SK282789B6 - Spôsob výroby fenylheterocyklických zlúčenín a medziprodukt - Google Patents

Spôsob výroby fenylheterocyklických zlúčenín a medziprodukt Download PDF

Info

Publication number: SK282789B6
Authority: SK; Slovakia
Prior art keywords: compound; formula; solvent; carried out; alkyl
Prior art date: 1994-09-16

Application number

SK316-97A

Other languages

English (en)

Slovak (sk)

Other versions

SK31697A3 (en

Inventor

Richard Desmond

Ulf H. Dolling

Ben Marcune

Richard D. Tillyer

David M. Tschaen

Original Assignee

Merck & Co., Inc.

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.)

1994-09-16

Filing date

1995-09-12

Publication date

2002-12-03

1995-09-12 Application filed by Merck & Co., Inc. filed Critical Merck & Co., Inc.

1997-10-08 Publication of SK31697A3 publication Critical patent/SK31697A3/sk

2002-12-03 Publication of SK282789B6 publication Critical patent/SK282789B6/sk

Links

238000000034 method Methods 0.000 title claims description 21
230000008569 process Effects 0.000 title claims description 18
150000001875 compounds Chemical class 0.000 claims description 98
239000000460 chlorine Substances 0.000 claims description 36
239000002904 solvent Substances 0.000 claims description 31
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
238000006243 chemical reaction Methods 0.000 claims description 19
239000003795 chemical substances by application Substances 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 17
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 15
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 15
230000003213 activating effect Effects 0.000 claims description 14
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 14
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
239000003054 catalyst Substances 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 11
-1 potassium alkoxide Chemical class 0.000 claims description 11
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 11
238000002360 preparation method Methods 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229910052723 transition metal Inorganic materials 0.000 claims description 10
150000003624 transition metals Chemical class 0.000 claims description 10
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 9
125000004429 atom Chemical group 0.000 claims description 9
230000008878 coupling Effects 0.000 claims description 9
238000010168 coupling process Methods 0.000 claims description 9
238000005859 coupling reaction Methods 0.000 claims description 9
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
239000011591 potassium Substances 0.000 claims description 8
229910000029 sodium carbonate Inorganic materials 0.000 claims description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
125000005270 trialkylamine group Chemical group 0.000 claims description 8
229910052700 potassium Inorganic materials 0.000 claims description 7
239000011734 sodium Substances 0.000 claims description 7
229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
229910052708 sodium Inorganic materials 0.000 claims description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 5
239000003495 polar organic solvent Substances 0.000 claims description 5
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229910052701 rubidium Inorganic materials 0.000 claims description 5
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238000007254 oxidation reaction Methods 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
230000003647 oxidation Effects 0.000 claims description 3
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
KLKFAASOGCDTDT-UHFFFAOYSA-N ethoxymethoxyethane Chemical compound CCOCOCC KLKFAASOGCDTDT-UHFFFAOYSA-N 0.000 claims 4
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ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
239000004480 active ingredient Substances 0.000 description 11
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ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
229910052751 metal Inorganic materials 0.000 description 8
239000002184 metal Substances 0.000 description 8
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239000000725 suspension Substances 0.000 description 7
238000005160 1H NMR spectroscopy Methods 0.000 description 6
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
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239000003444 phase transfer catalyst Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
230000035790 physiological processes and functions Effects 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
230000004044 response Effects 0.000 description 1
201000003068 rheumatic fever Diseases 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
150000003839 salts Chemical class 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
210000001625 seminal vesicle Anatomy 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000007779 soft material Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
238000003860 storage Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
201000004595 synovitis Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
229910021515 thallium hydroxide Inorganic materials 0.000 description 1
QGYXCSSUHCHXHB-UHFFFAOYSA-M thallium(i) hydroxide Chemical compound [OH-].[Tl+] QGYXCSSUHCHXHB-UHFFFAOYSA-M 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
208000004371 toothache Diseases 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000012546 transfer Methods 0.000 description 1
NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
201000010653 vesiculitis Diseases 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000009736 wetting Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/675—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids of saturated hydroxy-carboxylic acids
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- 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
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/58—One oxygen atom, e.g. butenolide

