JP5193400B2 - 重水素化フェニルプロピオン酸誘導体 - Google Patents
重水素化フェニルプロピオン酸誘導体 Download PDFInfo
- Publication number
- JP5193400B2 JP5193400B2 JP2012544770A JP2012544770A JP5193400B2 JP 5193400 B2 JP5193400 B2 JP 5193400B2 JP 2012544770 A JP2012544770 A JP 2012544770A JP 2012544770 A JP2012544770 A JP 2012544770A JP 5193400 B2 JP5193400 B2 JP 5193400B2
- Authority
- JP
- Japan
- Prior art keywords
- propionic acid
- deuterated
- tetrahydro
- tetramethyl
- naphthalenyl
- Prior art date
- 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.)
- Expired - Fee Related
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/72—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms
- C07C235/74—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/001—Acyclic or carbocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/65—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Nutrition Science (AREA)
- Addiction (AREA)
- Emergency Medicine (AREA)
- Transplantation (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pulmonology (AREA)
- Ophthalmology & Optometry (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
3-(4-カルボキシフェニル)プロピオン酸メチル(365 mg)を1/2当量の炭酸ナトリウムを含む重水(D2O、重水化率99.9%、10 ml)に懸濁させ、10% Pd/Cを37 mg加えて反応容器空間(約10 ml)を水素ガス(H2)で満たして密栓し、110〜140℃でよく攪拌した。反応物をセライトでろ過し、クロロホルム/メタノールで抽出した。収量360 mg。
3-(4-カルボキシフェニル)プロピオン酸(2.0 g)を2当量以下の炭酸ナトリウムを含む重水(40 ml)中で200 mgの10% Pd/C及び水素ガス(100 ml)の存在下に密閉容器中で125℃で48時間加熱攪拌した。一旦セライトでろ過の後、Pd/Cを追加し、水素ガスを交換して同様にして合計3回反応を繰り返した。生成物を中和して目的の重水素化ジカルボン酸を1.93 g得た。このカルボン酸は難溶であるが、NMR(1%Na2CO3/D2O)から、2位と3位の炭素上のプロトンは1%以下であることが確認できた。ベンゼン環上の水素原子の置換は起こっていないことは4-アミノナフタレンとの反応物のNMRから確認することができた。
HRMS: Calcd for C10H6D4O4 198.0830 Found: 198.0825
MS(m/z): 198(M+, 67),181(11), 152(50),137(61),109(100),83(19),79(25), 45(28)
NMR(1%Na2CO3-D2O) 2.35(0.02H, br.s),2.79(0.01H,br.s),7.22(2H, J=8),7.68(2H, J=8).
上記例2で得たジカルボン酸(1.9 g)をメタノール(30 ml)に懸濁して触媒量のチオニルクロリド(14μl, 2mol%)を加えて室温下に16時間攪拌した。メタノールを溜去し、10%炭酸ナトリウム水溶液で抽出した後、濃塩酸で酸性にして析出する結晶を濾取し、1.8 gの3-(4-カルボキシフェニル)(2-d,d-3-d,d)プロピオン酸メチルを得た。少量の原料ジカルボン酸を回収し、ジエステル体の副生も確認された。
HRMS: Calcd for C11H8D4O4 212.0986 Found 212.1001
MS(m/z): 212(M+,34), 195(4), 181(12),152(100),137(40),134(18),123(15),109(76),79(16)
NMR(CDCl3): 2.65(0.02H, br.s), 3.01(0 02H,br.s), 3.67(3H, s), 7.32(2H, J=8.5), 8.04(2H, J=8.5)
3-(4-カルボキシフェニル)プロピオン酸-2,2,3,3-d4メチル(0.105 g, 1.2当量)及びベンゼン4 ml中で少量のDMF(又はピリジン)存在下にチオニルクロリドから調製した酸クロリド、5,6,7,8-テトラヒドロ-5,5,8,8-テトラメチル-2-ナフチルアミン(1当量)、並びにトリエチルアミン(1当量)を室温で5時間反応させた。反応液を希塩酸及び炭酸水素ナトリウムで順次洗浄した後、無水炭酸カリウムで脱水して溶媒を溜去し、表題化合物0.174 gを得た。
