JP2014510746A5 - - Google Patents
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- JP2014510746A5 JP2014510746A5 JP2014501719A JP2014501719A JP2014510746A5 JP 2014510746 A5 JP2014510746 A5 JP 2014510746A5 JP 2014501719 A JP2014501719 A JP 2014501719A JP 2014501719 A JP2014501719 A JP 2014501719A JP 2014510746 A5 JP2014510746 A5 JP 2014510746A5
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- JP
- Japan
- Prior art keywords
- compound
- formula
- compound according
- pharmaceutical composition
- hcv
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 4
- 208000005721 HIV Infections Diseases 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 201000001820 human immunodeficiency virus infectious disease Diseases 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 206010047461 Viral infection Diseases 0.000 claims 2
- 208000001756 Virus Disease Diseases 0.000 claims 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims 2
- 229940121363 anti-inflammatory agents Drugs 0.000 claims 2
- 239000003018 immunosuppressive agent Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 239000011780 sodium chloride Substances 0.000 claims 2
- 230000017613 viral reproduction Effects 0.000 claims 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- -1 aldehyde macrocycle Chemical class 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000000468 ketone group Chemical group 0.000 claims 1
- 230000002829 reduced Effects 0.000 description 10
- 230000036499 Half live Effects 0.000 description 3
- 230000036740 Metabolism Effects 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 239000000134 cyclophilin inhibitor Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 230000035786 metabolism Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 102000003849 Cytochrome P450 Human genes 0.000 description 2
- 108050008488 Cytochrome P450 Proteins 0.000 description 2
- 108009000164 Glucuronidation Proteins 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000001506 immunosuppresive Effects 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OLROWHGDTNFZBH-XEMWPYQTSA-N Alisporivir Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(CC)C(=O)[C@@H](C)N(C)C1=O OLROWHGDTNFZBH-XEMWPYQTSA-N 0.000 description 1
- LBKDOKHAKPIWCL-NSVPLCITSA-N CC(C)[C@@H](C(N[C@](C1)(C1C(CC(O)=C1)C=C1F)C(N(CCC1)N[C@@H]1C(O[C@@H](C/C=C/C=C/[C@@H]([C@H](C)[C@H]([C@H]1CCC(C)=O)O)O)/C(/C)=C/C=O)=O)=O)=O)NC1=O Chemical compound CC(C)[C@@H](C(N[C@](C1)(C1C(CC(O)=C1)C=C1F)C(N(CCC1)N[C@@H]1C(O[C@@H](C/C=C/C=C/[C@@H]([C@H](C)[C@H]([C@H]1CCC(C)=O)O)O)/C(/C)=C/C=O)=O)=O)=O)NC1=O LBKDOKHAKPIWCL-NSVPLCITSA-N 0.000 description 1
- 102100004057 CYP3A4 Human genes 0.000 description 1
- 101710007540 CYP3A4 Proteins 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 206010020578 Hyperbilirubinaemia Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 210000004185 Liver Anatomy 0.000 description 1
- 208000003627 Muscular Dystrophy Diseases 0.000 description 1
- 208000010125 Myocardial Infarction Diseases 0.000 description 1
- 230000035536 Oral bioavailability Effects 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000003110 anti-inflammatory Effects 0.000 description 1
