(Cl)=NN=C1Cl RUVVGCRPPJVNMC-UHFFFAOYSA-N 0.000 description 1
• OIVNHVRINWMDTH-UHFFFAOYSA-N 3,7-diphenyl-6-(pyridin-2-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 OIVNHVRINWMDTH-UHFFFAOYSA-N 0.000 description 1
• VXIUXRNTQNASBZ-UHFFFAOYSA-N 3,7-diphenyl-6-[[1-(pyridin-2-ylmethyl)-1,2,4-triazol-3-yl]methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N1=CN(CC=2N=CC=CC=2)N=C1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CC=C1 VXIUXRNTQNASBZ-UHFFFAOYSA-N 0.000 description 1
• 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 1
• KBXIMXGMCDDYNJ-UHFFFAOYSA-N 3-(2-trimethylsilylethoxymethyl)triazole-4-carbaldehyde Chemical compound C[Si](C)(C)CCOCN1N=NC=C1C=O KBXIMXGMCDDYNJ-UHFFFAOYSA-N 0.000 description 1
• HPHNQRHXQRLRLZ-UHFFFAOYSA-N 3-(4-methylphenyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-7-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C1=CC(C)=CC=C1C1=NN=C2N1N=C(OCC1=NN(C)C=N1)C(C=1C=CC=CC=1)=C2 HPHNQRHXQRLRLZ-UHFFFAOYSA-N 0.000 description 1
• RCXZRLWXLRUDFH-UHFFFAOYSA-N 3-(5-methylthiophen-2-yl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-7-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound S1C(C)=CC=C1C1=NN=C2N1N=C(OCC1=NN(C)C=N1)C(C=1C=CC=CC=1)=C2 RCXZRLWXLRUDFH-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 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 1
• YPRMWCKXOZFJGF-UHFFFAOYSA-N 3-bromofuran-2,5-dione Chemical compound BrC1=CC(=O)OC1=O YPRMWCKXOZFJGF-UHFFFAOYSA-N 0.000 description 1
• XWFUSBPVIYJBML-UHFFFAOYSA-N 3-chloro-6-(chloromethyl)pyridazine Chemical compound ClCC1=CC=C(Cl)N=N1 XWFUSBPVIYJBML-UHFFFAOYSA-N 0.000 description 1
• FCFAREUMSQVSLJ-UHFFFAOYSA-N 3-cyclopropyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-7-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C2CC2)C=2C=CC=CC=2)=N1 FCFAREUMSQVSLJ-UHFFFAOYSA-N 0.000 description 1
• AXGOOCLYBPQWNG-UHFFFAOYSA-N 3-ethylfuran-2,5-dione Chemical compound CCC1=CC(=O)OC1=O AXGOOCLYBPQWNG-UHFFFAOYSA-N 0.000 description 1
• VMZSDAQEWPNOIB-UHFFFAOYSA-N 3-methoxybenzohydrazide Chemical compound COC1=CC=CC(C(=O)NN)=C1 VMZSDAQEWPNOIB-UHFFFAOYSA-N 0.000 description 1
• VFAQDMYUCHBIJL-UHFFFAOYSA-N 3-methyltriazole-4-carbaldehyde Chemical compound CN1N=NC=C1C=O VFAQDMYUCHBIJL-UHFFFAOYSA-N 0.000 description 1
• AVDYSIRPQQXPMM-UHFFFAOYSA-N 3-phenyl-6-(pyridin-2-ylmethoxy)-7-thiophen-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C=CC=NC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1=CC=CS1 AVDYSIRPQQXPMM-UHFFFAOYSA-N 0.000 description 1
• IDEZPOJTOXGVQI-UHFFFAOYSA-N 3-phenyl-7-thiophen-3-yl-6-(1h-1,2,4-triazol-5-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1C=NNC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C=1C=CSC=1 IDEZPOJTOXGVQI-UHFFFAOYSA-N 0.000 description 1
• UHMARZNHEMRXQH-UHFFFAOYSA-N 3a,4,5,7a-tetrahydro-2-benzofuran-1,3-dione Chemical compound C1=CCCC2C(=O)OC(=O)C21 UHMARZNHEMRXQH-UHFFFAOYSA-N 0.000 description 1
• 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 1
• HMMBJOWWRLZEMI-UHFFFAOYSA-N 4,5,6,7-tetrahydro-2-benzofuran-1,3-dione Chemical compound C1CCCC2=C1C(=O)OC2=O HMMBJOWWRLZEMI-UHFFFAOYSA-N 0.000 description 1
• FSVOMBDSHMMPER-UHFFFAOYSA-N 4,5-dihydrobenzo[e][2]benzofuran-1,3-dione Chemical compound C1CC2=CC=CC=C2C2=C1C(=O)OC2=O FSVOMBDSHMMPER-UHFFFAOYSA-N 0.000 description 1
