NO323422B1 - Ny krystallinsk form av N-[4-[2-(2-amino-4,7-dihydro-4-okso-3H-pyrrolo[2,3-d]pyrimidin-5-yl)etyl]benzoyl]-L-glutaminsyre og fremgangsmate for fremstilling derav - Google Patents

Ny krystallinsk form av N-[4-[2-(2-amino-4,7-dihydro-4-okso-3H-pyrrolo[2,3-d]pyrimidin-5-yl)etyl]benzoyl]-L-glutaminsyre og fremgangsmate for fremstilling derav Download PDF

Info

Publication number: NO323422B1
Authority: NO; Norway
Prior art keywords: heptahydrate; pyrrolo; oxo; amino; dihydro
Prior art date: 2000-02-25

Application number

NO20023974A

Other languages

English (en)

Norwegian (no)

Other versions

NO20023974L (no

NO20023974D0 (no

Inventor

Erik Christopher Chelius

Susan Marie Reutzel-Edens

Sharon Van Den Berghe Snorek

Original Assignee

Lilly Co Eli

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.)

2000-02-25

Filing date

2002-08-21

Publication date

2007-04-30

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22679017&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO323422(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

2002-08-21 Application filed by Lilly Co Eli filed Critical Lilly Co Eli

2002-08-21 Publication of NO20023974L publication Critical patent/NO20023974L/no

2002-08-21 Publication of NO20023974D0 publication Critical patent/NO20023974D0/no

2007-04-30 Publication of NO323422B1 publication Critical patent/NO323422B1/no

Links

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UANBXQTVHOIGGQ-LMOVPXPDSA-N diethyl (2s)-2-[[4-[2-(2-amino-4-oxo-1,7-dihydropyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino]pentanedioate;4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.C1=CC(C(=O)N[C@@H](CCC(=O)OCC)C(=O)OCC)=CC=C1CCC1=CNC2=C1C(=O)N=C(N)N2 UANBXQTVHOIGGQ-LMOVPXPDSA-N 0.000 title 1
239000013078 crystal Substances 0.000 claims description 50
150000004688 heptahydrates Chemical class 0.000 claims description 47
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 41
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 32
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 10
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125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
238000002441 X-ray diffraction Methods 0.000 claims description 8
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 7
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
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-1 disodium N-[4-[2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo[2,3-d] Pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid salt Chemical class 0.000 claims description 3
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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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicinal Preparation (AREA)

NO20023974A 2000-02-25 2002-08-21 Ny krystallinsk form av N-[4-[2-(2-amino-4,7-dihydro-4-okso-3H-pyrrolo[2,3-d]pyrimidin-5-yl)etyl]benzoyl]-L-glutaminsyre og fremgangsmate for fremstilling derav NO323422B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US18496400P	2000-02-25	2000-02-25
PCT/US2001/001229 WO2001062760A2 (en)	2000-02-25	2001-02-12	A NOVEL CRYSTALLINE FORM OF N-[4-[2-(2-AMINO-4,7-DIHYDRO-4-OXO-3H-PYRROLO[2,3-d]PYRIMIDIN-5-YL)ETHYL]BENZOYL]-L-GLUTAMIC ACID AND PROCESS THEREFOR

