PT1784409E - Amidas do ácido tienopirrolecarboxílico, amidas do ácido pirrolotiazole carboxílico substituídas e análogos relacionados, como inibidores de caseína cinase i épsilon - Google Patents

Info

Publication number

PT1784409E

PT1784409E PT05826812T PT05826812T PT1784409E PT 1784409 E PT1784409 E PT 1784409E PT 05826812 T PT05826812 T PT 05826812T PT 05826812 T PT05826812 T PT 05826812T PT 1784409 E PT1784409 E PT 1784409E

Authority

PT

Portugal

Prior art keywords

alkyl

carboxylic acid

thieno

acid amide

pyrrole

Prior art date

2004-08-19

Links

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• 239000003112 inhibitor Substances 0.000 title description 13
• 150000001732 carboxylic acid derivatives Chemical class 0.000 title description 10
• YRVMMDZANCTYNL-UHFFFAOYSA-N 2h-pyrrolo[2,3-d][1,3]thiazole-2-carboxamide Chemical class C1=NC2=NC(C(=O)N)SC2=C1 YRVMMDZANCTYNL-UHFFFAOYSA-N 0.000 title 1
• 102000008122 Casein Kinase I Human genes 0.000 title 1
• 108010049812 Casein Kinase I Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 165
• -1 methylenedioxy Chemical group 0.000 claims description 115
• 238000000034 method Methods 0.000 claims description 66
• 125000000623 heterocyclic group Chemical group 0.000 claims description 62
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 43
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
• 125000003118 aryl group Chemical group 0.000 claims description 35
• 229910052799 carbon Inorganic materials 0.000 claims description 30
• 229910052739 hydrogen Inorganic materials 0.000 claims description 28
• 150000001408 amides Chemical class 0.000 claims description 26
• 229910052757 nitrogen Inorganic materials 0.000 claims description 26
• 208000019116 sleep disease Diseases 0.000 claims description 26
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 25
• 238000006243 chemical reaction Methods 0.000 claims description 24
• 229910052717 sulfur Inorganic materials 0.000 claims description 23
• 208000035475 disorder Diseases 0.000 claims description 22
• 230000007958 sleep Effects 0.000 claims description 21
• 238000011282 treatment Methods 0.000 claims description 21
• 125000004432 carbon atom Chemical group C* 0.000 claims description 20
• 208000024714 major depressive disease Diseases 0.000 claims description 18
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 150000002367 halogens Chemical class 0.000 claims description 17
• 238000002360 preparation method Methods 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 16
• 125000002252 acyl group Chemical group 0.000 claims description 15
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
• 208000020401 Depressive disease Diseases 0.000 claims description 14
• 208000019022 Mood disease Diseases 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 13
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 12
• 125000002619 bicyclic group Chemical group 0.000 claims description 12
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 11
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 11
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 11
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
• 208000020685 sleep-wake disease Diseases 0.000 claims description 10