• LBXZLFZVTDYSIZ-UHFFFAOYSA-N 4-(3-bromo-6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-7-yl)morpholine Chemical compound ClC1=NN2C(Br)=NN=C2C=C1N1CCOCC1 LBXZLFZVTDYSIZ-UHFFFAOYSA-N 0.000 description 1
• CRZPXVXJMFQSOL-UHFFFAOYSA-N 4-(chloromethyl)-2-ethyl-1,3-thiazole Chemical compound CCC1=NC(CCl)=CS1 CRZPXVXJMFQSOL-UHFFFAOYSA-N 0.000 description 1
• AQBBZYVPKBIILN-UHFFFAOYSA-N 4-(chloromethyl)-2-methyl-1,3-thiazole Chemical compound CC1=NC(CCl)=CS1 AQBBZYVPKBIILN-UHFFFAOYSA-N 0.000 description 1
• ZTEQVWJRCAKHMR-UHFFFAOYSA-N 4-[(7-cyclobutyl-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxy]-n,n-dimethylbut-2-yn-1-amine Chemical compound CN(C)CC#CCOC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1CCC1 ZTEQVWJRCAKHMR-UHFFFAOYSA-N 0.000 description 1
• LTMYXBJRKUILMN-UHFFFAOYSA-N 4-[4-[(7-cyclobutyl-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxy]but-2-ynyl]-2,6-dimethylmorpholine Chemical compound C1C(C)OC(C)CN1CC#CCOC(C(=C1)C2CCC2)=NN2C1=NN=C2C1=CC=CC=C1 LTMYXBJRKUILMN-UHFFFAOYSA-N 0.000 description 1
• IUEGWDIGIFAMBR-UHFFFAOYSA-N 4-[6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-7-yl]morpholine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)N2CCOCC2)=N1 IUEGWDIGIFAMBR-UHFFFAOYSA-N 0.000 description 1
• VZFOZTUIYKQSDP-UHFFFAOYSA-N 4-[6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-7-yl]morpholine Chemical compound CN1N=CN=C1COC(C(=C1)N2CCOCC2)=NN2C1=NN=C2C1=CC=CC=C1 VZFOZTUIYKQSDP-UHFFFAOYSA-N 0.000 description 1
• 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 1
• REKQLYUAUXYJSZ-UHFFFAOYSA-N 4-methoxybenzohydrazide Chemical compound COC1=CC=C(C(=O)NN)C=C1 REKQLYUAUXYJSZ-UHFFFAOYSA-N 0.000 description 1
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• MFFVZXOPRXMVET-UHFFFAOYSA-N 4-methylbenzohydrazide Chemical compound CC1=CC=C(C(=O)NN)C=C1 MFFVZXOPRXMVET-UHFFFAOYSA-N 0.000 description 1
• WJHYLPADRKEKNI-UHFFFAOYSA-N 4-methylcyclohexene-1,2-dicarboxylic acid Chemical compound CC1CCC(C(O)=O)=C(C(O)=O)C1 WJHYLPADRKEKNI-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
• YGFXNNJIVZUYCL-UHFFFAOYSA-N 5-(chloromethyl)-2-methyltetrazole Chemical compound CN1N=NC(CCl)=N1 YGFXNNJIVZUYCL-UHFFFAOYSA-N 0.000 description 1
• FYDQQEVRVKAASZ-UHFFFAOYSA-N 5-(chloromethyl)-3-methyl-1,2,4-oxadiazole Chemical compound CC1=NOC(CCl)=N1 FYDQQEVRVKAASZ-UHFFFAOYSA-N 0.000 description 1
• HCQUWYYALIXUBW-UHFFFAOYSA-N 5-(dibromomethyl)pyrimidine Chemical compound BrC(Br)C1=CN=CN=C1 HCQUWYYALIXUBW-UHFFFAOYSA-N 0.000 description 1
• 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 1
• VDORHDUUIQZRDL-UHFFFAOYSA-N 5-[2-[(3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)oxy]ethyl]-4-methyl-1,3-thiazole Chemical compound N1=CSC(CCOC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C VDORHDUUIQZRDL-UHFFFAOYSA-N 0.000 description 1
• AGQOIYCTCOEHGR-UHFFFAOYSA-N 5-methyl-1,2-oxazole Chemical compound CC1=CC=NO1 AGQOIYCTCOEHGR-UHFFFAOYSA-N 0.000 description 1
• TWGNOYAGHYUFFR-UHFFFAOYSA-N 5-methylpyrimidine Chemical compound CC1=CN=CN=C1 TWGNOYAGHYUFFR-UHFFFAOYSA-N 0.000 description 1
• GZXDOXSIKJNUEW-UHFFFAOYSA-N 5-methylthiophene Chemical compound CC1=C=C[CH]S1 GZXDOXSIKJNUEW-UHFFFAOYSA-N 0.000 description 1
• QKBZWDHIYGDNHZ-UHFFFAOYSA-N 6-(4-chlorobut-2-ynoxy)-7-cyclobutyl-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound ClCC#CCOc1nn2c(nnc2cc1C1CCC1)-c1ccccc1 QKBZWDHIYGDNHZ-UHFFFAOYSA-N 0.000 description 1
• 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 1