H1-NMR(CDCl3): δ 1.28(6H,s),1.30(6H,s),1.69(4H,s), 2.64(0.06〜0.08, br. C2-H), 2.99(0.02H, br.s, C1H), 3.68(3H,s),7.30(1H, d, J=8.4Hz), 7.32 (2H, d, J=8.4Hz), 7.42(1H, dd,J=8.4, 2.4Hz), 7.52(1H,d, J=2.4Hz), 7.69(1H,br.s), 7.80(2H,d,J=8.4Hz)
MS(m/z) 397 (M+)
例4で得られたメチルエステル(0.17g)をエタノール5mlに懸濁し、2M NaOH溶液1 mlを加え、室温にて4時間攪拌した。反応物に2M HClを加えて酸性とし、クロロホルムにて抽出した。有機層を食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後に溶媒を溜去し、残渣を酢酸エチル/ヘキサンから再結晶して122 mgの表記化合物を得た。
H1NMR(CD3OD): δ1.28(6H,s), 1.30(6H,s),1.72(4H,s),2.62(0.06〜0.08, br, C2H),2.96(0.02H,br,C1H),7.30(1H,d,J=8.7Hz),7.38(2H,d,J=8.1),7.43(1H,dd,J=8.7,2.1Hz), 7.63(1H,d,J=2.1Hz),7.86(2H,d=8.1)
MS: 383 (M+)
4-CD3-安息香酸(0.511 g)及びNBS(0.784 g)の四塩化炭素(10 ml)懸濁液にAIBN(0.121 g)を加えて4時間還流下に加熱した。残渣に10% Na2S2O3水溶液を加えてクロロホルムで抽出した。有機層を食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後に溶媒を溜去し、残渣をメタノール/クロロホルムから再結晶して0.530 gの臭素化物を得た。
H1NMR(CDCl3): δ 1.28(6H,s), 1.30(6H,s),1.42(9H,s), 1.69(4H,s), 2.71(2H,s),7.30(1H,d,J=8.7Hz), 7.33(2H,d,J=8.4),7.42(1H, dd,J=8.7,2.1Hz),7.53(1H,d, J=2.1Hz),7.77(1H,br.s),7.81(2H,d,J=8.4Hz)
NMRから重水素化純度は95%以上であった。
4-[(5,6,7,8-テトラヒドロ-5,5,8,8-テトラメチル-2-ナフタレニル)カルバモイル]ベンズアルデヒド(0.125 g)のアセトニトリル(3 ml)懸濁液にメラドルム酸(0.059 g)及びHantzschエステル(0.099 g)を加えた。反応混合物にL-プロリンを加えて一晩攪拌した後に溶媒を溜去した。残渣をカラムクロマトグラフ(シリカゲル5 g)に付し、酢酸エチル/ヘキサン(1:2)溶出部から縮合体0.146 gを得た。その0.125 gを乾燥ピリジン(5 ml)に溶解して重水(0.5 ml)を加え、一晩還流した後に放冷し、2N HClにより酸性とした後にクロロホルムで抽出した。有機層を洗浄して脱水した後に溶媒を溜去した。残渣を酢酸エチル/ヘキサンより再結晶した。
H1NMR(CDCl3): δ 1.28(6H,s),1.30(6H,s),1.69(4H,s),3.02(2H,br.s),7.30(1H,d,J=8.4Hz),7.32(2H,d,J=8.4),7.42(1H,dd,J=8.4,1.8Hz),7.53(1H,d,J=1.8), 7.76(1H, br.s), 7.81(2H,d,J=8.4)
NMRデータから重水素化純度は95%以上であった。
6週齢のddY系雄性マウスを12時間以上絶食させ実験に供した。マウスにAm80(3.30 mg/kg)、3-[4-[(5,6,7,8-テトラヒドロ-5,5,8,8-テトラメチル-2-ナフタレニル)カルバモイル]フェニル]プロピオン酸(軽水素体:M700, 3.56 mg/kg)、又は3-[4-[(5,6,7,8-テトラヒドロ-5,5,8,8-テトラメチル-2-ナフタレニル)カルバモイルフェニル]プロピオン酸-2,2,3,3-d4(重水素化プロピオン酸誘導体:Y616, 3.60 mg/kg)を経口投与した(各化合物の投与量をmolに換算するといずれも9.4 μmol/kgとなる)。各化合物の94 mM DMSO溶液を調製し、0.5%メチルセルロースで100倍に希釈及び懸濁した後、1 mlシリンジと経口用ゾンデを用いて10ml/kgを経口投与した。
Claims (4)
- 3-[4-[(5,6,7,8-テトラヒドロ-5,5,8,8-テトラメチル-2-ナフタレニル)カルバモイル]フェニル]プロピオン酸においてプロピオン酸を構成するエチレン基の水素原子の一部又は全部が重水素で置換された化合物又はその塩、あるいはそのエステル。
- 3-[4-[(5,6,7,8-テトラヒドロ-5,5,8,8-テトラメチル-2-ナフタレニル)カルバモイル]フェニル]プロピオン酸−2,2,3,3-d4, 3-[4-[(5,6,7,8-テトラヒドロ-5,5,8,8-テトラメチル-2-ナフタレニル)カルバモイル]フェニル]プロピオン酸-2,2-d2、 3-[4-[(5,6,7,8-テトラヒドロ-5,5,8,8-テトラメチル-2-ナフタレニル)カルバモイル]フェニル]プロピオン酸-3,3-d2、又はその塩、あるいはそのエステル。
- 生体内に吸収された後に活性薬物としてAm80を放出するためのプロドラッグであって、3-[4-[(5,6,7,8-テトラヒドロ-5,5,8,8-テトラメチル-2-ナフタレニル)カルバモイル]フェニル]プロピオン酸においてプロピオン酸を構成するエチレン基の水素原子の一部又は全部が重水素で置換された化合物又はその塩、あるいはそのエステルを有効成分として含むプロドラッグ。
