JP2009527538A - Cd80アンタゴニストの塩 - Google Patents
Cd80アンタゴニストの塩 Download PDFInfo
- Publication number
- JP2009527538A JP2009527538A JP2008555857A JP2008555857A JP2009527538A JP 2009527538 A JP2009527538 A JP 2009527538A JP 2008555857 A JP2008555857 A JP 2008555857A JP 2008555857 A JP2008555857 A JP 2008555857A JP 2009527538 A JP2009527538 A JP 2009527538A
- Authority
- JP
- Japan
- Prior art keywords
- choline salt
- ethyl
- pyrazolo
- fluoro
- difluoro
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Abstract
【選択図】 なし
Description
この発明は、化合物(A)のコリン塩が望ましい良好な水溶性を有していることを見出したことに基づいている。
本発明によれば、上記の式(A)の4-(6-フルオロ-3-オキソ-1,3-ジヒドロ-ピラゾロ[4,3-c]シンノリン-2-イル)-N-(2,2-ジフルオロ-エチル)-ベンズアミドのコリン塩が提供される。
上記のコリン塩の注射可能な水性溶液、および上記のコリン塩を含み局所に適用できる水をベースとする液状またはクリーム状の組成物は、本発明のもう一つの目的である。
経口投与用の錠剤およびカプセル剤は、1回投与用の形態であってよく、結合剤、例えばシロップ、アカシア、ゼラチン、ソルビトール、トラガントもしくはポリビニルピロリドン;充填剤、例えばラクトース、砂糖、トウモロコシ澱粉、燐酸カルシウム、ソルビトールもしくはグリシン; 打錠用の滑沢剤、例えばステアリン酸マグネシウム、タルク、ポリエチレングリコールもしくはシリカ;崩壊剤、例えばバレイショ澱粉、またはラウリル硫酸ナトリウムのような許容される湿潤剤のような、通常の賦形剤を含んでいてもよい。錠剤は、通常の製薬業界で周知の方法に従ってコーティングされていてもよい。
次のようにして、4-(6-フルオロ-3-オキソ-1,3-ジヒドロ-ピラゾロ[4,3-c]シンノリン-2-イル)-N-(2,2-ジフルオロ-エチル)-ベンズアミドを製造し、そのコリン(すなわち、(2-ヒドロキシ-エチル)-トリメチル-アンモニウム)塩を製造した。
磁石撹拌器、還流濃縮器およびガスバブラーを備えた丸底フラスコに、WO 2004/081011の実施例5のようにして製造された、4-(6-フルオロ-3-オキソ-1,3-ジヒドロ-ピラゾロ[4,3-c]シンノリン-2-イル)-安息香酸(12.9 g)を入れた。塩化チオニル(65 ml)をゆっくり加えた。窒素雰囲気を適用し、混合物を加熱還流した。加熱するとガスの発生が見られ、そのガスをスクラバー中にトラップした。
LC-MS: 目的物の一つのピーク。この物質のQC 分析は、91.6%の純度を示した。
磁石撹拌器を備えた丸底フラスコに、N-(2,2-ジフルオロ-エチル)-4-(6-フルオロ-3-オキソ-1,3-ジヒドロ-ピラゾロ[4,3-c]シンノリン-2-イル)-ベンズアミド(2.50 g)を入れた。固形物をメタノール(25 ml)中に懸濁し、コリン水酸化物(782 mg、1.74 ml 45重量% メタノール中) を滴下した。この滴下により、澄明な暗褐色の溶液が生成した。
LC-MS: 単離された固形物; 一つの主ピーク [M+H]+ 388、純度 95%。
固形の塩は、褐色の粗い粉末(2.26 g、4.61 mmol、71%)であった。
融点:172-180℃(分解)。
N-(2,2-ジフルオロ-エチル)-4-(6-フルオロ-3-オキソ-1,3-ジヒドロ-ピラゾロ[4,3-c]シンノリン-2-イル)-ベンズアミドの塩になっていない形態(遊離の酸)、および一連のその他の塩の溶解性も、同じ分析で試験した。
試験化合物10 mgをバイアル中に秤取し、溶媒1 ml を加えた。澄明な溶液の形成により証明されるように、サンプルが直ちに溶解したら、試験物質をさらに加え、バイアルを15分間超音波処理した。懸濁液の形成により証明されるように、試験化合物がもはや溶解しなくなるまで、この手順を繰り返した。次いで、懸濁液を含むバイアルを15分間超音波処理し、25 ℃/60% 相対湿度で24時間シェイカー上に置いた。シェイカーから外し、サンプルを遠心分離し、上澄液をHPLCで分析した。結果を表1に示す。
Claims (4)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0603522.4 | 2006-02-22 | ||
GBGB0603522.4A GB0603522D0 (en) | 2006-02-22 | 2006-02-22 | Kinase inhibition |
PCT/GB2007/000550 WO2007096588A1 (en) | 2006-02-22 | 2007-02-19 | Salt of cd 80 antagonist |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009527538A true JP2009527538A (ja) | 2009-07-30 |
JP5102785B2 JP5102785B2 (ja) | 2012-12-19 |
Family
ID=36178528
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008555857A Active JP5102785B2 (ja) | 2006-02-22 | 2007-02-19 | Cd80アンタゴニストの塩 |
Country Status (20)
Country | Link |
---|---|
US (3) | US20090221590A1 (ja) |
EP (1) | EP1991548B1 (ja) |
JP (1) | JP5102785B2 (ja) |
KR (1) | KR101433738B1 (ja) |
CN (1) | CN101384595B (ja) |
AU (1) | AU2007217170B2 (ja) |
BR (1) | BRPI0708114B8 (ja) |
CA (1) | CA2643668C (ja) |
DK (1) | DK1991548T3 (ja) |
