DE19948436A1 - New azolo-fused bicyclic imidazolyl-amine compounds, useful as alpha-2 adrenergic receptor ligands and analgesics - Google Patents
New azolo-fused bicyclic imidazolyl-amine compounds, useful as alpha-2 adrenergic receptor ligands and analgesicsInfo
- Publication number
- DE19948436A1 DE19948436A1 DE1999148436 DE19948436A DE19948436A1 DE 19948436 A1 DE19948436 A1 DE 19948436A1 DE 1999148436 DE1999148436 DE 1999148436 DE 19948436 A DE19948436 A DE 19948436A DE 19948436 A1 DE19948436 A1 DE 19948436A1
- Authority
- DE
- Germany
- Prior art keywords
- imidazo
- phenyl
- amine
- tert
- thiazol
- 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
- -1 bicyclic imidazolyl-amine compounds Chemical class 0.000 title claims abstract description 235
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 title 1
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 title 1
- 229940035676 analgesics Drugs 0.000 title 1
- 239000000730 antalgic agent Substances 0.000 title 1
- 239000003446 ligand Substances 0.000 title 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 45
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims abstract description 8
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims abstract description 6
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims abstract description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims abstract description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims abstract description 6
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 6
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 5
- 150000003233 pyrroles Chemical class 0.000 claims abstract description 5
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims abstract description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims abstract description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 3
- 229930192474 thiophene Natural products 0.000 claims abstract description 3
- 150000003577 thiophenes Chemical class 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 21
- 125000002619 bicyclic group Chemical group 0.000 claims description 13
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 10
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 9
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 6
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 6
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 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 6
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 6
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims description 6
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 6
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 6
- LNNOABBVCVKLMY-UHFFFAOYSA-N 2-[5-(cyclohexylamino)-6-methylimidazo[2,1-b][1,3]thiazol-3-yl]acetic acid Chemical compound CC=1N=C2SC=C(CC(O)=O)N2C=1NC1CCCCC1 LNNOABBVCVKLMY-UHFFFAOYSA-N 0.000 claims description 5
- FTOROHDRSVXGPR-UHFFFAOYSA-N 2-[5-(cyclohexylamino)-6-pyridin-2-ylimidazo[2,1-b][1,3]thiazol-3-yl]acetic acid Chemical compound N12C(CC(=O)O)=CSC2=NC(C=2N=CC=CC=2)=C1NC1CCCCC1 FTOROHDRSVXGPR-UHFFFAOYSA-N 0.000 claims description 5
- KHBWFYHLIUIHAK-UHFFFAOYSA-N 2-[5-(tert-butylamino)-6-(2-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-3-yl]acetic acid Chemical compound COC1=CC=CC=C1C1=C(NC(C)(C)C)N2C(CC(O)=O)=CSC2=N1 KHBWFYHLIUIHAK-UHFFFAOYSA-N 0.000 claims description 5
- KEHFIZQNMNMELE-UHFFFAOYSA-N 2-[5-(tert-butylamino)-6-(furan-2-yl)imidazo[2,1-b][1,3]thiazol-3-yl]acetic acid Chemical compound N1=C2SC=C(CC(O)=O)N2C(NC(C)(C)C)=C1C1=CC=CO1 KEHFIZQNMNMELE-UHFFFAOYSA-N 0.000 claims description 5
- RGSQRYHTBPGBNU-UHFFFAOYSA-N 2-[6-cyclohexyl-5-(cyclohexylamino)imidazo[2,1-b][1,3]thiazol-3-yl]acetic acid Chemical compound C1CCCCC1NC=1N2C(CC(=O)O)=CSC2=NC=1C1CCCCC1 RGSQRYHTBPGBNU-UHFFFAOYSA-N 0.000 claims description 5
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 5
- SKSVTGFHNSNQBZ-UHFFFAOYSA-N 3-[5-(tert-butylamino)imidazo[2,1-b][1,3]thiazol-6-yl]phenol Chemical compound N1=C2SC=CN2C(NC(C)(C)C)=C1C1=CC=CC(O)=C1 SKSVTGFHNSNQBZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- BQWRASZIBMTOET-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-6-pyridin-2-ylimidazo[2,1-b][1,3]thiazol-5-amine Chemical compound CC1=CC=CC(C)=C1NC1=C(C=2N=CC=CC=2)N=C2N1C=CS2 BQWRASZIBMTOET-UHFFFAOYSA-N 0.000 claims description 5
- UHJKVIKRLZEECP-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-6-pyridin-3-ylimidazo[2,1-b][1,3]thiazol-5-amine Chemical compound CC1=CC=CC(C)=C1NC1=C(C=2C=NC=CC=2)N=C2N1C=CS2 UHJKVIKRLZEECP-UHFFFAOYSA-N 0.000 claims description 5
- BZNYNBXTIVGBCG-UHFFFAOYSA-N n-(2,6-dimethylphenyl)-6-pyridin-4-ylimidazo[2,1-b][1,3]thiazol-5-amine Chemical compound CC1=CC=CC(C)=C1NC1=C(C=2C=CN=CC=2)N=C2N1C=CS2 BZNYNBXTIVGBCG-UHFFFAOYSA-N 0.000 claims description 5
- DWYNLJQDBCJIRE-UHFFFAOYSA-N n-cyclohexyl-6-pyridin-2-ylimidazo[2,1-b][1,3]thiazol-5-amine Chemical compound C1CCCCC1NC1=C(C=2N=CC=CC=2)N=C2N1C=CS2 DWYNLJQDBCJIRE-UHFFFAOYSA-N 0.000 claims description 5
- IRSVVMGONBYANC-UHFFFAOYSA-N n-tert-butyl-2-phenyl-5h-imidazo[1,2-b]pyrazol-3-amine Chemical compound N1=C2C=CNN2C(NC(C)(C)C)=C1C1=CC=CC=C1 IRSVVMGONBYANC-UHFFFAOYSA-N 0.000 claims description 5
- CTZVPDDBQHEOJI-UHFFFAOYSA-N n-tert-butyl-6-(2,3-dichlorophenyl)imidazo[2,1-b][1,3]thiazol-5-amine Chemical compound N1=C2SC=CN2C(NC(C)(C)C)=C1C1=CC=CC(Cl)=C1Cl CTZVPDDBQHEOJI-UHFFFAOYSA-N 0.000 claims description 5
- YFSNIIOBVMRDCA-UHFFFAOYSA-N n-tert-butyl-6-(2,3-dimethoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-amine Chemical compound COC1=CC=CC(C2=C(N3C=CSC3=N2)NC(C)(C)C)=C1OC YFSNIIOBVMRDCA-UHFFFAOYSA-N 0.000 claims description 5
- SOCIMUBFPSFONO-UHFFFAOYSA-N n-tert-butyl-6-(2,4-dichlorophenyl)imidazo[2,1-b][1,3]thiazol-5-amine Chemical compound N1=C2SC=CN2C(NC(C)(C)C)=C1C1=CC=C(Cl)C=C1Cl SOCIMUBFPSFONO-UHFFFAOYSA-N 0.000 claims description 5
- IWRXIBUAPAAHJE-UHFFFAOYSA-N n-tert-butyl-6-(2-methylphenyl)imidazo[2,1-b][1,3]thiazol-5-amine Chemical compound CC1=CC=CC=C1C1=C(NC(C)(C)C)N2C=CSC2=N1 IWRXIBUAPAAHJE-UHFFFAOYSA-N 0.000 claims description 5
- CDAVLFVNHWLDPV-UHFFFAOYSA-N n-tert-butyl-6-(3,4-dimethoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-amine Chemical compound C1=C(OC)C(OC)=CC=C1C1=C(NC(C)(C)C)N2C=CSC2=N1 CDAVLFVNHWLDPV-UHFFFAOYSA-N 0.000 claims description 5
- ZRGYZZRVSFRLQD-UHFFFAOYSA-N n-tert-butyl-6-(4-methylphenyl)imidazo[2,1-b][1,3]thiazol-5-amine Chemical compound C1=CC(C)=CC=C1C1=C(NC(C)(C)C)N2C=CSC2=N1 ZRGYZZRVSFRLQD-UHFFFAOYSA-N 0.000 claims description 5
- HPZMQBYGFLVSBR-UHFFFAOYSA-N n-tert-butyl-6-(furan-2-yl)imidazo[2,1-b][1,3]thiazol-5-amine Chemical compound N1=C2SC=CN2C(NC(C)(C)C)=C1C1=CC=CO1 HPZMQBYGFLVSBR-UHFFFAOYSA-N 0.000 claims description 5
- VBEGQGISJGICBS-UHFFFAOYSA-N n-tert-butyl-6-pyridin-2-ylimidazo[2,1-b][1,3]thiazol-5-amine Chemical compound N1=C2SC=CN2C(NC(C)(C)C)=C1C1=CC=CC=N1 VBEGQGISJGICBS-UHFFFAOYSA-N 0.000 claims description 5
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 4
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 4
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 4
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims description 4
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 4
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 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
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims description 4
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- QRZMXADUXZADTF-UHFFFAOYSA-N imidazo-5-amine Natural products NC1=CNC=N1 QRZMXADUXZADTF-UHFFFAOYSA-N 0.000 claims description 3
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
- LTOQUFIOYDCJFJ-UHFFFAOYSA-N 1-(4-chlorophenyl)pyrrole Chemical compound C1=CC(Cl)=CC=C1N1C=CC=C1 LTOQUFIOYDCJFJ-UHFFFAOYSA-N 0.000 claims description 2
- PPPXRIUHKCOOMU-UHFFFAOYSA-N 1-(benzenesulfonyl)pyrrole Chemical compound C1=CC=CN1S(=O)(=O)C1=CC=CC=C1 PPPXRIUHKCOOMU-UHFFFAOYSA-N 0.000 claims description 2
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 2
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000002425 furfuryl group Chemical group C(C1=CC=CO1)* 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- KROZLPZGYWISDQ-UHFFFAOYSA-N n-tert-butyl-6-(2-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-amine Chemical compound COC1=CC=CC=C1C1=C(NC(C)(C)C)N2C=CSC2=N1 KROZLPZGYWISDQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 9
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims 2
- IEWRGYRCGQVEMJ-UHFFFAOYSA-N 1-(3,5-dichlorophenyl)pyrrole Chemical compound ClC1=CC(Cl)=CC(N2C=CC=C2)=C1 IEWRGYRCGQVEMJ-UHFFFAOYSA-N 0.000 claims 1
- RMSGQZDGSZOJMU-UHFFFAOYSA-N 1-butyl-2-phenylbenzene Chemical group CCCCC1=CC=CC=C1C1=CC=CC=C1 RMSGQZDGSZOJMU-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 abstract description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 abstract 2
- DEPDDPLQZYCHOH-UHFFFAOYSA-N 1h-imidazol-2-amine Chemical class NC1=NC=CN1 DEPDDPLQZYCHOH-UHFFFAOYSA-N 0.000 abstract 1
- 241000347391 Umbrina cirrosa Species 0.000 abstract 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 369
- 239000000243 solution Substances 0.000 description 121
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 78
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 76
- 230000015572 biosynthetic process Effects 0.000 description 41
- 239000000126 substance Substances 0.000 description 40
- 238000003786 synthesis reaction Methods 0.000 description 40
- 238000012512 characterization method Methods 0.000 description 38
- FAGLEPBREOXSAC-UHFFFAOYSA-N tert-butyl isocyanide Chemical compound CC(C)(C)[N+]#[C-] FAGLEPBREOXSAC-UHFFFAOYSA-N 0.000 description 25
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 21
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 13
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 7
- XYZMOVWWVXBHDP-UHFFFAOYSA-N cyclohexyl isocyanide Chemical compound [C-]#[N+]C1CCCCC1 XYZMOVWWVXBHDP-UHFFFAOYSA-N 0.000 description 7
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 6
- DYCLHZPOADTVKK-UHFFFAOYSA-N 2-(2-azaniumyl-1,3-thiazol-4-yl)acetate Chemical compound NC1=NC(CC(O)=O)=CS1 DYCLHZPOADTVKK-UHFFFAOYSA-N 0.000 description 5
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- JIVGSHFYXPRRSZ-UHFFFAOYSA-N 2,3-dimethoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1OC JIVGSHFYXPRRSZ-UHFFFAOYSA-N 0.000 description 4
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 4
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 4
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- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
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- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft substituierte bicyclische Imidazo-5-amine und Arzneimittel enthaltend diese Verbindungen.The present invention relates to substituted Containing bicyclic imidazo-5-amines and medicaments these connections.