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Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN100364993C (zh) *	2003-05-30	2008-01-30	江苏恒瑞医药股份有限公司	培美曲噻盐及其制备方法
CN100364994C (zh) *	2004-11-25	2008-01-30	重庆医药工业研究院有限责任公司	培美曲塞二钠的一种新晶型及其制备方法
WO2007056135A1 (en) *	2005-11-04	2007-05-18	Merck & Co., Inc.	Method of treating cancers with saha and pemetrexed
EP1942907A2 (en) *	2005-11-04	2008-07-16	Merck and Co., Inc.	Methods of using saha and erlotinib for treating cancer
EP2311838A1 (en) *	2006-08-14	2011-04-20	Sicor, Inc.	Crystalline form of pemetrexed diacid and process for the preparation thereof
JP2008543976A (ja) *	2006-08-14	2008-12-04	シコールインコーポレイティド	ペメトレキセド二酸の医薬上許容される凍結乾燥塩の調製方法
US7994180B2 (en) *	2006-08-14	2011-08-09	Sicor Inc.	Processes for preparing intermediates of pemetrexed
JP2008543975A (ja) *	2006-08-14	2008-12-04	シコールインコーポレイティド	高度に純粋なペメトレキセド二酸およびその調製方法
CA2667348A1 (en) *	2006-11-03	2008-05-15	University Of Maryland, Baltimore	Methods of using saha and bortezomib for treating multiple myeloma
CN101687872A (zh) *	2007-04-03	2010-03-31	雷迪博士实验室有限公司	培美曲塞的固体形式
CN101417998B (zh) *	2007-10-24	2012-10-24	重庆医药工业研究院有限责任公司	一种培美曲塞盐的纯化方法
EP2072518A1 (en)	2007-12-23	2009-06-24	Sun Pharma Advanced Research Company Limited	Stable Amorphous Form of Pemextred Disodium
EP2334685A4 (en) *	2008-09-08	2011-10-26	Reddys Lab Ltd Dr	AMORPHOUS PEMETREXED DISODIUM
WO2010030598A2 (en) *	2008-09-11	2010-03-18	Dr. Reddy's Laboratories Limited	Pharmaceutical formulations comprising pemetrexed
CN101684121B (zh) *	2008-09-22	2013-04-03	重庆医药工业研究院有限责任公司	培美曲塞二酸的新晶型及其制备方法
CN102050825B (zh) *	2009-11-05	2014-12-17	上海创诺制药有限公司	制备培美曲塞二钠2.5水结晶的方法
WO2011064256A1 (en)	2009-11-24	2011-06-03	Azad Pharmaceutical Ingredients Ag	A new crystalline form of pemetrexed disodium
CN102372719B (zh) *	2010-08-26	2013-10-30	齐鲁制药有限公司	培美曲塞二甲酯对甲苯磺酸盐晶型及其制备方法
KR101069128B1 (ko) *	2011-03-10	2011-09-30	건일제약 주식회사	페메트렉시드 또는 그의 염을 포함하는 항산화제-비함유 주사용 용액 형태의 약학적 제제의 제조방법
US9051322B2 (en)	2011-03-23	2015-06-09	Scinopharm Taiwan, Ltd.	Process for the production of a pemetrexed salt
ES2639639T3 (es) *	2011-03-25	2017-10-27	Scinopharm Taiwan, Ltd.	Proceso para la producción de pemetrexed disódico
ITRM20120398A1 (it)	2012-08-08	2014-02-09	Berlin Chemie Ag	Procedimento di sintesi pemetrexed e suo sale di lisina.
CN102911176B (zh) *	2012-10-10	2015-07-22	德州德药制药有限公司	一种培美曲塞二钠的制备方法
WO2014060959A1 (en) *	2012-10-17	2014-04-24	Shilpa Medicare Limited	Crystalline pemetrexed dipotassium process
ZA201400898B (en)	2013-02-06	2015-12-23	Cipla Ltd	Pemetrexed complexes and pharmaceutical compositions containing pemetrexed complexes
EP3308770A1 (en)	2013-04-12	2018-04-18	Actavis Group PTC EHF	Pemetrexed formulation
KR101485243B1 (ko) *	2013-05-08	2015-01-21	씨제이헬스케어 주식회사	안정화된 페메트렉시드 제제
JP6094388B2 (ja) *	2013-06-07	2017-03-15	ニプロ株式会社	ペメトレキセドを含む注射用組成物
WO2014198338A1 (en)	2013-06-14	2014-12-18	Synthon B.V.	Stable pemetrexed arginine salt and compositions comprising it
EP3021849B1 (en)	2013-07-16	2019-10-09	Dr. Reddy's Laboratories Ltd.	Novel crystalline forms of pemetrexed tromethamine salts
WO2015050230A1 (ja)	2013-10-03	2015-04-09	富士フイルム株式会社	注射液製剤及びその製造方法
NZ630292A (en) *	2013-11-25	2015-02-27	Shilpa Medicare Ltd	Process for crystalline pemetrexed dipotassium salt
NZ630299A (en)	2014-06-30	2014-11-28	Shilpa Medicare Ltd	Pemetrexed dipotassium formulations
CA3015436C (en)	2014-10-30	2020-07-21	Scinopharm Taiwan, Ltd.	Crystalline forms of pemetrexed diacid and manufacturing processes therefor
CN105566328B (zh) *	2014-11-06	2018-04-24	博瑞生物医药（苏州）股份有限公司	培美曲塞二酸多晶型的制备方法
WO2019073482A1 (en) *	2017-10-10	2019-04-18	Sun Pharmaceutical Industries Limited	INTRAVENOUS INFUSION TYPE DOSAGE FORM FOR PETREXED
EP3749311A4 (en)	2018-02-07	2022-07-06	L.E.A.F Holdings Group LLC	PEMETREXED POLYGLUTAMATE GAMMA COMPOSITIONS AND THEIR USES
JP7491572B2 (ja)	2018-02-07	2024-05-28	エル．イー．エー．エフ．ホールディングスグループエルエルシー	アルファポリグルタミン酸化ペメトレキセドおよびその使用
WO2025244944A1 (en) *	2024-05-20	2025-11-27	Opna Bio SA	Crystal forms of an agent

