JP2002514169A - Gaba受容体に対するリガンドとしての置換トリアゾローピリダジン誘導体 - Google Patents
Gaba受容体に対するリガンドとしての置換トリアゾローピリダジン誘導体Info
- Publication number
- JP2002514169A JP2002514169A JP50858598A JP50858598A JP2002514169A JP 2002514169 A JP2002514169 A JP 2002514169A JP 50858598 A JP50858598 A JP 50858598A JP 50858598 A JP50858598 A JP 50858598A JP 2002514169 A JP2002514169 A JP 2002514169A
- Authority
- JP
- Japan
- Prior art keywords
- triazolo
- phenyl
- methyl
- pyridazine
- ylmethoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000003446 ligand Substances 0.000 title abstract description 7
- CBHTTYDJRXOHHL-UHFFFAOYSA-N 2h-triazolo[4,5-c]pyridazine Chemical class N1=NC=CC2=C1N=NN2 CBHTTYDJRXOHHL-UHFFFAOYSA-N 0.000 title description 6
- 102000005915 GABA Receptors Human genes 0.000 title description 2
- 108010005551 GABA Receptors Proteins 0.000 title description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 44
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 25
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 11
- 206010010904 Convulsion Diseases 0.000 claims abstract description 8
- 230000036506 anxiety Effects 0.000 claims abstract description 8
- 230000036461 convulsion Effects 0.000 claims abstract description 7
- -1 pyridin-2-ylmethoxy Chemical group 0.000 claims description 620
- 150000001875 compounds Chemical class 0.000 claims description 523
- 238000000034 method Methods 0.000 claims description 221
- 239000000203 mixture Substances 0.000 claims description 151
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 149
- 229910052757 nitrogen Inorganic materials 0.000 claims description 57
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 125000004076 pyridyl group Chemical group 0.000 claims description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 25
- 239000000651 prodrug Substances 0.000 claims description 24
- 229940002612 prodrug Drugs 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 20
- 230000027455 binding Effects 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 12
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 12
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 claims description 12
- 230000004044 response Effects 0.000 claims description 12
- 238000012360 testing method Methods 0.000 claims description 12
- 125000000335 thiazolyl group Chemical group 0.000 claims description 12
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 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 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 8
- 150000001412 amines Chemical class 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
- 125000002541 furyl group Chemical group 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
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 230000000949 anxiolytic effect Effects 0.000 claims description 7
- 229940049706 benzodiazepine Drugs 0.000 claims description 7
- 239000004305 biphenyl Substances 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
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 6
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 6
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 6
- 239000002249 anxiolytic agent Substances 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- QUSNBJAOOMFDIB-UHFFFAOYSA-N monoethyl amine Natural products CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 5
- 230000001624 sedative effect Effects 0.000 claims description 5
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 5
- 241001024304 Mino Species 0.000 claims description 4
- 206010039897 Sedation Diseases 0.000 claims description 4
- 229910001870 ammonium persulfate Inorganic materials 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 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 description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 230000036280 sedation Effects 0.000 claims description 4
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 4
- 229910052723 transition metal Inorganic materials 0.000 claims description 4
- 150000003624 transition metals Chemical class 0.000 claims description 4
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 3
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 3
- 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 3
- 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 claims description 3
- 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 3
- 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 claims description 3
