JP2010511728A - Ｉｌ−８受容体アンタゴニスト - Google Patents

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Publication number

JP2010511728A

JP2010511728A JP2009540442A JP2009540442A JP2010511728A JP 2010511728 A JP2010511728 A JP 2010511728A JP 2009540442 A JP2009540442 A JP 2009540442A JP 2009540442 A JP2009540442 A JP 2009540442A JP 2010511728 A JP2010511728 A JP 2010511728A

Authority

JP

Japan

Prior art keywords

thiadiazol

sulfonyl

benzamide

fluoro

ethylamino

Prior art date

2006-12-05

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.)

Withdrawn

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• 239000002464 receptor antagonist Substances 0.000 title claims description 6
• 229940044551 receptor antagonist Drugs 0.000 title claims description 6
• 102000010681 interleukin-8 receptors Human genes 0.000 title description 8
• 108010038415 interleukin-8 receptors Proteins 0.000 title description 7
• 150000001875 compounds Chemical class 0.000 claims abstract description 168
• 102000019034 Chemokines Human genes 0.000 claims abstract description 26
• 108010012236 Chemokines Proteins 0.000 claims abstract description 26
• 238000011282 treatment Methods 0.000 claims abstract description 19
• 230000001404 mediated effect Effects 0.000 claims abstract description 12
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 181
• -1 methylpropyl Chemical group 0.000 claims description 138
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 89
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 79
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 67
• 150000003839 salts Chemical class 0.000 claims description 48
• 125000000217 alkyl group Chemical group 0.000 claims description 37
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 33
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 33
• 238000000034 method Methods 0.000 claims description 33
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 32
• 229910052736 halogen Inorganic materials 0.000 claims description 25
• 150000002367 halogens Chemical class 0.000 claims description 25
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 23
• 238000004519 manufacturing process Methods 0.000 claims description 23
• 239000008194 pharmaceutical composition Substances 0.000 claims description 21
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 15
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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
• 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims description 9
• 239000001257 hydrogen Substances 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 8
• 125000006308 propyl amino group Chemical group 0.000 claims description 8
• WBJJWRWZBFYIOL-UHFFFAOYSA-N 5-(ethylsulfamoyl)-2,3-difluoro-n-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]benzamide Chemical compound CCNS(=O)(=O)C1=CC(F)=C(F)C(C(=O)NC=2SC(=NN=2)C=2C=CC(F)=CC=2)=C1 WBJJWRWZBFYIOL-UHFFFAOYSA-N 0.000 claims description 7
• 229910052801 chlorine Inorganic materials 0.000 claims description 7
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• 229910052731 fluorine Inorganic materials 0.000 claims description 7
• 125000001424 substituent group Chemical group 0.000 claims description 7
• CZMBBLFKJWKXON-UHFFFAOYSA-N 2-chloro-n-(5-cyclohexyl-1,3,4-thiadiazol-2-yl)-5-sulfamoylbenzamide Chemical compound NS(=O)(=O)C1=CC=C(Cl)C(C(=O)NC=2SC(=NN=2)C2CCCCC2)=C1 CZMBBLFKJWKXON-UHFFFAOYSA-N 0.000 claims description 6
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• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
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• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