Einzelne Vertreter aus der Klasse der bicyclischen Imidazo-5-amine sind in der EP-A-0 518 033 beschrieben. Dabei handelt es sich stets um solche Verbindungen, die an dem nicht den anellierten Ringsystemen angehörenden Imidazol-Stickstoff einen über eine kurze Alkylbrücke gebundenen aromatischen Substituenten tragen. Die entsprechenden Verbindungen werden in der EP-A-0 518 033 als starke Angiotensin-Antagonisten beschrieben, die in Arzneimitteln zur Behandlung von Kreislauferkrankungen wie Bluthochdruck eingesetzt werden können.Individual representatives from the class of bicyclic Imidazo-5-amines are described in EP-A-0 518 033. These are always such connections that on the non-fused ring systems Imidazole nitrogen over a short alkyl bridge bound aromatic substituents. The corresponding compounds are described in EP-A-0 518 033 described as strong angiotensin antagonists which in medicines for the treatment of Circulatory diseases such as high blood pressure are used can be.
In der Folge wurden Versuche unternommen, auch solche bicyclischen Imidazo-5-amine herzustellen, die an dem nicht den anellierten Ringsystemen angehörenden Imidazol-Stickstoff nicht substituiert sind. Diese Versuche hatten jedoch keinen (K. Groebke et al., Synlett 1998, 661) oder nur geringen Erfolg (H. Bienayme, K. Bouzid, Angew. Chem. 1998, 110 (16), 2349).As a result, attempts have been made, including those to produce bicyclic imidazo-5-amines based on the not belonging to the fused ring systems Imidazole nitrogen are not substituted. This However, no attempts had been made (K. Groebke et al., Synlett 1998, 661) or little success (H. Bienayme, K. Bouzid, Angew. Chem. 1998, 110 (16), 2349).
Der vorliegenden Erfindung lag daher die Aufgabe zugrunde, bicyclischen Imidazo-5-amine, die an dem nicht den anellierten Ringsystemen angehörenden Imidazol-Stickstoff nicht substituiert sind, und diese enthaltende Arzneimittel bereitzustellen.The present invention was therefore the object based, bicyclic imidazo-5-amines, which on the not belonging to the fused ring systems Imidazole nitrogen are not substituted, and this to provide containing medicinal products.
Gegenstand der Erfindung sind daher bicyclische
Imidazo-5-amine der allgemeinen Formel I,
The invention therefore relates to bicyclic imidazo-5-amines of the general formula I,
worin
R1 C(CH3)3, (CH2)6CN, gegebenenfalls substituiertes
Phenyl, C4-C8-Cycloalkyl, CH2CH2R (R = 4-Morpholino),
1,1,3,3-Tetramethylbutyl oder CH2Ra, wobei Ra für
Wasserstoff, C1-C8-Alkyl (verzweigt oder unverzweigt),
Phenyl, CO(OR') (mit R' = C1-C8-Alkyl (verzweigt oder
unverzweigt)), PO(OR")2 (mit R" = C1-C4-Alkyl
(verzweigt oder unverzweigt))oder Si(RxRyRz) (mit Rx, Ry,
und Rz jeweils unabhängig voneinander C1-C8-
Alkyl(verzweigt oder unverzweigt), C4-C9-Cycloalkyl oder
Phenyl) steht, bedeutet,
R2 Wasserstoff, CORb, wobei Rb für Wasserstoff, C1-C8-
Alkyl (verzweigt oder unverzweigt), C3-C8-Cycloalkyl,
CH2CH2CO(OR') (mit R' = C1-C8-Alkyl (verzweigt oder
unverzweigt)), Adamantyl, gegebenenfalls substituiertes
Phenyl, gegebenenfalls substituiertes 1-Naphtyl, 2-
Naphtyl, 2-Pyridyl, 3-Pyridyl, 4-Pyridyl, Thiazolyl
oder Furoyl steht, CH2Rc wobei Rc für Wasserstoff, C1-
C8-Alkyl (verzweigt oder unverzweigt) oder gegebenenfalls
substituiertes Phenyl steht, CH2CH2Rd, wobei Rd für
gegebenenfalls substituiertes Phenyl steht, oder CONHRe,
wobei Re für Phenyl steht, bedeutet,
R3 C1-C8-Alkyl (verzweigt oder unverzweigt), C1-C8-
Cycloalkyl, gegebenenfalls substituiertes Phenyl,
gegebenenfalls substituiertes 1-Naphtyl, 2-Naphtyl,
Chinolin, Anthracen, Phenanthren, Benzothiophen,
Benzofurfuryl, gegebenenfalls substituiertes Pyrrol, 2-
Pyridyl, 3-Pyridyl, 4-Pyridyl, gegebenenfalls
substituiertes Furfuryl oder gegebenenfalls
substituiertes Thiophen bedeutet,
X CR5, N oder S bedeutet und Y für den Fall, daß X S
bedeutet, CR6 oder N und in allen anderen Fällen N
bedeutet,
R4, R5 und R6 unabhängig voneinander Wasserstoff, C1-C8-
Alkyl (verzweigt oder unverzweigt), Fluor, Chlor, Brom,
CF3, CN, NO2, NHRf, wobei Rf für Wasserstoff, C1-C8-Alkyl
(verzweigt oder unverzweigt), oder gegebenenfalls
substituiertes Phenyl steht, SRg wobei Rg für
Wasserstoff, C1-C8-Alkyl (verzweigt oder unverzweigt),
Phenyl, Pyridin, Benzyl oder Fluorenyl steht, ORh,
wobei Rh für C1-C8-Alkyl (verzweigt oder unverzweigt),
gegebenenfalls substituiertes Phenyl oder CO(OR') (R' =
C1-C8-Alkyl (verzweigt oder unverzweigt)) steht, CO(OR')
oder CH2CO(OR'), wobei R' jeweils die oben angegebene
Bedeutung hat, oder eine gegebenenfalls substituierte
Phenylgruppe bedeuten oder R4 und R6 gemeinsam eine
Brücke =CRi-CH=CH-CH= oder =CH-CRi=CH-CH= bilden, wobei
Ri für H, F, Cl, Br, I oder C1-C8-Alkyl (verzweigt oder
unverzweigt) steht, und deren pharmazeutisch akzeptable
Salze
ausgenommen Verbindungen, bei denen entweder
gleichzeitig R1 C(CH3)3, R2 Wasserstoff, R3
unsubstituiertes Phenyl, X S und Y N oder CR6 mit R6 =
Wasserstoff oder CH2-CO2-Ethyl oder gleichzeitig R1
C(CH3)3, R2 Wasserstoff, R3 unsubstituiertes Phenyl, Y NH
und X N oder CR5 mit R5 = CO2Ethyl bedeutet.wherein
R 1 C (CH 3 ) 3 , (CH 2 ) 6 CN, optionally substituted phenyl, C 4 -C 8 cycloalkyl, CH 2 CH 2 R (R = 4-morpholino), 1,1,3,3-tetramethylbutyl or CH 2 R a , where R a is hydrogen, C 1 -C 8 alkyl (branched or unbranched), phenyl, CO (OR ') (with R' = C 1 -C 8 alkyl (branched or unbranched)) , PO (OR ") 2 (with R" = C 1 -C 4 alkyl (branched or unbranched)) or Si (R x R y R z ) (with R x , R y , and R z each independently of one another C 1 -C 8 alkyl (branched or unbranched), C 4 -C 9 cycloalkyl or phenyl),
R 2 is hydrogen, COR b , where R b is hydrogen, C 1 -C 8 alkyl (branched or unbranched), C 3 -C 8 cycloalkyl, CH 2 CH 2 CO (OR ') (with R' = C 1 -C 8 alkyl (branched or unbranched)), adamantyl, optionally substituted phenyl, optionally substituted 1-naphthyl, 2-naphthyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, thiazolyl or furoyl, CH 2 R c where R c represents hydrogen, C 1 -C 8 -alkyl (branched or unbranched) or optionally substituted phenyl, CH 2 CH 2 R d , where R d stands for optionally substituted phenyl, or CONHR e , where R e stands for phenyl, means
R 3 C 1 -C 8 alkyl (branched or unbranched), C 1 -C 8 cycloalkyl, optionally substituted phenyl, optionally substituted 1-naphthyl, 2-naphthyl, quinoline, anthracene, phenanthrene, benzothiophene, benzofurfuryl, optionally substituted pyrrole , 2-pyridyl, 3-pyridyl, 4-pyridyl, optionally substituted furfuryl or optionally substituted thiophene,
X denotes CR 5 , N or S and Y in the case that XS denotes CR 6 or N and in all other cases N denotes
R 4 , R 5 and R 6 independently of one another are hydrogen, C 1 -C 8 -alkyl (branched or unbranched), fluorine, chlorine, bromine, CF 3 , CN, NO 2 , NHR f , where R f is hydrogen, C 1 -C 8 alkyl (branched or unbranched), or optionally substituted phenyl, SR g where R g represents hydrogen, C 1 -C 8 alkyl (branched or unbranched), phenyl, pyridine, benzyl or fluorenyl, OR h , where R h is C 1 -C 8 alkyl (branched or unbranched), optionally substituted phenyl or CO (OR ') (R' = C 1 -C 8 alkyl (branched or unbranched)), CO (OR ') or CH 2 CO (OR '), where R' each has the meaning given above, or an optionally substituted phenyl group or R 4 and R 6 together are a bridge = CR i -CH = CH-CH = or = CH-CR i = CH-CH = form, where R i is H, F, Cl, Br, I or C 1 -C 8 alkyl (branched or unbranched), and their pharmaceutically acceptable salts, except for compounds in which either R 1 C (CH 3 ) 3 , R 2 hydrogen, R 3 unsubstituted phenyl, XS and YN or CR 6 with R 6 = hydrogen or CH 2 -CO 2 ethyl or simultaneously R 1 C (CH 3 ) 3 , R 2 hydrogen, R 3 unsubstituted phenyl, Y means NH and XN or CR 5 with R 5 = CO 2 ethyl.
Für den Fall, daß R3 eine substituierte Phenylgruppe ist, ist diese vorzugsweise ausgewählt aus der Gruppe 4-Acetamidophenyl, 2-Bromphenyl, 3-Bromphenyl, 4- Bromphenyl, 4-Brom-2-fluorphenyl, 5-Brom-2-fluorphenyl, 3-Brom-4-fluorphenyl, 4-tert.Butylphenyl, 2-Chlor-4- fluorphenyl, 2-Chlor-6-fluorphenyl, 2-Chlorphenyl, 3- Chlorphenyl, 4-Chlorphenyl, 4-Cyanophenyl, 2,3- Dichlorphenyl, 2,4-Dichlorphenyl, 3,4-Dichlorphenyl, 2,3-Dimethoxyphenyl, 3,4-Dimethoxyphenyl, 2,4- Dimethylphenyl, 2,5-Dimethylphenyl, 2-Fluorphenyl, 3- Fluorphenyl, 4-Fluorphenyl, 4-Hexylphenyl, 3-Hydroxy phenyl, 2-Methoxyphenyl, 2-Methylphenyl, 3- Methylphenyl, 4-Methylphenyl, 4-Nitrophenyl, 3- Phenoxyphenyl, 4-(1-Pyrrolidino)phenyl, 2- (Trifluormethyl)phenyl, 3-(Tri-fluormethyl)phenyl, 4- (Trifluormethyl)phenyl, 3,4,5-Trimethoxyphenyl, 3-(4- Chlorphenoxy)phenyl, 4-Acetoxy-3-methoxyphenyl.In the event that R 3 is a substituted phenyl group, this is preferably selected from the group 4-acetamidophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-bromo-2-fluorophenyl, 5-bromo-2-fluorophenyl , 3-bromo-4-fluorophenyl, 4-tert-butylphenyl, 2-chloro-4-fluorophenyl, 2-chloro-6-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-cyanophenyl, 2,3 - dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,3-dimethoxyphenyl, 3,4-dimethoxyphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl , 4-hexylphenyl, 3-hydroxyphenyl, 2-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-nitrophenyl, 3-phenoxyphenyl, 4- (1-pyrrolidino) phenyl, 2- (trifluoromethyl) phenyl, 3- (trifluoromethyl) phenyl, 4- (trifluoromethyl) phenyl, 3,4,5-trimethoxyphenyl, 3- (4-chlorophenoxy) phenyl, 4-acetoxy-3-methoxyphenyl.
Für den Fall, daß R3 eine substituierte 1-Naphthylgruppe ist, ist diese vorzugsweise ausgewählt aus der Gruppe 4-Dimethylaminonaphthyl, 2-Ethoxynaphthyl, 4- Methoxynaphthyl.In the event that R 3 is a substituted 1-naphthyl group, this is preferably selected from the group 4-dimethylaminonaphthyl, 2-ethoxynaphthyl, 4-methoxynaphthyl.