EA (1) | EA014101B1 (ja) |
ES (1) | ES2449569T3 (ja) |
GB (1) | GB0603522D0 (ja) |
HK (1) | HK1125376A1 (ja) |
IL (1) | IL192954A (ja) |
NZ (1) | NZ570055A (ja) |
PL (1) | PL1991548T3 (ja) |
PT (1) | PT1991548E (ja) |
UA (1) | UA91904C2 (ja) |
WO (1) | WO2007096588A1 (ja) |
ZA (1) | ZA200806508B (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT1603917E (pt) * | 2003-03-14 | 2011-02-04 | Medigene Ag | Compostos heterocíclicos imunomoduladores |
CA2576256C (en) | 2004-08-09 | 2012-01-03 | Avidex Limited | Immunomodulating oxopyrrazolocinnolines as cd80 inhibitors |
WO2010049525A1 (en) | 2008-10-31 | 2010-05-06 | C-A-I-R Biosciences Gmbh | Choline and tromethamine salt of licofelone |
CN102753557B (zh) * | 2010-02-10 | 2015-10-14 | 橘生药品工业株式会社 | 稠合杂环衍生物的盐及其晶体 |
UA109287C2 (uk) * | 2010-11-02 | 2015-08-10 | Солі органічного аміну похідних амінобензойної кислоти і спосіб їх одержання | |
EP4119128A1 (en) * | 2021-07-13 | 2023-01-18 | Dr. Falk Pharma Gmbh | Pharmaceutical composition for the oral administration of poorly soluble drugs comprising an amorphous solid dispersion |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS523818A (en) * | 1975-06-26 | 1977-01-12 | Hoffmann La Roche | Salt of penicillanic acid |
WO2004081011A1 (en) * | 2003-03-14 | 2004-09-23 | Avidex Limited | Immunomodulating heterocyclic compounds |
WO2005041867A2 (en) * | 2003-10-22 | 2005-05-12 | Smithkline Beecham Corporation | 2-(3,4-dimethylphenyl)-4-{[2-hydroxy-3’(1h-tetrazol-5-yl)biphenyl-3-yl]-hydrazono}-5-methyl-2,4-dihydropyrozol-3-one choline |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2670350A (en) * | 1952-08-08 | 1954-02-23 | Nepera Chemical Co Inc | Method of preparing choline salt of theophylline |
US3576637A (en) * | 1967-04-20 | 1971-04-27 | Konishiroku Photo Ind | Lith-type of emulsion containing pyrozolone |
US3778150A (en) * | 1971-10-27 | 1973-12-11 | K Aston | Printing of photographic colour negatives |
US4591589A (en) * | 1985-01-16 | 1986-05-27 | Roussel Uclaf | 2-aryl pyrazolo[4,3-c]cinnolin-3-ones |
DE3903993A1 (de) * | 1989-02-10 | 1990-08-16 | Basf Ag | Diarylsubstituierte heterocyclische verbindungen, ihre herstellung und arzneimittel daraus |
IT1290448B1 (it) * | 1997-04-01 | 1998-12-03 | Schiena Michele Giuseppe Di | Nimesulide sale di colina,metodo di preparazione e composizioni farmaceutiche che lo contengono |
GB0325644D0 (en) * | 2003-11-04 | 2003-12-10 | Avidex Ltd | Immuno ihibitory pyrazolone compounds |
GB0411770D0 (en) * | 2004-05-26 | 2004-06-30 | Avidex Ltd | Immuno inhibitory heterocyclic compouds |
CA2576256C (en) * | 2004-08-09 | 2012-01-03 | Avidex Limited | Immunomodulating oxopyrrazolocinnolines as cd80 inhibitors |
WO2006083687A1 (en) * | 2005-01-28 | 2006-08-10 | Cardiome Pharma Corp. | Crystal salt of xanthine oxidase inhibitors |
-
2006
- 2006-02-22 GB GBGB0603522.4A patent/GB0603522D0/en not_active Ceased
-
2007
- 2007-02-19 EP EP07712727.2A patent/EP1991548B1/en active Active
