TWI400072B - Ｃ型肝炎病毒抑制劑 - Google Patents

Ｃ型肝炎病毒抑制劑 Download PDF

Info

Publication number: TWI400072B
Authority: TW; Taiwan
Prior art keywords: imidazol; methyl; tetrahydropyrrolyl; biphenyl; hcv
Prior art date: 2006-08-11

Application number

TW097105080A

Other languages

English (en)

Chinese (zh)

Other versions

TW200934486A (en

Inventor

巴查德卡羅

貝雷碼馬柯南

戴昂丹尼爾Ｈ.

古德安德魯Ｃ.

古瑞奇傑森

詹姆斯可林Ａ.

拉威瑞可

洛裴茲歐瑪Ｄ.

馬特爾阿連

米恩威爾尼可拉斯Ａ

恩古顏范恩Ｎ

李洛明傑佛瑞

魯迪格艾德華Ｈ.

辛德勞倫斯Ｂ.

聖羅倫丹尼斯Ｒ.

楊福康

蘭利大衛Ｒ.

王剛

哈曼勞倫斯Ｇ.

Original Assignee

必治妥美雅史谷比公司

Priority date (The priority date 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 date listed.)

2006-08-11

Filing date

2008-02-13

Publication date

2013-07-01

2008-02-13 Application filed by 必治妥美雅史谷比公司 filed Critical 必治妥美雅史谷比公司

2009-08-16 Publication of TW200934486A publication Critical patent/TW200934486A/zh

2013-07-01 Application granted granted Critical

2013-07-01 Publication of TWI400072B publication Critical patent/TWI400072B/zh

Links

239000003112 inhibitor Substances 0.000 title claims 2
241000711549 Hepacivirus C Species 0.000 title description 42
239000000203 mixture Substances 0.000 claims description 178
150000001875 compounds Chemical class 0.000 claims description 160
-1 4,4'-biphenyldiyl Chemical group 0.000 claims description 147
229910052739 hydrogen Inorganic materials 0.000 claims description 74
150000003839 salts Chemical class 0.000 claims description 52
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 51
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 45
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 42
229910052757 nitrogen Inorganic materials 0.000 claims description 32
239000001257 hydrogen Substances 0.000 claims description 25
GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
239000002253 acid Substances 0.000 claims description 23
108010047761 Interferon-alpha Proteins 0.000 claims description 21
102000006992 Interferon-alpha Human genes 0.000 claims description 21
230000000694 effects Effects 0.000 claims description 20
102000014150 Interferons Human genes 0.000 claims description 18
108010050904 Interferons Proteins 0.000 claims description 18
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239000008194 pharmaceutical composition Substances 0.000 claims description 16
239000002777 nucleoside Substances 0.000 claims description 14
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239000003795 chemical substances by application Substances 0.000 claims description 12
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DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 11
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108010006035 Metalloproteases Proteins 0.000 claims description 7
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NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 7
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238000011161 development Methods 0.000 claims description 6
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
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125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 4
XLSZMDLNRCVEIJ-UHFFFAOYSA-N 4-methylimidazole Chemical compound CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 claims 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 2
PQJFJRGZSZKPTF-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O.COC(N)=O PQJFJRGZSZKPTF-UHFFFAOYSA-N 0.000 claims 2
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BUMSXOMPQQXECH-QCHLLITLSA-N (2s)-3-methyl-1-[(1r,3s,5r)-3-[5-[4-[4-[2-[(1r,3s,5r)-2-[(2s)-3-methyl-2-(pyrimidin-2-ylamino)butanoyl]-2-azabicyclo[3.1.0]hexan-3-yl]-1h-imidazol-5-yl]phenyl]phenyl]-1h-imidazol-2-yl]-2-azabicyclo[3.1.0]hexan-2-yl]-2-(pyrimidin-2-ylamino)butan-1-one Chemical compound N([C@@H](C(C)C)C(=O)N1[C@@H](C[C@H]2C[C@H]21)C=1NC=C(N=1)C=1C=CC(=CC=1)C=1C=CC(=CC=1)C=1N=C(NC=1)[C@H]1N([C@@H]2C[C@@H]2C1)C(=O)[C@@H](NC=1N=CC=CN=1)C(C)C)C1=NC=CC=N1 BUMSXOMPQQXECH-QCHLLITLSA-N 0.000 claims 1
UMPWFNPLHSVRAN-UHFFFAOYSA-N 2-(diethylamino)-2-phenylacetaldehyde Chemical compound CCN(CC)C(C=O)C1=CC=CC=C1 UMPWFNPLHSVRAN-UHFFFAOYSA-N 0.000 claims 1
VKYKDJZVZBURQF-UHFFFAOYSA-N 2-hydroxy-3-methylbutanal Chemical compound CC(C)C(O)C=O VKYKDJZVZBURQF-UHFFFAOYSA-N 0.000 claims 1
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108010020056 Hydrogenase Proteins 0.000 claims 1
GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 claims 1
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims 1
230000002378 acidificating effect Effects 0.000 claims 1
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125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims 1
125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims 1
108700027921 interferon tau Proteins 0.000 claims 1
210000001161 mammalian embryo Anatomy 0.000 claims 1
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KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims 1
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DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 183
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ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
229940120293 vaginal suppository Drugs 0.000 description 1
239000006216 vaginal suppository Substances 0.000 description 1
238000010200 validation analysis Methods 0.000 description 1
239000004474 valine Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
210000002845 virion Anatomy 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
239000000230 xanthan gum Substances 0.000 description 1
235000010493 xanthan gum Nutrition 0.000 description 1
229920001285 xanthan gum Polymers 0.000 description 1
229940082509 xanthan gum Drugs 0.000 description 1
229930195724 β-lactose Natural products 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

