NO328548B1 - Nye mandelatsalter av substituerte tetracykliske tetrahydrofuranderivater - Google Patents

Nye mandelatsalter av substituerte tetracykliske tetrahydrofuranderivater Download PDF

Info

Publication number: NO328548B1
Authority: NO; Norway
Prior art keywords: mandelate salt; dibenzo; furan; tetrahydro; cyclohepta
Prior art date: 2001-11-09

Application number

NO20041848A

Other languages

English (en)

Norwegian (no)

Other versions

NO20041848L (no

Inventor

Johannes Josephus Maria Willems

Bart Petrus Anna Maria Jozef Medaer

Sigrid Carl Maria Stokbroekx

Yves Georges Ruysschaert

Johan Erwin Edmond Weerts

Original Assignee

Janssen Pharmaceutica Nv

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.)

2001-11-09

Filing date

2004-05-05

Publication date

2010-03-15

2004-05-05 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2004-05-05 Publication of NO20041848L publication Critical patent/NO20041848L/no

2010-03-15 Publication of NO328548B1 publication Critical patent/NO328548B1/no

Links

150000003839 salts Chemical class 0.000 title description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 title description 12
210000004373 mandible Anatomy 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 52
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239000008194 pharmaceutical composition Substances 0.000 claims description 10
238000002360 preparation method Methods 0.000 claims description 10
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PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
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239000012442 inert solvent Substances 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
208000014674 injury Diseases 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
150000004668 long chain fatty acids Chemical class 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
230000004899 motility Effects 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
229960002748 norepinephrine Drugs 0.000 description 1
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
239000002674 ointment Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000001451 organic peroxides Chemical class 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
LDCYZAJDBXYCGN-UHFFFAOYSA-N oxitriptan Natural products C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
208000019906 panic disease Diseases 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
208000022821 personality disease Diseases 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
238000000053 physical method Methods 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
230000008569 process Effects 0.000 description 1
239000000047 product Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
JQRYUMGHOUYJFW-UHFFFAOYSA-N pyridine;trihydrobromide Chemical compound [Br-].[Br-].[Br-].C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1.C1=CC=[NH+]C=C1 JQRYUMGHOUYJFW-UHFFFAOYSA-N 0.000 description 1
238000010992 reflux Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
208000012201 sexual and gender identity disease Diseases 0.000 description 1
208000015891 sexual disease Diseases 0.000 description 1
238000005055 short column chromatography Methods 0.000 description 1
208000022925 sleep disturbance Diseases 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
238000001694 spray drying Methods 0.000 description 1
238000012430 stability testing Methods 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003509 tertiary alcohols Chemical class 0.000 description 1
230000009466 transformation Effects 0.000 description 1
230000008733 trauma Effects 0.000 description 1
238000011179 visual inspection Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
- 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
- A61P25/06—Antimigraine agents
- 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
- A61P25/20—Hypnotics; Sedatives
- 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
- A61P25/22—Anxiolytics
- 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
- A61P25/24—Antidepressants
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Anesthesiology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Addiction (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Plural Heterocyclic Compounds (AREA)
Furan Compounds (AREA)

NO20041848A 2001-11-09 2004-05-05 Nye mandelatsalter av substituerte tetracykliske tetrahydrofuranderivater NO328548B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP01204465		2001-11-09
PCT/EP2002/011136 WO2003040122A1 (en)	2001-11-09	2002-11-08	Novel mandelate salts of substituted tetracyclic tetrahydrofuran derivatives

Publications (2)

Publication Number	Publication Date
NO20041848L NO20041848L (no)	2004-05-05
NO328548B1 true NO328548B1 (no)	2010-03-15

Family

ID=8181272

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20041848A NO328548B1 (no)	2001-11-09	2004-05-05	Nye mandelatsalter av substituerte tetracykliske tetrahydrofuranderivater

Country Status (25)

Country	Link
US (1)	US7317115B2 (de)
EP (1)	EP1446397B1 (de)
JP (1)	JP2005508988A (de)
KR (1)	KR100962325B1 (de)
CN (1)	CN1582282B (de)
AR (1)	AR037285A1 (de)
AT (1)	ATE299138T1 (de)
AU (1)	AU2002349327B2 (de)
BR (1)	BR0212770A (de)
CA (1)	CA2465043C (de)
DE (1)	DE60204982T2 (de)
EA (1)	EA006980B1 (de)
ES (1)	ES2244818T3 (de)
HR (1)	HRP20040395A2 (de)
HU (1)	HUP0402224A3 (de)
IL (2)	IL161866A0 (de)
MX (1)	MXPA04004365A (de)
MY (1)	MY128237A (de)
NO (1)	NO328548B1 (de)
NZ (1)	NZ531739A (de)
PL (1)	PL368456A1 (de)
TW (1)	TW200407117A (de)
UA (1)	UA79248C2 (de)
WO (1)	WO2003040122A1 (de)
ZA (1)	ZA200403454B (de)