Für den Fall, daß R3 eine substituierte Pyrrolgruppe ist, ist diese vorzugsweise ausgewählt aus der Gruppe 2-(1-(Phenylsulfonyl)-pyrrol), 2-(N-Methylpyrrol), 2- (N-(3,5-Dichlorphenyl)-pyrrol), 2(1-(4-Chloro phenyl)pyrrol).In the event that R 3 is a substituted pyrrole group, this is preferably selected from the group 2- (1- (phenylsulfonyl) pyrrole), 2- (N-methylpyrrole), 2- (N- (3,5-dichlorophenyl) ) -pyrrole), 2 (1- (4-chlorophenyl) pyrrole).
Für den Fall, daß R3 eine substituierte Furfurylgruppe ist, ist diese vorzugsweise ausgewählt aus der Gruppe 2-(5-Acetoxymethylfurfuryl), 2-(5-Methylfurfuryl), 2- (5-Nitrofurfuryl), 2-[5-(3-Nitrophenyl)furfuryl], 2-[5- (2-Nitrophenyl)furfuryl], 2-(5-Bromfurfuryl), 2-[5-(4- Chlorphenyl)furfuryl], 2-(4,5-Dimethylfurfuryl), 2-[5- (2-Chlorophenyl)furfuryl], 2-(5-Ethylfurfuryl), 2-[5- (1,3-Dioxalan)furfuryl].In the event that R 3 is a substituted furfuryl group, this is preferably selected from the group 2- (5-acetoxymethylfurfuryl), 2- (5-methylfurfuryl), 2- (5-nitrofurfuryl), 2- [5- (3 -Nitrophenyl) furfuryl], 2- [5- (2-nitrophenyl) furfuryl], 2- (5-bromofurfuryl), 2- [5- (4-chlorophenyl) furfuryl], 2- (4,5-dimethylfurfuryl), 2- [5- (2-chlorophenyl) furfuryl], 2- (5-ethylfurfuryl), 2- [5- (1,3-dioxalane) furfuryl].
Für den Fall, daß R3 eine substituierte Thiophengruppe ist, diese ausgewählt ist aus der Gruppe 2-(5- Chlorthiophenyl), 2-(5-Methylthiophenyl), 2-(5- Ethylthiophenyl), 2-(3-Methylthiophenyl), 2-(4-Bromo thiophenyl), 2-(5-Nitrothiophenyl), 5-(2- Carbonsäurethiophenyl), 2-[4-(Phenylethyl)thiophenyl], 2-[5-(Methylthio)thiophenyl], 2-(3-Bromothioplenyl), 2- (3-Phenoxythiophenyl), 2-(5-Bromthiophenyl).In the event that R 3 is a substituted thiophene group, this is selected from the group 2- (5-chlorothiophenyl), 2- (5-methylthiophenyl), 2- (5-ethylthiophenyl), 2- (3-methylthiophenyl), 2- (4-bromothiophenyl), 2- (5-nitrothiophenyl), 5- (2-carboxylic acid thiophenyl), 2- [4- (phenylethyl) thiophenyl], 2- [5- (methylthio) thiophenyl], 2- ( 3-bromothioplenyl), 2- (3-phenoxythiophenyl), 2- (5-bromothiophenyl).
Bevorzugt sind erfindungsgemäß außerdem solche
Verbindungen, bei denen
für den Fall, daß Rb eine substituierte Phenylgruppe
ist, diese ausgewählt ist aus der Gruppe 3,5-
Bis(Trifluormethyl)phenyl, 2-Bromphenyl, 2-Fluorphenyl,
Pentafluorphenyl, 2,4-Difluorphenyl, 2,6-Difluorphenyl,
2-Chlorphenyl, 2,4-Dichlorphenyl, 2-Acetylphenyl, 2-
Methoxyphenyl, 2,6-Dimethoxyphenyl, 2-(Trifluor
methyl)phenyl, 2-Methylphenyl, 3-Bromphenyl, 3-
Fluorphenyl, 3-Chlorphenyl, 3,4-Dichlorphenyl, 3-
Methoxyphenyl, 3,4-Dimethoxyphenyl, 3,4,5-
Trimethoxyphenyl, 3,5-Dimethoxyphenyl, 3-
(Trifluormethyl)phenyl, 3-Methoxyphenyl, 4-Bromphenyl,
4-Fluorphenyl, 4-Chlorphenyl, 4-Methoxyphenyl, 4-
(Trifluormethyl-phenyl, 4-tert.Butylphenyl, 4-
Methylphenyl, 2-Iodphenyl, 4-Iodphenyl, 4-Cyanophenyl,
2-Nitrophenyl, 3-Nitrophenyl, 3,5-Dinitrophenyl, 4-
Nitrophenyl, 3,5-Dichlorphenyl, 2,5-Difluorphenyl, 2,4-
Dimethoxyphenyl, 3-Nitro-4-methylphenyl, 2,5-
Dichlorphenyl, 2,3-Difluorphenyl, 4-(Trifluormethoxy)-
phenyl, 2-(Trifluormethoxy)phenyl, 3-(Trifluormethoxy)-
phenyl,
für den Fall, daß Rc eine substituierte Phenylgruppe
ist, diese ausgewählt ist aus der Gruppe 2-Fluorphenyl,
2-Chlorphenyl, 2-Methylphenyl, 2-
(Trifluormethyl)phenyl, 2-Bromphenyl, 3-Methoxyphenyl,
3-Nitrophenyl, 3-Chlorphenyl, 3-Fluorphenyl,
Phenoxyphenyl, 3-(Trifluormethoxy)phenyl, 3-Bromphenyl,
3-Chlorphenyl, 3-Methylphenyl, 4-tert.-Butylphenyl, 4-
Fluorphenyl, 4-Chlorphenyl, 4-Vinylphenyl, 4-
(Trifluormethoxy)phenyl, 3,5-Dimethoxyphenyl, 3,5-
Difluorphenyl, 3,5-Di(trifluormethyl)phenyl, 3,5-
Difluorphenyl, 3,5-Dimethylphenyl, 2,3-Dichlorphenyl,
2,3-Dimethylphenyl, 2,3-Difluorphenyl, 3-Chlor-2-
fluorphenyl, 2-Chlor-4-Fluorphenyl, 2,4-
Di(Trifluormethyl)phenyl, 2,4-Dichlorphenyl, 2,4-
Difluorphenyl, 2,4-Dimethylphenyl, 2,5-Dichlorphenyl,
2,5-Dimethylphenyl, 2,5-Difluorphenyl, 3,4-
Dichlorphenyl, 3,4-Difluorphenyl, 3,4-Dimethylphenyl,
2,3,4-Trifluorphenyl, 2,3,6-Trifluorphenyl, 2,4,5-
Trifluorphenyl, 2,4,6-Trimethylphenyl,
Pentafluorphenyl, und
für den Fall, daß Rd eine substituierte Phenylgruppe
ist, diese ausgewählt ist aus der Gruppe 3-Chlorphenyl,
4-Chlorphenyl, 4-Carboxyphenyl, 4-Acetylphenyl, 4-
Methoxy-phenyl, 4-Fluorphenyl, 4-Nitrophenyl, 4-
Hydroxyphenyl.According to the invention, preference is also given to those compounds in which
in the event that R b is a substituted phenyl group, this is selected from the group 3,5-bis (trifluoromethyl) phenyl, 2-bromophenyl, 2-fluorophenyl, pentafluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 2-chlorophenyl, 2,4-dichlorophenyl, 2-acetylphenyl, 2-methoxyphenyl, 2,6-dimethoxyphenyl, 2- (trifluoromethyl) phenyl, 2-methylphenyl, 3-bromophenyl, 3-fluorophenyl, 3-chlorophenyl, 3, 4-dichlorophenyl, 3-methoxyphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3,5-dimethoxyphenyl, 3- (trifluoromethyl) phenyl, 3-methoxyphenyl, 4-bromophenyl, 4-fluorophenyl, 4-chlorophenyl , 4-methoxyphenyl, 4- (trifluoromethylphenyl, 4-tert-butylphenyl, 4-methylphenyl, 2-iodophenyl, 4-iodophenyl, 4-cyanophenyl, 2-nitrophenyl, 3-nitrophenyl, 3,5-dinitrophenyl, 4- Nitrophenyl, 3,5-dichlorophenyl, 2,5-difluorophenyl, 2,4-dimethoxyphenyl, 3-nitro-4-methylphenyl, 2,5-dichlorophenyl, 2,3-difluorophenyl, 4- (trifluoromethoxy) phenyl, 2- (Trifluoromethoxy) phenyl, 3- (trifluoromethoxy) phenyl,
in the event that R c is a substituted phenyl group, this is selected from the group 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 2- (trifluoromethyl) phenyl, 2-bromophenyl, 3-methoxyphenyl, 3-nitrophenyl, 3 -Chlorophenyl, 3-fluorophenyl, phenoxyphenyl, 3- (trifluoromethoxy) phenyl, 3-bromophenyl, 3-chlorophenyl, 3-methylphenyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-vinylphenyl, 4- ( Trifluoromethoxy) phenyl, 3,5-dimethoxyphenyl, 3,5-difluorophenyl, 3,5-di (trifluoromethyl) phenyl, 3,5-difluorophenyl, 3,5-dimethylphenyl, 2,3-dichlorophenyl, 2,3-dimethylphenyl, 2,3-difluorophenyl, 3-chloro-2-fluorophenyl, 2-chloro-4-fluorophenyl, 2,4-di (trifluoromethyl) phenyl, 2,4-dichlorophenyl, 2,4-difluorophenyl, 2,4-dimethylphenyl, 2,5-dichlorophenyl, 2,5-dimethylphenyl, 2,5-difluorophenyl, 3,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, 2,3,4-trifluorophenyl, 2,3,6- Trifluorophenyl, 2,4,5-trifluorophenyl, 2,4,6-trimethylphenyl, pentafluorophenyl, and
in the event that R d is a substituted phenyl group, this is selected from the group 3-chlorophenyl, 4-chlorophenyl, 4-carboxyphenyl, 4-acetylphenyl, 4-methoxy-phenyl, 4-fluorophenyl, 4-nitrophenyl, 4- hydroxyphenyl.
