JP2007525521A

JP2007525521A - Ｃ型肝炎ウイルスｎｓ３セリンプロテアーゼのインヒビターとしてのシクロブテンジオン基含有化合物

Ｃ型肝炎ウイルスｎｓ３セリンプロテアーゼのインヒビターとしてのシクロブテンジオン基含有化合物 Download PDF

Info

Publication number: JP2007525521A
Authority: JP; Japan
Prior art keywords: compound; group; alkyl; hcv; membered
Prior art date: 2004-02-27
Legal status : Pending

Application number

JP2007501006A

Other languages

English (en)

Japanese (ja)

Other versions

JP2007525521A5 (fr

Inventor

ステファンエル．ボーゲン，

ウェイドンパン，

スメイルアン，

エフ．ジョージヌジョロジ，

Current Assignee

Merck Sharp and Dohme LLC

Original Assignee

Schering Corp

Priority date

2004-02-27

Filing date

2005-02-24

Publication date

2007-09-06

2005-02-24 Application filed by Schering Corp filed Critical Schering Corp

2007-09-06 Publication of JP2007525521A publication Critical patent/JP2007525521A/ja

2008-03-21 Publication of JP2007525521A5 publication Critical patent/JP2007525521A5/ja

Status Pending legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 168
239000003112 inhibitor Substances 0.000 title description 21
108010022999 Serine Proteases Proteins 0.000 title description 12
102000012479 Serine Proteases Human genes 0.000 title description 12
RGBVWCQARBEPPW-UHFFFAOYSA-N cyclobut-3-ene-1,2-dione Chemical compound O=C1C=CC1=O RGBVWCQARBEPPW-UHFFFAOYSA-N 0.000 title description 2
108700012707 hepatitis C virus NS3 Proteins 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 115
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 29
108091005804 Peptidases Proteins 0.000 claims abstract description 26
239000004365 Protease Substances 0.000 claims abstract description 26
108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 20
102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 15
229920001184 polypeptide Polymers 0.000 claims abstract description 12
208000005176 Hepatitis C Diseases 0.000 claims abstract description 10
208000024891 symptom Diseases 0.000 claims abstract description 7
230000002401 inhibitory effect Effects 0.000 claims abstract description 6
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 7
241000711549 Hepacivirus C Species 0.000 claims description 76
-1 heteroalkenyl Chemical group 0.000 claims description 62
125000000217 alkyl group Chemical group 0.000 claims description 59
125000003118 aryl group Chemical group 0.000 claims description 33
150000003839 salts Chemical class 0.000 claims description 32
125000000753 cycloalkyl group Chemical group 0.000 claims description 29
125000000623 heterocyclic group Chemical group 0.000 claims description 27
125000001072 heteroaryl group Chemical group 0.000 claims description 26
239000012453 solvate Substances 0.000 claims description 19
125000000304 alkynyl group Chemical group 0.000 claims description 18
229940079322 interferon Drugs 0.000 claims description 18
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
125000003342 alkenyl group Chemical group 0.000 claims description 16
150000002148 esters Chemical class 0.000 claims description 16
239000003814 drug Substances 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 15
125000003710 aryl alkyl group Chemical group 0.000 claims description 14
108010050904 Interferons Proteins 0.000 claims description 13
102000014150 Interferons Human genes 0.000 claims description 13
239000004480 active ingredient Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
238000011282 treatment Methods 0.000 claims description 11
125000004404 heteroalkyl group Chemical group 0.000 claims description 9
125000003545 alkoxy group Chemical group 0.000 claims description 8
230000000694 effects Effects 0.000 claims description 8
125000002877 alkyl aryl group Chemical group 0.000 claims description 7
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229910052799 carbon Inorganic materials 0.000 claims description 7
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 7
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
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238000012545 processing Methods 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
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125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical group N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 claims description 4
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
125000005110 aryl thio group Chemical group 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
229910002091 carbon monoxide Inorganic materials 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
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HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 claims description 4
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
RGICCULPCWNRAB-UHFFFAOYSA-N 2-[2-(2-hexoxyethoxy)ethoxy]ethanol Chemical compound CCCCCCOCCOCCOCCO RGICCULPCWNRAB-UHFFFAOYSA-N 0.000 claims description 2
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229930194542 Keto Natural products 0.000 claims description 2
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
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125000000468 ketone group Chemical group 0.000 claims description 2
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