TW097105080A 2006-08-11 2008-02-13 Ｃ型肝炎病毒抑制劑 TWI400072B (zh)

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EP2550278A1 (en) *	2010-03-24	2013-01-30	Vertex Pharmaceuticals Incorporated	Analogues for the treatment or prevention of flavivirus infections
WO2012061552A1 (en) *	2010-11-04	2012-05-10	Theravance, Inc.	Novel inhibitors of hepatitis c virus
PT2730564T (pt) *	2010-11-19	2018-07-24	Ligand Pharm Inc	Aminas heterocíclicas e suas utilizações
US8552047B2 (en) *	2011-02-07	2013-10-08	Bristol-Myers Squibb Company	Hepatitis C virus inhibitors
US9546160B2 (en) *	2011-05-12	2017-01-17	Bristol-Myers Squibb Company	Hepatitis C virus inhibitors
US9212168B2 (en) *	2011-11-03	2015-12-15	Theravance Biopharma R&D Ip, Llc	Hepatitis C virus inhibitors
CN103304551B (zh) *	2012-03-14	2017-06-13	北京凯因科技股份有限公司	丙肝聚合酶抑制剂
JP6333372B2 (ja) *	2013-07-09	2018-05-30	ブリストル−マイヤーズスクイブカンパニーＢｒｉｓｔｏｌ−ＭｙｅｒｓＳｑｕｉｂｂＣｏｍｐａｎｙ	Ｃ型肝炎ウイルス阻害剤の組み合わせ
CN105073740B (zh) *	2014-01-21	2017-06-27	杭州普晒医药科技有限公司	一种化合物的盐及晶型或无定型物、其制备方法、含有它们的药物组合物和用途
CN108084172A (zh) *	2014-02-21	2018-05-29	常州寅盛药业有限公司	抗丙肝病毒化合物
WO2015184644A1 (zh) *	2014-06-06	2015-12-10	爱博新药研发(上海)有限公司	抑制丙肝病毒的化合物、药物组合物及其应用
CN105524049B (zh) *	2014-09-28	2018-11-06	正大天晴药业集团股份有限公司	氘代的丙型肝炎病毒ns5a蛋白抑制剂
CN104546780A (zh) *	2014-12-12	2015-04-29	安徽一灵药业有限公司	一种达卡他韦薄膜包衣片制剂及其制备方法
WO2017076358A1 (zh) *	2015-11-06	2017-05-11	苏州晶云药物科技有限公司	咪唑基联苯基化合物盐的新晶型及其制备方法
CN106496199A (zh) *	2016-10-19	2017-03-15	上海博志研新药物技术有限公司	达卡他韦及其中间体的制备方法
US10766912B2 (en)	2017-03-22	2020-09-08	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	Silicon-containing compound for resistance to hepatitis C virus infection
CN115448892B (zh) *	2022-09-19	2023-07-07	郑州铁路职业技术学院	一种苯并噻二唑杂环化合物的合成方法

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AR108411A2 (es)	2018-08-15
TW200934486A (en)	2009-08-16
CN101558059B (zh)	2014-12-03
CN101558059A (zh)	2009-10-14

Publication	Publication Date	Title
TWI400072B (zh)	2013-07-01	Ｃ型肝炎病毒抑制劑
TWI432426B (zh)	2014-04-01	Ｃ型肝炎病毒抑制劑
JP5312486B2 (ja)	2013-10-09	Ｃ型肝炎ウイルス阻害剤
JP5232148B2 (ja)	2013-07-10	Ｃ型肝炎ウイルス阻害剤
JP5314053B2 (ja)	2013-10-16	Ｃ型肝炎ウイルス阻害剤
JP5306203B2 (ja)	2013-10-02	Ｃ型肝炎ウイルス阻害剤
US7741347B2 (en)	2010-06-22	Hepatitis C virus inhibitors
US8846023B2 (en)	2014-09-30	Hepatitis C virus inhibitors
HK1126486B (en)	2014-08-15	Hepatitis c virus inhibitors

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