Besonders bevorzugt sind erfindungsgemäß bicyclische
Imidazo-5-amine ausgewählt aus der Gruppe
tert-Butyl-(5-furan-2-yl-3H-imidazo[1,2-
b][1,2,4]triazol-6-yl)-amin,
tert-Butyl-(6-furan-2-yl-imidazo[2,1-b]thiazol-5-yl)-
amin,
(5-tert-Butylamino-6-furan-2-yl-imidazo[2,1-b]thiazol-
3-yl)-essigsäure,
tert-Butyl-(5-pyridin-2-yl-3H-imidazo[1,2-b]
[1,2,4]triazol-6-yl)-amin,
tert-Butyl-(6-pyridin-2-yl-imidazo[2,1-b]thiazol-5-yl)-
amin,
tert-Butyl-(5-pyridin-3-yl-3H-imidazo[1,2-b]
[1,2,4]triazol-6-yl)-amin,
tert-Butyl-(5-pyridin-4-yl-3H-imidazo[1,2-b]
[1,2,4]triazol-6-yl)-amin,
tert-Butyl-(6-cyclohexyl-imidazo[2,1-b]thiazol-5-yl)-
amin,
tert-Butyl-(5-methyl-3H-imidazo[1,2-b][1,2,4]triazol-6-
yl)-amin,
tert-Butyl-(6-methyl-imidazo[2,1-b]thiazol-5-yl)-amin,
Cyclohexyl-(5-pyridin-2-yl-3H-imidazo[1,2-b]
[1,2,4]triazol-6-yl)-amin,
Cyclohexyl-(6-pyridin-2-yl-imidazo[2,1-b]thiazol-5-yl)-
amin,
(5-Cyclohexylamino-6-pyridin-2-yl-imidazo[2,1-
b]thiazol-3-yl)-essigsäure,
Cyclohexyl-(6-pyridin-4-yl-imidazo[2,1-b]thiazol-5-yl)-
amin,
Cyclohexyl-(6-cyclohexyl-imidazo[2,1-b]thiazol-5-yl)-
amin,
(6-Cyclohexyl-5-cyclohexylamino-imidazo[2,1-b]thiazol-
3-yl)-essigsäure,
(5-Cyclohexylamino-6-methyl-imidazo[2,1-b]thiazol-3-
yl)-essig-säure,
(2,6-Dimethyl-phenyl)-(5-furan-2-yl-3H-imidazo[1,2-b]
[1,2,4]triazol-6-yl)-amin,
(2,6-Dimethyl-phenyl)-(6-pyridin-2-yl-imidazo[2,1-
b]thiazol-5-yl)-amin,
(2,6-Dimethyl-phenyl)-(6-pyridin-3-yl-imidazo[2,1-b]
thiazol-5-yl)-amin,
(2,6-Dimethyl-phenyl)-(6-pyridin-4-yl-imidazo[2,1-b]
thiazol-5-yl)-amin,
(6-Cyclohexyl-imidazo[2,1-b]thiazol-5-ylamino)-
essigsäuremethylester,
(6-Methyl-imidazo[2,1-b]thiazol-5-ylamino)-essigsäure-
methylester,
tert-Butyl-(2-phenyl-5H-imidazo[1,2-b]pyrazol-3-yl)-
amin,
3-(5-tert-Butylamino-imidazo[2,1-b]thiazol-6-yl)-
phenol,
tert-Butyl-[6-(3,4-dimethoxy-phenyl)-imidazo[2,1-
b]thiazol-5-yl]-amin,
tert-Butyl-[5-(2,3-dichloro-phenyl)-3H-imidazo[1,2-b]
[1,2,4]triazol-6-yl]-amin,
tert-Butyl-[6-(2,3-dichloro-phenyl)-imidazo[2,1-
b]thiazol-5-yl]-amin,
tert-Butyl-[5-(2,4-dichloro-phenyl)-3H-imidazo[1,2-b]
[1,2,4]triazol-6-yl]-amin,
tert-Butyl-[6-(2,4-dichloro-phenyl)-imidazo[2,1-
b]thiazol-5-yl]-amin,
tert-Butyl-[5-(2-methoxy-phenyl)-3H-imidazo[1,2-b]
[1,2,4]triazol-6-yl]-amin,
tert-Butyl-[6-(2-methoxy-phenyl)-imidazo[2,1-b]thiazol-
5-yl]-amin,
[5-tert-Butylamino-6-(2-methoxy-phenyl)-imidazo[2,1-b]
thiazol-3-yl]-essigsäure,
tert-Butyl-(5-o-tolyl-3H-imidazo[1,2-b][1,2,4]triazol-
6-yl)-amin,
tert-Butyl-(6-o-tolyl-imidazo[2,1-b]thiazol-5-yl)-amin,
tert-Butyl-[5-(2,3-dimethoxy-phenyl)-3H-imidazo[1,2-
b][1,2,4]triazol-6-yl]-amin,
tert-Butyl-[6-(2,3-dimethoxy-phenyl)-imidazo[2,1-b]
thiazol-5-yl]-amin,
tert-Butyl-(6-p-tolyl-imidazo[2,1-b]thiazol-5-yl)-amin.According to the invention, bicyclic imidazo-5-amines selected from the group are particularly preferred
tert-butyl- (5-furan-2-yl-3H-imidazo [1,2- b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (6-furan-2-yl-imidazo [2,1-b] thiazol-5-yl) amine,
(5-tert-butylamino-6-furan-2-yl-imidazo [2,1-b] thiazol-3-yl) acetic acid,
tert-butyl- (5-pyridin-2-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (6-pyridin-2-yl-imidazo [2,1-b] thiazol-5-yl) amine,
tert-butyl- (5-pyridin-3-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (5-pyridin-4-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (6-cyclohexyl-imidazo [2,1-b] thiazol-5-yl) amine,
tert-butyl- (5-methyl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
tert-butyl (6-methyl-imidazo [2,1-b] thiazol-5-yl) -amine,
Cyclohexyl- (5-pyridin-2-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
Cyclohexyl- (6-pyridin-2-yl-imidazo [2,1-b] thiazol-5-yl) amine,
(5-cyclohexylamino-6-pyridin-2-yl-imidazo [2,1-b] thiazol-3-yl) acetic acid,
Cyclohexyl- (6-pyridin-4-yl-imidazo [2,1-b] thiazol-5-yl) amine,
Cyclohexyl- (6-cyclohexyl-imidazo [2,1-b] thiazol-5-yl) amine,
(6-cyclohexyl-5-cyclohexylamino-imidazo [2,1-b] thiazol-3-yl) acetic acid,
(5-cyclohexylamino-6-methyl-imidazo [2,1-b] thiazol-3-yl) acetic acid,
(2,6-dimethylphenyl) - (5-furan-2-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
(2,6-dimethyl-phenyl) - (6-pyridin-2-yl-imidazo [2,1-b] thiazol-5-yl) amine,
(2,6-dimethyl-phenyl) - (6-pyridin-3-yl-imidazo [2,1-b] thiazol-5-yl) amine,
(2,6-dimethyl-phenyl) - (6-pyridin-4-yl-imidazo [2,1-b] thiazol-5-yl) amine,
(6-cyclohexyl-imidazo [2,1-b] thiazol-5-ylamino) - methyl acetate,
(6-methyl-imidazo [2,1-b] thiazol-5-ylamino) acetic acid methyl ester,
tert-butyl- (2-phenyl-5H-imidazo [1,2-b] pyrazol-3-yl) amine,
3- (5-tert-butylamino-imidazo [2,1-b] thiazol-6-yl) phenol,
tert-butyl- [6- (3,4-dimethoxyphenyl) imidazo [2,1- b] thiazol-5-yl] amine,
tert-butyl- [5- (2,3-dichloro-phenyl) -3H-imidazo [1,2-b] [1,2,4] triazol-6-yl] amine,
tert-butyl- [6- (2,3-dichloro-phenyl) imidazo [2,1- b] thiazol-5-yl] amine,
tert-butyl- [5- (2,4-dichloro-phenyl) -3H-imidazo [1,2-b] [1,2,4] triazol-6-yl] amine,
tert-butyl- [6- (2,4-dichlorophenyl) imidazo [2,1- b] thiazol-5-yl] amine,
tert-butyl- [5- (2-methoxyphenyl) -3H-imidazo [1,2-b] [1,2,4] triazol-6-yl] amine,
tert-butyl- [6- (2-methoxyphenyl) imidazo [2,1-b] thiazol-5-yl] amine,
[5-tert-butylamino-6- (2-methoxyphenyl) imidazo [2,1-b] thiazol-3-yl] acetic acid,
tert-butyl- (5-o-tolyl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
tert-butyl (6-o-tolyl-imidazo [2,1-b] thiazol-5-yl) -amine,
tert-butyl- [5- (2,3-dimethoxyphenyl) -3H-imidazo [1,2- b] [1,2,4] triazol-6-yl] amine,
tert-butyl- [6- (2,3-dimethoxyphenyl) imidazo [2,1-b] thiazol-5-yl] amine,
tert-butyl (6-p-tolyl-imidazo [2,1-b] thiazol-5-yl) -amine.
Soweit die erfindungsgemäßen bicyclischen Imidazo-5- amine optisch aktive Kohlenstoffatome enthalten, sind auch die Enantiomeren dieser Verbindungen und deren Mischungen sowie deren pharmazeutisch akzeptable Salze Gegenstand der vorliegenden Erfindung.As far as the bicyclic imidazo-5 according to the invention amines contain optically active carbon atoms also the enantiomers of these compounds and their Mixtures and their pharmaceutically acceptable salts Subject of the present invention.
Gegenstand der Erfindung sind außerdem Arzneimittel enthaltend als Wirkstoff mindestens ein bicyclisches Imidazo-5-amin der allgemeinen Formel I, in der R1 bis R6, X und Y die oben angegebene Bedeutung haben, in Form der Base oder von pharmazeutisch akzeptablen Salzen, vorzugsweise der Bromwasserstoffsäure, Schwefelsäure, Methansulfonsäure, Ameisensäure, Essigsäure, Oxalsäure, Bernsteinsäure, Weinsäure, Mandelsäure, Furmarsäure, Milchsäure, Zitronensäure, Glutaminsäure und/oder Asparaginsäure oder insbesondere der Salzsäure.The invention also relates to medicaments containing as active ingredient at least one bicyclic imidazo-5-amine of the general formula I, in which R 1 to R 6 , X and Y have the meaning given above, in the form of the base or of pharmaceutically acceptable salts, preferably hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid, citric acid, glutamic acid and / or aspartic acid or in particular hydrochloric acid.
Zur Herstellung entsprechender Arzneimittel werden neben mindestens einem erfindungsgemäßen Wirkstoff Trägermaterialien, Füllstoffe, Lösungsmittel, Verdünnungsmittel, Farbstoffe und/oder Bindemittel eingesetzt. Die Auswahl der Hilfsstoffe sowie die einzusetzenden Mengen derselben hängt davon ab, ob das Arzneimittel oral, intravenös, intraperitoneal, intradermal, intramuskulär, intranasal, buccal oder örtlich appliziert werden soll. Für orale Applikation eignen sich Zubereitungen in Form von Tabletten, Dragees, Kapseln, Granulaten, Tropfen, Säften und Sirupen, für die parenterale, topische und inhalative Applikation Lösungen, Suspensionen, leicht rekonstituierbare Trockenzubereitungen sowie Sprays. Erfindungsgemäße Wirkstoffe in einem Depot, in gelöster Form oder in einem Pflaster, gegebenenfalls unter Zusatz von die Hautpenetration fördernden Mittel, sind geeignete perkutane Applikationszubereitungen. Oral oder perkutan anwendbare Zubereitungsformen können die erfindungsgemäßen Wirkstoffe verzögert freisetzen.For the manufacture of appropriate drugs in addition to at least one active ingredient according to the invention Carrier materials, fillers, solvents, Diluents, dyes and / or binders used. The selection of excipients as well as the the amounts to be used depends on whether the Drugs orally, intravenously, intraperitoneally, intradermal, intramuscular, intranasal, buccal or to be applied locally. For oral application preparations in the form of tablets are suitable, Dragees, capsules, granules, drops, juices and Syrups, for parenteral, topical and inhalation Application solutions, suspensions, light reconstitutable dry preparations and sprays. Active substances according to the invention in a depot, in dissolved form Form or in a plaster, optionally under Addition of agents that promote skin penetration suitable percutaneous application preparations. Orally or percutaneously applicable preparation forms can Release active substances according to the invention with a delay.
Die an den Patienten zu verabreichende Wirkstoffmenge variiert in Abhängigkeit vom Gewicht des Patienten, von der Applikationsart, der Indikation und dem Schweregrad der Erkrankung.The amount of drug to deliver to the patient varies depending on the weight of the patient, from the type of application, the indication and the severity the disease.
Die Synthese der erfindungsgemäßen Verbindungen erfolgt in der Weise, daß man Amidine mit der allgemeinen Formel II, insbesondere 3-Aminopyrazol-, 3-Amino-1,2,4- triazol-, 2-Amino-, 1,3,4-Thiadiazol- und 2- Aminothiazolderivate, die von Firmen wie beispielsweise Acros, Avocado, Aldrich, Fluka, Lancaster, Maybridge, Merck, Sigma oder TCI-Jp kommerziell angeboten werden, mit verschiedensten Aldehyden III und Isonitrilen IV in Gegenwart von 20%-iger Perchlorsäure gemäß einer Dreikomponentenreaktion umsetzt. R1 bis R3, X und Y haben dabei die oben für Verbindungen der Formel I angegebene Bedeutung. The compounds of the invention are synthesized in such a way that one can amidine with the general Formula II, in particular 3-aminopyrazole, 3-amino-1,2,4- triazole, 2-amino, 1,3,4-thiadiazole and 2- Aminothiazole derivatives, made by companies such as Acros, Avocado, Aldrich, Fluka, Lancaster, Maybridge, Merck, Sigma or TCI-Jp are offered commercially, with various aldehydes III and isonitriles IV in Presence of 20% perchloric acid according to one Three-component reaction implemented. R1 to R3, X and Y have the above for compounds of formula I. given meaning.
Vorzugsweise werden die Reaktionen in Dichlormethan (DCM) bei einer Temperatur von 0°C bis 40°C, insbesondere bei 1.0°C bis 20°C durchgeführt.The reactions are preferably carried out in dichloromethane (DCM) at a temperature of 0 ° C to 40 ° C, especially at 1.0 ° C to 20 ° C.
