BRPI0716804A2 - Derivados de dibenzofuranco como inibidores de pde-4 e pde-10 - Google Patents

Info

Publication number

BRPI0716804A2

BRPI0716804A2 BRPI0716804-7A2A BRPI0716804A BRPI0716804A2 BR PI0716804 A2 BRPI0716804 A2 BR PI0716804A2 BR PI0716804 A BRPI0716804 A BR PI0716804A BR PI0716804 A2 BRPI0716804 A2 BR PI0716804A2

Authority

BR

Brazil

Prior art keywords

formula

furan

compound according

methoxydibenzo

compound

Prior art date

2006-09-11

Links

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• 239000003112 inhibitor Substances 0.000 title claims description 18
• TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical class C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 title description 6
• 101100296719 Caenorhabditis elegans pde-4 gene Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 185
• -1 cyano, carboxy Chemical group 0.000 claims description 107
• 238000006243 chemical reaction Methods 0.000 claims description 73
• 239000000243 solution Substances 0.000 claims description 47
• 229920006395 saturated elastomer Polymers 0.000 claims description 36
• 239000000203 mixture Substances 0.000 claims description 35
• 125000000217 alkyl group Chemical group 0.000 claims description 32
• 239000001257 hydrogen Substances 0.000 claims description 31
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 238000000034 method Methods 0.000 claims description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
• 125000005842 heteroatom Chemical group 0.000 claims description 23
• 150000003839 salts Chemical class 0.000 claims description 21
• 125000003118 aryl group Chemical group 0.000 claims description 20
• 150000002431 hydrogen Chemical group 0.000 claims description 20
• 208000006673 asthma Diseases 0.000 claims description 19
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
• 125000004122 cyclic group Chemical group 0.000 claims description 18
• 229910052760 oxygen Inorganic materials 0.000 claims description 18
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 17
• 229910052717 sulfur Inorganic materials 0.000 claims description 17
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 16
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• 125000001072 heteroaryl group Chemical group 0.000 claims description 16
• 125000000623 heterocyclic group Chemical group 0.000 claims description 16
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 16
• 230000004968 inflammatory condition Effects 0.000 claims description 14
• 125000003545 alkoxy group Chemical group 0.000 claims description 13
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
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• 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 10
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• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
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• DEOOIBVIBRHOOO-UHFFFAOYSA-N 1-(4-methoxydibenzofuran-1-yl)-4-oxocyclohexane-1-carbonitrile Chemical compound O1C2=CC=CC=C2C2=C1C(OC)=CC=C2C1(C#N)CCC(=O)CC1 DEOOIBVIBRHOOO-UHFFFAOYSA-N 0.000 claims description 6
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• MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 3
• VXLSJDHGLZNWCZ-UHFFFAOYSA-N 2-amino-6-(4-methoxydibenzofuran-1-yl)-7,8-dihydro-5h-quinazoline-6-carbonitrile Chemical compound C1CC2=NC(N)=NC=C2CC1(C#N)C1=CC=C(OC)C2=C1C1=CC=CC=C1O2 VXLSJDHGLZNWCZ-UHFFFAOYSA-N 0.000 claims description 3
• MSYGAHOHLUJIKV-UHFFFAOYSA-N 3,5-dimethyl-1-(3-nitrophenyl)-1h-pyrazole-4-carboxylic acid ethyl ester Chemical compound CC1=C(C(=O)OCC)C(C)=NN1C1=CC=CC([N+]([O-])=O)=C1 MSYGAHOHLUJIKV-UHFFFAOYSA-N 0.000 claims description 3
• JAARYBGJMQKFRG-UHFFFAOYSA-N 5-(4-methoxydibenzofuran-1-yl)-1,4,6,7-tetrahydroindazole-5-carbonitrile Chemical compound C1CC2=NNC=C2CC1(C#N)C1=CC=C(OC)C2=C1C1=CC=CC=C1O2 JAARYBGJMQKFRG-UHFFFAOYSA-N 0.000 claims description 3
• LWSHOUNKKLOUGA-UHFFFAOYSA-N 5-(4-methoxydibenzofuran-1-yl)-1-phenyl-6,7-dihydro-4h-indazole-5-carbonitrile Chemical compound C1=2C3=CC=CC=C3OC=2C(OC)=CC=C1C(C1)(C#N)CCC2=C1C=NN2C1=CC=CC=C1 LWSHOUNKKLOUGA-UHFFFAOYSA-N 0.000 claims description 3
• YOIULBPZMKZVOO-UHFFFAOYSA-N 5-(4-methoxydibenzofuran-1-yl)-2-phenyl-6,7-dihydro-4h-indazole-5-carbonitrile Chemical compound C1=2C3=CC=CC=C3OC=2C(OC)=CC=C1C(CC1=C2)(C#N)CCC1=NN2C1=CC=CC=C1 YOIULBPZMKZVOO-UHFFFAOYSA-N 0.000 claims description 3
• VSFHCICWCLDERG-UHFFFAOYSA-N 6-(4-methoxydibenzofuran-1-yl)-7,8-dihydro-5h-quinazoline-6-carbonitrile Chemical compound C1CC2=NC=NC=C2CC1(C#N)C1=CC=C(OC)C2=C1C1=CC=CC=C1O2 VSFHCICWCLDERG-UHFFFAOYSA-N 0.000 claims description 3
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• QIZKODSPPKGICU-UHFFFAOYSA-N 5-(4-ethoxydibenzofuran-1-yl)-6,7-dihydro-4h-2,1-benzoxazole-5-carbonitrile Chemical compound C1CC2=NOC=C2CC1(C#N)C1=CC=C(OCC)C2=C1C1=CC=CC=C1O2 QIZKODSPPKGICU-UHFFFAOYSA-N 0.000 claims description 2
• LTLBUSHXQYASQU-UHFFFAOYSA-N 6-(4-methoxydibenzofuran-1-yl)-4-oxo-1,5,7,8-tetrahydroquinazoline-6-carbonitrile Chemical compound N1=CNC(=O)C(C2)=C1CCC2(C#N)C1=CC=C(OC)C2=C1C1=CC=CC=C1O2 LTLBUSHXQYASQU-UHFFFAOYSA-N 0.000 claims description 2
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