• RIXHBDMRLPVSEE-UHFFFAOYSA-N 6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 RIXHBDMRLPVSEE-UHFFFAOYSA-N 0.000 description 1
• GEWLTTZNZPUIOR-UHFFFAOYSA-N 6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-7-phenyl-3-pyridin-3-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=NC=CC=2)C=2C=CC=CC=2)=N1 GEWLTTZNZPUIOR-UHFFFAOYSA-N 0.000 description 1
• SVTAFDIHWQPZDR-UHFFFAOYSA-N 6-[(1-methyltriazol-4-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N1=NN(C)C=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 SVTAFDIHWQPZDR-UHFFFAOYSA-N 0.000 description 1
• OTYBGZZAPBCLPB-UHFFFAOYSA-N 6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-7-thiophen-2-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C=2SC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 OTYBGZZAPBCLPB-UHFFFAOYSA-N 0.000 description 1
• VLQWBRAFRPJRJG-UHFFFAOYSA-N 6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1 VLQWBRAFRPJRJG-UHFFFAOYSA-N 0.000 description 1
• LTHHNAJLVMPSRA-UHFFFAOYSA-N 6-[(4-methyl-1,2,4-triazol-3-yl)methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NN=C1COC(C(=C1)C=2C=CC=CC=2)=NN2C1=NN=C2C1=CC=CC=C1 LTHHNAJLVMPSRA-UHFFFAOYSA-N 0.000 description 1
• USZJBAPIJYTILI-UHFFFAOYSA-N 6-[[1-(1-methylpiperidin-4-yl)-1,2,4-triazol-3-yl]methoxy]-3,7-diphenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C1CN(C)CCC1N1N=C(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)N=C1 USZJBAPIJYTILI-UHFFFAOYSA-N 0.000 description 1
• GBOIAGNROOVCES-UHFFFAOYSA-N 6-chloro-3-(furan-3-yl)-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound N=1N=C2C=3CCCCC=3C(Cl)=NN2C=1C=1C=COC=1 GBOIAGNROOVCES-UHFFFAOYSA-N 0.000 description 1
• VJHOEKXSWORTRP-UHFFFAOYSA-N 6-chloro-3-phenyl-7-piperidin-1-yl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound ClC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1N1CCCCC1 VJHOEKXSWORTRP-UHFFFAOYSA-N 0.000 description 1
• CTKDTIYRVIGDLE-UHFFFAOYSA-N 6-chloro-3-phenyl[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(Cl)C=CC2=NN=C1C1=CC=CC=C1 CTKDTIYRVIGDLE-UHFFFAOYSA-N 0.000 description 1
• VOCMNGMXRYQFJN-UHFFFAOYSA-N 6-chloro-7-(1-methylcyclopentyl)-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound C=1C2=NN=C(C=3C=CC=CC=3)N2N=C(Cl)C=1C1(C)CCCC1 VOCMNGMXRYQFJN-UHFFFAOYSA-N 0.000 description 1
• KHTBOHFYNQGICR-UHFFFAOYSA-N 6-chloro-7-cyclobutyl-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound ClC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1CCC1 KHTBOHFYNQGICR-UHFFFAOYSA-N 0.000 description 1
• NXKGFOMUOFNBSO-UHFFFAOYSA-N 6-chloro-7-morpholin-4-yl-2h-[1,2,4]triazolo[4,3-b]pyridazin-3-one Chemical compound ClC1=NN(C(NN=2)=O)C=2C=C1N1CCOCC1 NXKGFOMUOFNBSO-UHFFFAOYSA-N 0.000 description 1
• MIJRCEROMPNYTM-UHFFFAOYSA-N 6-chloro-8,8-dimethyl-3-phenyl-9,10-dihydro-7h-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound C1C(C)(C)CCC(C2=NN=3)=C1C(Cl)=NN2C=3C1=CC=CC=C1 MIJRCEROMPNYTM-UHFFFAOYSA-N 0.000 description 1
• USEKBXDJGHEZOR-UHFFFAOYSA-N 6-chloro-9-methyl-3-phenyl-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine Chemical compound N=1N=C2C=3CC(C)CCC=3C(Cl)=NN2C=1C1=CC=CC=C1 USEKBXDJGHEZOR-UHFFFAOYSA-N 0.000 description 1
• MDUDQSYGSILSJB-UHFFFAOYSA-N 6-chloro-n,n-diethyl-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-7-amine Chemical compound N12N=C(Cl)C(N(CC)CC)=CC2=NN=C1C1=CC=CC=C1 MDUDQSYGSILSJB-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• CESPVUDQHYWYLM-UHFFFAOYSA-N 7,7-dimethyl-6,8-dihydro-5h-phthalazine-1,4-dione Chemical compound O=C1N=NC(=O)C2=C1CC(C)(C)CC2 CESPVUDQHYWYLM-UHFFFAOYSA-N 0.000 description 1