- 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 description 3
- 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 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
- DKJVVUVRFFFLLC-UHFFFAOYSA-N 4-[6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-3-thiophen-2-yl-[1,2,4]triazolo[4,3-b]pyridazin-7-yl]morpholine Chemical compound CN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2SC=CC=2)N2CCOCC2)=N1 DKJVVUVRFFFLLC-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
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 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
- 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 claims 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 claims description 3
- 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 3
- 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 3
- 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 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
- 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 claims description 3
- 241000009298 Trigla lyra Species 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 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
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 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
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 3
- 238000010561 standard procedure Methods 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 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 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
- HWGNAWBPLYPUJG-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-dimethylethanamine Chemical compound CN(C)CCN1C=NC(COC=2C(=CC3=NN=C(N3N=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 HWGNAWBPLYPUJG-UHFFFAOYSA-N 0.000 claims description 2
- 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 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 claims description 2
- 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 claims description 2
- 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 description 2
- QEWCWAZIROCRRH-UHFFFAOYSA-N 3-(4-fluorophenyl)-6-[(1-methyl-1,2,4-triazol-3-yl)methoxy]-7-thiophen-3-yl-[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)C2=CSC=C2)=N1 QEWCWAZIROCRRH-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
- 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 claims description 2
- RRAWTSZJLAMHFE-UHFFFAOYSA-N 3-(furan-2-yl)-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=2OC=CC=2)C=2C=CC=CC=2)=N1 RRAWTSZJLAMHFE-UHFFFAOYSA-N 0.000 claims description 2
- QRVATIMYRMQIKG-UHFFFAOYSA-N 3-(furan-3-yl)-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)C2=COC=C2)C=2C=CC=CC=2)=N1 QRVATIMYRMQIKG-UHFFFAOYSA-N 0.000 claims 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 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
- 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 2
- 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 2
- 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 claims description 2
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- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960003188 temazepam Drugs 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 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 1
- 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 1
- 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 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
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- 238000004809 thin layer chromatography Methods 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 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
- 238000003325 tomography Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- JPMCMQORJRTDKK-UHFFFAOYSA-N triazol-1-ylmethanol Chemical compound OCN1C=CN=N1 JPMCMQORJRTDKK-UHFFFAOYSA-N 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
- UKTDFYOZPFNQOQ-UHFFFAOYSA-N tributyl(thiophen-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CS1 UKTDFYOZPFNQOQ-UHFFFAOYSA-N 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