• 208000020925 Bipolar disease Diseases 0.000 claims description 9
• 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 9
• 208000028683 bipolar I disease Diseases 0.000 claims description 8
• 208000022257 bipolar II disease Diseases 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 8
• 125000002950 monocyclic group Chemical group 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
• 229920006395 saturated elastomer Polymers 0.000 claims description 7
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 230000008569 process Effects 0.000 claims description 6
• 239000002253 acid Substances 0.000 claims description 5
• 201000007034 advanced sleep phase syndrome Diseases 0.000 claims description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 claims description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
• 239000002798 polar solvent Substances 0.000 claims description 5
• PYQIOYKMCRUWPT-UHFFFAOYSA-N 6-phenylsulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound NC(=O)C=1NC=2C=CSC=2C=1SC1=CC=CC=C1 PYQIOYKMCRUWPT-UHFFFAOYSA-N 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 125000004414 alkyl thio group Chemical group 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• UVOWKGFSUGZCGS-UHFFFAOYSA-N 4-(3-methylphenyl)sulfanyl-6h-thieno[2,3-b]pyrrole-5-carboxamide Chemical compound CC1=CC=CC(SC=2C=3C=CSC=3NC=2C(N)=O)=C1 UVOWKGFSUGZCGS-UHFFFAOYSA-N 0.000 claims description 3
• IAGGBMKLGCTCCG-UHFFFAOYSA-N 6-(2-aminophenyl)sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound NC(=O)C=1NC=2C=CSC=2C=1SC1=CC=CC=C1N IAGGBMKLGCTCCG-UHFFFAOYSA-N 0.000 claims description 3
• ZZCCDNLZKPNSCR-UHFFFAOYSA-N 6-(2-methoxyphenyl)sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound COC1=CC=CC=C1SC1=C(C(N)=O)NC2=C1SC=C2 ZZCCDNLZKPNSCR-UHFFFAOYSA-N 0.000 claims description 3
• DJCKEACUJYXBFG-UHFFFAOYSA-N 6-(3-methoxyphenyl)sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound COC1=CC=CC(SC=2C=3SC=CC=3NC=2C(N)=O)=C1 DJCKEACUJYXBFG-UHFFFAOYSA-N 0.000 claims description 3
• RAABJMMDMKLJDD-UHFFFAOYSA-N 6-pyridin-4-ylsulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound NC(=O)C=1NC=2C=CSC=2C=1SC1=CC=NC=C1 RAABJMMDMKLJDD-UHFFFAOYSA-N 0.000 claims description 3
• GGNIKGLUPSHSBV-UHFFFAOYSA-N thiazole-5-carboxamide Chemical compound NC(=O)C1=CN=CS1 GGNIKGLUPSHSBV-UHFFFAOYSA-N 0.000 claims description 3
• IGBKCQSMFSPUPQ-UHFFFAOYSA-N 2-methyl-6-phenylsulfanyl-4h-pyrrolo[3,2-d][1,3]thiazole-5-carboxamide Chemical compound NC(=O)C=1NC=2SC(C)=NC=2C=1SC1=CC=CC=C1 IGBKCQSMFSPUPQ-UHFFFAOYSA-N 0.000 claims description 2
• DUKMKYDNILKJJY-UHFFFAOYSA-N 2H-pyrrolo[2,3-d][1,3]thiazole-5-carboxamide Chemical compound S1CN=C2C1=CC(=N2)C(=O)N DUKMKYDNILKJJY-UHFFFAOYSA-N 0.000 claims description 2
• YKZLNVSFLNFVOY-UHFFFAOYSA-N 4-(3-methoxyphenyl)sulfanyl-6h-thieno[2,3-b]pyrrole-5-carboxamide Chemical compound COC1=CC=CC(SC=2C=3C=CSC=3NC=2C(N)=O)=C1 YKZLNVSFLNFVOY-UHFFFAOYSA-N 0.000 claims description 2
• JYSYZRVJGHEJDK-UHFFFAOYSA-N 4-thiophen-2-ylsulfanyl-6h-thieno[2,3-b]pyrrole-5-carboxamide Chemical compound NC(=O)C=1NC=2SC=CC=2C=1SC1=CC=CS1 JYSYZRVJGHEJDK-UHFFFAOYSA-N 0.000 claims description 2
• PTCCVJFAQYJGKI-UHFFFAOYSA-N 6-(2-ethylphenyl)sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound CCC1=CC=CC=C1SC1=C(C(N)=O)NC2=C1SC=C2 PTCCVJFAQYJGKI-UHFFFAOYSA-N 0.000 claims description 2