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Oncology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Engineering & Computer Science (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Virology (AREA)
Communicable Diseases (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

SK316-97A 1994-09-16 1995-09-12 Spôsob výroby fenylheterocyklických zlúčenín a medziprodukt SK282789B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/307,972 US5585504A (en)	1994-09-16	1994-09-16	Process of making cox-2 inhibitors having a lactone bridge
PCT/US1995/011539 WO1996008482A1 (en)	1994-09-16	1995-09-12	Process for making phenyl heterocycles useful as cox-2 inhibitors

Publications (2)

Publication Number	Publication Date
SK31697A3 SK31697A3 (en)	1997-10-08
SK282789B6 true SK282789B6 (sk)	2002-12-03

Family

ID=23191976

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK316-97A SK282789B6 (sk)	1994-09-16	1995-09-12	Spôsob výroby fenylheterocyklických zlúčenín a medziprodukt

Country Status (12)

Country	Link
US (1)	US5585504A (fi)
CN (1)	CN1065533C (fi)
AU (1)	AU3510595A (fi)
BR (1)	BR9508927A (fi)
CZ (1)	CZ288797B6 (fi)
FI (1)	FI106376B (fi)
RO (1)	RO118585B1 (fi)
RU (1)	RU2160257C2 (fi)
SK (1)	SK282789B6 (fi)
TW (1)	TW325468B (fi)
UA (1)	UA49809C2 (fi)
WO (1)	WO1996008482A1 (fi)