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- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 式I (式中、 Yは水素またはC1-6アルキルであり、 ZはC1-6アルキル,C3-7シクロアルキル、C4-7シクロアルケニル、アリー ル、C3-7ヘテロシクロアルキル、ヘテロアリールまたはジ(C1-6)アルキルア ミノであり、これらの基は任意に置換されていてもよく、或いは YとZは2つの介在炭素原子と一緒になって、C5-9シクロアルケニル、C6-1 0 ビシクロアルケニル、テトラヒドロピリジニル、ピリジニル及びフェニルから 選択される環を形成し、これらの環は任意にベンゾ融合及び/または置換されて いてもよく、 R1はC3-7シクロアルキル、フェニル、フリル、チエニルまたはピリジニルで あり、これらの基は任意に置換されていてもよく、 R2はシアノ(C1-6)アルキル、ヒドロキシ(C1-6)アルキル、C3-7シクロ アルキル(C1-6)アルキル、プロパルギル、C3-7ヘテロシクロアルキルカルボ ニル(C1-6)アルキル、アリール(C1-6)アルキルまたはヘテロアリール(C1-6 )アルキルであり、これらの基は任意に置換されていてもよい、 ただしYとZが2つの介在炭素原子と一緒になって任意に置換されたフェニル 基を形成するときR2はヒドロキシ(C1-6)アルキル以外である) の化合物、またはその塩もしくはプロドラッグ。 2. 式IIA(式中、 R1は請求の範囲第1項に定義した通りであり、 nは1、2、3または4であり、 R12はヒドロキシであるか、または任意に置換されたC3-7シクロアルキル、 C3-7ヘテロシクロアルキルカルボニル、アリールまたはヘテロアリールである ) で表される請求の範囲第1項に記載の化合物、並びにその塩及びプロドラッグ。 3. 式IIB (式中、 Y1は水素またはメチルであり、 Z1はC1-6アルキル,C3-7シクロアルキル、C4-7シクロアルケニル、アリー ル、C3-7ヘテロシクロアルキル、ヘテロアリールまたはジ(C1-6)アルキルア ミノであり、これら の基は任意に置換されていてもよく、 R1は請求の範囲第1項に定義した通りであり、 mは1または2であり、 R22は任意に置換されたアリールまたはヘテロアリールである) で表される請求の範囲第1項に記載の化合物、並びにその塩及びプロドラッグ。 4. 式IIC (式中、 R1は請求の範囲第1項に定義した通りであり、 Qはシクロプロピル、シクロブチル、シクロペンチルまたはシクロヘキシル環 の残基であり、 R5は水素またはメチルであり、 R6は水素またはメチルである) で表される請求の範囲第3項に記載の化合物、並びに医薬的に許容可能なその塩 。 5. 3−フェニル−6−(2−ピリジル)メチルオキシ−7,8,9,10−テトラ ヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a]フタラ ジン、 3,7−ジフェニル−6−(2−ピリジル)メチルオキシ−1,2,4−トリア ゾロ[4,3−b]ピリダジン、 3−フェニル−6−(2−ピリジル)メチルオキシ−7,8,9,10−テトラ ヒドロ−1,2,4−トリアゾロ[3,4−a]フタラジン、 7,8−ジメチル−3−フェニル−6−(2−ピリジル)メチルオキシ−1,2 ,4−トリアゾロ[4,3−b]ピリダジン、 7−メチル−3−フェニル−6−(2−ピリジル)メチルオキシ−1,2,4− トリアゾロ[4,3−b]ピリダジン、 7−エチル−3−フェニル−6−(2−ピリジル)メチルオキシ−1,2,4− トリアゾロ[4,3−b]ピリダジン、 7,8−ベンゾ−3−フェニル−6−(2−ピリジル)メチル オキシ−7,8,9,10−テトラヒドロ−1,2,4−トリアゾロ[3,4− a]フタラジン、 8−メチル−3,7−ジフェニル−6−(2−ピリジル)メチルオキシ−1,2 ,4−トリアゾロ[4,3−b]ピリダジン、 3−フェニル−6−(2−ピリジル)メチルオキシ−7,8,9,10−テトラ ヒドロ−(7,10−メタノ)−1,2,4−トリアゾロ[3,4−a]フタラ ジン、 3−フェニル−5−(ピリジン−2−イルメトキシ)−1,2,3a,4,7− ペンタアザシクロペンタ−[α]ナフタレン、 3−フェニル−5−(ピリジン−2−イルメトキシ)−1,2,3a,4,8− ペンタアザシクロペンタ−[α]ナフタレン、 8−メチル−3−フェニル−6−(2−ピリジル)メチルオキシ−7,8,9, 10−テトラヒドロ−1,2,4−トリアゾロ[3,4−a]フタラジン、 3−フェニル−6−(2−ピリジル)メチルオキシ−(7,8−ペンタノ)−1 ,2,4−トリアゾロ[4,3−b]ピリダジン、 8,8−ジメチル−3−フェニル−6−(2−ピリジル)メチルオキシ−7,8 ,9,10−テトラヒドロ−1,2,4−ト リアゾロ[3,4−a]フタラジン、 3−フェニル−7−(ピペリジン−1−イル)−6−(ピリジン−2−イルメト キシ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−フェニル−7−(ピリジン−4−イル)−6−(ピリジン−2−イルメトキ シ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−フェニル−5−(ピリジン−2−イルメトキシ)−6,7,8,9−テトラ ヒドロ−1,2,3a,4,8−ペンタアザシクロペンタ[α]ナフタレン、 3−フェニル−5−(ピリジン−2−イルメトキシ)−6,7,8,9−テトラ ヒドロ−1,2,3a,4,7−ペンタアザシクロペンタ[α]ナフタレン、 7−メチル−3−フェニル−5−(ピリジン−2−イルメトキシ)−6,7,8 ,9−テトラヒドロ−1,2,3a,4,7−ペンタアザシクロペンタ[α]ナ フタレン、 3−フェニル−6−(ピリジン−2−イルメトキシ)−7−(チオフェン−2− イル)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−フェニル−6−(ピリジン−2−イルメトキシ)−7−(チオフェン−3− イル)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−フェニル−6−(2−ピリジル)メチルオキシ−7,8,9,10−テトラ ヒドロ−(7,10−プロパノ)−1,2,4−トリアゾロ[3,4−a]フタ ラジン、 3−(4−メチル)フェニル−6−(2−ピリジル)メチルオキシ−7,8,9 ,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3, 4−a]フタラジン、 3−(3−メトキシ)フェニル−6−(2−ピリジル)メチルオキシ−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 3−(2−フルオロ)フェニル−6−(2−ピリジル)メチルオキシ−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 3−(3−ピリジル)−6−(2−ピリジル)メチルオキシ−7,8,9,10 −テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a ]フタラジン、 3−シクロプロピル−6−(2−ピリジル)メチルオキシ−7, 8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ [3,4−a]フタラジン、 6−[(6−メチル)−2−ピリジル]メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−7,10−エタノ)−1,2,4−トリアゾロ[3, 4−a]フタラジン、 6−[(3−メチル)−2−ピリジル]メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 6−[(4−メチル)−2−ピリジル]メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 6−[(5−メチル)−2−ピリジル]メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 3−フェニル−6−(3−ピリジル)メチルオキシ−7,8,9,10−テトラ ヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a]フタラ ジン、 3−フェニル−6−(4−ピリジル)メチルオキシ−7,8,9,10−テトラ ヒドロ−(7,10−エタノ)−1,2,4 −トリアゾロ[3,4−a]フタラジン、 3−フェニル−6−[2−(1−メチル)イミダゾリル]メチルオキシ−7,8 ,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[ 3,4−a]フタラジン、 6−(3−シアノフェニル)メチルオキシ−3−フェニル−7,8,9,10− テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a] フタラジン、 6−[1−(3,5−ジメチル)ピラゾリル]メチルオキシ−3−フェニル−7 ,8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾ ロ[3,4−a]フタラジン、 6−[4−(2−メチル)チアゾリル]メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 3−フェニル−6−(2−キノキサリニル)メチルオキシ−7,8,9,10− テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a] フタラジン、 3−フェニル−6−(3−ピリダジニル)メチルオキシ−7,8,9,10−テ トラヒドロ−(7,10−エタノ)−1,2, 4−トリアゾロ[3,4−a]フタラジン、 6−(1−ベンジルイミダゾル−2−イル)メチルオキシ−3−フェニル−7, 8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ [3,4−a]フタラジン、 3−フェニル−6−(イソキノリン−1−イル)メチルオキシ−7,8,9,1 0−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4− a]フタラジン、 6−(1−エチルイミタゾル−2−イル)メチルオキシ−3−フェニル−7,8 ,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[ 3,4−a]フタラジン、 3−フェニル−6−(1−ピラゾリル)メチルオキシ−7,8,9,10−テト ラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a]フタ ラジン、 3−フェニル−6−(N−ピロリジニルカルボニル)メチルオキシ−7,8,9 ,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3, 4−a]フタラジン、 6−[4−(3−メチル)ピリジル]メチルオキシ−3−フェニル−7,8,9 ,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3, 