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EP2335700A1 (de)	2001-07-25	2011-06-22	Boehringer Ingelheim (Canada) Ltd.	Hepatitis C Virus Polymerase Inhibitoren mit heterobicylischer Struktur
ATE294168T1 (de) *	2001-12-07	2005-05-15	Janssen Pharmaceutica Nv	Herstellung von trans-kondensierte 3,3a,8,12b- tetrahydro-2h-dibenzo(3,4:6,7)cyclohepta(1,2- b)furan derivaten
WO2005013969A1 (en) *	2003-07-15	2005-02-17	Janssen Pharmaceutica N.V.	Antipsychotic agent with socializing properties
RU2401257C2 (ru)	2004-12-07	2010-10-10	Янссен Фармацевтика Н.В.	Новые замещенные тетрациклические производные тетрагидрофурана, пирролидина и тетрагидротиофена
MX2007009092A (es)	2005-01-27	2007-09-12	Janssen Pharmaceutica Nv	Derivados de tetrahidrofurano tetraciclicos heterociclicos como inhibidores de 5ht2 en el tratamiento de trastornos del sistema nervioso central.
CN101228154B (zh)	2005-06-17	2014-01-29	詹森药业有限公司	包含环状胺侧链的四环四氢呋喃衍生物
US8765223B2 (en) *	2008-05-08	2014-07-01	Air Products And Chemicals, Inc.	Binary and ternary metal chalcogenide materials and method of making and using same
US8507040B2 (en)	2008-05-08	2013-08-13	Air Products And Chemicals, Inc.	Binary and ternary metal chalcogenide materials and method of making and using same
US8962675B1 (en) *	2013-09-12	2015-02-24	Abbvie Inc.	Atrasentan mandelate salts

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DE3644462A1 (de) *	1986-12-24	1988-07-07	Basf Ag	Verfahren zur herstellung von 5h-dibenzo(a,d)cyclohepten-5-onen
JP2656720B2 (ja) *	1992-12-09	1997-09-24	武田薬品工業株式会社	光学活性アミノクマラン誘導体
DK0750616T3 (da) *	1994-03-16	2001-07-23	Cenes Ltd	Syreadditionssalte af 2,3,4,5-tetrahydro-1H-3-benzazapinforbindelser
DE69720709T2 (de) *	1996-04-12	2004-03-11	Janssen Pharmaceutica N.V.	Substituierte tetracyclische tetrahydrofuranderivate
DK0904060T3 (da)	1996-05-20	2004-04-13	Janssen Pharmaceutica Nv	Antifungale præparater med forbedret biotilgængelighed
UA52778C2 (uk)	1997-10-10	2003-01-15	Янссен Фармацевтика Н.В.	Галогенозаміщені тетрациклічні похідні тетрагідрофурану, спосіб їх отримання та композиція на їх основі
US6281247B1 (en) *	1998-03-03	2001-08-28	Novo Nordisk A/S	Salt forms of (2E)-5-amino-5-methylhex-2-enoic acid N-methyl-N-((1R)-1-(N-methyl-N-((1R)-1-(methylcarbamoyl)-2-phenylethyl)carbamoyl)-2-(2-naphthyl)ethyl)amide
HUP9904624A2 (hu) *	1999-12-17	2002-01-28	Sanofi-Synthelabo	Szacharinszármazékok, eljárás előállításukra, az ezeket tartalmazó gyógyszerkészítmények és intermedierjeik
EP1186303A3 (de) *	2000-09-06	2003-12-10	Pfizer Products Inc.	Ein Neutrophilhemmender Faktor und ein selektive NMDA-NR2B Rezeptor Antagonisten enthaltende Kombinationspräparate zur Behandlung von Schlaganfällen und traumatischen Gehirnschäden

2002
- 2002-08-11 UA UA20040604168A patent/UA79248C2/uk unknown
- 2002-11-07 MY MYPI20024166A patent/MY128237A/en unknown
- 2002-11-08 MX MXPA04004365A patent/MXPA04004365A/es active IP Right Grant
- 2002-11-08 EP EP02781214A patent/EP1446397B1/de not_active Expired - Lifetime
- 2002-11-08 EA EA200400656A patent/EA006980B1/ru not_active IP Right Cessation
- 2002-11-08 KR KR1020047002379A patent/KR100962325B1/ko not_active Expired - Fee Related
- 2002-11-08 CN CN02821918XA patent/CN1582282B/zh not_active Expired - Fee Related
- 2002-11-08 BR BR0212770-9A patent/BR0212770A/pt not_active IP Right Cessation
- 2002-11-08 DE DE60204982T patent/DE60204982T2/de not_active Expired - Lifetime
- 2002-11-08 IL IL16186602A patent/IL161866A0/xx unknown
- 2002-11-08 AR ARP020104298A patent/AR037285A1/es unknown
- 2002-11-08 NZ NZ531739A patent/NZ531739A/en not_active IP Right Cessation
- 2002-11-08 HR HR20040395A patent/HRP20040395A2/hr not_active Application Discontinuation
- 2002-11-08 PL PL02368456A patent/PL368456A1/xx unknown
- 2002-11-08 US US10/491,799 patent/US7317115B2/en not_active Expired - Fee Related
- 2002-11-08 ES ES02781214T patent/ES2244818T3/es not_active Expired - Lifetime
- 2002-11-08 HU HU0402224A patent/HUP0402224A3/hu unknown
- 2002-11-08 CA CA2465043A patent/CA2465043C/en not_active Expired - Fee Related
- 2002-11-08 AU AU2002349327A patent/AU2002349327B2/en not_active Ceased
- 2002-11-08 JP JP2003542168A patent/JP2005508988A/ja active Pending
- 2002-11-08 TW TW091132840A patent/TW200407117A/zh unknown
- 2002-11-08 WO PCT/EP2002/011136 patent/WO2003040122A1/en not_active Ceased
- 2002-11-08 AT AT02781214T patent/ATE299138T1/de not_active IP Right Cessation
2004
- 2004-05-05 NO NO20041848A patent/NO328548B1/no not_active IP Right Cessation
- 2004-05-06 IL IL161866A patent/IL161866A/en not_active IP Right Cessation
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Also Published As