• YUNYEPKAWNWTCM-UHFFFAOYSA-N 7-(2-methylbutan-2-yl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(OCC3=NN(C)C=N3)C(C(C)(C)CC)=CC2=NN=C1C1=CC=CC=C1 YUNYEPKAWNWTCM-UHFFFAOYSA-N 0.000 description 1
• RZMOWUBQZJZECS-UHFFFAOYSA-N 7-(furan-3-yl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C2=COC=C2)=N1 RZMOWUBQZJZECS-UHFFFAOYSA-N 0.000 description 1
• YJZKDERWZGYTGA-UHFFFAOYSA-N 7-cyclobutyl-3-phenyl-5h-[1,2,4]triazolo[4,3-b]pyridazin-6-one Chemical compound OC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1CCC1 YJZKDERWZGYTGA-UHFFFAOYSA-N 0.000 description 1
• WFQGCGNGOVKICN-UHFFFAOYSA-N 7-cyclobutyl-3-phenyl-6-(1h-1,2,4-triazol-5-ylmethoxy)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N=1C=NNC=1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C=C1C1CCC1 WFQGCGNGOVKICN-UHFFFAOYSA-N 0.000 description 1
• NRVMDUPYHCGRQW-UHFFFAOYSA-N 7-cyclobutyl-8-methyl-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N1=CN(C)N=C1COC1=NN2C(C=3C=CC=CC=3)=NN=C2C(C)=C1C1CCC1 NRVMDUPYHCGRQW-UHFFFAOYSA-N 0.000 description 1
• KUZSRQBJRMHMFJ-UHFFFAOYSA-N 7-ethyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(OCC=3N(N=CN=3)C)C(CC)=CC2=NN=C1C1=CC=CC=C1 KUZSRQBJRMHMFJ-UHFFFAOYSA-N 0.000 description 1
• CUCYVGNNTAIIAN-UHFFFAOYSA-N 7-tert-butyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-phenyl-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C(C)(C)C)=NN2C1=NN=C2C1=CC=CC=C1 CUCYVGNNTAIIAN-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• 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 1
• JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 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
• 241000416162 Astragalus gummifer Species 0.000 description 1
• IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
• 239000004342 Benzoyl peroxide Substances 0.000 description 1
• OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• NIZSDHRDZYPEHD-UHFFFAOYSA-N CC1CCc2c(C1)c(Cl)nn1c(nnc21)-c1ccccc1 Chemical compound CC1CCc2c(C1)c(Cl)nn1c(nnc21)-c1ccccc1 NIZSDHRDZYPEHD-UHFFFAOYSA-N 0.000 description 1
• SGFXSDMEHSGVMJ-UHFFFAOYSA-N CN1NC(N=C1)CO Chemical compound CN1NC(N=C1)CO SGFXSDMEHSGVMJ-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 244000060011 Cocos nucifera Species 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-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
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
• 229940121909 GABA receptor agonist Drugs 0.000 description 1
• 108010010803 Gelatin Proteins 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
• 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
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 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 1
• NLLYHHNRUBNOEJ-UHFFFAOYSA-N OCC1(NC=CC=N1)C Chemical compound OCC1(NC=CC=N1)C NLLYHHNRUBNOEJ-UHFFFAOYSA-N 0.000 description 1
• UALYRYOBSOPBHG-UHFFFAOYSA-N OCC1=C(N=NN1OCC[Si](C)(C)C)C Chemical compound OCC1=C(N=NN1OCC[Si](C)(C)C)C UALYRYOBSOPBHG-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 102100035591 POU domain, class 2, transcription factor 2 Human genes 0.000 description 1
• 101710084411 POU domain, class 2, transcription factor 2 Proteins 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 1