4−a]フタラジン、 3−フェニル−6−(2−キノリニル)メチルオキシ−7,8,9,10−テト ラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a]フタ ラジン、 6−(2−イミダゾリル)メチルオキシ−3−フェニル−7,8,9,10−テ トラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a]フ タラジン、 3−フェニル−6−(2−チアゾリル)メチルオキシ−7,8,9,10−テト ラヒドロ−(7.10−エタノ)−1,2,4−トリアゾロ[3,4−a]フタ ラジン、 6−[2−(5−メチル)チアゾリル]メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 6−[2−(4−メチル)チアゾリル]メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 6−[2−(3,5−ジメチル)ピリジル]メチルオキシ−3−フェニル−7, 8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ [3,4−a]フタラジン、 3−フェニル−6−(2−ピラジニル)メチルオキシ−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 6−[2−(4,6−ジメチル)ピリジル]メチルオキシ−3−フェニル−7, 8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ [3,4−a]フタラジン、 3−フェニル−6−(4−チアゾリル)メチルオキシ−7,8,9,10−テト ラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a]フタ ラジン、 6−[2−(5,6−ジメチル)ピリジル]メチルオキシ−3−フェニル−7, 8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ [3,4−a]フタラジン 6−(4−メチルイミダゾル−2−イル)メチルオキシ−3−フェニル−7,8 ,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[ 3,4−a]フタラジン、 3−フェニル−6−(4−ピリミジニル)メチルオキシ−7,8,9,10−テ トラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a]フ タラジン、 6−[4−(2−エチル)チアゾリル]メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−(7,10−エタ ノ)−1,2,4−トリアゾロ[3,4−a]フタラジン、 6−(6−クロロピリダジン−3−イル)メチルオキシ−3−フェニル−7,8 ,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[ 3,4−a]フタラジン、 6−(2−イミダゾリル)メチルオキシ−3−(4−メチルフェニル)−7,8 ,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[ 3,4−a]フタラジン、 6−(4−ヒドロキシメチルフェニル)メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3 ,4−a]フタラジン、 6−(4−ヒドロキシブチル)オキシ−3−フェニル−7,8,9,10−テト ラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3,4−a]フタ ラジン、 6−(4−ヒドロキシメチルシクロヘキシル)メチルオキシ−3−フェニル−7 ,8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾ ロ[3,4−a]フタラジン、 6−(3−ヒドロキシメチルフェニル)メチルオキシ−3−フェニル−7,8, 9,10−テトラヒドロ−(7,10−エタ ノ)−1,2,4−トリアゾロ[3,4−a]フタラジン、 6−(1−メチル−1,2,4−トリアゾル−3−イル)メチルオキシ−3−フ ェニル−7,8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4 −トリアゾロ[3,4−a]フタラジン、 6−(2−メチル−1,2,4−トリアゾル−3−イル)メチルオキシ−3−フ ェニル−7,8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4 −トリアゾロ[3,4−a]フタラジン、 3−フェニル−6−(3−シクロプロピルメチルオキシ−2−ピリジル)メチル オキシ−7,8,9,10−テトラヒドロ−(7,10−エタノ)−1,2,4 −トリアゾロ[3,4−a]フタラジン、 3−フェニル−6−(3−エトキシ−2−ピリジル)メチルオキシ−7,8,9 ,10−テトラヒドロ−(7,10−エタノ)−1,2,4−トリアゾロ[3, 4−a]フタラジン から選択される化合物、並びにその塩及びプロドラッグ。 6. 6−(6−メチルピリジン−2−イル)メチルオキシ−3−フェニル−1 ,2,4−トリアゾロ[3,4−a]フタラ ジンから選択される化合物、並びにその塩及びプロドラッグ。 7. 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−3, 7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−3, 7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3,7−ジフェニル−6−(2H−1,2,4−トリアゾル−3−イルメトキシ )−1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−(2−メチル−2H−テトラゾル−5−イルメトキシ)−3,7−ジフェニ ル−1,2,4−トリアゾロ[4,3−b]−ピリダジン、 3,7−ジフェニル−6−(2−プロピル−2H−1,2,4−トリアゾル−3 −イルメトキシ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3,7−ジフェニル−6−(1−プロピル−1H−1,2,4−トリアゾル−3 −イルメトキシ)−1,2,4−トリアゾロ [4,3−b]ピリダジン、 6−(1−メチル−1H−イミダゾル−4−イルメトキシ)−3,7−ジフェニ ル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−(3−メチル−3H−イミダゾル−4−イルメトキシ)−3,7−ジフェニ ル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−(4−メチル−4H−1,2,4−トリアゾル−3−イルメトキシ)−3, 7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−(5−メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−3, 7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−(3−メチル−3H−1,2,3−トリアゾル−4−イルメトキシ)−3, 7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−(4−メトキシフェニル)−6−(1−メチル−1H−1,2,4−トリア ゾル−3−イルメトキシ)−7−フェニル−1,2,4−トリアゾロ[4,3− b]ピリダジン、 6−(3−メチルピリジン−2−イルメトキシ)−3−フェニル−7−(ピペリ ジン−1−イル)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−(モルホリン−4−イル)−3−フェニル−6−(ピリジン−2−イルメト キシ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−フェニル−7−(ピリジン−3−イル)−6−(ピリジン−2−イルメトキ シ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 8−メチル−6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメト キシ)−3,7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジ ン、 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−7− (モルホリン−4−イル)−3−フェニル−1,2,4−トリアゾロ[4,3− b]ピリダジン、 6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−7− (モルホリン−4−イル)−3−フェニル−1,2,4−トリアゾロ[4,3− b]ピリダジン、 7−シクロヘキシル−6−(2−メチル−2H−1,2,4− トリアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4 ,3−b]ピリダジン、 7−シクロヘキシル−6−(1−メチル−1H−1,2,4−トリアゾル−3− イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダ ジン、 7−シクロペンチル−6−(2−メチル−2H−1,2,4−トリアゾル−3− イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダ ジン、 8−メチル−6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメト キシ)−3,7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジ ン、 7−シクロブチル−6−(1−メチル−1H−1,2,4−トリアゾル−3−イ ルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジ ン、 7−tert−ブチル−6−(2−メチル−2H−1,2,4−トリアゾル−3 −イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリ ダジン、 7−シクロブチル−6−(2−メチル−2H−1,2,4−トリアゾル−3−イ ルメトキシ)−3−フェニル−1,2,4− トリアゾロ[4,3−b]ピリダジン、 7−エチル−6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメト キシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−tert−ブチル−6−(1−メチル−1H−1,2,4−トリアゾル−3 −イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリ ダジン、 7−エチル−6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメト キシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン 7−メチル−6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメト キシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−(1−メチルシクロブチル)−6−(2−メチル−2H−1,2,4−トリ アゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3 −b]ピリダジン、 7−メチル−6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメト キシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−シクロブチル−3−フェニル−6−(2H−1,2,4−トリアゾル−3− イルメトキシ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−シクロペンチル−6−(ピリジン−2−イルメトキシ)−3−(チオフェン −2−イル)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−シクロペンチル−3−(2,4−ジフルオロフェニル)−6−(1−メチル −1H−1,2,4−トリアゾル−3−イルメトキシ)−1,2,4−トリアゾ ロ[4,3−b]ピリダジン、 7−シクロペンチル−6−(1−メチル−1H−1,2,4−トリアゾル−3− イルメトキシ)−3−(チオフェン−2−イル)−1,2,4−トリアゾロ[4 ,3−b]ピリダジン、 7−シクロペンチル−6−(2−メチル−2H−1,2,4−トリアゾル−3− イルメトキシ)−3−(チオフェン−2−イル)−1,2,4−トリアゾロ[4 ,3−b]ピリダジン、 7−シクロペンチル−6−(2−メチル−2H−1,2,4−トリアゾル−3− イルメトキシ)−3−(ピリジン−4−イル)−1,2,4−トリアゾロ[4, 3−b]ピリダジン、 7−シクロペンチル−3−(2−フルオロフェニル)−6−(1−メチル−1H −1,2,4−トリアゾル−3−イルメトキシ)−1,2,4−トリアゾロ[4 ,3−b]ピリダジン、 7−シクロペンチル−3−(2−フルオロフェニル)−6−(2−メチル−2H −1,2,4−トリアゾル−3−イルメトキシ)−1,2,4−トリアゾロ[4 ,3−b]ピリダジン、 7−シクロペンチル−3−(2−フルオロフェニル)−6−(ピリジン−2−イ ルメトキシ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−シクロペンチル−3−(2,4−シフルオロフェニル)−6−(2−メチル −2H−1,2,4−トリアゾル−3−イルメトキシ)−1,2,4−トリアゾ ロ[4,3−b]ピリダジン、 7−シクロペンチル−3−フェニル−6−(ピリジン−2−イルメトキシ)−1 ,2,4−トリアゾロ[4,3−b]ピリダジン、 7−シクロペンチル−8−メチル−6−(2−メチル−2H−1,2,4−トリ アゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3 −b]ピリダジン、 7−シクロペンチル−3−フェニル−6−(2H−1,2,4−トリアゾル−3 −イルメトキシ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−(4−メチルフェニル)−7−フェニル−6−(ピリジン−2−イルメトキ シ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−(4−メチルフェニル)−6−(3−メチルピリジン−2−イルメトキシ) −7−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−(1−エチル−1H−イミタゾル−2−イルメトキシ)−3−(4−メチル フェニル)−7−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン 、 3−フェニル−6−(ピリジン−2−イルメトキシ)−7−(チオモルホリン− 4−イル)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−[2−(4−メチルチアゾル−5−イル)エトキシ]−3,7−ジフェニル −1,2,4−トリアゾロ[4,3−b]ピリダジン、 (±)−7−(2−メチルピロリジン−1−イル)−3−フェ ニル−6−(ピリジン−2−イルメトキシ)−1,2,4−トリアゾロ[4,3 −b]ピリダジン、 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−3− フェニル−7−(ピリジン−4−イル)−1,2,4−トリアゾロ[4,3−b ]ピリダジン、 7−シクロペンチル−6−(1−メチル−1H−1,2,4−トリアゾル−3− イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダ ジン、 7−イソプロピル−6−(1−メチル−1H−1,2,4−トリアゾル−3−イ ルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジ ン、 3−シクロプロピル−6−(1−メチル−1H−1,2,4−トリアゾル−3− イルメトキシ)−7−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダ ジン、 3−(2−フルオロフェニル)−6−(2−メチル−2H−1,2,4−トリア ゾル−3−イルメトキシ)−7−フェニル−1,2,4−トリアゾロ[4,3− b]ピリダジン、 3−(2−フルオロフェニル)−6−(1−メチル−1H−1,2,4−トリア ゾル−3−イルメトキシ)−7−フェニル−1, 2,4−トリアゾロ[4,3−b]ピリダジン、 6−(1−メチル−1H−1,2,4−トリアゾロ−3−イルメトキシ)−7− フェニル−3−(チオフェン−2−イル)−1,2,4−トリアゾロ[4,3− b]ピリダジン 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−7− フェニル−3−(ピリジン−3−イル)−1,2,4−トリアゾロ[4,3−b ]ピリダジン、 6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−7− フェニル−3−(チオフェン−2−イル)−1,2,4−トリアゾロ[4,3− b]ピリダジン、 6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−7− フェニル−3−(ピリジン−3−イル)−1,2,4−トリアゾロ[4,3−b ]ピリダジン、 3−(フラン−3−イル)−6−(1−メチル−1H−1,2,4−トリアゾル −3−イルメトキシ)−7−フェニル−1,2,4−トリアゾロ[4,3−b] ピリダジン、 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−7− フェニル−3−(チオフェン−2−イル)−1,2,4−トリアゾロ[4,3− b]ピリダジン、 6−(5−メチル−1,2,4−オキサジアゾル−3−イルメトキシ)−3,7 −ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−フェニル−3−(チオフェン−2−イル)−6−(2H−1,2,4−トリ アゾル−3−イルメトキシ)−1,2,4−トリアゾロ[4,3−b]ピリダジ ン、 3−(フラン−2−イル)−6−(1−メチル−1H−1,2,4−トリアゾル −3−イルメトキシ)−7−フェニル−1,2,4−トリアゾロ[4,3−b] ピリダジン、 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−3− フェニル−7−(チオフェン−3−イル)−1,2,4−トリアゾロ[4,3− b]ピリダジン、 6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−7− (チオフェン−3−イル)−1,2,4−トリアゾロ[4,3−b]ピリダジン 、 3−フェニル−7−(チオフェン−3−イル)−6−(2H−1,2,4−トリ アゾル−3−イルメトキシ)−1,2,4−トリアゾロ[4,3−b]ピリダジ ン、 6−(2−メチル−2H−1,2,4−トリアゾル−3−イル メトキシ)−3−フェニル−7−(チオフェン−2−イル)−1,2,4−トリ アゾロ[4,3−b]ピリダジン、 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−3− フェニル−7−(チオフェン−2−イル)−1,2,4−トリアゾロ[4,3− b]ピリダジン 7−(フラン−2−イル)−6−(2−メチル−2H−1,2,4−トリアゾル −3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b] ピリダジン、 