• SLYFMXMWIGEZPA-UHFFFAOYSA-N 6-(2-methylphenyl)sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound CC1=CC=CC=C1SC1=C(C(N)=O)NC2=C1SC=C2 SLYFMXMWIGEZPA-UHFFFAOYSA-N 0.000 claims description 2
• KVNUDRZMWWEVIU-UHFFFAOYSA-N 6-(3-chlorophenyl)sulfanyl-2-methyl-4h-pyrrolo[3,2-d][1,3]thiazole-5-carboxamide Chemical compound NC(=O)C=1NC=2SC(C)=NC=2C=1SC1=CC=CC(Cl)=C1 KVNUDRZMWWEVIU-UHFFFAOYSA-N 0.000 claims description 2
• RQWWELNBPALKAG-UHFFFAOYSA-N 6-(3-fluorophenyl)sulfanylthieno[2,3-b]pyrrole-5-carboxamide Chemical compound NC(=O)C1=CC=2C=CSC=2N1SC1=CC=CC(F)=C1 RQWWELNBPALKAG-UHFFFAOYSA-N 0.000 claims description 2
• KHHVIGWHUFDFSL-UHFFFAOYSA-N 6-(4-chlorophenyl)sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound NC(=O)C=1NC=2C=CSC=2C=1SC1=CC=C(Cl)C=C1 KHHVIGWHUFDFSL-UHFFFAOYSA-N 0.000 claims description 2
• FPYSUIWAQIUWQH-UHFFFAOYSA-N 6-(4-methylphenyl)sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound C1=CC(C)=CC=C1SC1=C(C(N)=O)NC2=C1SC=C2 FPYSUIWAQIUWQH-UHFFFAOYSA-N 0.000 claims description 2
• ZURZOOVHMHWWTI-UHFFFAOYSA-N 6-phenylsulfanyl-4h-pyrrolo[2,3-d][1,3]thiazole-5-carboxamide Chemical compound NC(=O)C=1NC=2N=CSC=2C=1SC1=CC=CC=C1 ZURZOOVHMHWWTI-UHFFFAOYSA-N 0.000 claims description 2
• UPDWMYIJHGNQLV-UHFFFAOYSA-N OC(=O)C=1NC=2SC=CC=2C=1SC1=CC=CC(Cl)=C1 Chemical compound OC(=O)C=1NC=2SC=CC=2C=1SC1=CC=CC(Cl)=C1 UPDWMYIJHGNQLV-UHFFFAOYSA-N 0.000 claims description 2
• 239000003814 drug Substances 0.000 claims description 2
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims 3
• 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims 2
• SVGBHSTYOGQVPE-UHFFFAOYSA-N 2,6-bis[(3-methoxyphenyl)sulfanyl]-4h-pyrrolo[3,2-d][1,3]thiazole-5-carboxamide Chemical compound COC1=CC=CC(SC=2SC=3NC(=C(SC=4C=C(OC)C=CC=4)C=3N=2)C(N)=O)=C1 SVGBHSTYOGQVPE-UHFFFAOYSA-N 0.000 claims 1
• KHLCUPKDEHFRCJ-UHFFFAOYSA-N 2-methyl-6-[3-(trifluoromethoxy)phenyl]sulfanyl-4h-pyrrolo[3,2-d][1,3]thiazole-5-carboxamide Chemical compound NC(=O)C=1NC=2SC(C)=NC=2C=1SC1=CC=CC(OC(F)(F)F)=C1 KHLCUPKDEHFRCJ-UHFFFAOYSA-N 0.000 claims 1
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• JBLCKTNGYXHRDT-UHFFFAOYSA-N 6-(3,5-dichlorophenyl)sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound NC(=O)C=1NC=2C=CSC=2C=1SC1=CC(Cl)=CC(Cl)=C1 JBLCKTNGYXHRDT-UHFFFAOYSA-N 0.000 claims 1
• DZRGVTJILNYAEW-UHFFFAOYSA-N 6-(3-methoxyphenyl)sulfanyl-4h-pyrrolo[3,2-d][1,3]thiazole-5-carboxamide Chemical compound COC1=CC=CC(SC=2C=3N=CSC=3NC=2C(N)=O)=C1 DZRGVTJILNYAEW-UHFFFAOYSA-N 0.000 claims 1
• QZAPRLOGXQRWDW-UHFFFAOYSA-N 6-(3-methylphenyl)sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound CC1=CC=CC(SC=2C=3SC=CC=3NC=2C(N)=O)=C1 QZAPRLOGXQRWDW-UHFFFAOYSA-N 0.000 claims 1
• DBFNMLATEPIVEF-UHFFFAOYSA-N 6-[3-(trifluoromethoxy)phenyl]sulfanyl-4h-thieno[3,2-b]pyrrole-5-carboxamide Chemical compound NC(=O)C=1NC=2C=CSC=2C=1SC1=CC=CC(OC(F)(F)F)=C1 DBFNMLATEPIVEF-UHFFFAOYSA-N 0.000 claims 1
• VFCHWLOHRQUEDF-UHFFFAOYSA-N 6-pyridin-2-ylsulfanyl-4h-pyrrolo[2,3-d][1,3]thiazole-5-carboxamide Chemical compound NC(=O)C=1NC=2N=CSC=2C=1SC1=CC=CC=N1 VFCHWLOHRQUEDF-UHFFFAOYSA-N 0.000 claims 1
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