- 2007-02-19 NZ NZ570055A patent/NZ570055A/en unknown
- 2007-02-19 CA CA2643668A patent/CA2643668C/en active Active
- 2007-02-19 AU AU2007217170A patent/AU2007217170B2/en active Active
- 2007-02-19 PL PL07712727T patent/PL1991548T3/pl unknown
- 2007-02-19 UA UAA200811363A patent/UA91904C2/ru unknown
- 2007-02-19 BR BRPI0708114A patent/BRPI0708114B8/pt active IP Right Grant
- 2007-02-19 CN CN2007800051162A patent/CN101384595B/zh active Active
- 2007-02-19 WO PCT/GB2007/000550 patent/WO2007096588A1/en active Application Filing
- 2007-02-19 DK DK07712727.2T patent/DK1991548T3/en active
- 2007-02-19 KR KR1020087019729A patent/KR101433738B1/ko active IP Right Grant
- 2007-02-19 US US12/279,898 patent/US20090221590A1/en not_active Abandoned
- 2007-02-19 ES ES07712727.2T patent/ES2449569T3/es active Active
- 2007-02-19 EA EA200801875A patent/EA014101B1/ru unknown
- 2007-02-19 PT PT77127272T patent/PT1991548E/pt unknown
- 2007-02-19 JP JP2008555857A patent/JP5102785B2/ja active Active
-
2008
- 2008-07-22 IL IL192954A patent/IL192954A/en active IP Right Grant
- 2008-07-25 ZA ZA200806508A patent/ZA200806508B/xx unknown
-
2009
- 2009-05-07 HK HK09104229.6A patent/HK1125376A1/xx unknown
-
2011
- 2011-09-15 US US13/233,634 patent/US20120004237A1/en not_active Abandoned
-
2017
- 2017-11-20 US US15/817,323 patent/US20180265514A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS523818A (en) * | 1975-06-26 | 1977-01-12 | Hoffmann La Roche | Salt of penicillanic acid |
WO2004081011A1 (en) * | 2003-03-14 | 2004-09-23 | Avidex Limited | Immunomodulating heterocyclic compounds |
WO2005041867A2 (en) * | 2003-10-22 | 2005-05-12 | Smithkline Beecham Corporation | 2-(3,4-dimethylphenyl)-4-{[2-hydroxy-3’(1h-tetrazol-5-yl)biphenyl-3-yl]-hydrazono}-5-methyl-2,4-dihydropyrozol-3-one choline |
Also Published As
Publication number | Publication date |
---|---|
CA2643668A1 (en) | 2007-08-30 |
NZ570055A (en) | 2011-08-26 |
CA2643668C (en) | 2014-05-13 |
HK1125376A1 (en) | 2009-08-07 |
ZA200806508B (en) | 2009-06-24 |
EA014101B1 (ru) | 2010-08-30 |
KR20080103523A (ko) | 2008-11-27 |
JP5102785B2 (ja) | 2012-12-19 |
BRPI0708114A2 (pt) | 2011-05-17 |
EA200801875A1 (ru) | 2008-12-30 |
CN101384595A (zh) | 2009-03-11 |
CN101384595B (zh) | 2011-02-09 |
AU2007217170B2 (en) | 2012-02-02 |
IL192954A0 (en) | 2009-02-11 |
UA91904C2 (en) | 2010-09-10 |
WO2007096588A1 (en) | 2007-08-30 |
BRPI0708114B8 (pt) | 2021-05-25 |
PT1991548E (pt) | 2014-03-10 |
US20090221590A1 (en) | 2009-09-03 |
EP1991548A1 (en) | 2008-11-19 |
AU2007217170A1 (en) | 2007-08-30 |
KR101433738B1 (ko) | 2014-08-25 |
GB0603522D0 (en) | 2006-04-05 |
EP1991548B1 (en) | 2013-12-11 |
ES2449569T3 (es) | 2014-03-20 |
BRPI0708114B1 (pt) | 2020-02-04 |
IL192954A (en) | 2015-01-29 |
PL1991548T3 (pl) | 2014-05-30 |
US20120004237A1 (en) | 2012-01-05 |
US20180265514A1 (en) | 2018-09-20 |
DK1991548T3 (en) | 2014-03-10 |
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