Zur Herstellung der erfindungsgemäßen Verbindungen, in
denen R2 nicht Wasserstoff bedeutet, werden die in der
zuvor beschriebenen Reaktion entstehenden Verbindungen
Ia, die vorzugsweise zunächst in THF gelöst wurden, je
nach gewünschtem Endprodukt mit einer Verbindung R2Hal,
wobei Hal für Brom, Iod oder insbesondere Chlor steht,
beispielsweise einem gegebenenfalls substituierten
Alkyl-, Aryl- oder Säurechlorid, oder einem
gegebenenfalls substituierten Isocyanat ReNCO in
Gegenwart eines Morpholin-Harzes (z. B. Polystyrol-
Morpholin der Firma Argonaut) in Dichlormethan
innerhalb von 12 bis 24 Stunden bei Temperaturen
zwischen 10°C und 40°C gemäß dem folgenden
Reaktionsschema umgesetzt:
To prepare the compounds according to the invention in which R 2 is not hydrogen, the compounds Ia formed in the reaction described above, which were preferably first dissolved in THF, are, depending on the desired end product, with a compound R 2 Hal, where Hal is bromine, iodine or in particular chlorine, (z. B. polystyrene morpholine company Argonaut), for example an optionally substituted alkyl, aryl or acid chloride, or an optionally substituted isocyanate R e NCO in the presence of a morpholine resin in dichloromethane within 12 to 24 Hours at temperatures between 10 ° C and 40 ° C according to the following reaction scheme:
Die überschüssigen Reagentien werden anschließend durch Filtration über eine Schicht mit polymergebundenem Tris(2-aminoethyl)amin (Hersteller: Novablochem) oder 3-(3-Mercaptophenyl)propanamidomethylpolystyrol aus dem Reaktionsgemisch entfernt und das Filtrat vorzugsweise in einer Vakuumzentrifuge aufkonzentriert. Das gesamte Verfahren läßt sich ohne weiteres auch in einer automatisierten Syntheseanlage durchführen. The excess reagents are then removed Filtration over a layer with polymer-bound Tris (2-aminoethyl) amine (manufacturer: Novablochem) or 3- (3-mercaptophenyl) propanamidomethylpolystyrene from the Reaction mixture removed and the filtrate preferably concentrated in a vacuum centrifuge. The entire The process can also be readily carried out in one perform automated synthesis plant.
Die Verbindungen der Formel I lassen sich mit physiologisch verträglichen Säuren, vorzugsweise Bromwasserstoffsäure, Schwefelsäure, Methansulfonsäure, Ameisensäure, Essigsäure, Oxalsäure, Bernsteinsäure, Weinsäure, Mandelsäure, Furmarsäure, Milchsäure, Zitronensäure, Glutaminsäure und/oder Asparaginsäure und insbesondere Salzsäure, in der an sich bekannten Weise in ihre pharmazeutisch akzeptablen Salze überführen. Vorzugsweise wird die Salzbildung in einem Lösungsmittel, insbesondere Diethylether, Diisopropylether, Essigsäurealkylester, Aceton oder 2- Butanon oder einem Gemisch dieser Lösungsmittel durchgeführt. Zur Herstellung der Hydrochloride eignet sich alternativ auch Trimethylsilan in wässriger Lösung.The compounds of formula I can be with physiologically acceptable acids, preferably Hydrobromic acid, sulfuric acid, methanesulfonic acid, Formic acid, acetic acid, oxalic acid, succinic acid, Tartaric acid, mandelic acid, fumaric acid, lactic acid, Citric acid, glutamic acid and / or aspartic acid and especially hydrochloric acid, in the known per se Way in their pharmaceutically acceptable salts convict. Salt formation is preferably carried out in one Solvents, especially diethyl ether, Diisopropyl ether, alkyl acetate, acetone or 2- Butanone or a mixture of these solvents carried out. Suitable for the production of the hydrochloride Alternatively, trimethylsilane in aqueous Solution.
Die folgenden Beispiele sollen die Erfindung erläutern, ohne sie darauf zu beschränken.The following examples are intended to illustrate the invention, without limiting it to that.
Die Synthese der erfolgte auf einer automatischen Anlage der Firma Zymark nach folgender allgemeiner Synthesevorschrift:The synthesis of the was done on an automatic System of the company Zymark according to the following general Synthesis Method:
Ein Rundbodenröhrchen aus Glas (Durchmesser 16 mm,
Länge 125 mm) mit Gewinde wurde manuell mit einem
Rührer versehen und auf der Capper-Station mit einem
Schraubdeckel mit Septum verschlossen. Das Röhrchen
wurde von Roboter 1 in den auf 15°C temperierten
Reaktorblock gestellt. Roboter 2 pipettierte
nacheinander folgende Reagenzien hinzu:
A round-bottomed tube made of glass (diameter 16 mm, length 125 mm) with thread was manually provided with a stirrer and closed with a screw cap with a septum on the capper station. Robot 1 placed the tube in the reactor block heated to 15 ° C. Robot 2 pipetted the following reagents one after the other:
- 1. 1) 1 ml einer 0,1 M Amidin-Lösung + 20% HClO4 in Dichlormethan1. 1) 1 ml of a 0.1 M amidine solution + 20% HClO 4 in dichloromethane
- 2. 2) 0,5 ml einer 0,3 M Aldehyd-Lösung in Dichlormethan2. 2) 0.5 ml of a 0.3 M aldehyde solution in dichloromethane
- 3. 3) 0,575 ml einer 0,2 M Isonitril-Lösung in Dichlormethan3. 3) 0.575 ml of a 0.2 M isonitrile solution in dichloromethane
Das Reaktionsgemisch wurde bei 15°C in einem der Rührblöcke 660 min lang gerührt. Danach wurde die Reaktionslösung an der Filtrations-Station abfiltriert. Das Röhrchen wurde dabei zweimal mit je 1 ml Dichlormethan und 200 µl Wasser gespült.The reaction mixture was at 15 ° C in one of the Stirring blocks stirred for 660 min. After that the Filtered reaction solution at the filtration station. The tube was filled twice with 1 ml each Dichloromethane and 200 ul water rinsed.
Das Rack mit den Röhrchen wurde anschließend manuell auf die Aufarbeitungsanlage gestellt. Dort wurde das Reaktionsgemisch auf einem Vortexer mit 3 ml einer 10°igen NaCl-Lösung und 1,5 ml Dichlormethan versetzt. Im Spin-Reaktor wurde zehn Minuten lang gründlich gemischt und durch die langsame Abnahme der Drehbewegung eine deutliche Phasengrenze ausgebildet. Diese Phasengrenze wurde optisch detektiert und die organische Phase abpipettiert. Im nächsten Schritt wurde das Reaktionsgemisch erneut mit 1,5 ml Dichlormethan versetzt. Die Lösung wurde geschüttelt, zentrifugiert und die organische Phase abpipettiert. Die vereinigten organischen Phasen wurden über 2,4 g MgSO4 (granuliert) getrocknet. Das Lösungsmittel wurde in einer Vakuumzentrifuge entfernt.The rack with the tubes was then manually placed on the processing plant. There, the reaction mixture was mixed on a vortexer with 3 ml of a 10 ° NaCl solution and 1.5 ml of dichloromethane. Mixing was carried out thoroughly in the spin reactor for ten minutes and a clear phase boundary was formed by the slow decrease in the rotational movement. This phase boundary was optically detected and the organic phase was pipetted off. In the next step, the reaction mixture was again mixed with 1.5 ml dichloromethane. The solution was shaken, centrifuged and the organic phase was pipetted off. The combined organic phases were dried over 2.4 g of MgSO 4 (granulated). The solvent was removed in a vacuum centrifuge.
Die eingesetzten Chemikalien und Lösungsmittel wurden kommerziell erworben. Jede Substanz wurde mit ESI-MS und/oder NMR analysiert. The chemicals and solvents used were acquired commercially. Each substance was identified using ESI-MS and / or NMR analyzed.
Verbindung 1 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Furfurylaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 1 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Furfuryl aldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 246 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 246 (M *)
Verbindung 2 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Furfurylaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 2 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Furfuryl aldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 262 (M*)
An ESI-MS was included for characterization:
MS (EI) m / z: 262 (M *)
Verbindung 3 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl)essigsäure-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Furfurylaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 3 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl) acetic acid solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) furfuryl aldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 320 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 320 (M *)
Verbindung 4 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Pyridinaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 4 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-pyridine aldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 257 (M*)
An ESI-MS was included for characterization:
MS (EI) m / z: 257 (M *)
Verbindung 5 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Pyridincarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 5 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-pyridinecarbaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 273 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 273 (M *)
Verbindung 6 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-Pyridincarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 6 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-pyridinecarbaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 257 (M*)
An ESI-MS was included for characterization:
MS (EI) m / z: 257 (M *)
Verbindung 7 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) ter t.-Butylisonitril-Lösung (0.2 M, DCM), 0. 500 ml (0.15 mmol) 4-Pyridincarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 7 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) ter t-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 4-pyridinecarbaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein FSI-MS aufgenommen:
MS(EI) m/z: 257 (M*)An FSI-MS was recorded for characterization:
MS (EI) m / z: 257 (M *)
Verbindung 8 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Cyclohexylcarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 8 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Cyclohexylcarbaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 278 (M*)
An ESI-MS was included for characterization:
MS (EI) m / z: 278 (M *)
Verbindung 9 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Acetaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 9 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Acetaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 194 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 194 (M *)
Verbindung 10 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Aldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 10 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Aldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 210 (M*)
An ESI-MS was included for characterization:
MS (EI) m / z: 210 (M *)
Verbindung 11 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Pyridinaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 11 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-pyridine aldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 283 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 283 (M *)
Verbindung 12 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Pyridinaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 12 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-pyridine aldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 299 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 299 (M *)
Verbindung 13 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl)essigsäure-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-Pyridincarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 13 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl) acetic acid solution (0.1 M, DCM), 0.575 ml (0.115 mmol) cyclohexylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-pyridinecarbaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 357 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 357 (M *)
Verbindung 14 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-Pyridincarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 14 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-pyridinecarbaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 299 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 299 (M *)
Verbindung 15 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Cyclohexylcarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 15 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Cyclohexylcarbaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 304 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 304 (M *)
Verbindung 16 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl)essigsäure-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Cyclohexylcarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 16 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl) acetic acid solution (0.1 M, DCM), 0.575 ml (0.115 mmol) cyclohexylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) cyclohexylcarbaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 318 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 318 (M *)
Verbindung 17 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl)essigsäure-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) Cyclohexylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Acetaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 17 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl) acetic acid solution (0.1 M, DCM), 0.575 ml (0.115 mmol) cyclohexylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) acetaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 250 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 250 (M *)
Verbindung 18 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) 2,6- Dimethylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Furfurylaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 18 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) 2.6- Dimethylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Furfuryl aldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 292 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 292 (M *)
Verbindung 19 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) 2,6- Dimethylphenylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Pyridincarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt. Compound 19 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) 2.6- Dimethylphenylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-pyridinecarbaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 321 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 321 (M *)
Verbindung 20 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) 2,6- Dimethylphenylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-Pyridincarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 20 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) 2.6- Dimethylphenylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-pyridinecarbaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 321 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 321 (M *)
Verbindung 21 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) 2,6- Dimethylphenylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 4-Pyridincarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 21 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) 2.6- Dimethylphenylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 4-pyridinecarbaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 321 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 321 (M *)
Verbindung 22 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) Methylisocyanacetat-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Cyclohexylcarbaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 22 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) Methyl isocyanate acetate solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Cyclohexylcarbaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 294 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 294 (M *)
Verbindung 23 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) Methylisocyanacetat-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Acetaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 23 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) Methyl isocyanate acetate solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Acetaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 226 (M*)
An ESI-MS was included for characterization:
MS (EI) m / z: 226 (M *)
Verbindung 24 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino pyrazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) Benzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 24 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino pyrazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) Benzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 255 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 255 (M *)
Verbindung 25 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-Hydroxybenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 25 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 3-hydroxybenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 288 (M*)
An ESI-MS was included for characterization:
MS (EI) m / z: 288 (M *)
Verbindung 26 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 3,4-Dimethoxybenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 26 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 3,4-dimethoxybenzaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 332 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 332 (M *)
Verbindung 27 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,3-Dichlorbenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 27 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,3-dichlorobenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 324 (M*)
An ESI-MS was included for characterization:
MS (EI) m / z: 324 (M *)
Verbindung 28 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,3-Dichlorbenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 28 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,3-dichlorobenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 340 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 340 (M *)
Verbindung 29 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,4-Dichlorbenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 29 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,4-dichlorobenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 324 (M*)
An ESI-MS was included for characterization:
MS (EI) m / z: 324 (M *)
Verbindung 30 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,4-Dichlorbenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 30 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,4-dichlorobenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 340 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 340 (M *)
Verbindung 31 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Methoxybenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 31 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-methoxybenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 286 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 286 (M *)
Verbindung 32 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Methoxybenzaldehyd-Läsung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 32 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-methoxybenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 302 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 302 (M *)
Verbindung 33 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl)essigsäure-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Methylbenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 33 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) (2- Aminothiazol-4-yl) acetic acid solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-methylbenzaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 321 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 321 (M *)
Verbindung 34 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Methylbenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 34 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-methylbenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 270 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 270 (M *)
Verbindung 35 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-Methylbenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 35 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2-methylbenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 321 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 321 (M *)
Verbindung 36 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 3-Amino-1,2,4- triazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,3-Dimethoxybenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 36 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 3-amino-1,2,4- triazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,3-dimethoxybenzaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 316 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 316 (M *)
Verbindung 37 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,3-Dimethoxybenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt.Compound 37 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 2,3-dimethoxybenzaldehyde solution (0.3 M, DCM) and 10 µl perchloric acid (w = 20%) in one Substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 332 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 332 (M *)
Verbindung 38 wurde gemäß der allgemeinen Synthesevorschrift aus 1.0 ml (0.1 mmol) 2-Amino thiazol-Lösung (0.1 M, DCM), 0.575 ml (0.115 mmol) tert.-Butylisonitril-Lösung (0.2 M, DCM), 0.500 ml (0.15 mmol) 4-Methylbenzaldehyd-Lösung (0.3 M, DCM) und 10 µl Perchlorsäure (w = 20%) in einer Substanzbibliothek dargestellt. Compound 38 was made according to the general Synthesis instructions from 1.0 ml (0.1 mmol) of 2-amino thiazole solution (0.1 M, DCM), 0.575 ml (0.115 mmol) tert-butylisonitrile solution (0.2 M, DCM), 0.500 ml (0.15 mmol) 4-methylbenzaldehyde solution (0.3 M, DCM) and 10 µl Perchloric acid (w = 20%) in a substance library shown.