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FR2747123B1 (fr) *	1996-04-04	1998-06-26	Union Pharma Scient Appl	Nouveaux derives diarylmethylidene tetrahydrofurane, leurs procedes de preparation, et leurs utilisations en therapeutique
US5883267A (en) *	1996-05-31	1999-03-16	Merck & Co., Inc.	Process for making phenyl heterocycles useful as cox-2 inhibitors
HRP970289A2 (en) *	1996-05-31	1998-04-30	Merck & Co Inc	Process for preparing phenyl heterocycles useful as cox-2 inhibitors
US5985930A (en)	1996-11-21	1999-11-16	Pasinetti; Giulio M.	Treatment of neurodegenerative conditions with nimesulide
US6200760B1 (en)	1997-02-24	2001-03-13	Cornell Research Foundation, Inc.	Method of screening agents as candidates for drugs or sources of drugs
US6071954A (en) *	1997-03-14	2000-06-06	Merk Frosst Canada, Inc.	(methylsulfonyl)phenyl-2-(5H)-furanones with oxygen link as COX-2 inhibitors
ATE244232T1 (de) *	1997-03-14	2003-07-15	Merck Frosst Canada Inc	(methylsulfonyl)phenyl-2-(5h)-furanone mit sauerstoff-bindung als cox-2-hemmer
US6727238B2 (en) *	1998-06-11	2004-04-27	Pfizer Inc.	Sulfonylbenzene compounds as anti-inflammatory/analgesic agents
TNSN99111A1 (fr) *	1998-06-11	2005-11-10	Pfizer	Derives de sulfonylbenzene nouveaux, procede pour leur preparation et compositions pharmaceutiques les contenant.
US6294558B1 (en) *	1999-05-31	2001-09-25	Pfizer Inc.	Sulfonylbenzene compounds as anti-inflammatory/analgesic agents
ES2249253T3 (es) *	1999-03-10	2006-04-01	G.D. Searle Llc	Metodo y composicion para administrar un inhibidor de la ciclooxigenasa-2.
DK1104760T3 (da)	1999-12-03	2003-06-30	Pfizer Prod Inc	Sulfamoylheteroarylpyrazolforbindelser som anti-inflammatoriske/analgetiske midler
DE60018792T2 (de)	1999-12-03	2006-01-26	Pfizer Products Inc., Groton	Heterocyclo-alkylsulfonylpyrazolderivate zur verwendung als anti-imflammatorische oder analgetische verbindungen
PT1104758E (pt)	1999-12-03	2003-12-31	Pfizer Prod Inc	Derivados de acetileno como agentes anti-inflamatorios/analgesicos
ATE252576T1 (de)	1999-12-03	2003-11-15	Pfizer Prod Inc	Heteroarylphenylpyrazolverbindungen zur verwendung als analgetisches/entzündungshemmendes mittel
SK12672001A3 (sk)	1999-12-08	2002-04-04	Pharmacia Corporation	Zloženia inhibítora cyklooxygenázy-2 s rýchlym nástupom terapeutického účinku
DE10012825B4 (de)	2000-03-16	2004-04-15	Bayer Corp.	Verfahren zur Herstellung von spirocyclischen Tetronsäurederivaten
CN1102586C (zh) *	2000-04-07	2003-03-05	中国科学院上海有机化学研究所	β位含有芳基取代基的γ－丁烯酸内酯及其固相合成法
CA2414674A1 (en) *	2000-07-13	2002-01-24	Pharmacia Corporation	Use of cox-2 inhibitors in the treatment and prevention of ocular cox-2 mediated disorders
WO2002017896A2 (en) *	2000-08-29	2002-03-07	Peter Van Patten	Combination for the treatment of migraine comprising a cyclooxygenase-2 inhibitor and acetylsalicylic acid
US7115565B2 (en) *	2001-01-18	2006-10-03	Pharmacia & Upjohn Company	Chemotherapeutic microemulsion compositions of paclitaxel with improved oral bioavailability
PE20021017A1 (es)	2001-04-03	2002-11-24	Pharmacia Corp	Composicion parenteral reconstituible
EP1273582B1 (en)	2001-07-05	2005-06-29	Pfizer Products Inc.	Heterocyclo-alkylsulfonyl pyrazoles as anti-inflammatory/analgesic agents
UA80682C2 (en) *	2001-08-06	2007-10-25	Pharmacia Corp	Orally deliverable stabilized oral suspension formulation and process for the incresaing physical stability of thixotropic pharmaceutical composition
GT200200183A (es)	2001-09-28	2003-05-23		Procedimiento para preparar derivados de heterocicloalquilsulfonil pirazol
WO2003037336A1 (en)	2001-11-02	2003-05-08	Pfizer Products Inc.	1-(5-sulfonyl-pyridin-2-yl)-5-(methylidene-cycloalkylmethoxy)-1h-pyrazole-4-carbonitrile derivatives and other compounds as cyclooxygenase inhibitors for the treatment of arthritis, neurodegeneration and colon cancer
ES2213485B1 (es)	2003-02-13	2005-12-16	Almirall Prodesfarma, S.A.	Derivados de la 2-fenilpiran-4-ona.
EP1745791B1 (en) *	2003-05-07	2013-06-26	Osteologix A/S	Treating cartilage/bone conditions with water-soluble strontium salts
EP2266584B1 (en) *	2003-05-07	2012-09-05	Osteologix A/S	Composition with strontium and vitamin D for the prophylaxis and/or treatment of cartilage and/or bone conditions
WO2005016906A1 (en) *	2003-08-14	2005-02-24	Shasun Chemicals And Drugs Limited	Process for the manufacture of rofecoxib
WO2005044227A1 (en) *	2003-11-05	2005-05-19	Glenmark Pharmaceuticals Limited	Topical pharmaceutical compositions
US20050100594A1 (en) *	2003-11-12	2005-05-12	Nilendu Sen	Pharmaceutical formulation containing muscle relaxant and COX-II inhibitor
JP7291220B2 (ja)	2018-11-21	2023-06-14	トレモ― ファーマシューティカルズ，インコーポレーテッド	ロフェコキシブの精製形態、製造方法および使用
US10945992B1 (en)	2019-11-13	2021-03-16	Tremeau Pharmaceuticals, Inc.	Dosage forms of rofecoxib and related methods
US11161833B1 (en)	2021-04-09	2021-11-02	Tremeau Pharmaceuticals, Inc.	Deuterated etoricoxib, methods of manufacture, and use thereof