Publication number	Publication date
AU2002349327B2 (en)	2008-10-23
EP1446397B1 (de)	2005-07-06
NO20041848L (no)	2004-05-05
IL161866A0 (en)	2005-11-20
ES2244818T3 (es)	2005-12-16
TW200407117A (en)	2004-05-16
EA200400656A1 (ru)	2004-10-28
MXPA04004365A (es)	2004-08-11
EA006980B1 (ru)	2006-06-30
KR20050044310A (ko)	2005-05-12
KR100962325B1 (ko)	2010-06-11
ATE299138T1 (de)	2005-07-15
MY128237A (en)	2007-01-31
CA2465043C (en)	2011-02-15
US7317115B2 (en)	2008-01-08
HUP0402224A2 (hu)	2005-02-28
WO2003040122A1 (en)	2003-05-15
CN1582282B (zh)	2012-06-06
BR0212770A (pt)	2004-10-13
HRP20040395A2 (en)	2005-04-30
DE60204982T2 (de)	2006-04-27
US20050085533A1 (en)	2005-04-21
JP2005508988A (ja)	2005-04-07
EP1446397A1 (de)	2004-08-18
IL161866A (en)	2010-04-29
CN1582282A (zh)	2005-02-16
UA79248C2 (en)	2007-06-11
DE60204982D1 (de)	2005-08-11
CA2465043A1 (en)	2003-05-15
HUP0402224A3 (en)	2007-05-29
ZA200403454B (en)	2005-08-31
AR037285A1 (es)	2004-11-03
PL368456A1 (en)	2005-03-21
NZ531739A (en)	2005-02-25

Legal Events

Date	Code	Title	Description
2012-05-21	CREP	Change of representative	Representative=s name: ZACCO NORWAY AS, POSTBOKS 2003 VIKA
2013-06-24	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO317159B1 (no)	2004-08-30	Halogensubstituerte tetrasykliske tetrahydrofuranderivater
NO317156B1 (no)	2004-08-30	Substituerte tetracykliske tetrahydrofuranderivater
NO314581B1 (no)	2003-04-14	Opplösning av aminer
AU2002349327B2 (en)	2008-10-23	Novel mandelate salts of substituted tetracyclic tetrahydrofuran derivatives
AU2002349327A1 (en)	2003-07-24	Novel mandelate salts of substituted tetracyclic tetrahydrofuran derivatives
EP1456193B1 (de)	2005-04-27	Herstellung von trans-kondensierte 3,3a,8,12b-tetrahydro-2h-dibenzo[3,4:6,7]cyclohepta[1,2-b]furan derivaten
EP1463722A2 (de)	2004-10-06	HERSTELLUNG CIS-ANELLIERTER 3,3a,8,12b-TETRAHYDRO-2H-DIBENZO[3,4:6,7]CYCLOHEPTA[1,2-b]FURANDERIVATE
FR2555580A1 (fr)	1985-05-31	Nouveaux composes azabicycliques, procede pour les preparer et medicaments les contenant
NO309084B1 (no)	2000-12-11	FremgangsmÕte for fremstilling av 5-okso-3-fenyl-3- cykloheksenkarboksylsyre
HK1072938A (en)	2005-09-16	Novel mandelate salts of substituted tetracyclic tetrahydrofuran derivatives
MXPA00003468A (en)	2001-12-04	Halogen substituted tetracyclic tetrahydrofuran derivatives
AU6547400A (en)	2001-04-26	Process for the preparation of piperidinylaminomethyl trifluoromethyl cyclic ether compounds
CN106928139A (zh)	2017-07-07	一种贝达喹啉杂质的合成方法
HK1029106B (en)	2003-07-18	Halogen substituted tetracyclic tetrahydrofuran derivatives