7−(フラン−2−イル)−6−(1−メチル−1H−1,2,4−トリアゾル −3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b] ピリダジン、 6−(3−メチル−1,2,4−オキサジアゾル−5−イルメトキシ)−3,7 −ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−(4−フルオロフェニル)−6−(1−メチル−1H−1,2,4−トリア ゾル−3−イルメトキシ)−7−フェニル−1,2,4−トリアゾロ[4,3− b]ピリダジン、 3,7−ジフェニル−6−(2H−1,2,3−トリアゾル−4−イルメトキシ )−1,2,4−トリアゾロ[4,3−b] ピリダジン、 3,7−ジフェニル−6−(ピラジン−2−イルメトキシ)−1,2,4−トリ アゾロ[4,3−b]ピリダジン、 3−(4−メチルフェニル)−6−(1−メチル−1H−1,2,4−トリアゾ ル−3−イルメトキシ)−7−フェニル−1,2,4−トリアゾロ[4,3−b ]ピリダジン、 6−(4−メチルチアゾル−2−イルメトキシ)−3,7−ジフェニル−1,2 ,4−トリアゾロ[4,3−b]ピリダジン、 6−(5−メチルチアゾル−2−イルメトキシ)−3,7−ジフェニル−1,2 ,4−トリアゾロ[4,3−b]ピリダジン、 3,7−ジフェニル−6−(ピリミジン−4−イルメトキシ)−1,2,4−ト リアゾロ[4,3−b]ピリダジン、 3,7−ジフェニル−6−(ピリダジン−3−イルメトキシ)−1,2,4−ト リアゾロ[4,3−b]ピリダジン、 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−7− (モルホリン−4−イル)−3−(チオフェン−2−イル)−1,2,4−トリ アゾロ[4,3−b]ピリダジン、 3,7−ジフェニル−6−(チアゾル−4−イルメトキシ)− 1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−(5−メチルイソオキサゾル−3−イルメトキシ)−3,7−ジフェニル− 1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−(3−フルオロフェニル)−6−(1−メチル−1H−1,2,4−トリア ゾル−3−イルメトキシ)−7−(モルホリン−4−イル)−1,2,4−トリ アゾロ[4,3−b]ピリダジン、 3,7−ジフェニル−6−(ピリミジン−2−イルメトキシ)−1,2,4−ト リアゾロ[4,3−b]ピリダジン、 6−(2−メチル−2H−1,2,3−トリアゾル−4−イルメトキシ)−3, 7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−(1−メチルシクロブチル)−6−(1−メチル−1H−1,2,4−トリ アゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3 −b]ピリダジン、 7−イソプロピル−6−(2−メチル−2H−1,2,4−トリアゾル−3−イ ルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジ ン、 7−tert−ブチル−3−(2−フルオロフェニル)−6−(1−メチル−1 H−1,2,4−トリアゾル−3−イルメトキシ)−1,2,4−トリアゾロ[ 4,3−b]ピリダジン、 7−シクロペンチル−3−(4−メトキシフェニル)−6−(2−メチル−2H −1,2,4−トリアゾル−3−イルメトキシ)−1,2,4−トリアゾロ[4 ,3−b]ピリダジン、 7−(1−メチルシクロペンチル)−6−(1−メチル−1H−1,2,4−ト リアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4, 3−b]ピリダジン、 7−(1−メチルシクロペンチル)−6−(2−メチル−2H−1,2,4−ト リアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4, 3−b]ピリダジン、 7−シクロペンチル−3−(フラン−2−イル)−6−(2−メチル−2H−1 ,2,4−トリアゾル−3−イルメトキシ)−1,2,4−トリアゾロ[4,3 −b]ピリダジン、 7−シクロペンチル−3−(フラン−2−イル)−6−(1−メチル−1H−1 ,2,4−トリアゾル−3−イルメトキシ)−1,2,4−トリアゾロ[4,3 −b]ピリダジン、 3−(3,7−ジフェニル−1,2,4−トリアゾロ[4,3 −b]ピリダジン−6−イルオキシメチル)−1,2,4−トリアゾル−1−イ ルアセトニトリル、 7−(1−メチルシクロプロピル)−6−(2−メチル−2H−1,2,4−ト リアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4, 3−b]ピリダジン、 7−(1−メチルシクロプロピル)−6−(1−メチル−1H−1,2,4−ト リアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4, 3−b]ピリダジン、3−(3−フルオロフェニル)−6−(1−メチル−1H −1,2,4−トリアゾル−3−イルメトキシ)−7−フェニル−1,2,4− トリアゾロ[4,3−b]ピリダジン、 7−(1−メチルシクロプロピル)−6−(3−メチルピリジン−2−イルメト キシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 6−(1−メチル−1H−1,2,3−トリアゾル−4−イルメトキシ)−3, 7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 3−(5−メチルチオフェン−2−イル)−6−(1−メチル−1H−1,2, 4−トリアゾル−3−イルメトキシ)−7− フェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 2−[3−(3,7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリ ダジン−6−イルオキシメチル)−1,2,4−トリアゾル−1−イル]−N, N−ジメチルアセトアミド、 3,7−ジフェニル−6−[1−(ピリジン−2−イルメチル)−1H−1,2 ,4−トリアゾル−3−イルメトキシ]−1,2,4−トリアゾロ[4,3−b ]ピリダジン、 6−(1−ベンジル−1H−1,2,4−トリアゾル−3−イルメトキシ)−3 ,7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリダジン、 2−[5−(3,7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリ ダジン−6−イルオキシメチル)−1,2,4−トリアゾル−1−イル]アセト アミド、 N−[2−[3−(3,7−ジフェニル−1,2,4−トリアゾロ[4,3−b ]ピリダジン−6−イルオキシメチル)−1,2,4−トリアゾル−1−イル] エチル]−N,N−ジメチルアミン、 3,7−ジフェニル−6−(ピリミジン−5−イルメトキシ)−1,2,4−ト リアゾロ[4,3−b]ピリダジン、 6−[1−(2−(モルホリン−4−イル)−エチル)−1H−1,2,4−ト リアゾル−3−イルメトキシ]−3,7−ジフェニル−1,2,4−トリアゾロ [4,3−b]ピリダジン、 6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−3− フェニル−7−(ピロリジン−1−イル)−1,2,4−トリアゾロ[4,3− b]ピリダジン、 7−(5−クロロチオフェン−2−イル)−6−(2−メチル−2H−1,2, 4−トリアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ [4,3−b]ピリダジン、 7−(5−クロロチオフェン−2−イル)−6−(1−メチル−1H−1,2, 4−トリアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ [4,3−b]ピリダジン、 6−(1H−ベンズイミダゾル−2−イルメトキシ)−3−(2,4−ジフルオ ロフェニル)−7−(1−メチルシクロペンチル)−1,2,4−トリアゾロ[ 4,3−b]ピリダジン、 3−(フラン−3−イル)−6−(2−ピリジル)メチルオキシ−7,8,9, 10−テトラヒドロ−1,2,4−トリアゾロ[4,3−a]フタラジン、 7−シクロブチル−3−フェニル−6−(プロパ−2−イニル オキシ)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 (7−シクロブチル−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピ リダジン−6−イルオキシ)アセトニトリル、 N−[4−(7−シクロブチル−3−フェニル−1,2,4−トリアゾロ[4, 3−b]ピリダジン−6−イルオキシ)ブタ−2−イニル]−N,N−ジメチル アミン から選択される化合物、並びにその塩及びプロドラッグ。 8. 