- 201000004532 bilirubin metabolic disease Diseases 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 201000009910 diseases by infectious agent Diseases 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003228 microsomal Effects 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 230000036220 oral bioavailability Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 210000000056 organs Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- BZKBCQXYZZXSCO-UHFFFAOYSA-N sodium hydride Inorganic materials [H-].[Na+] BZKBCQXYZZXSCO-UHFFFAOYSA-N 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000003612 virological Effects 0.000 description 1
Description
したがって、特にHCV感染の治療に効用を持ち得るが、HIV感染、筋ジストロフィー、若しくは心筋梗塞後の回復の促進などの、シクロフィリンの阻害が有用になり得る他の疾病分野、又は、免疫抑制若しくは抗炎症効果が有用である他の疾病分野の治療においても効用を持ち得る、新規のシクロフィリン阻害剤を特定する必要が未だ存在する。好ましくは、そのようなシクロフィリン阻害剤は、下記の性質の1つ以上を含む、現在利用可能なシクロフィリン阻害剤よりも向上した性質を有する:おそらくはP450代謝の低減及び/又はグルクロン酸抱合の低減による、より長い半減期若しくは増大した経口バイオアベイラビリティ、向上した水への溶解度、HCVに対する向上した効力、低減された毒性(肝毒性を含む)、標的臓器(例えば、HCVの場合は肝臓)に対する高い曝露及び/若しくは長い半減期(投薬頻度の減少を可能にする)などの向上した薬理プロファイル、低減されたレベルのCYP3A4の代謝及び阻害並びに低減された(Pgp)阻害(より容易な多剤組み合わせを可能にする)によるなどの低減された薬物-薬物相互作用、高ビリルビン血症の機会低下をもたらす、MRP2への低い結合などの向上した副作用プロファイル、より低い免疫抑制効果、耐性ウイルス種、特にCsA及びCsAアナログ(例えば、DEBIO-025)耐性ウイルス種に対する向上した活性、及びより高い治療(及び/又は選択性)指数。本発明は、上記の性質の1つ以上を有し得る新規のサングリフェリンアナログを開示する。特に、本発明は、新規の変異合成(mutasynthetic)サングリフェリンアナログを開示し、該サングリフェリンアナログは、例えば、増大したミクロソーム半減期により示されるとおりP450による代謝又はグルクロン酸抱合が低減されており、かつ/又は、例えば、低いレプリコンEC50により示されるとおりHCVに対する向上した効力を有すると予測される。
Claims (11)
- 固体結晶形である、請求項1記載の化合物。
- 形態I結晶性多形体の形態にある、請求項2記載の化合物。
- 医薬として使用するための、請求項1〜3のいずれか1項記載の化合物。
- HCV若しくはHIV感染などのウイルス感染症を治療するための医薬として、又は免疫抑制剤若しくは抗炎症剤として使用するための、請求項1〜3のいずれか1項記載の化合物。
- 請求項1〜3のいずれか1項記載の化合物を含む、医薬組成物。
- 請求項1〜3のいずれか1項記載の化合物を含み、さらに第2の又は二次の有効成分を含む、医薬組成物。
- HCV若しくはHIV感染などのウイルス感染症の治療のための、又は免疫抑制剤若しくは抗炎症剤として使用するための医薬組成物であって、請求項1〜3のいずれか1項記載の化合物を含む、前記医薬組成物。
- 請求項3記載の形態I結晶性多形体の形態の式(I)の化合物を製造する方法であって、式(I)の化合物をメチルイソブチルケトンから結晶化させる工程を含む、前記方法。
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1105293.3A GB201105293D0 (en) | 2011-03-29 | 2011-03-29 | Novel compounds and methods for their production |
GB1105293.3 | 2011-03-29 | ||
GB1113629.8 | 2011-08-08 | ||
GBGB1113629.8A GB201113629D0 (en) | 2011-08-08 | 2011-08-08 | Novel compounds and methods for their production |
GBGB1202060.8A GB201202060D0 (en) | 2012-02-07 | 2012-02-07 | Novel compounds and methods for their production |
GB1202060.8 | 2012-02-07 | ||
PCT/GB2012/050700 WO2012131371A1 (en) | 2011-03-29 | 2012-03-29 | Macrocyclic compound and methods for its production |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2014510746A JP2014510746A (ja) | 2014-05-01 |
JP2014510746A5 true JP2014510746A5 (ja) | 2015-05-14 |
JP6118792B2 JP6118792B2 (ja) | 2017-04-26 |
Family
ID=46001313
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014501719A Expired - Fee Related JP6118792B2 (ja) | 2011-03-29 | 2012-03-29 | マクロ環状化合物及びその製造方法 |
JP2014501720A Active JP6118793B2 (ja) | 2011-03-29 | 2012-03-29 | マクロ環状化合物及びそれらの製造方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014501720A Active JP6118793B2 (ja) | 2011-03-29 | 2012-03-29 | マクロ環状化合物及びそれらの製造方法 |
Country Status (29)
Country | Link |
---|---|
US (2) | US9139613B2 (ja) |
EP (2) | EP2691413B1 (ja) |
JP (2) | JP6118792B2 (ja) |
KR (2) | KR101911484B1 (ja) |
CN (3) | CN103619869B (ja) |
AR (1) | AR085724A1 (ja) |
AU (2) | AU2012235961B2 (ja) |
BR (2) | BR112013024974A2 (ja) |
CA (2) | CA2830827C (ja) |
CL (2) | CL2013002739A1 (ja) |
CY (2) | CY1116318T1 (ja) |
DK (2) | DK2691412T3 (ja) |
EA (2) | EA023907B1 (ja) |