• 244000000231 Sesamum indicum Species 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 229930006000 Sucrose Natural products 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
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• SEQDDYPDSLOBDC-UHFFFAOYSA-N Temazepam Chemical compound N=1C(O)C(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 SEQDDYPDSLOBDC-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 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 1
• KMXANNVLSSYIHB-UHFFFAOYSA-N [2-(2-trimethylsilylethoxymethyl)-1,2,4-triazol-3-yl]methanol Chemical compound C[Si](C)(C)CCOCN1N=CN=C1CO KMXANNVLSSYIHB-UHFFFAOYSA-N 0.000 description 1
• YWMLORGQOFONNT-UHFFFAOYSA-N [3-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=CC(CO)=C1 YWMLORGQOFONNT-UHFFFAOYSA-N 0.000 description 1
• YIMQCDZDWXUDCA-UHFFFAOYSA-N [4-(hydroxymethyl)cyclohexyl]methanol Chemical compound OCC1CCC(CO)CC1 YIMQCDZDWXUDCA-UHFFFAOYSA-N 0.000 description 1
• HCBUZOFBMBYMTM-UHFFFAOYSA-N [4-methyl-1-(2-trimethylsilylethoxymethyl)imidazol-2-yl]methanol Chemical compound CC1=CN(COCC[Si](C)(C)C)C(CO)=N1 HCBUZOFBMBYMTM-UHFFFAOYSA-N 0.000 description 1
• XCDLMXUNXHXCAG-UHFFFAOYSA-N [5-methyl-1-(2-trimethylsilylethoxymethyl)imidazol-2-yl]methanol Chemical compound CC1=CN=C(CO)N1COCC[Si](C)(C)C XCDLMXUNXHXCAG-UHFFFAOYSA-N 0.000 description 1
• QRZPWHITTFPBEO-UHFFFAOYSA-N [5-methyl-2-(2-trimethylsilylethoxy)-1,2,4-triazol-3-yl]methanol Chemical compound OCC=1N(N=C(N=1)C)OCC[Si](C)(C)C QRZPWHITTFPBEO-UHFFFAOYSA-N 0.000 description 1
• CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 229940081735 acetylcellulose Drugs 0.000 description 1
• 150000008065 acid anhydrides Chemical class 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000037328 acute stress Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 201000002426 animal phobia Diseases 0.000 description 1
• 230000001773 anti-convulsant effect Effects 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 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
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 235000019400 benzoyl peroxide Nutrition 0.000 description 1
• KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
• 229940073608 benzyl chloride Drugs 0.000 description 1
• NRIMHVFWRMABGJ-UHFFFAOYSA-N bicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylic acid Chemical compound C1C2C(C(=O)O)=C(C(O)=O)C1C=C2 NRIMHVFWRMABGJ-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 230000017531 blood circulation Effects 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
• 229920002301 cellulose acetate Polymers 0.000 description 1
• 210000003710 cerebral cortex Anatomy 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 238000004140 cleaning Methods 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000004090 cyclononenyl group Chemical group C1(=CCCCCCCC1)* 0.000 description 1
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
• YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
• 229960002887 deanol Drugs 0.000 description 1
• 230000003001 depressive effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229960003529 diazepam Drugs 0.000 description 1
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
• 125000004987 dibenzofuryl group Chemical group C1(=CC=CC=2OC3=C(C21)C=CC=C3)* 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
