JP2010505881A - ステアロイルＣｏＡデサチュラーゼインヒビターとして使用するための二環式窒素含有複素環式化合物 - Google Patents

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Publication number

JP2010505881A

JP2010505881A JP2009531633A JP2009531633A JP2010505881A JP 2010505881 A JP2010505881 A JP 2010505881A JP 2009531633 A JP2009531633 A JP 2009531633A JP 2009531633 A JP2009531633 A JP 2009531633A JP 2010505881 A JP2010505881 A JP 2010505881A

Authority

JP

Japan

Prior art keywords

amino

methyl

oxo

hydropyridino

ethyl

Prior art date

2006-10-05

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.)

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• -1 Bicyclic nitrogen-containing heterocyclic compounds Chemical class 0.000 title claims abstract description 234
• 108010087894 Fatty acid desaturases Proteins 0.000 title claims abstract description 66
• 102000016553 Stearoyl-CoA Desaturase Human genes 0.000 title claims abstract 6
• 239000003112 inhibitor Substances 0.000 title abstract description 14
• 150000001875 compounds Chemical class 0.000 claims abstract description 171
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 59
• 201000010099 disease Diseases 0.000 claims abstract description 45
• 238000000034 method Methods 0.000 claims abstract description 41
• 241000124008 Mammalia Species 0.000 claims abstract description 7
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 216
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 162
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 160
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 144
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 131
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 105
• 125000000217 alkyl group Chemical group 0.000 claims description 90
• 125000001072 heteroaryl group Chemical group 0.000 claims description 75
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 71
• 125000001424 substituent group Chemical group 0.000 claims description 69
• 125000003118 aryl group Chemical group 0.000 claims description 65
• 239000001257 hydrogen Substances 0.000 claims description 43
• 229910052739 hydrogen Inorganic materials 0.000 claims description 43
• 125000000623 heterocyclic group Chemical group 0.000 claims description 32
• 125000003545 alkoxy group Chemical group 0.000 claims description 31
• 125000003342 alkenyl group Chemical group 0.000 claims description 26
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 23
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 23
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
• 150000003839 salts Chemical class 0.000 claims description 20
• 125000000304 alkynyl group Chemical group 0.000 claims description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
• 125000002947 alkylene group Chemical group 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims description 15
• BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical compound C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 claims description 14
• 229910052757 nitrogen Inorganic materials 0.000 claims description 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 13
• LAQJGAKLLZAETL-UHFFFAOYSA-N 2h-pyrazin-3-one Chemical compound O=C1CN=CC=N1 LAQJGAKLLZAETL-UHFFFAOYSA-N 0.000 claims description 12
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 12
• DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 11
• 239000002253 acid Substances 0.000 claims description 10
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 10
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
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• 235000019260 propionic acid Nutrition 0.000 claims description 7
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 6
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• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
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• 229940002612 prodrug Drugs 0.000 claims description 5
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 claims description 5
• AGRIQBHIKABLPJ-UHFFFAOYSA-N 1-Pyrrolidinecarboxaldehyde Chemical compound O=CN1CCCC1 AGRIQBHIKABLPJ-UHFFFAOYSA-N 0.000 claims description 4
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 4
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
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• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 239000005711 Benzoic acid Substances 0.000 claims description 3
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• 150000001408 amides Chemical class 0.000 claims description 3
• 235000010233 benzoic acid Nutrition 0.000 claims description 3
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• 125000002950 monocyclic group Chemical group 0.000 claims description 3
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 3
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• 125000000094 2-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
• 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
• 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• JWSWKNZAKWPCIZ-UHFFFAOYSA-N C(C)(=O)NN1CC=NC=C1 Chemical compound C(C)(=O)NN1CC=NC=C1 JWSWKNZAKWPCIZ-UHFFFAOYSA-N 0.000 claims description 2
• 101100240528 Caenorhabditis elegans nhr-23 gene Proteins 0.000 claims description 2
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
• 239000005977 Ethylene Substances 0.000 claims description 2
• YZWMUTWKHHJGHC-UHFFFAOYSA-N acetamide;acetic acid Chemical compound CC(N)=O.CC(O)=O YZWMUTWKHHJGHC-UHFFFAOYSA-N 0.000 claims description 2
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 2
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
• 229940095102 methyl benzoate Drugs 0.000 claims description 2
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• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
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• 125000001475 halogen functional group Chemical group 0.000 claims 5
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• LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims 1
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