SK50102006A3 - Spôsob prípravy kryštalického polymorfu inhibítora zrážania krvných doštičiek - Google Patents

Spôsob prípravy kryštalického polymorfu inhibítora zrážania krvných doštičiek Download PDF

Info

Publication number: SK50102006A3
Authority: SK; Slovakia
Prior art keywords: solvent; mixture; clopidogrel; type; solvents
Prior art date: 2003-07-02

Application number

SK5010-2006A

Other languages

English (en)

Slovak (sk)

Inventor

Nagy Pter Ktay

Gyula Simig

Jzsef Barkczy

Tam�S Gregor

B�La Farkas

Don�Th Gy�Rgyi Vereczkeyn�

Klmn Nagy

Gyul�N� K�Rtv�Lyessy

Zsuzsanna Szent-Kir�Llyi

Original Assignee

Egis Gy�Gyszergy�R Rt.

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.)

2003-07-02

Filing date

2004-06-30

Publication date

2006-05-04

2003-07-02 Priority claimed from HU0302028A external-priority patent/HU0302028D0/hu

2004-06-23 Priority claimed from HU0401272A external-priority patent/HU226773B1/hu

2004-06-30 Application filed by Egis Gy�Gyszergy�R Rt. filed Critical Egis Gy�Gyszergy�R Rt.

2006-05-04 Publication of SK50102006A3 publication Critical patent/SK50102006A3/sk

Links

238000002360 preparation method Methods 0.000 title claims abstract description 18
238000000034 method Methods 0.000 title claims description 24
101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 title 1
101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 title 1
229940127218 antiplatelet drug Drugs 0.000 title 1
239000000106 platelet aggregation inhibitor Substances 0.000 title 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 64
229950010477 clopidogrel hydrogen sulphate Drugs 0.000 claims abstract description 64
FDEODCTUSIWGLK-UHFFFAOYSA-N hydrogen sulfate;hydron;methyl 2-(2-chlorophenyl)-2-(6,7-dihydro-4h-thieno[3,2-c]pyridin-5-yl)acetate Chemical compound OS(O)(=O)=O.C1CC=2SC=CC=2CN1C(C(=O)OC)C1=CC=CC=C1Cl FDEODCTUSIWGLK-UHFFFAOYSA-N 0.000 claims abstract description 62
239000002904 solvent Substances 0.000 claims abstract description 62
239000000203 mixture Substances 0.000 claims abstract description 42
239000005552 B01AC04 - Clopidogrel Substances 0.000 claims abstract description 29
229960003009 clopidogrel Drugs 0.000 claims abstract description 29
GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 claims abstract description 29
239000002244 precipitate Substances 0.000 claims abstract description 19
239000000725 suspension Substances 0.000 claims abstract description 13
238000001914 filtration Methods 0.000 claims abstract description 7
238000001035 drying Methods 0.000 claims abstract description 6
238000005406 washing Methods 0.000 claims abstract description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 36
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 17
239000000010 aprotic solvent Substances 0.000 claims description 9
238000003756 stirring Methods 0.000 claims description 8
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
-1 6,7-dihydro-4 H -thieno [3,2-c] pyridin-5-yl Chemical group 0.000 claims description 4
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
238000001816 cooling Methods 0.000 claims description 3
150000002576 ketones Chemical class 0.000 claims description 3
239000012454 non-polar solvent Substances 0.000 claims description 3
239000003880 polar aprotic solvent Substances 0.000 claims description 3
239000003586 protic polar solvent Substances 0.000 claims description 3
239000011877 solvent mixture Substances 0.000 claims description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
150000002148 esters Chemical class 0.000 claims 1
229930195733 hydrocarbon Natural products 0.000 claims 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
239000000047 product Substances 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
239000013078 crystal Substances 0.000 description 7
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
238000005160 1H NMR spectroscopy Methods 0.000 description 6
230000000052 comparative effect Effects 0.000 description 5
239000012296 anti-solvent Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
238000002441 X-ray diffraction Methods 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
FDEODCTUSIWGLK-RSAXXLAASA-N clopidogrel sulfate Chemical compound [H+].OS([O-])(=O)=O.C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl FDEODCTUSIWGLK-RSAXXLAASA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 2
238000005259 measurement Methods 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
229930195734 saturated hydrocarbon Natural products 0.000 description 2
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
LFHDINMNPBZSNH-UHFFFAOYSA-N C1N(OC(=O)C)CCC2=C1C=CS2 Chemical compound C1N(OC(=O)C)CCC2=C1C=CS2 LFHDINMNPBZSNH-UHFFFAOYSA-N 0.000 description 1
206010053567 Coagulopathies Diseases 0.000 description 1
229910016523 CuKa Inorganic materials 0.000 description 1
UCTLHLZWKJIXJI-LXIBVNSESA-N [(3s,8r,9s,10r,13s,14s)-17-chloro-16-formyl-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1h-cyclopenta[a]phenanthren-3-yl] acetate Chemical compound C([C@@H]12)C[C@]3(C)C(Cl)=C(C=O)C[C@H]3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)C)C1 UCTLHLZWKJIXJI-LXIBVNSESA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
230000035602 clotting Effects 0.000 description 1
229910003460 diamond Inorganic materials 0.000 description 1
239000010432 diamond Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000005284 excitation Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000010445 mica Substances 0.000 description 1
229910052618 mica group Inorganic materials 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
QZDWODWEESGPLC-UHFFFAOYSA-N pyridin-3-yl acetate Chemical compound CC(=O)OC1=CC=CN=C1 QZDWODWEESGPLC-UHFFFAOYSA-N 0.000 description 1
230000005855 radiation Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Hematology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Steroid Compounds (AREA)