ES (2) | ES2533437T3 (ja) |
HK (2) | HK1189236A1 (ja) |
HR (2) | HRP20150187T1 (ja) |
IL (2) | IL228509B (ja) |
JO (1) | JO3063B1 (ja) |
MX (2) | MX345351B (ja) |
MY (2) | MY170637A (ja) |
PL (2) | PL2691412T3 (ja) |
PT (2) | PT2691413E (ja) |
RS (2) | RS53963B1 (ja) |
SG (2) | SG193569A1 (ja) |
SI (2) | SI2691413T1 (ja) |
TW (1) | TWI525098B (ja) |
UY (1) | UY33993A (ja) |
WO (2) | WO2012131377A1 (ja) |
ZA (2) | ZA201307149B (ja) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR112012019866A8 (pt) | 2010-02-09 | 2017-12-26 | Biotica Tech Limited | Composto, uso do mesmo, composição farmacêutica, e, processo para preparar um composto |
JO3063B1 (ar) * | 2011-03-29 | 2017-03-15 | Neurovive Pharmaceutical Ab | مركب مبتكر وطرق لانتاجه |
CN103130734A (zh) * | 2011-12-01 | 2013-06-05 | 上海药明康德新药开发有限公司 | 一种合成1,2-吗啉盐酸盐的方法 |
CN105695541B (zh) * | 2016-03-10 | 2019-03-15 | 苏州华赛生物工程技术有限公司 | 一种抗生素nvp018中间体的分离纯化方法 |
KR20180036522A (ko) | 2016-09-30 | 2018-04-09 | (주)나노믹스 | 스틸벤 유도체 및 그 제조 방법 |
AU2017361856A1 (en) * | 2016-11-18 | 2019-05-23 | Neurovive Pharmaceutical Ab | Use of sanglifehrin macrocyclic analogues as anticancer compounds |
CN112410353B (zh) * | 2019-08-23 | 2023-01-24 | 上海医药工业研究院 | 一种fkbS基因、含其的基因工程菌及其制备方法和用途 |
CN115028681B (zh) * | 2022-08-11 | 2022-11-15 | 中国科学院微生物研究所 | 一种降解亲环素a的嵌合体化合物及其制备方法与应用 |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR006514A1 (es) | 1995-07-04 | 1999-09-08 | Sandoz Ag | Un macrolido, sus usos, un proceso para producirlo, un aislado biologicamente puro capaz de producirlo, y una composicion farmaceutica quelo comprende |
US6124453A (en) | 1995-07-04 | 2000-09-26 | Novartis Ag | Macrolides |
CN101242842A (zh) * | 2005-06-17 | 2008-08-13 | 诺瓦提斯公司 | Sanglifehrin在hcv中的用途 |
MX2009007045A (es) | 2007-01-04 | 2009-10-07 | Debiopharm Sa | Ciclosporina no inmunosupresora para el tratamiento de distrofia muscular congenita de ullrich. |
US8962329B2 (en) | 2008-09-24 | 2015-02-24 | Shanghai Institute Of Organic Chemistry, Chinese Academy Of Sciences | Gene cluster |
CN101691575B (zh) * | 2008-09-24 | 2013-06-05 | 中国科学院上海有机化学研究所 | 一种萨菲菌素的生物合成基因簇 |
BR112012019866A8 (pt) * | 2010-02-09 | 2017-12-26 | Biotica Tech Limited | Composto, uso do mesmo, composição farmacêutica, e, processo para preparar um composto |
WO2011098808A1 (en) | 2010-02-09 | 2011-08-18 | Biotica Technology Limited | Sanglifehrin based compounds |
WO2011098805A1 (en) * | 2010-02-09 | 2011-08-18 | Biotica Technology Limited | Sanglifehrin based compounds |
EA022408B1 (ru) * | 2010-12-20 | 2015-12-30 | Ньюроувив Фармасьютикал Аб | Производные санглиферина и способы их получения |
JO3063B1 (ar) * | 2011-03-29 | 2017-03-15 | Neurovive Pharmaceutical Ab | مركب مبتكر وطرق لانتاجه |
-
2012
- 2012-03-12 JO JOP/2012/0053A patent/JO3063B1/ar active
- 2012-03-28 TW TW101110673A patent/TWI525098B/zh not_active IP Right Cessation
- 2012-03-28 AR ARP120101043A patent/AR085724A1/es unknown
- 2012-03-29 CN CN201280026190.3A patent/CN103619869B/zh not_active Expired - Fee Related
- 2012-03-29 AU AU2012235961A patent/AU2012235961B2/en not_active Ceased
- 2012-03-29 WO PCT/GB2012/050707 patent/WO2012131377A1/en active Application Filing
- 2012-03-29 AU AU2012235880A patent/AU2012235880B2/en not_active Ceased
- 2012-03-29 EA EA201391396A patent/EA023907B1/ru not_active IP Right Cessation
- 2012-03-29 US US14/006,341 patent/US9139613B2/en active Active