Zur Charakterisierung wurde ein ESI-MS aufgenommen:
MS(EI) m/z: 286 (M*)An ESI-MS was included for characterization:
MS (EI) m / z: 286 (M *)
Claims (5)
worin
R1 C(CH3)3, (CH2)6CN, gegebenenfalls substituiertes Phenyl, C4-C8-Cycloalkyl, CH2CH2R (R = 4- Morpholino), 1,1,3,3-Tetramethylbutyl oder Gut, wobei Ra für Wasserstoff, C1-C8-Alkyl (verzweigt oder unverzweigt), Phenyl, CO(OR') (mit R' = C1-C8- Alkyl (verzweigt oder unverzweigt)), PO(OR")2 (mit R" = C1-C4-Alkyl (verzweigt oder unverzweigt)) oder Si(RxRyRz) (mit Rx, Ry und Rz jeweils unabhängig voneinander C1-C8-Alkyl (verzweigt oder unverzweigt), C4-C8-Cycloalkyl oder Phenyl) steht, bedeutet,
R2 Wasserstoff, CORb, wobei Rb für Wasserstoff, C1- C8-Alkyl (verzweigt oder unverzweigt), C1-C8- Cycloalkyl, CH2CH2CO(OR') (mit R' = C1-C8-Alkyl (verzweigt oder unverzweigt)), Adamantyl, gegebenenfalls substituiertes Phenyl, gegebenenfalls substituiertes 1-Naphtyl, 2- Naphtyl, 2-Pyridyl, 3-Pyridyl, 4-Pyridyl, Thiazolyl oder Furoyl steht, CH2Rc, wobei Rc für Wasserstoff, C1-C8-Alkyl (verzweigt oder unverzweigt) oder gegebenenfalls substituiertes Phenyl steht, CH2CH2Rd, wobei Rd für gegebenenfalls substituiertes Phenyl steht, oder CONHRe, wobei Re für Phenyl steht, bedeutet,
R3 C1-C8-Alkyl (verzweigt oder unverzweigt), C3-C8- Cycloalkyl, gegebenenfalls substituiertes Phenyl, gegebenenfalls substituiertes 1-Naphtyl, 2- Naphtyl, Chinolin, Anthracen, Phenanthren, Benzothiophen, Benzofurfuryl, gegebenenfalls substituiertes Pyrrol, 2-Pyridyl, 3-Pyridyl, 4- Pyridyl, gegebenenfalls substituiertes Furfuryl oder gegebenenfalls substituiertes Thiophen bedeutet,
X CR5, N oder S bedeutet und Y für den Fall, daß X S bedeutet, CR6 oder N und in allen anderen Fällen N bedeutet,
R4, R5 und R6 unabhängig voneinander Wasserstoff, C1-C8-Alkyl (verzweigt oder unverzweigt), Fluor, Chlor, Brom, CF3, CN, NO2, NHRf, wobei Rf für Wasserstoff, C1-C8-Alkyl (verzweigt oder unverzweigt), oder gegebenenfalls substituiertes Phenyl steht, SRg, wobei Rg für Wasserstoff, C1-C8- Alkyl (verzweigt oder unverzweigt), Phenyl, Pyridin, Benzyl oder Fluorenyl steht, ORh, wobei Rh für C1-C8-Alkyl (verzweigt oder unverzweigt), gegebenenfalls substituiertes Phenyl oder CO(OR') (R' = C1-C8-Alkyl (verzweigt oder unverzweigt)) steht, CO(OR') oder CH2CO(OR'), wobei R' jeweils die oben angegebene Bedeutung hat, oder eine gegebenenfalls substituierte Phenylgruppe bedeuten oder R4 und R5 gemeinsam eine Brücke =CRi-CH=CH-CH= oder =CH-CRi=CH-CH= bilden, wobei Ri für H, F, Cl, Br, I oder C1-C8-Alkyl (verzweigt oder unverzweigt) steht, und deren pharmazeutisch akzeptable Salze
ausgenommen Verbindungen, bei denen entweder gleichzeitig R1 C(CH3)3, R2 Wasserstoff, R3 unsubstituiertes Phenyl, X S und Y N oder CR6 mit R6 = Wasserstoff oder CH2-CO2-Ethyl oder gleichzeitig R1 C(CH3)3, R2 Wasserstoff, R3 unsubstituiertes Phenyl, Y NH und X N oder CR5 mit R5 = CO2 Ethyl bedeutet.1. bicyclic imidazo-5-amines of the general formulas (I),
wherein
R 1 C (CH 3 ) 3 , (CH 2 ) 6 CN, optionally substituted phenyl, C 4 -C 8 cycloalkyl, CH 2 CH 2 R (R = 4-morpholino), 1,1,3,3-tetramethylbutyl or Gut, where R a is hydrogen, C 1 -C 8 alkyl (branched or unbranched), phenyl, CO (OR ') (with R' = C 1 -C 8 alkyl (branched or unbranched)), PO ( OR ") 2 (with R" = C 1 -C 4 alkyl (branched or unbranched)) or Si (R x R y R z ) (with R x , R y and R z each independently of one another C 1 -C 8 Alkyl (branched or unbranched), C 4 -C 8 -cycloalkyl or phenyl),
R 2 is hydrogen, COR b , where R b is hydrogen, C 1 -C 8 alkyl (branched or unbranched), C 1 -C 8 cycloalkyl, CH 2 CH 2 CO (OR ') (with R' = C 1 -C 8 alkyl (branched or unbranched)), adamantyl, optionally substituted phenyl, optionally substituted 1-naphthyl, 2-naphthyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, thiazolyl or furoyl, CH 2 R c , where R c is hydrogen, C 1 -C 8 alkyl (branched or unbranched) or optionally substituted phenyl, CH 2 CH 2 R d , where R d is optionally substituted phenyl, or CONHR e , where R e is phenyl means
R 3 C 1 -C 8 alkyl (branched or unbranched), C 3 -C 8 cycloalkyl, optionally substituted phenyl, optionally substituted 1-naphthyl, 2-naphthyl, quinoline, anthracene, phenanthrene, benzothiophene, benzofurfuryl, optionally substituted pyrrole , 2-pyridyl, 3-pyridyl, 4-pyridyl, optionally substituted furfuryl or optionally substituted thiophene,
X denotes CR 5 , N or S and Y in the case that XS denotes CR 6 or N and in all other cases N denotes
R 4 , R 5 and R 6 independently of one another are hydrogen, C 1 -C 8 -alkyl (branched or unbranched), fluorine, chlorine, bromine, CF 3 , CN, NO 2 , NHR f , where R f is hydrogen, C 1 -C 8 alkyl (branched or unbranched), or optionally substituted phenyl, SR g , where R g represents hydrogen, C 1 -C 8 alkyl (branched or unbranched), phenyl, pyridine, benzyl or fluorenyl, OR h , where R h is C 1 -C 8 -alkyl (branched or unbranched), optionally substituted phenyl or CO (OR ') (R' = C 1 -C 8 -alkyl (branched or unbranched)), CO (OR ' ) or CH 2 CO (OR '), where R' each has the meaning given above, or an optionally substituted phenyl group or R 4 and R 5 together represent a bridge = CR i -CH = CH-CH = or = CH-CR i = CH-CH = form, where R i is H, F, Cl, Br, I or C 1 -C 8 -alkyl (branched or unbranched), and their pharmaceutically acceptable salts
except for compounds in which either R 1 C (CH 3 ) 3 , R 2 hydrogen, R 3 unsubstituted phenyl, XS and YN or CR 6 with R 6 = hydrogen or CH 2 -CO 2 ethyl or R 1 C ( CH 3 ) 3 , R 2 is hydrogen, R 3 is unsubstituted phenyl, Y NH and XN or CR 5 with R 5 = CO 2 ethyl.
für den Fall, daß R3 eine substituierte Phenylgruppe ist, diese ausgewählt ist aus der Gruppe 4-Acetamidophenyl, 2-Bromphenyl, 3- Bromphenyl, 4-Bromphenyl, 4-Brom-2-fluorphenyl, 5- Brom-2-fluorphenyl, 3-Brom-4-fluorphenyl, 4-tert- Butylphenyl, 2-Chlor-4-fluorphenyl, 2-Chlor-6- fluorphenyl, 2-Chlorphenyl, 3-Chlorphenyl, 4- Chlorphenyl, 4-Cyanophenyl, 2,3-Dichlorphenyl, 2,4-Dichlorphenyl, 3,4-Dichlorphenyl, 2,3- Dimethoxyphenyl, 3,4-Di-methoxyphenyl, 2,4- Dimethylphenyl, 2,5-Di-methylphenyl, 2- Fluorphenyl, 3-Fluorphenyl, 4-Fluorphenyl, 4- Hexylphenyl, 3-Hydroxy-phenyl, 2-Methoxyphenyl, 2- Methylphenyl, 3-Methylphenyl, 4-Methylphenyl, 4- Nitrophenyl, 3-Phenoxyphenyl, 4-(1- Pyrrolidino)phenyl, 2-(Trifluormethyl)phenyl, 3- (Tri-fluormethyl)phenyl, 4-(Trifluormethyl) phenyl, 3,4,5-Trimethoxyphenyl, 3-(4-Chlorphenoxy)phenyl, 4-Acetoxy-3-methoxyphenyl,
für den Fall, daß R3 eine substituierte 1- Naphthylgruppe ist, diese ausgewählt ist aus der Gruppe 4-Dimethylaminonaphthyl, 2-Ethoxynaphthyl, 4-Methoxynaphthyl,
für den Fall, daß R3 eine substituierte Pyrrolgruppe ist, diese ausgewählt ist aus der Gruppe 2-(1-(Phenylsulfonyl)pyrrol), 2-(N- Methylpyrrol), 2-(N-(3,5-Dichlorphenyl)pyrrol), 2(1-(4-Chlorophenyl)pyrrol),
für den Fall, daß R3 eine substituierte Furfurylgruppe ist, diese ausgewählt ist aus der Gruppe 2-(5-Acetoxymethylfurfuryl), 2-(5-Methyl furfuryl), 2-(5-Nitrofurfuryl), 2-[5-(3- Nitrophenyl)furfuryl], 2-[5-(2-Nitro phenyl)furfuryl], 2-(5-Bromfurfuryl), 2-[5-3- Chlorphenyl)furfuryl], 2-(4,5-Dimethylfurfuryl), 2-[5-(2-Chlorophenyl]furfuryl], 2-(5- Ethylfurfuryl), 2-[5-(1,3-Dioxalan)furfuryl], und
für den Fall, daß R3 eine substituierte Thiophengruppe ist, diese ausgewählt ist aus der Gruppe 2-(5-Chlorthiophenyl), 2-(5- Methylthiophenyl), 2-(5-Ethylthiophenyl), 2-(3- Methylthiophenyl), 2-(4-Bromothiophenyl), 2-(5- Nitrothiophenyl), 5-(2-Carbonsäurethiophenyl), 2- [4-(Phenylethyl)thiophenyl], 2-[5- (Methylthio)thiophenyl], 2-(3-Bromothiophenyl), 2- (3-Phenoxythiophenyl), 2-(5-Bromthiophenyl).2. Bicyclic imidazo-5-amines according to claim 1, characterized in that
in the event that R 3 is a substituted phenyl group, this is selected from the group 4-acetamidophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-bromo-2-fluorophenyl, 5-bromo-2-fluorophenyl, 3-bromo-4-fluorophenyl, 4-tert-butylphenyl, 2-chloro-4-fluorophenyl, 2-chloro-6-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-cyanophenyl, 2,3- Dichlorophenyl, 2,4-dichlorophenyl, 3,4-dichlorophenyl, 2,3-dimethoxyphenyl, 3,4-dimethoxyphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 4-hexylphenyl, 3-hydroxyphenyl, 2-methoxyphenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 4-nitrophenyl, 3-phenoxyphenyl, 4- (1- pyrrolidino) phenyl, 2- ( Trifluoromethyl) phenyl, 3- (trifluoromethyl) phenyl, 4- (trifluoromethyl) phenyl, 3,4,5-trimethoxyphenyl, 3- (4-chlorophenoxy) phenyl, 4-acetoxy-3-methoxyphenyl,
in the event that R 3 is a substituted 1-naphthyl group, this is selected from the group 4-dimethylaminonaphthyl, 2-ethoxynaphthyl, 4-methoxynaphthyl,
in the event that R 3 is a substituted pyrrole group, this is selected from the group 2- (1- (phenylsulfonyl) pyrrole), 2- (N-methylpyrrole), 2- (N- (3,5-dichlorophenyl) pyrrole ), 2 (1- (4-chlorophenyl) pyrrole),
in the event that R 3 is a substituted furfuryl group, this is selected from the group 2- (5-acetoxymethylfurfuryl), 2- (5-methyl furfuryl), 2- (5-nitrofurfuryl), 2- [5- (3 - nitrophenyl) furfuryl], 2- [5- (2-nitrophenyl) furfuryl], 2- (5-bromofurfuryl), 2- [5-3-chlorophenyl) furfuryl], 2- (4,5-dimethylfurfuryl), 2- [5- (2-chlorophenyl] furfuryl], 2- (5-ethylfurfuryl), 2- [5- (1,3-dioxalane) furfuryl], and
in the event that R 3 is a substituted thiophene group, this is selected from the group 2- (5-chlorothiophenyl), 2- (5-methylthiophenyl), 2- (5-ethylthiophenyl), 2- (3-methylthiophenyl), 2- (4-bromothiophenyl), 2- (5-nitrothiophenyl), 5- (2-carboxylic acid thiophenyl), 2- [4- (phenylethyl) thiophenyl], 2- [5- (methylthio) thiophenyl], 2- (3rd -Bromothiophenyl), 2- (3-phenoxythiophenyl), 2- (5-bromothiophenyl).