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1994
- 1994-09-16 US US08/307,972 patent/US5585504A/en not_active Expired - Fee Related
1995
- 1995-09-08 TW TW084109387A patent/TW325468B/zh active
- 1995-09-12 RU RU97106093/04A patent/RU2160257C2/ru not_active IP Right Cessation
- 1995-09-12 BR BR9508927A patent/BR9508927A/pt not_active Application Discontinuation
- 1995-09-12 CN CN95195075A patent/CN1065533C/zh not_active Expired - Fee Related
- 1995-09-12 WO PCT/US1995/011539 patent/WO1996008482A1/en active Search and Examination
- 1995-09-12 SK SK316-97A patent/SK282789B6/sk unknown
- 1995-09-12 RO RO97-00484A patent/RO118585B1/ro unknown
- 1995-09-12 CZ CZ1997792A patent/CZ288797B6/cs not_active IP Right Cessation
- 1995-09-12 UA UA97041788A patent/UA49809C2/uk unknown
- 1995-09-12 AU AU35105/95A patent/AU3510595A/en not_active Abandoned
1997
- 1997-03-14 FI FI971104A patent/FI106376B/fi not_active IP Right Cessation

Also Published As

Publication number	Publication date
CN1159191A (zh)	1997-09-10
WO1996008482A1 (en)	1996-03-21
FI971104A0 (fi)	1997-03-14
CZ288797B6 (cs)	2001-09-12
RO118585B1 (ro)	2003-07-30
SK31697A3 (en)	1997-10-08
CZ79297A3 (en)	1997-07-16
BR9508927A (pt)	1997-12-30
TW325468B (en)	1998-01-21
UA49809C2 (uk)	2002-10-15
FI971104L (fi)	1997-03-14
AU3510595A (en)	1996-03-29
FI106376B (fi)	2001-01-31
RU2160257C2 (ru)	2000-12-10
US5585504A (en)	1996-12-17
CN1065533C (zh)	2001-05-09

Publication	Publication Date	Title
SK282789B6 (sk)	2002-12-03	Spôsob výroby fenylheterocyklických zlúčenín a medziprodukt
US5604253A (en)	1997-02-18	N-benzylindol-3-yl propanoic acid derivatives as cyclooxygenase inhibitors
US5436265A (en)	1995-07-25	1-aroyl-3-indolyl alkanoic acids and derivatives thereof useful as anti-inflammatory agents
AU749618B2 (en)	2002-06-27	Biaryl-acetic acid derivatives and their use as COX-2 inhibitors
EP1246809B1 (en)	2003-07-16	5-aryl-1h-1,2,4-triazole compounds as inhibitors of cyclooxygenase-2 and pharmaceutical compositions containing them
US6204387B1 (en)	2001-03-20	Process for making diaryl pyridines useful as COX-2 inhibitors
US6127545A (en)	2000-10-03	Process for making 2-aryl-3-aryl-5-halo pyridines useful as COX-2 inhibitors
SK284114B6 (sk)	2004-09-08	Fenylheterocyklické deriváty, spôsob ich výroby, ich použitie a farmaceutické prostriedky s ich obsahom
SK283811B6 (sk)	2004-02-03	Spôsob výroby diarylpyridínov a jeho medziproduktov
US6130334A (en)	2000-10-10	Process for making 2-aryl-3-aryl-5-halo pyridines useful as COX-2 inhibitors
WO1999014194A1 (en)	1999-03-25	2,3,5-trisubstituted pyridines as inhibitors of cyclooxygenase-2
WO2004103955A1 (en)	2004-12-02	Nitric oxide releasing prodrugs of diaryl-2-(5h)-furanones as cyclooxygenase-2 inhibitors
US6080876A (en)	2000-06-27	Process for making phenyl heterocycles useful as COX-2 inhibitors
ES2223128T3 (es)	2005-02-16	Procedimiento de fabricacion de 2-aril-3-aril-5-halopiridinas utiles como inhibidoras de cox-2.
CZ241698A3 (cs)	1998-12-16	Difenylstilbenové deriváty a farmaceutický prostředek
EP2459532B1 (en)	2014-04-09	Antitumor 1,2-diphenylpyrrole compounds and their preparation process
US6495713B2 (en)	2002-12-17	Synthesis of ketosulfone esters
AU2004240700B2 (en)	2010-02-11	Nitric oxide releasing prodrugs of diaryl-2-(5H)-furanones as cyclooxygenase-2 inhibitors