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• AFEMEFAXKSZWOZ-UHFFFAOYSA-N 2,3-dichloro-n-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-5-sulfamoylbenzamide Chemical compound NS(=O)(=O)C1=CC(Cl)=C(Cl)C(C(=O)NC=2SC(=NN=2)C=2C=CC(F)=CC=2)=C1 AFEMEFAXKSZWOZ-UHFFFAOYSA-N 0.000 claims description 5
• SDMYKGWZCNUGDR-UHFFFAOYSA-N 3-chloro-5-(ethylsulfamoyl)-2-fluoro-n-[5-(2-phenylpropan-2-yl)-1,3,4-thiadiazol-2-yl]benzamide Chemical compound CCNS(=O)(=O)C1=CC(Cl)=C(F)C(C(=O)NC=2SC(=NN=2)C(C)(C)C=2C=CC=CC=2)=C1 SDMYKGWZCNUGDR-UHFFFAOYSA-N 0.000 claims description 5
• IHTHRSGOWDLRKO-UHFFFAOYSA-N 5-(ethylsulfamoyl)-2-fluoro-n-[5-(2-phenylpropan-2-yl)-1,3,4-thiadiazol-2-yl]benzamide Chemical compound CCNS(=O)(=O)C1=CC=C(F)C(C(=O)NC=2SC(=NN=2)C(C)(C)C=2C=CC=CC=2)=C1 IHTHRSGOWDLRKO-UHFFFAOYSA-N 0.000 claims description 5
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• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
• IMXYTMQVTROOPF-UHFFFAOYSA-N n-(5-cyclopentyl-1,3,4-thiadiazol-2-yl)-2-fluoro-5-sulfamoylbenzamide Chemical compound NS(=O)(=O)C1=CC=C(F)C(C(=O)NC=2SC(=NN=2)C2CCCC2)=C1 IMXYTMQVTROOPF-UHFFFAOYSA-N 0.000 claims description 5
• KDNIOKSLVIGAAN-UHFFFAOYSA-N 2-sulfamoylbenzoic acid Chemical class NS(=O)(=O)C1=CC=CC=C1C(O)=O KDNIOKSLVIGAAN-UHFFFAOYSA-N 0.000 claims description 4
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• JOFHDDWDYUTOBG-UHFFFAOYSA-N 5-(ethylsulfamoyl)-2-fluoro-n-[5-(2-methyl-1-phenylpropan-2-yl)-1,3,4-thiadiazol-2-yl]benzamide Chemical compound CCNS(=O)(=O)C1=CC=C(F)C(C(=O)NC=2SC(=NN=2)C(C)(C)CC=2C=CC=CC=2)=C1 JOFHDDWDYUTOBG-UHFFFAOYSA-N 0.000 claims description 4
• 125000006309 butyl amino group Chemical group 0.000 claims description 4
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• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 150000002431 hydrogen Chemical class 0.000 claims description 4
• NSHYKZOFKZRXMU-UHFFFAOYSA-N n-(5-cyclopentyl-1,3,4-thiadiazol-2-yl)-5-(ethylsulfamoyl)-2-fluorobenzamide Chemical compound CCNS(=O)(=O)C1=CC=C(F)C(C(=O)NC=2SC(=NN=2)C2CCCC2)=C1 NSHYKZOFKZRXMU-UHFFFAOYSA-N 0.000 claims description 4
• DSQHVORBYGJWAQ-UHFFFAOYSA-N n-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-3-chloro-5-(ethylsulfamoyl)-2-fluorobenzamide Chemical compound CCNS(=O)(=O)C1=CC(Cl)=C(F)C(C(=O)NC=2SC(=NN=2)C(C)(C)C)=C1 DSQHVORBYGJWAQ-UHFFFAOYSA-N 0.000 claims description 4
• FHUNRMPYAHFSOM-UHFFFAOYSA-N n-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5-(ethylsulfamoyl)-2,3-difluorobenzamide Chemical compound CCNS(=O)(=O)C1=CC(F)=C(F)C(C(=O)NC=2SC(=NN=2)C(C)(C)C)=C1 FHUNRMPYAHFSOM-UHFFFAOYSA-N 0.000 claims description 4
• LHPCPOVAUCMAHZ-UHFFFAOYSA-N n-[5-(2-chloro-4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-5-(cyclopropylmethylsulfamoyl)-2-fluorobenzamide Chemical compound ClC1=CC(F)=CC=C1C(S1)=NN=C1NC(=O)C1=CC(S(=O)(=O)NCC2CC2)=CC=C1F LHPCPOVAUCMAHZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 3
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• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• OEAKEHAWPNEVFL-UHFFFAOYSA-N n-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-3-chloro-5-(ethylsulfamoyl)-2,4-difluorobenzamide Chemical compound ClC1=C(F)C(S(=O)(=O)NCC)=CC(C(=O)NC=2SC(=NN=2)C(C)(C)C)=C1F OEAKEHAWPNEVFL-UHFFFAOYSA-N 0.000 claims description 3
• FCZOUUVHBZBFNI-UHFFFAOYSA-N n-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-5-(ethylsulfamoyl)-2-iodobenzamide Chemical compound CCNS(=O)(=O)C1=CC=C(I)C(C(=O)NC=2SC(=NN=2)C(C)(C)C)=C1 FCZOUUVHBZBFNI-UHFFFAOYSA-N 0.000 claims description 3
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• PCGUMWRXTCKSCQ-UHFFFAOYSA-N 5-(cyclopropylsulfamoyl)-2-fluoro-n-[5-(2-methyl-1-phenylpropan-2-yl)-1,3,4-thiadiazol-2-yl]benzamide Chemical compound N=1N=C(NC(=O)C=2C(=CC=C(C=2)S(=O)(=O)NC2CC2)F)SC=1C(C)(C)CC1=CC=CC=C1 PCGUMWRXTCKSCQ-UHFFFAOYSA-N 0.000 claims description 2
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