JP6034960B2 - フッ素置換(3r、4r、5s)−5−グアニジノ−4−アセトアミド−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸、そのエステル及びその使用 - Google Patents
フッ素置換(3r、4r、5s)−5−グアニジノ−4−アセトアミド−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸、そのエステル及びその使用 Download PDFInfo
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- JP6034960B2 JP6034960B2 JP2015512601A JP2015512601A JP6034960B2 JP 6034960 B2 JP6034960 B2 JP 6034960B2 JP 2015512601 A JP2015512601 A JP 2015512601A JP 2015512601 A JP2015512601 A JP 2015512601A JP 6034960 B2 JP6034960 B2 JP 6034960B2
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- Prior art keywords
- cyclohexene
- pentan
- yloxy
- guanidino
- influenza
- Prior art date
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- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/16—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to carbon atoms of rings other than six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
“アルケニル”は、2−7個の炭素原子を含んでなり、そして少なくとも一つの炭素−炭素二重結合を含む脂肪族の直鎖又は分枝鎖の炭化水素鎖を意味する。分枝は、アルケニル直鎖が、一つ又はそれより多い低級アルキル基、例えばメチル、エチル又はプロピルを含有することを意味する。アルキル基は、一つ又はそれより多い置換基、例えば、ハロゲン、アルケニルオキシ、シクロアルキル、シアノ、ヒドロキシ、アルコキシ、カルボキシ、アルキニルオキシ、アラルコキシ、アリールオキシ、アリールオキシカルボニル、アルキルチオ、ヘテロアラルキルオキシ、ヘテロシクリル、ヘテロシクリルアルキルオキシ、アルコキシカルボニル、アラルコキシカルボニル、ヘテロアラルキルオキシカルボニル又はRk aRk+1 aN−、Rk aRk+1 aNC(=O)−、Rk aRk+1 aNSO2−を有することができ、ここで、Rk a及びRk+1 aは、互いに独立にその意味がこの項で定義される“アミノ基置換基”、例えば水素、アルキル、アリール、アラルキル、ヘテロアラルキル、ヘテロシクリル又はヘテロアリールであるか、或いは、Rk a及びRk+1 aは、これらが接続している窒素原子と一緒に、Rk a及びRk+1 aを通る4−7員のヘテロシクリル又はヘテロシクレニルを形成する。好ましいアルキル基は、メチル、トリフルオロメチル、シクロプロピルメチル、シクロペンチルメチル、エチル、n−プロピル、イソ−プロピル、n−ブチル、tert−ブチル、n−ペンチル、3−ペンチル、メトキシエチル、カルボキシメチル、メトキシカルボニルメチル、ベンジルオキシカルボニルメチル及びピリジルメチルオキシカルボニルメチルである。好ましいアルケニル基は、エテニル、プロペニル、n−ブテニル、イソ−ブテニル、3−メチルブタ−2−エニル、n−ペンテニル及びシクロヘキシルブテニルである。
Rは、水素、所望により置換されていてもよいC1−C5アルキル、C2−C5アルケニル又はC2−C5アルキニルであり;
Rfは、CH2F又はCHF2である]
の、以前には未知のフッ素置換(3R、4R、5S)−4−アセトアミド−5−グアニジノ−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸及びそのエステル、並びに医薬的に受容可能なその塩及び/又は水和物である新規なノイラミニダーゼ阻害剤を見出している。
(3R、4R、5S)−5−グアニジノ−4−(2,2−ジフルオロアセトアミド)−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸2−シクロヘキシル1.9(LCMS(M+H):実測値460;計算値459.55、A/California/04/09ウイルスに対してIC50<1nM;
(3R、4R、5S)−5−グアニジノ−4−(2,2−ジフルオロアセトアミド)−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸2−フェニルエチル1.10(LCMS(M+H):実測値454;計算値453.51、A/California/04/09ウイルスに対してIC50<1nM;
(3R、4R、5S)−5−グアニジノ−4−(2,2−ジフルオロアセトアミド)−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸2−ピリジン−3−イルエチル1.11(LCMS(M+H):実測値455;計算値454.49、A/California/04/09ウイルスに対してIC50<1nM);