SK5010-2006A 2003-07-02 2004-06-30 Spôsob prípravy kryštalického polymorfu inhibítora zrážania krvných doštičiek SK50102006A3 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
HU0302028A HU0302028D0 (en)	2003-07-02	2003-07-02	Process for the production of crystalline polymorphous form of an anticoagulant agent
HU0401272A HU226773B1 (en)	2004-06-23	2004-06-23	Process for the production of clopidogrel hydrogensulfate polymorph 1
PCT/HU2004/000070 WO2005003139A1 (en)	2003-07-02	2004-06-30	Process for the preparation of crystalline polymorph of a platelet aggregation inhibitor drug

Publications (1)

Publication Number	Publication Date
SK50102006A3 true SK50102006A3 (sk)	2006-05-04

Family

ID=89985327

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK5010-2006A SK50102006A3 (sk)	2003-07-02	2004-06-30	Spôsob prípravy kryštalického polymorfu inhibítora zrážania krvných doštičiek

Country Status (14)

Country	Link
US (1)	US20070142637A1 (cs)
EP (1)	EP1644381B1 (cs)
JP (1)	JP4681545B2 (cs)
KR (1)	KR101155679B1 (cs)
CN (1)	CN1812993B (cs)
AT (1)	ATE461201T1 (cs)
BG (1)	BG109429A (cs)
CA (1)	CA2530449C (cs)
CZ (1)	CZ200641A3 (cs)
DE (1)	DE602004026059D1 (cs)
EA (1)	EA010684B1 (cs)
PL (2)	PL1644381T3 (cs)
SK (1)	SK50102006A3 (cs)
WO (1)	WO2005003139A1 (cs)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EA010198B1 (ru) *	2004-04-19	2008-06-30	Крка, Товарна Здравил, Д.Д., Ново Место	Способы получения полиморфной формы i гидросульфата клопидогрела
EP1902058A2 (en) *	2005-07-12	2008-03-26	RPG Life Sciences Limited	A process for preparation of methyl-(+)-(s)-alpha-(2-chlorophenyl)-6,7-dihydrothieno(3,2-c)pyridine-5(4h)-acetic acid methyl ester or salts thereof having higher chiral purity and products thereof
CA2655844A1 (en) *	2006-08-03	2008-02-14	Teva Pharmaceutical Industries Ltd.	Process for preparing clopidogrel bisulphate
WO2011010318A1 (en) *	2009-07-23	2011-01-27	Praveen Laboratories Private Limited	Process for the preparation of clopidogrel polymorphous form 1 using seed chrystals
CN102070648A (zh) *	2010-12-07	2011-05-25	天津红日药业股份有限公司	I型硫酸氢氯吡格雷的制备方法
CN102702224A (zh) *	2012-06-25	2012-10-03	山东齐都药业有限公司	I型硫酸氢氯吡格雷的制备方法
CN107337683B (zh) *	2017-08-16	2019-08-16	中荣凯特（北京）生物科技有限公司	一种噻吩并吡啶类衍生物硫酸氢盐的晶型ⅱ及其制备方法和应用
CN113121559B (zh) *	2019-12-31	2023-08-29	惠州信立泰药业有限公司	一种高堆密度的ii型硫酸氢氯吡格雷球形结晶及制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2623810B2 (fr) *	1987-02-17	1992-01-24	Sanofi Sa	Sels de l'alpha-(tetrahydro-4,5,6,7 thieno(3,2-c) pyridyl-5) (chloro-2 phenyl) -acetate de methyle dextrogyre et compositions pharmaceutiques en contenant
FR2779726B1 (fr) *	1998-06-15	2001-05-18	Sanofi Sa	Forme polymorphe de l'hydrogenosulfate de clopidogrel
WO2002059128A2 (en) *	2001-01-24	2002-08-01	Cadila Healthcare Ltd.	Process for preparing clopidogrel
GB0125708D0 (en) *	2001-10-26	2001-12-19	Generics Uk Ltd	Novel compounds and processes
IL162461A0 (en) *	2001-12-18	2005-11-20	Teva Pharma	Polymorphs of clopidogrel hydrogensulfate