• SQKZZFWTOOPCDQ-UHFFFAOYSA-N dichloromethane;ethyl acetate;hexane Chemical compound ClCCl.CCCCCC.CCOC(C)=O SQKZZFWTOOPCDQ-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 125000004212 difluorophenyl group Chemical group 0.000 description 1
• 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
• 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 239000012972 dimethylethanolamine Substances 0.000 description 1
• GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 210000001198 duodenum Anatomy 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000012055 enteric layer Substances 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
• GNCPGXBJUUAXGA-UHFFFAOYSA-N ethyl 4-methyl-2-(trifluoromethylsulfonyloxy)cyclohexene-1-carboxylate Chemical compound CCOC(=O)C1=C(OS(=O)(=O)C(F)(F)F)CC(C)CC1 GNCPGXBJUUAXGA-UHFFFAOYSA-N 0.000 description 1
• FFVHHWOJYFCNJP-UHFFFAOYSA-N ethyl 4-methyl-2-oxocyclohexane-1-carboxylate Chemical compound CCOC(=O)C1CCC(C)CC1=O FFVHHWOJYFCNJP-UHFFFAOYSA-N 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 239000012054 flavored emulsion Substances 0.000 description 1
• 235000020375 flavoured syrup Nutrition 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• CYEFKCRAAGLNHW-UHFFFAOYSA-N furan-3-ylboronic acid Chemical compound OB(O)C=1C=COC=1 CYEFKCRAAGLNHW-UHFFFAOYSA-N 0.000 description 1
• KFKMGUPDWTWQFM-UHFFFAOYSA-N furo[3,4-c]pyridine-1,3-dione Chemical compound N1=CC=C2C(=O)OC(=O)C2=C1 KFKMGUPDWTWQFM-UHFFFAOYSA-N 0.000 description 1
• 239000007789 gas 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
• 239000011521 glass Substances 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 239000005337 ground glass Substances 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• SKVRYQUMKJQZFN-UHFFFAOYSA-N hydron;2-(hydroxymethyl)pyridin-3-ol;chloride Chemical compound Cl.OCC1=NC=CC=C1O SKVRYQUMKJQZFN-UHFFFAOYSA-N 0.000 description 1
• 239000003326 hypnotic agent Substances 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 229910010272 inorganic material Inorganic materials 0.000 description 1
• 239000011147 inorganic material Substances 0.000 description 1
• 239000002198 insoluble material Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 230000001678 irradiating effect Effects 0.000 description 1
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
• 229960003350 isoniazid Drugs 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 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
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
• SFXQJROVECIHKO-UHFFFAOYSA-N methyl 5,5-dimethyl-2-oxocyclohexane-1-carboxylate Chemical compound COC(=O)C1CC(C)(C)CCC1=O SFXQJROVECIHKO-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 1
• DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 1
• PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
• 229920001206 natural gum Polymers 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 238000012587 nuclear overhauser effect experiment Methods 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000012053 oil suspension Substances 0.000 description 1
• 125000000962 organic group Chemical group 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 125000002524 organometallic group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 239000003182 parenteral nutrition solution Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 229960005152 pentetrazol Drugs 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004344 phenylpropyl group Chemical group 0.000 description 1