für den Fall, daß Rb eine substituierte Phenylgruppe ist, diese ausgewählt ist aus der Gruppe 3,5-Bis(Trifluormethyl)phenyl, 2- Bromphenyl, 2-Fluorphenyl, Pentafluorphenyl, 2,4- Difluorphenyl, 2,6-Difluorphenyl, 2-Chlorphenyl, 2,4-Dichlorphenyl, 2-Acetyl-phenyl, 2- Methoxyphenyl, 2,6-Dimethoxy-phenyl, 2-(Trifluor methyl)phenyl, 2-Methylphenyl, 3-Bromphenyl, 3- Fluorphenyl, 3-Chlorphenyl, 3,4-Dichlorphenyl, 3- Methoxyphenyl, 3,4-Dimethoxyphenyl, 3,4,5- Trimethoxyphenyl, 3,5-Dimethoxyphenyl, 3- (Trifluormethyl)phenyl, 3-Methoxyphenyl, 4- Bromphenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4- Methoxyphenyl, 4-(Trifluormethylphenyl, 4-tert. Butylphenyl, 4-Methylphenyl, 2-Iodphenyl, 4- Iodphenyl, 4-Cyanophenyl, 2-Nitrophenyl, 3- Nitrophenyl, 3,5-Dinitrophenyl, 4-Nitrophenyl, 3,5-Dichlorphenyl, 2,5-Difluorphenyl, 2,4- Dimethoxyphenyl, 3-Nitro-4-methylphenyl, 2,5- Dichlorphenyl, 2,3-Difluorphenyl, 4- (Trifluormethoxy)-phenyl, 2-(Trifluormethoxy)- phenyl, 3-(Trifluormethoxy)-phenyl,
für den Fall, daß Rc eine substituierte Phenyl gruppe ist, diese ausgewählt ist aus der Gruppe 2- Fluorphenyl, 2-Chlorphenyl, 2-Methylphenyl, 2- (Trifluormethyl)phenyl, 2-Bromphenyl, 3-Methoxy phenyl, 3-Nitrophenyl, 3-Chlorphenyl, 3-Fluor phenyl, 3-Phenoxyphenyl, 3-(Trifluor methoxy)phenyl, 3-Bromphenyl, 3-Chlorphenyl, 3- Methylphenyl, 4-tert.-Butylphenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4-Vinylphenyl, 4-(Trifluor methoxy)phenyl, 3,5-Dimethoxyphenyl, 3,5-Difluor phenyl, 3,5-Di(trifluormethyl)phenyl, 3,5-Difluorphenyl, 3,5-Dimethylphenyl, 2,3-Dichlor-phenyl, 2,3-Dimethylphenyl, 2,3-Difluorphenyl, 3-Chlor-2- fluorphenyl, 2-Chlor-4-Fluorphenyl, 2,4- Di(Trifluormethyl)phenyl, 2,4-Dichlorphenyl, 2,4- Difluorphenyl, 2,4-Dimethylphenyl, 2,5-Dichlor phenyl, 2,5-Dimethylphenyl, 2,5-Difluorphenyl, 3,4-Dichlorphenyl, 3,4-Difluorphenyl, 3,4- Dimethylphenyl, 2,3,4-Trifluorphenyl, 2,3,6- Trifluorphenyl, 2,4,5-Trifluorphenyl, 2,4,6- Trimethylphenyl, Pentafluorphenyl,
für den Fall, daß Rd eine substituierte Phenylgruppe ist, diese ausgewählt ist aus der Gruppe 3-Chlorphenyl, 4-Chlorphenyl, 4- Carboxyphenyl, 4-Acetylphenyl, 4-Methoxy-phenyl, 4-Fluorphenyl, 4-Nitrophenyl, 4-Hydroxyphenyl.3. Bicyclic imidazo-5-amines according to claim 1 or 2, characterized in that
in the event that R b is a substituted phenyl group, this is selected from the group 3,5-bis (trifluoromethyl) phenyl, 2-bromophenyl, 2-fluorophenyl, pentafluorophenyl, 2,4-difluorophenyl, 2,6-difluorophenyl, 2-chlorophenyl, 2,4-dichlorophenyl, 2-acetylphenyl, 2-methoxyphenyl, 2,6-dimethoxy-phenyl, 2- (trifluoromethyl) phenyl, 2-methylphenyl, 3-bromophenyl, 3-fluorophenyl, 3- Chlorophenyl, 3,4-dichlorophenyl, 3-methoxyphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3,5-dimethoxyphenyl, 3- (trifluoromethyl) phenyl, 3-methoxyphenyl, 4-bromophenyl, 4-fluorophenyl , 4-chlorophenyl, 4-methoxyphenyl, 4- (trifluoromethylphenyl, 4-tert.butylphenyl, 4-methylphenyl, 2-iodophenyl, 4-iodophenyl, 4-cyanophenyl, 2-nitrophenyl, 3-nitrophenyl, 3,5-dinitrophenyl, 4-nitrophenyl, 3,5-dichlorophenyl, 2,5-difluorophenyl, 2,4-dimethoxyphenyl, 3-nitro-4-methylphenyl, 2,5-dichlorophenyl, 2,3-difluorophenyl, 4- (trifluoromethoxy) phenyl, 2- (trifluoromethoxy) phenyl, 3- (trifluoromethoxy) phenyl,
in the event that R c is a substituted phenyl group, this is selected from the group 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 2- (trifluoromethyl) phenyl, 2-bromophenyl, 3-methoxyphenyl, 3-nitrophenyl , 3-chlorophenyl, 3-fluorophenyl, 3-phenoxyphenyl, 3- (trifluoromethoxy) phenyl, 3-bromophenyl, 3-chlorophenyl, 3-methylphenyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4 -Vinylphenyl, 4- (trifluoromoxy) phenyl, 3,5-dimethoxyphenyl, 3,5-difluorophenyl, 3,5-di (trifluoromethyl) phenyl, 3,5-difluorophenyl, 3,5-dimethylphenyl, 2,3- Dichlorophenyl, 2,3-dimethylphenyl, 2,3-difluorophenyl, 3-chloro-2-fluorophenyl, 2-chloro-4-fluorophenyl, 2,4-di (trifluoromethyl) phenyl, 2,4-dichlorophenyl, 2, 4- difluorophenyl, 2,4-dimethylphenyl, 2,5-dichlorophenyl, 2,5-dimethylphenyl, 2,5-difluorophenyl, 3,4-dichlorophenyl, 3,4-difluorophenyl, 3,4-dimethylphenyl, 2,3 , 4-trifluorophenyl, 2,3,6-trifluorophenyl, 2,4,5-trifluorophenyl, 2,4,6-trimethylphenyl, pentafluorophenyl,
in the event that R d is a substituted phenyl group, this is selected from the group 3-chlorophenyl, 4-chlorophenyl, 4-carboxyphenyl, 4-acetylphenyl, 4-methoxy-phenyl, 4-fluorophenyl, 4-nitrophenyl, 4- hydroxyphenyl.