2−[3−(3,7−ジフェニル−1,2,4−トリアゾロ[4,3−b]ピリ ダジン−6−イルオキシメチル)−1,2,4−トリアゾル−1−イル]エチル アミン、 3,7−ジフェニル−6−[1−(2−(ピロリジン−1−イル)エチル)−1 H−1,2,4−トリアゾル−3−イルメトキシ]−1,2,4−トリアゾロ[ 4,3−b]ピリダジン、 6−[1−(1−メチルピペリジン−4−イル)−1H−1,2,4−トリアゾ ル−3−イルメトキシ]−3,7−ジフェニル−1,2,4−トリアゾロ[4, 3−b]ピリダジン、 3,7−ジフェニル−6−[1−(2−(ピペラジン−1−イル)エチル)−1 H−1,2,4−トリアゾル−3−イルメト キシ]−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−(1−メチルシクロペンチル)−6−(2−メチル−2H−1,2,4−ト リアゾル−3−イルメトキシ)−3−(2,4−ジフルオロフェニル)−1,2 ,4−トリアゾロ[4,3−b]ピリダジン、 7−(シクロブタ−1−エニル)−6−(2−メチル−2H−1,2,4−トリ アゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3 −b]ピリダジン、 7−(フラン−3−イル)−6−(1−メチル−1H−1,2,4−トリアゾル −3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b] ピリダジン、 N,N−シエチル−N−[6−(1−メチル−1H−1,2,4−トリアゾル− 3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3−b]ピ リダジン−7−イル]アミン、7−(1−メチルシクロペンチル)−6−(1− メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−3−(2,4− ジフルオロフェニル)−1,2,4−トリアゾロ[4,3−b]ピリダジン、 7−(1,1−ジメチルプロピル)−6−(1−メチル−1H −1,2,4−トリアゾル−3−イルメトキシ)−3−フェニル−1,2,4− トリアゾロ[4,3−b]ピリダジン、 6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−3− (4−フルオロフェニル)−7−(チオフェン−3−イル)−1,2,4−トリ アゾロ[4,3−b]ピリダジン、 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−3− (4−フルオロフェニル)−7−(チオフェン−3−イル)−1,2,4−トリ アゾロ[4,3−b]ピリダジン、 6−(2−メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−3− (2−フルオロフェニル)−7−(チオフェン−3−イル)−1,2,4−トリ アゾロ[4,3−b]ピリダジン、 3−(2−フルオロフェニル)−7−(1−メチルシクロブチル)−6−(2− メチル−2H−1,2,4−トリアゾル−3−イルメトキシ)−1,2,4−ト リアゾロ[4,3−b]ピリダジン 3−(2−フルオロフェニル)−7−(1−メチルシクロブチ ル)−6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ) −1,2,4−トリアゾロ[4,3−b]ピリダジン 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−3− (2−フルオロフェニル)−7−(チオフェン−3−イル)−1,2,4−トリ アゾロ[4,3−b]ピリダジン、 8−メチル−7−(1−メチルシクロブチル)−6−(1−メチル−1H−1, 2,4−トリアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリア ゾロ[4,3−b]ピリダジン、 8−メチル−7−(1−メチルシクロブチル)−6−(2−メチル−2H−1, 2,4−トリアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリア ゾロ[4,3−b]ピリダジン、 6−(1−メチル−1H−1,2,4−トリアゾル−3−イルメトキシ)−3− フェニル−7−(ピロリジン−1−イル)−1,2,4−トリアゾロ[4,3− b]ピリダジン、 7−シクロブチル−8−メチル−6−(2−メチル−2H−1, 2,4−トリアゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリア ゾロ[4,3−b]ピリダジン、 7−シクロブチル−8−メチル−6−(1−メチル−1H−1,2,4−トリア ゾル−3−イルメトキシ)−3−フェニル−1,2,4−トリアゾロ[4,3− b]ピリダジン、 7−(1−メチルシクロペンチル)−6−(2−メチル−2H−1,2,4−ト リアゾル−3−イルメトキシ)−3−(2−フルオロフェニル)−1,2,4− トリアゾロ[4,3−b]ピリダジン、 7−(1−メチルシクロペンチル)−6−(1−メチル−1H−1,2,4−ト リアゾル−3−イルメトキシ)−3−(2−フルオロフェニル)−1,2,4− トリアゾロ[4,3−b]ピリダジン、 7−シクロブチル−6−[4−(2,6−ジメチルモルホリン−4−イル)ブタ −2−イニルオキシ]−3−フェニル−1,2,4−トリアゾロ[4,3−b] ピリダジン から選択される化合物、並びにその塩及びプロドラッグ。 9. 請求の範囲第1項に定義する式Iの化合物、その医薬的に許容され得る塩 またはそのプロドラッグを医薬的に許容され 得る担体と共に含む医薬組成物。 10. 請求の範囲第1項〜第8項のいずれか1項に記載の化合物の、不安症の 治療及び/または予防用薬剤の製造のための使用。 11. 請求の範囲第1項〜第8項のいずれか1項に記載の化合物の、痙攣の治 療及び/または予防用薬剤の製造のための使用。 12. 不安症の治療及び/または予防方法であって、該治療を要する患者に対 して有効量の請求の範囲第1項に定義する式Iの化合物、その医薬的に許容され 得る塩またはそのプロドラッグを投与することを含む前記方法。 13. 痙攣の治療及び/または予防方法であって、該治療を要する患者に対し て有効量の請求の範囲第1項に定義する式Iの化合物、その医薬的に許容され得 る塩またはそのプロドラッグを投与することを含む前記方法。 14. ヒトGABAA受容体のα3サブユニットに対する結合アフィニティー (Ki)が10nM以下のヒトGABAA受容体のベンゾジアゼピン結合部位のモ ジュレーターである化合物であって、ヒトGABAA受容体のα3サブユニット を発現 する安定的にトランスフェクトされた組換え細胞系におけるGABA EC20応 答を少なくとも40%増大させ、ヒトGABAA受容体のα1サブユニットを発 現する安定的にトランスフェクトされた細胞系におけるGABA EC20応答を 多くとも30%しか増大させない化合物。 15. 経口投与後に有利な治療効果を発揮し得る請求の範囲第14項に記載の 化合物。 16. 請求の範囲第14項または第15項に記載の化合物を医薬的に許容され 得る担体と共に含む医薬組成物。 17. 経口投与に適した請求の範囲第16項に記載の組成物。 18. 請求の範囲第14項または第15項に記載の化合物の、実質的な鎮静作 用なしに不安症を治療及び/または予防するための薬剤の製造のための使用。 19. 請求の範囲第14項または第15項に記載の化合物の、痙攣を治療及び /または予防するための薬剤の製造のための使用。 20. 実質的な鎮静作用なしに不安症を治療及び/または予防するための方法 であって、該治療を要する患者に対して有効量の請求の範囲第14項に記載の化 合物を投与することを含む 前記方法。 21. 痙攣を治療及び/または予防するための方法であって、該治療を要する 患者に対して有効量の請求の範囲第14項に記載の化合物を投与することを含む 前記方法。 22. 非鎮静抗不安性化合物のスクリーニング方法であって、 (1)試験化合物のパネルを(a)ヒトGABAA受容体のα3サブユニットを発現 する安定的にトランスフェクトされた組換え細胞系及び(b)ヒトGABAA受容体 のα1サブユニットを発現する安定的にトランスフェクトされた組換え細胞系を 接触させ、 (2)安定的にトランスフェクトされた組換え細胞系(a)及び(b)の各々において 各試験化合物によるGABA EC20応答の増大を測定し、 (3)α3サブユニットを発現する細胞系におけるGABAEC20応答を少なく とも40%を増大させ且つα1サブユニットを発現する細胞系におけるGABA EC20応答を最大30%しか増大させない試験化合物を選択することからなる 前記方法。 23. 請求の範囲第1項に記載の化合物の製造方法であって、 (A)式IIIの化合物を式IVの化合物 (式中、Y、Z、R1及びR2は請求の範囲第1項に定義した通りであり、L1は 適当な離脱基である) と反応させるか、 (B)式VIIの化合物を式VIIIの化合物 (式中、Y、Z、R1及びR2は請求の範囲第1項に定義した通りであり、L3は 適当な離脱基である) と反応させるか、 (C)式Z−CO2Hの化合物を式IXの化合物(式中、Y、Z、R1及びR2は請求の範囲第1項に定義した通りである) と硝酸銀及び過硫酸アンモニウムの存在下で反応させるか、または (D)式Xの化合物を式XIの化合物 (式中、Y、Z、R1及びR2は請求の範囲第1項に定義した通りであり、Alk はC1-6アルキルであり、L4は適当な離脱基である) と遷移金属触媒の存在下で反応させ、 (E)所望により、得られた式Iの化合物を標準的な方法により別の式Iの化合 物に変換することからなる前記方法。
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CA1080712A (en) * | 1976-09-22 | 1980-07-01 | Jay D. Albright | Hypotensive agents |
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US4487930A (en) * | 1982-09-07 | 1984-12-11 | The Dow Chemical Company | 6-[(Cyclic amino)alkylamino]-tetrahydrotriazolo[3,4-a]phthalazines |
IT1194310B (it) * | 1983-07-12 | 1988-09-14 | Lepetit Spa | Derivati triazolo (3,4-a) ftalazinici 3,6-disostituiti |
US4578464A (en) * | 1983-11-22 | 1986-03-25 | Merrell Dow Pharmaceuticals Inc. | 6-Hydroxyalkylamino-8-methyl-1,2,4-triazolo-[4,3-b]pyridazine and related compounds |
FR2562071B1 (fr) * | 1984-03-30 | 1986-12-19 | Sanofi Sa | Triazolo(4,3-b)pyridazines, procede pour leur preparation et compositions pharmaceutiques les contenant |