- 3-(4-カルボキシフェニル)プロピオン酸においてプロピオン酸を構成するエチレン基の水素原子の一部又は全部が重水素で置換された化合物(ただしベンゼン環上の水素原子はいずれも重水素ではない)又はその塩、あるいはそのエステル。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161504374P | 2011-07-05 | 2011-07-05 | |
US61/504,374 | 2011-07-05 | ||
PCT/JP2012/067033 WO2013005753A1 (ja) | 2011-07-05 | 2012-07-04 | 重水素化フェニルプロピオン酸誘導体 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP5193400B2 true JP5193400B2 (ja) | 2013-05-08 |
JPWO2013005753A1 JPWO2013005753A1 (ja) | 2015-02-23 |
Family
ID=47437101
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012544770A Expired - Fee Related JP5193400B2 (ja) | 2011-07-05 | 2012-07-04 | 重水素化フェニルプロピオン酸誘導体 |
Country Status (4)
Country | Link |
---|---|
US (1) | US20140121407A1 (ja) |
EP (1) | EP2730559A4 (ja) |
JP (1) | JP5193400B2 (ja) |
WO (1) | WO2013005753A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9830864B2 (en) | 2012-07-03 | 2017-11-28 | Nippon Seiki Co., Ltd. | Field sequential image display device |
US10147395B2 (en) | 2011-09-27 | 2018-12-04 | Nippon Seiki Co., Ltd. | Field sequential image display device |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HUE060240T2 (hu) | 2015-03-20 | 2023-02-28 | Gaba Therapeutics Inc | Az etifoxin deuterált analógjai, származékaik és azok felhasználása |
JP7163288B2 (ja) * | 2017-07-04 | 2022-10-31 | 第一三共株式会社 | 視細胞変性を伴う網膜変性疾患用薬 |
WO2020138011A1 (ja) * | 2018-12-25 | 2020-07-02 | 第一三共株式会社 | 縮環構造を有するテレフタル酸誘導体 |
US11534434B2 (en) | 2019-11-15 | 2022-12-27 | Karuna Therapeutics, Inc. | Xanomeline derivatives and methods for treating neurological disorders |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008094727A (ja) * | 2006-10-06 | 2008-04-24 | Research Foundation Itsuu Laboratory | レチノイドプロドラッグ化合物 |
WO2009057199A1 (ja) * | 2007-10-31 | 2009-05-07 | Research Foundation Itsuu Laboratory | レチノイドプロドラッグ化合物 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6176440A (ja) | 1984-09-19 | 1986-04-18 | Koichi Shiyudo | 安息香酸誘導体 |
JPS6122047A (ja) | 1984-07-07 | 1986-01-30 | Koichi Shiyudo | 安息香酸誘導体 |
-
2012
- 2012-07-04 JP JP2012544770A patent/JP5193400B2/ja not_active Expired - Fee Related
- 2012-07-04 US US14/126,460 patent/US20140121407A1/en not_active Abandoned
- 2012-07-04 WO PCT/JP2012/067033 patent/WO2013005753A1/ja active Application Filing
- 2012-07-04 EP EP12807516.5A patent/EP2730559A4/en not_active Withdrawn
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008094727A (ja) * | 2006-10-06 | 2008-04-24 | Research Foundation Itsuu Laboratory | レチノイドプロドラッグ化合物 |