(3R、4R、5S)−5−グアニジノ−4−(2,2−ジフルオロアセトアミド)−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸2−メトキシエチル1.12(LCMS(M+H):実測値422;計算値421.46、A/California/04/09ウイルスに対してIC50<1nM)。
Claims (8)
- 以下の一般式1:
[式中:
Rは、水素、C1−C3アルキルである]
の(3R、4R、5S)−4−フルオロアセトアミド−5−グアニジノ−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸及びそのエステル、並びに医薬的に受容可能なその塩及び/又は水和物。 - (3R、4R、5S)−5−グアニジノ−4−フルオロアセトアミド−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸 1.1、
(3R、4R、5S)−5−グアニジノ−4−フルオロアセトアミド−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸メチル 1.2、
(3R、4R、5S)−5−グアニジノ−4−フルオロアセトアミド−3−(ペンタン−3−イルオキシ)シクロヘキセン−1−カルボン酸エチル 1.3
である、請求項1に記載の化合物。 - インフルエンザウイルスのノイラミニダーゼに対する活性を示し、そして請求項1、2のいずれか1項に記載の化合物である活性成分。
- 抗ウイルス性活性を示し、そして治療的に有効な量の請求項3に記載の活性成分を含んでなる、インフルエンザ及びインフルエンザウイルスによって起こされる同時疾病を治療することを意図する医薬組成物。
- 医薬的に受容可能な包装に入れられた錠剤、カプセル、又は注射の形態の、請求項4に記載の医薬組成物。
- 有効な量における、インフルエンザウイルスによって起こされた肺炎の治療のための、請求項4又は5のいずれか1項に記載の医薬組成物。
- 請求項1、2のいずれか1項に記載の化合物を含有する、インフルエンザウイルスのノイラミニダーゼ活性の阻害のための医薬。
- 治療的に有効な量の請求項3に記載の活性成分を含有する、インフルエンザウイルスによって起こされるインフルエンザ及び疾病の予防或いは治療のための医薬。
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RU2012119272 | 2012-05-12 | ||
RU2012119272/04A RU2489422C1 (ru) | 2012-05-12 | 2012-05-12 | Фторзамещенные (3r,4r,5s)-5-гуанидино-4-ациламино-3-(пентан-3-илокси)циклогексен-1-карбоновые кислоты, их эфиры и способ применения |
PCT/RU2013/000384 WO2013172741A2 (ru) | 2012-05-12 | 2013-05-07 | Фторзамещенные (3r,4r,5s)-5-гуанидино-4-ациламино-3-(пентан-3-илокси) циклогексен-1-карбоновые кислоты, их эфиры и способ применения |
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CN110272381A (zh) * | 2019-06-19 | 2019-09-24 | 五邑大学 | 含吡啶片段的奥司他韦类似物及其应用 |
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EA201401238A1 (ru) | 2015-02-27 |
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CA2872733C (en) | 2017-03-21 |
EA024765B1 (ru) | 2016-10-31 |
DK2848606T3 (en) | 2017-10-02 |
HUE035856T2 (hu) | 2018-05-28 |
CN104284884A (zh) | 2015-01-14 |
ZA201408026B (en) | 2015-11-25 |
BR112014028362B1 (pt) | 2022-02-01 |
WO2013172741A3 (ru) | 2014-01-09 |
WO2013172741A2 (ru) | 2013-11-21 |
KR101902567B1 (ko) | 2018-09-28 |
AU2013263513B2 (en) | 2016-10-06 |
US8895613B2 (en) | 2014-11-25 |
CN104284884B (zh) | 2016-07-13 |
EP2848606A2 (en) | 2015-03-18 |
RU2489422C1 (ru) | 2013-08-10 |
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JP2015521186A (ja) | 2015-07-27 |
BR112014028362A2 (pt) | 2018-04-17 |
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