2004
- 2004-06-30 PL PL04743729T patent/PL1644381T3/pl unknown
- 2004-06-30 AT AT04743729T patent/ATE461201T1/de not_active IP Right Cessation
- 2004-06-30 EA EA200600138A patent/EA010684B1/ru not_active IP Right Cessation
- 2004-06-30 CZ CZ20060041A patent/CZ200641A3/cs unknown
- 2004-06-30 KR KR1020067000012A patent/KR101155679B1/ko not_active Expired - Fee Related
- 2004-06-30 CA CA2530449A patent/CA2530449C/en not_active Expired - Fee Related
- 2004-06-30 EP EP04743729A patent/EP1644381B1/en not_active Expired - Lifetime
- 2004-06-30 DE DE602004026059T patent/DE602004026059D1/de not_active Expired - Fee Related
- 2004-06-30 WO PCT/HU2004/000070 patent/WO2005003139A1/en not_active Ceased
- 2004-06-30 PL PL378710A patent/PL378710A1/pl not_active Application Discontinuation
- 2004-06-30 CN CN2004800181228A patent/CN1812993B/zh not_active Expired - Fee Related
- 2004-06-30 US US10/563,133 patent/US20070142637A1/en not_active Abandoned
- 2004-06-30 SK SK5010-2006A patent/SK50102006A3/sk unknown
- 2004-06-30 JP JP2006516497A patent/JP4681545B2/ja not_active Expired - Fee Related
2006
- 2006-02-02 BG BG109429A patent/BG109429A/en unknown

Also Published As

Publication number	Publication date
PL1644381T3 (pl)	2010-08-31
CN1812993A (zh)	2006-08-02
BG109429A (en)	2006-10-31
JP2007516167A (ja)	2007-06-21
CZ200641A3 (cs)	2006-05-17
KR20060026119A (ko)	2006-03-22
EA010684B1 (ru)	2008-10-30
PL378710A1 (pl)	2006-05-15
CA2530449A1 (en)	2005-01-13
CA2530449C (en)	2010-03-23
EP1644381B1 (en)	2010-03-17
WO2005003139A1 (en)	2005-01-13
JP4681545B2 (ja)	2011-05-11
KR101155679B1 (ko)	2012-06-13
EP1644381A1 (en)	2006-04-12
US20070142637A1 (en)	2007-06-21
CN1812993B (zh)	2011-06-29
DE602004026059D1 (de)	2010-04-29
EA200600138A1 (ru)	2006-08-25
ATE461201T1 (de)	2010-04-15

Legal Events

Date	Code	Title	Description
2012-09-03	FB9A	Suspension of patent application procedure

Publication	Publication Date	Title
EP1740593B1 (en)	2016-04-06	Processes for the preparation of clopidogrel hydrogen sulfate polymorphic form i
EP1656381B1 (en)	2011-03-09	Crystallisation of solid forms of clopidogrel addition salts
WO2005012300A1 (en)	2005-02-10	A novel process for the manufacture of (+)-(s)-clopidogrel bisulfate form-i
PL196069B1 (pl)	2007-12-31	Sposób wytwarzania zasadniczo czystej postaci II olanzapiny
SK50102006A3 (sk)	2006-05-04	Spôsob prípravy kryštalického polymorfu inhibítora zrážania krvných doštičiek
EP0733634B1 (en)	2000-11-22	Process for preparing a thieno(2,3-B)(1,5) benzodiazepine derivative
SK50942005A3 (sk)	2006-02-02	Polymorfy hydrochloridu olanzapínu
EA008055B1 (ru)	2007-02-27	Кристаллические формы оланзапина и способы их получения
SK50112006A3 (sk)	2006-05-04	Spôsob prípravy amorfnej formy liečiva - inhibítora zrážania krvných doštičiek
WO2006087226A1 (en)	2006-08-24	Process for preparing clopidogrel hydrogen sulfate of form i
HU226773B1 (en)	2009-09-28	Process for the production of clopidogrel hydrogensulfate polymorph 1
US20090036683A1 (en)	2009-02-05	Method for preparing clopidogrel 1,5-naphthalenedisulfonate or hydrate thereof
HU226565B1 (en)	2009-04-28	Process for the production of the amorphous form of clopidogrel hydrogen sulfate
WO2005085256A1 (en)	2005-09-15	Isopropanol water solvate of olanzapine
PL204250B1 (pl)	2009-12-31	Sposób wytwarzania postaci amorficznej wodorosiarczanu klopidogrelu
SI21749A (sl)	2005-10-31	Postopek za pripravo polimorfne oblike I klopidogrel hidrogen sulfata
CN1812994A (zh)	2006-08-02	制备无定形的血小板凝集抑制剂药物的方法
WO2011010318A1 (en)	2011-01-27	Process for the preparation of clopidogrel polymorphous form 1 using seed chrystals