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NO169490C (no)	1988-03-24	1992-07-01	Takeda Chemical Industries Ltd	Analogifremgangsmaate for fremstilling av terapeutisk aktive pyrrolopyrimidinderivater
KR0162654B1 (ko)	1989-12-11	1998-11-16	알렌 제이. 시니스갤리	N-(피롤로[2,3-d]피리미딘-3-일아크릴)-글루타민산 유도체
US5416211A (en)	1992-09-25	1995-05-16	Eli Lilly And Company	Process for preparing 5-substituted pyrrolo-[2,3-d]pyrimidines
JP2000516961A (ja) *	1996-08-30	2000-12-19	イーライ・リリー・アンド・カンパニー	非古典的ピロロ［２，３―ｄ］ピリミジン抗葉酸物質
AU740087B2 (en) *	1997-09-26	2001-11-01	Eli Lilly And Company	Processes and intermediates useful to make antifolates
ZA987550B (en) *	1997-09-26	2000-02-21	Lilly Co Eli	Processes and intermediates useful to make antifolates.
EP1212325A2 (en) *	1999-08-23	2002-06-12	Eli Lilly And Company	A novel crystalline form of disodium n-[4-[2-(2-amino-4,7-dihydro-4-oxo-3h-pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid salt and processes therefor

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Publication number	Publication date
US7138521B2 (en)	2006-11-21
EG24073A (en)	2008-05-11
SK11862002A3 (sk)	2003-01-09
HK1051856A1 (en)	2003-08-22
UA72791C2 (uk)	2005-04-15
AU777047B2 (en)	2004-09-30
SV2002000321A (es)	2002-07-16
PL208061B1 (pl)	2011-03-31
DE60100750T2 (de)	2004-07-29
NZ519796A (en)	2003-01-31
MXPA02008242A (es)	2002-11-29
WO2001062760A2 (en)	2001-08-30
HRP20020701A2 (en)	2003-12-31
MY124784A (en)	2006-07-31
HRP20020701B1 (en)	2011-02-28
CA2400155A1 (en)	2001-08-30
CN1406238A (zh)	2003-03-26
ATE249462T1 (de)	2003-09-15
CZ303772B6 (cs)	2013-05-02
KR20020075449A (ko)	2002-10-04
US20030216416A1 (en)	2003-11-20
HUP0204232A2 (hu)	2003-04-28
AU3445101A (en)	2001-09-03
SI1259513T1 (en)	2003-12-31
BR0108604A (pt)	2002-11-19
ZA200205265B (en)	2003-11-11
NO20023974L (no)	2002-08-21
IL150480A (en)	2007-12-03
EA004684B1 (ru)	2004-06-24
TWI237024B (en)	2005-08-01
CO5261585A1 (es)	2003-03-31
CZ20022875A3 (cs)	2003-02-12
EP1259513A2 (en)	2002-11-27
HUP0204232A3 (en)	2006-01-30
SK287375B6 (sk)	2010-08-09
EP1259513B1 (en)	2003-09-10
NO20023974D0 (no)	2002-08-21
PL356423A1 (en)	2004-06-28
IL150480A0 (en)	2002-12-01
HU229704B1 (en)	2014-05-28
PT1259513E (pt)	2004-02-27
PE20011082A1 (es)	2001-10-22
DK1259513T3 (da)	2004-01-12
KR100744917B1 (ko)	2007-08-01
ES2206403T3 (es)	2004-05-16
AR029471A1 (es)	2003-07-02
EA200200905A1 (ru)	2003-02-27
CN1183135C (zh)	2005-01-05
DE60100750D1 (de)	2003-10-16
JP4846158B2 (ja)	2011-12-28
DZ3283A1 (fr)	2001-08-30
CA2400155C (en)	2009-09-15
WO2001062760A3 (en)	2001-12-06
JP2003530321A (ja)	2003-10-14

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NO323422B1 (no)	2007-04-30	Ny krystallinsk form av N-[4-[2-(2-amino-4,7-dihydro-4-okso-3H-pyrrolo[2,3-d]pyrimidin-5-yl)etyl]benzoyl]-L-glutaminsyre og fremgangsmate for fremstilling derav
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HK1051856B (en)	2004-05-28	A novel crystalline form of n-[4-[2-(2-amino-4,7-dihydro-4-oxo-3h-pyrrolo [2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-l-glutamic acid and process therefor
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