WO2009057199A1 (ja) * | 2007-10-31 | 2009-05-07 | Research Foundation Itsuu Laboratory | レチノイドプロドラッグ化合物 |
Non-Patent Citations (3)
Title |
---|
JPN6012059250; Journal of Chemical Research no.1, 1996, p.6-7 * |
JPN6012059253; Biol. Pharm. Bull. vol.32, no.12, 2009, p.1997-2001 * |
JPN6012059255; Nature vol.458, no.19, 2009, p.269 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10147395B2 (en) | 2011-09-27 | 2018-12-04 | Nippon Seiki Co., Ltd. | Field sequential image display device |
US9830864B2 (en) | 2012-07-03 | 2017-11-28 | Nippon Seiki Co., Ltd. | Field sequential image display device |
Also Published As
Publication number | Publication date |
---|---|
EP2730559A1 (en) | 2014-05-14 |
EP2730559A4 (en) | 2015-03-04 |
WO2013005753A1 (ja) | 2013-01-10 |
US20140121407A1 (en) | 2014-05-01 |
JPWO2013005753A1 (ja) | 2015-02-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5193400B2 (ja) | 重水素化フェニルプロピオン酸誘導体 | |
JP5684126B2 (ja) | グルカゴンアンタゴニスト | |
TWI225864B (en) | Amino acids with affinity for the alpha2delta-protein | |
CN1207727A (zh) | 具有类视色素样生物活性的取代芳基或杂芳基酰胺类化合物 | |
WO1999024415A1 (fr) | Agonistes du recepteur du retinoide | |
JP5284574B2 (ja) | レチノイドプロドラッグ化合物 | |
US8633335B2 (en) | Retinoid prodrug compound | |
JP2506337B2 (ja) | フエニルメチルベンゾキノン誘導体 | |
JP4005160B2 (ja) | レチノイドアンタゴニスト | |
JP5399248B2 (ja) | 3環系アミド化合物 | |
JP5399249B2 (ja) | 3環系アミン化合物 | |
JP5284964B2 (ja) | 5員複素環化合物 | |
JP2948923B2 (ja) | レチノイン酸およびその異性体の製造方法 | |
JP4121853B2 (ja) | レチノイド作用性物質 | |
JP2835195B2 (ja) | ビタミンa酸エステル化合物 | |
JP2953817B2 (ja) | 安息香酸誘導体 | |
EP2734496A1 (en) | Indene derivatives for use in the treatment of inflammatory bowel disease | |
JPH09100270A (ja) | レチノイドアンタゴニスト | |
JP5572783B1 (ja) | ケイ素含有カルボン酸誘導体 | |
JP2015137253A (ja) | フッ素含有カルボン酸誘導体 | |
JP2005047879A (ja) | 高度不飽和脂肪酸誘導体およびそれを含有する医薬組成物 | |
CA2344919A1 (en) | Active enantiomer of rar.gamma.-specific agonist | |
WO2015054476A1 (en) | C-halogen bond formation | |
CN1319083A (zh) | 具有类维生素a样活性的5,6-二氢萘基衍生物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130129 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130201 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20160208 Year of fee payment: 3 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
R360 | Written notification for declining of transfer of rights |
Free format text: JAPANESE INTERMEDIATE CODE: R360 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
LAPS | Cancellation because of no payment of annual fees |