- 2012-03-29 BR BR112013024974A patent/BR112013024974A2/pt not_active Application Discontinuation
- 2012-03-29 ES ES12716538.9T patent/ES2533437T3/es active Active
- 2012-03-29 EA EA201391399A patent/EA023848B1/ru not_active IP Right Cessation
- 2012-03-29 PL PL12716538T patent/PL2691412T3/pl unknown
- 2012-03-29 MY MYPI2013701788A patent/MY170637A/en unknown
- 2012-03-29 PT PT127165397T patent/PT2691413E/pt unknown
- 2012-03-29 JP JP2014501719A patent/JP6118792B2/ja not_active Expired - Fee Related
- 2012-03-29 EP EP12716539.7A patent/EP2691413B1/en active Active
- 2012-03-29 SI SI201230146T patent/SI2691413T1/sl unknown
- 2012-03-29 KR KR1020137028095A patent/KR101911484B1/ko active IP Right Grant
- 2012-03-29 US US13/433,944 patent/US9090657B2/en active Active
- 2012-03-29 RS RS20150161A patent/RS53963B1/en unknown
- 2012-03-29 MX MX2013011043A patent/MX345351B/es active IP Right Grant
- 2012-03-29 MY MYPI2013701789A patent/MY170618A/en unknown
- 2012-03-29 JP JP2014501720A patent/JP6118793B2/ja active Active
- 2012-03-29 CN CN201611126823.4A patent/CN107417766A/zh active Pending
- 2012-03-29 ES ES12716539.7T patent/ES2533438T3/es active Active
- 2012-03-29 CA CA2830827A patent/CA2830827C/en not_active Expired - Fee Related
- 2012-03-29 CA CA2830831A patent/CA2830831C/en not_active Expired - Fee Related
- 2012-03-29 PT PT127165389T patent/PT2691412E/pt unknown
- 2012-03-29 RS RS20150162A patent/RS53964B1/en unknown
- 2012-03-29 SI SI201230145T patent/SI2691412T1/sl unknown
- 2012-03-29 SG SG2013070974A patent/SG193569A1/en unknown
- 2012-03-29 UY UY0001033993A patent/UY33993A/es not_active Application Discontinuation
- 2012-03-29 SG SG2013070966A patent/SG193568A1/en unknown
- 2012-03-29 PL PL12716539T patent/PL2691413T3/pl unknown
- 2012-03-29 CN CN201280026793.3A patent/CN103635484B/zh active Active
- 2012-03-29 DK DK12716538T patent/DK2691412T3/en active
- 2012-03-29 BR BR112013024965A patent/BR112013024965A2/pt not_active Application Discontinuation
- 2012-03-29 WO PCT/GB2012/050700 patent/WO2012131371A1/en active Application Filing
- 2012-03-29 EP EP12716538.9A patent/EP2691412B1/en active Active
- 2012-03-29 MX MX2013011051A patent/MX345352B/es active IP Right Grant
- 2012-03-29 DK DK12716539T patent/DK2691413T3/en active
- 2012-03-29 KR KR1020137027773A patent/KR101868084B1/ko active IP Right Grant
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2013
- 2013-09-17 IL IL228509A patent/IL228509B/en active IP Right Grant
- 2013-09-17 IL IL228508A patent/IL228508B/en active IP Right Grant
- 2013-09-23 ZA ZA2013/07149A patent/ZA201307149B/en unknown
- 2013-09-25 CL CL2013002739A patent/CL2013002739A1/es unknown
- 2013-09-25 CL CL2013002740A patent/CL2013002740A1/es unknown
- 2013-09-26 ZA ZA2013/07231A patent/ZA201307231B/en unknown
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2014
- 2014-02-13 HK HK14101335.6A patent/HK1189236A1/xx not_active IP Right Cessation
- 2014-02-13 HK HK14101336.5A patent/HK1189237A1/xx not_active IP Right Cessation
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2015
- 2015-02-17 HR HRP20150187TT patent/HRP20150187T1/hr unknown
- 2015-02-17 HR HRP20150184TT patent/HRP20150184T1/hr unknown
- 2015-02-27 CY CY20151100207T patent/CY1116318T1/el unknown
- 2015-03-06 CY CY20151100236T patent/CY1116186T1/el unknown
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