GB9321162D0 (en) * | 1993-10-13 | 1993-12-01 | Boots Co Plc | Therapeutic agents |
GB9507348D0 (en) * | 1995-04-08 | 1995-05-31 | Knoll Ag | Therapeutic agents |
GB9726702D0 (en) * | 1997-12-18 | 1998-02-18 | Merck Sharp & Dohme | Therapeutic use |
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1997
- 1997-07-17 NZ NZ333768A patent/NZ333768A/xx unknown
- 1997-07-17 AT AT97931960T patent/ATE236904T1/de not_active IP Right Cessation
- 1997-07-17 KR KR1019997000606A patent/KR20000029548A/ko not_active Application Discontinuation
- 1997-07-17 EE EEP199900027A patent/EE9900027A/xx unknown
- 1997-07-17 ES ES97931960T patent/ES2194205T3/es not_active Expired - Lifetime
- 1997-07-17 SK SK93-99A patent/SK9399A3/sk unknown
- 1997-07-17 CZ CZ99181A patent/CZ18199A3/cs unknown
- 1997-07-17 DE DE69720732T patent/DE69720732T2/de not_active Expired - Lifetime
- 1997-07-17 EP EP97931960A patent/EP0915875B1/en not_active Expired - Lifetime
- 1997-07-17 EA EA199900164A patent/EA002436B1/ru not_active IP Right Cessation
- 1997-07-17 AU AU35539/97A patent/AU723098B2/en not_active Ceased
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- 1997-07-17 WO PCT/GB1997/001946 patent/WO1998004559A2/en active IP Right Grant
- 1997-07-17 CN CN97196641A patent/CN1251589A/zh active Pending
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-
1999
- 1999-01-19 IS IS4949A patent/IS4949A/is unknown
- 1999-01-22 NO NO990304A patent/NO990304L/no not_active Application Discontinuation
- 1999-01-25 BG BG103112A patent/BG103112A/xx unknown
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JP4672820B2 (ja) * | 1997-05-08 | 2011-04-20 | メルク シャープ エンド ドーム リミテッド | GABAα5リガンドとしての置換1,2,4−トリアゾロ[3,4−a]フタラジン誘導体 |
JP2001525802A (ja) * | 1997-05-08 | 2001-12-11 | メルク シヤープ エンド ドーム リミテツド | GABAα5リガンドとしての置換1,2,4−トリアゾロ[3,4−a]フタラジン誘導体 |
JP2006513208A (ja) * | 2002-12-18 | 2006-04-20 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼインヒビターとしてのトリアゾロピリダジン |
JP4817661B2 (ja) * | 2002-12-18 | 2011-11-16 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼインヒビターとしてのトリアゾロピリダジン |
JP2008543764A (ja) * | 2005-06-09 | 2008-12-04 | ブリストル−マイヤーズ スクイブ カンパニー | 11β−ヒドロキシステロイドデヒドロゲナーゼI型阻害剤としてのイミダゾおよびトリアゾロピリジン類 |
US9925189B2 (en) | 2006-12-28 | 2018-03-27 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
US9737537B2 (en) | 2006-12-28 | 2017-08-22 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
JP2010533721A (ja) * | 2007-07-19 | 2010-10-28 | メタボレックス, インコーポレイテッド | 糖尿病および代謝疾患の治療のためのRUP3またはGPRl19受容体のアゴニストとしてのN−アザ環状置換ピロール、ピラゾール、イミダゾール、トリアゾールおよびテトラゾール誘導体 |
JP2013100322A (ja) * | 2008-08-29 | 2013-05-23 | Concert Pharmaceuticals Inc | 置換トリアゾロ−ピリダジン誘導体 |
US9150567B2 (en) | 2009-10-01 | 2015-10-06 | Cymabay Therapeutics, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
JP2015536959A (ja) * | 2012-11-07 | 2015-12-24 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | トリアゾロ化合物 |
JP2019507736A (ja) * | 2016-01-27 | 2019-03-22 | ウニヴェルズィテート・ツューリヒ | 掻痒の処置のためのgabaa受容体モジュレーターの使用 |
JP2022088620A (ja) * | 2016-01-27 | 2022-06-14 | ウニヴェルズィテート・ツューリヒ | 掻痒の処置のためのgabaa受容体モジュレーターの使用 |
JP7115746B2 (ja) | 2016-01-27 | 2022-08-09 | ウニヴェルズィテート・ツューリヒ | 掻痒の処置のためのgabaa受容体モジュレーターの使用 |
US11529359B2 (en) | 2016-01-27 | 2022-12-20 | Universitat Zurich | Use of GABAA receptor modulators for treatment of itch |
US10292983B2 (en) | 2016-08-03 | 2019-05-21 | Cymabay Therapeutics, Inc. | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
Also Published As
Publication number | Publication date |
---|---|
ATE236904T1 (de) | 2003-04-15 |
EA002436B1 (ru) | 2002-04-25 |
CN1251589A (zh) | 2000-04-26 |
BG103112A (en) | 1999-09-30 |
BR9710729A (pt) | 1999-08-17 |
AU723098B2 (en) | 2000-08-17 |
EP0915875B1 (en) | 2003-04-09 |
DE69720732T2 (de) | 2004-01-29 |
NZ333768A (en) | 2000-09-29 |
PL331072A1 (en) | 1999-06-21 |
SK9399A3 (en) | 2000-04-10 |
US6255305B1 (en) | 2001-07-03 |
WO1998004559A2 (en) | 1998-02-05 |
EE9900027A (et) | 1999-08-16 |
IS4949A (is) | 1999-01-19 |
KR20000029548A (ko) | 2000-05-25 |
AU3553997A (en) | 1998-02-20 |
DE69720732D1 (de) | 2003-05-15 |
CZ18199A3 (cs) | 1999-06-16 |
NO990304L (no) | 1999-03-25 |
EA199900164A1 (ru) | 2000-04-24 |
YU2899A (sh) | 2000-03-21 |
EP0915875A2 (en) | 1999-05-19 |
TR199900047T2 (xx) | 1999-03-22 |
HUP0600527A2 (en) | 2006-11-28 |
JP4216905B2 (ja) | 2009-01-28 |
NO990304D0 (no) | 1999-01-22 |
ES2194205T3 (es) | 2003-11-16 |
IL127911A0 (en) | 1999-11-30 |
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