• 208000019899 phobic disease Diseases 0.000 description 1
• 239000008055 phosphate buffer solution Substances 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 1
• 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
• 229920001296 polysiloxane Polymers 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
• 159000000001 potassium salts Chemical class 0.000 description 1
• LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 238000004237 preparative chromatography Methods 0.000 description 1
• 238000012746 preparative thin layer chromatography Methods 0.000 description 1
• TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
• SXBRULKJHUOQCD-UHFFFAOYSA-N propanoic acid Chemical compound CCC(O)=O.CCC(O)=O SXBRULKJHUOQCD-UHFFFAOYSA-N 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 238000011403 purification operation Methods 0.000 description 1
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
• NIPZZXUFJPQHNH-UHFFFAOYSA-M pyrazine-2-carboxylate Chemical compound [O-]C(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-M 0.000 description 1
• BYUMAPPWWKNLNX-UHFFFAOYSA-N pyrazol-1-ylmethanol Chemical compound OCN1C=CC=N1 BYUMAPPWWKNLNX-UHFFFAOYSA-N 0.000 description 1
• TVPRCLHSULCNLV-UHFFFAOYSA-N pyridazin-3-one Chemical compound O=C1C=CC=N[N]1 TVPRCLHSULCNLV-UHFFFAOYSA-N 0.000 description 1
• 150000004892 pyridazines Chemical class 0.000 description 1
• 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 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
• KFUSANSHCADHNJ-UHFFFAOYSA-N pyridine-3-carbohydrazide Chemical compound NNC(=O)C1=CC=CN=C1 KFUSANSHCADHNJ-UHFFFAOYSA-N 0.000 description 1
• HZGCZRCZOMANHK-UHFFFAOYSA-N pyrimidin-2-ylmethanol Chemical compound OCC1=NC=CC=N1 HZGCZRCZOMANHK-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 229940044601 receptor agonist Drugs 0.000 description 1
• 239000000018 receptor agonist Substances 0.000 description 1
• 238000005932 reductive alkylation reaction Methods 0.000 description 1
• 239000000932 sedative agent Substances 0.000 description 1
• 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 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 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 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000001476 sodium potassium tartrate Substances 0.000 description 1
• 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 229960003188 temazepam Drugs 0.000 description 1
• JNYVFHASMHPMFL-UHFFFAOYSA-N tert-butyl-(1h-imidazol-5-ylmethoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCC1=CNC=N1 JNYVFHASMHPMFL-UHFFFAOYSA-N 0.000 description 1
• XKQMRIVZVLGFFZ-UHFFFAOYSA-N tert-butyl-dimethyl-(1h-1,2,4-triazol-5-ylmethoxy)silane Chemical compound CC(C)(C)[Si](C)(C)OCC1=NC=NN1 XKQMRIVZVLGFFZ-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000003146 transient transfection Methods 0.000 description 1
• SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 1
• DHWQQVXDRKXOCV-UHFFFAOYSA-N trimethyl-[2-(1,2,4-triazol-1-ylmethoxy)ethyl]silane Chemical compound C[Si](C)(C)CCOCN1C=NC=N1 DHWQQVXDRKXOCV-UHFFFAOYSA-N 0.000 description 1
• RZLMQJSSMROKSS-UHFFFAOYSA-N trimethyl-[2-(triazol-1-ylmethoxy)ethyl]silane Chemical compound C[Si](C)(C)CCOCN1C=CN=N1 RZLMQJSSMROKSS-UHFFFAOYSA-N 0.000 description 1
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 229960001475 zolpidem Drugs 0.000 description 1
• ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1