tert-Butyl-(5-furan-2-yl-3H-imidazo[1,2- b][1,2,4]triazol-6-yl)-amin,
tert-Butyl-(6-furan-2-yl-imidazo[2,1-b]thiazol-5- yl)-amin,
(5-tert-Butylamino-6-furan-2-yl-imidazo[2,1- b]thiazol-3-yl)-essigsäure,
tert-Butyl-(5-pyridin-2-yl-3H-imidazo[1,2-b] [1,2,4]triazol-6-yl)-amin,
tert-Butyl-(6-pyridin-2-yl-imidazo[2,1-b]thiazol- 5-yl)-amin,
tert-Butyl-(5-pyridin-3-yl-3H-imidazo[1,2-b] [1,2,4]triazol-6-yl)-amin,
tert-Butyl-(5-pyridin-4-yl-3H-imidazo[1,2-b] [1,2,4]triazol-6-yl)-amin,
tert-Butyl-(6-cyclohexyl-imidazo[2,1-b]thiazol-5- yl)-amin,
tert-Butyl-(5-methyl-3H-imidazo[1,2- b][1,2,4]triazol-6-yl)-amin,
tert-Butyl-(6-methyl-imidazo[2,1-b]thiazol-5-yl)- amin,
Cyclohexyl-(5-pyridin-2-yl-3H-imidazo[1,2-b] [1,2,4]triazol-6-yl)-amin,
Cyclohexyl-(6-pyridin-2-yl-imidazo[2,1-b]thiazol- 5-yl)-amin, (5-Cyclohexylamino-6-pyridin-2-yl-imidazo[2,1- b]thiazol-3-yl)-essigsäure,
Cyclohexyl-(6-pyridin-4-yl-imidazo[2,1-b]thiazol- 5-yl)-amin,
Cyclohexyl-(6-cyclohexyl-imidazo[2,1-b]thiazol-5- yl)-amin,
(6-Cyclohexyl-5-cyclohexylamino-imidazo[2,1- b]thiazol-3-yl)-essigsäure,
(5-Cyclohexylamino-6-methyl-imidazo[2,1-b]thiazol- 3-yl)-essig-säure,
(2,6-Dimethyl-phenyl)-(5-furan-2-yl-3H- imidazo[1,2-b][1,2,4]triazol-6-yl)-amin,
(2,6-Dimethyl-phenyl)-(6-pyridin-2-yl-imidazo[2,1- b]thiazol-5-yl)-amin,
(2,6-Dimethyl-phenyl)-(6-pyridin-3-yl-imidazo[2,1- b]thiazol-5-yl)-amin,
(2,6-Dimethyl-phenyl)-(6-pyridin-4-yl-imidazo[2,1- b]thiazol-5-yl)-amin,
(6-Cyclohexyl-imidazo[2,1-b]thiazol-5-ylamino)- essigsäure-methylester,
(6-Methyl-imidazo[2,1-b]thiazol-5-ylamino)- essigsäure-methylester,
tert-Butyl-(2-phenyl-5H-imidazo[1,2-b]pyrazol-3- yl)-amin,
3-(5-tert-Butylamino-imidazo[2,1-b]thiazol-6-yl)- phenol,
tert-Butyl-[6-(3,4-dimethoxy-phenyl)-imidazo[2,1- b]thiazol-5-yl]-amin,
tert-Butyl-[5-(2,3-dichloro-phenyl)-3H- imidazo[1,2-b][1,2,4]triazol-6-yl]-amin,
tert-Butyl-[6-(2,3-dichloro-phenyl)-imidazo[2,1- b]thiazol-5-yl]-amin,
tert-Butyl- [5-(2,4-dichloro-phenyl)-3H- imidazo[1,2-b][1,2,4]triazol-6-yl]-amin,
tert-Butyl-[6-(2,4-dichloro-phenyl)-imidazo[2,1- b]thiazol-5-yl]-amin,
tert-Butyl-[5-(2-methoxy-phenyl)-3H-imidazo[1,2-b] [1,2,4]triazol-6-yl]-amin,
tert-Butyl-[6-(2-methoxy-phenyl)-imidazo[2,1- b]thiazol-5-yl]-amin,
[5-tert-Butylamino-6-(2-methoxy-phenyl)- imidazo[2,1-b]thiazol-3-yl]-essigsäure,
tert-Butyl-(5-o-tolyl-3H-imidazo[1,2- b][1,2,4]triazol-6-yl)-amin,
tert-Butyl-(6-o-tolyl-imidazo[2,1-b]thiazol-5-yl)- amin,
tert-Butyl-[5-(2,3-dimethoxy-phenyl)-3H- imidazo[1,2-b][1,2,4] triazol-6-yl]-amin,
tert-Butyl-[6-(2,3-dimethoxy-phenyl)-imidazo[2,1- b]thiazol-5-yl]-amin,
tert-Butyl-(6-p-tolyl-imidazo[2,1-b]thiazol-5-yl)- amin,
oder der pharmazeutisch akzeptablen Salze dieser Verbindungen enthält.5. Medicament according to claim 4, characterized in that it is selected as active ingredient at least one bicyclic imidazo-5-amine from the group
tert-butyl- (5-furan-2-yl-3H-imidazo [1,2- b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (6-furan-2-yl-imidazo [2,1-b] thiazol-5-yl) amine,
(5-tert-butylamino-6-furan-2-yl-imidazo [2,1-b] thiazol-3-yl) acetic acid,
tert-butyl- (5-pyridin-2-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (6-pyridin-2-yl-imidazo [2,1-b] thiazol-5-yl) amine,
tert-butyl- (5-pyridin-3-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (5-pyridin-4-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (6-cyclohexyl-imidazo [2,1-b] thiazol-5-yl) amine,
tert-butyl- (5-methyl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (6-methylimidazo [2,1-b] thiazol-5-yl) amine,
Cyclohexyl- (5-pyridin-2-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
Cyclohexyl- (6-pyridin-2-yl-imidazo [2,1-b] thiazol-5-yl) amine, (5-cyclohexylamino-6-pyridin-2-yl-imidazo [2,1-b] thiazole -3-yl) acetic acid,
Cyclohexyl- (6-pyridin-4-yl-imidazo [2,1-b] thiazol-5-yl) amine,
Cyclohexyl- (6-cyclohexyl-imidazo [2,1-b] thiazol-5-yl) amine,
(6-cyclohexyl-5-cyclohexylamino-imidazo [2,1-b] thiazol-3-yl) acetic acid,
(5-cyclohexylamino-6-methyl-imidazo [2,1-b] thiazol-3-yl) acetic acid,
(2,6-dimethyl-phenyl) - (5-furan-2-yl-3H-imidazo [1,2-b] [1,2,4] triazol-6-yl) amine,
(2,6-dimethyl-phenyl) - (6-pyridin-2-yl-imidazo [2,1-b] thiazol-5-yl) amine,
(2,6-dimethyl-phenyl) - (6-pyridin-3-yl-imidazo [2,1-b] thiazol-5-yl) amine,
(2,6-dimethyl-phenyl) - (6-pyridin-4-yl-imidazo [2,1-b] thiazol-5-yl) amine,
(6-cyclohexyl-imidazo [2,1-b] thiazol-5-ylamino) methyl acetate,
(6-methylimidazo [2,1-b] thiazol-5-ylamino) methyl acetate,
tert-butyl- (2-phenyl-5H-imidazo [1,2-b] pyrazol-3-yl) amine,
3- (5-tert-butylamino-imidazo [2,1-b] thiazol-6-yl) phenol,
tert-butyl- [6- (3,4-dimethoxyphenyl) imidazo [2,1- b] thiazol-5-yl] amine,
tert-butyl- [5- (2,3-dichloro-phenyl) -3H-imidazo [1,2-b] [1,2,4] triazol-6-yl] amine,
tert-butyl- [6- (2,3-dichloro-phenyl) imidazo [2,1- b] thiazol-5-yl] amine,
tert-butyl- [5- (2,4-dichlorophenyl) -3H- imidazo [1,2-b] [1,2,4] triazol-6-yl] amine,
tert-butyl- [6- (2,4-dichlorophenyl) imidazo [2,1- b] thiazol-5-yl] amine,
tert-butyl- [5- (2-methoxyphenyl) -3H-imidazo [1,2-b] [1,2,4] triazol-6-yl] amine,
tert-butyl- [6- (2-methoxyphenyl) imidazo [2,1- b] thiazol-5-yl] amine,
[5-tert-butylamino-6- (2-methoxyphenyl) imidazo [2,1-b] thiazol-3-yl] acetic acid,
tert-butyl- (5-o-tolyl-3H-imidazo [1,2- b] [1,2,4] triazol-6-yl) amine,
tert-butyl- (6-o-tolylimidazo [2,1-b] thiazol-5-yl) amine,
tert-butyl- [5- (2,3-dimethoxyphenyl) -3H-imidazo [1,2-b] [1,2,4] triazol-6-yl] amine,
tert-butyl- [6- (2,3-dimethoxyphenyl) imidazo [2,1- b] thiazol-5-yl] amine,
tert-butyl- (6-p-tolylimidazo [2,1-b] thiazol-5-yl) amine,
or which contains pharmaceutically acceptable salts of these compounds.
Priority Applications (33)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1999148436 DE19948436B4 (en) | 1999-10-08 | 1999-10-08 | Bicyclic imidazo-5-amine derivatives |
| PT00967693T PT1218383E (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| SK464-2002A SK4642002A3 (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives method for producing thereof, use thereof and pharmaceutical compositions containing said compounds |
| CA002388476A CA2388476C (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| KR1020027004442A KR20020068515A (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| SI200031017T SI1218383T1 (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| CNB008163650A CN1211385C (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivs. |
| DE50015443T DE50015443D1 (en) | 1999-10-08 | 2000-09-18 | BICYCLIC IMIDAZO-5-YL-AMINE DERIVATIVES |
| ES00967693T ES2316388T3 (en) | 1999-10-08 | 2000-09-18 | BICYCLE DERIVATIVES OF IMIDAZO-5-ILAMIMA. |
| HU0203140A HUP0203140A3 (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives, process for their preparation and pharmaceutical compositions containing them |
| PL00355019A PL355019A1 (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| AT00967693T ATE413403T1 (en) | 1999-10-08 | 2000-09-18 | BICYCLIC IMIDAZO-5-YL AMINE DERIVATIVES |
| HK02109381.6A HK1047746B (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| BR0014817-2A BR0014817A (en) | 1999-10-08 | 2000-09-18 | Imidazo-5-yl-bicyclic amines, medicines that contain them, their use for the preparation of medicines and procedure for their preparation |
| EP00967693A EP1218383B1 (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| MXPA02002837A MXPA02002837A (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo 5 yl amine derivatives. |
| CZ20021242A CZ20021242A3 (en) | 1999-10-08 | 2000-09-18 | Bicyclic derivatives of imidaz-5-yl-amine, process of their preparation, their use and medicament containing these substances |
| IL14901000A IL149010A0 (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| DK00967693T DK1218383T3 (en) | 1999-10-08 | 2000-09-18 | Biocyclic imidazo-5-yl amino derivatives |
| PCT/EP2000/009097 WO2001027118A2 (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| JP2001530336A JP2003511456A (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| AU77772/00A AU781227B2 (en) | 1999-10-08 | 2000-09-18 | Bicyclic imidazo-5-yl-amine derivatives |
| RU2002110112/04A RU2002110112A (en) | 1999-10-08 | 2000-09-18 | Bicyclic derivatives of imidazo-5-ylamine |
| CO00074644A CO5200851A1 (en) | 1999-10-08 | 2000-10-02 | IMIDAZO-5-IL-BICYCLES, DRUGS THAT CONTAIN THEM, THEIR USE FOR THE PREPARATION OF MEDICINES AND PROCEDURE FOR THEIR PREPARATION |
| UY26370A UY26370A1 (en) | 1999-10-08 | 2000-10-05 | "IMIDAZO-5-IL-AMICAS BICÍCLICAS, DRUGS CONTAINING THEM, THEIR USE FOR THE PREPARATION OF DRUGS AND PROCEDURE FOR THE PREPARATION". |
| ARP000105252A AR030030A1 (en) | 1999-10-08 | 2000-10-05 | IMIDAZO-5-IL-BICYCLE AMINES, MEDICINES CONTAINING THEM, ITS USE FOR THE PREPARATION OF MEDICINES AND PROCEDURE FOR THEIR PREPARATION |
| PE2000001066A PE20010638A1 (en) | 1999-10-08 | 2000-10-06 | IMIDAZO-5-IL-BICYCLE AMINES, DRUGS THAT CONTAIN THEM, THEIR USE FOR THE PREPARATION OF DRUGS AND THE PROCEDURE FOR THEIR PREPARATION |
| NO20021566A NO20021566L (en) | 1999-10-08 | 2002-04-03 | Bicyclic imidazo-5-yl amine derivatives |
| IL149010A IL149010A (en) | 1999-10-08 | 2002-04-04 | Bicyclic imidazo-5-yl-amine derivatives, their preparation and pharmaceutical compositions containing them |
| US10/117,335 US6657064B2 (en) | 1999-10-08 | 2002-04-08 | Bicyclic imidazo-5-yl-amine derivatives |
| ZA200203582A ZA200203582B (en) | 1999-10-08 | 2002-05-06 | Bicyclic imidazo-5-yl-amine derivatives. |
| US10/633,579 US6936631B2 (en) | 1999-10-08 | 2003-08-05 | Bicyclic imidazo-5-yl-amine derivatives |
| CY20091100104T CY1110416T1 (en) | 1999-10-08 | 2009-01-28 | IMIDAZ-5-YL-AMINE BICYCLE PRODUCTS |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1999148436 DE19948436B4 (en) | 1999-10-08 | 1999-10-08 | Bicyclic imidazo-5-amine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE19948436A1 true DE19948436A1 (en) | 2001-06-07 |
| DE19948436B4 DE19948436B4 (en) | 2006-11-16 |
Family
ID=7924889
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1999148436 Expired - Fee Related DE19948436B4 (en) | 1999-10-08 | 1999-10-08 | Bicyclic imidazo-5-amine derivatives |
Country Status (2)
| Country | Link |
|---|---|
| DE (1) | DE19948436B4 (en) |
| ZA (1) | ZA200203582B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10150172A1 (en) * | 2001-10-11 | 2003-04-30 | Morphochem Ag | New 5-amino-4-phenyl-1H-imidazole derivatives useful as protein tyrosine phosphatase 1B inhibitors, for treating e.g. diabetes and obesity |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| DE3030982A1 (en) * | 1979-08-21 | 1981-03-12 | Yamanouchi Pharmaceutical Co., Ltd., Tokyo | 2-PHENYLIMIDAZO (2,1-B) BENZOTHIAZOLE DERIVATIVES |
| EP0518033A1 (en) * | 1991-04-16 | 1992-12-16 | Takeda Chemical Industries, Ltd. | Fused heterocyclic compounds, their production and use |
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1999
- 1999-10-08 DE DE1999148436 patent/DE19948436B4/en not_active Expired - Fee Related
-
2002
- 2002-05-06 ZA ZA200203582A patent/ZA200203582B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3030982A1 (en) * | 1979-08-21 | 1981-03-12 | Yamanouchi Pharmaceutical Co., Ltd., Tokyo | 2-PHENYLIMIDAZO (2,1-B) BENZOTHIAZOLE DERIVATIVES |
| EP0518033A1 (en) * | 1991-04-16 | 1992-12-16 | Takeda Chemical Industries, Ltd. | Fused heterocyclic compounds, their production and use |
Non-Patent Citations (3)
| Title |
|---|
| H.Bienayme,K. Bouzid, Angew. Chem. 1998, 110, 2349-2352 * |
| JP 01319488 als Chemical Abstract 1990, Vol.113, No.6341k. * |
| JP 57040492 A als Derwent Abstract 1980, No.29881 E/15 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10150172A1 (en) * | 2001-10-11 | 2003-04-30 | Morphochem Ag | New 5-amino-4-phenyl-1H-imidazole derivatives useful as protein tyrosine phosphatase 1B inhibitors, for treating e.g. diabetes and obesity |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200203582B (en) | 2003-11-26 |
| DE19948436B4 (en) | 2006-11-16 |
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