NO174805B - Analogifremgangsmåte for fremstilling av terapeutisk aktive oksimkarbamater og oksim-karbonater - Google Patents

Analogifremgangsmåte for fremstilling av terapeutisk aktive oksimkarbamater og oksim-karbonater Download PDF

Info

Publication number: NO174805B
Authority: NO; Norway
Prior art keywords: mmol; oxime; methylene chloride; methoxyphenyl; cyclopentyloxy
Prior art date: 1990-08-08

Application number

NO913065A

Other languages

English (en)

Norwegian (no)

Other versions

NO174805C (cs

NO913065D0 (no

NO913065L (no

Inventor

Louis John Lombardo

Original Assignee

American Home Prod

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.)

1990-08-08

Filing date

1991-08-07

Publication date

1994-04-05

1991-08-07 Application filed by American Home Prod filed Critical American Home Prod

1991-08-07 Publication of NO913065D0 publication Critical patent/NO913065D0/no

1992-02-10 Publication of NO913065L publication Critical patent/NO913065L/no

1994-04-05 Publication of NO174805B publication Critical patent/NO174805B/no

1994-07-13 Publication of NO174805C publication Critical patent/NO174805C/no

Links

238000000034 method Methods 0.000 title claims description 42
238000002360 preparation method Methods 0.000 title claims description 10
150000001875 compounds Chemical class 0.000 claims abstract description 67
150000002923 oximes Chemical class 0.000 claims abstract description 27
-1 loweralkylamino Chemical group 0.000 claims abstract description 19
125000000217 alkyl group Chemical group 0.000 claims abstract description 11
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 5
238000006243 chemical reaction Methods 0.000 claims description 18
VWNHESFEFMDDOY-UHFFFAOYSA-N 1-(3-butoxy-4-methoxyphenyl)ethanone Chemical compound CCCCOC1=CC(C(C)=O)=CC=C1OC VWNHESFEFMDDOY-UHFFFAOYSA-N 0.000 claims description 6
239000007858 starting material Substances 0.000 claims description 6
STUPRJVKLDILNL-UHFFFAOYSA-N 1-(3-cyclopentyloxy-4-methoxyphenyl)-2-phenylethanone Chemical compound COC1=CC=C(C(=O)CC=2C=CC=CC=2)C=C1OC1CCCC1 STUPRJVKLDILNL-UHFFFAOYSA-N 0.000 claims description 5
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
BFQYBNXJQBXNSS-UHFFFAOYSA-N 1-(3-cyclopentyloxy-4-methoxyphenyl)-3-phenylpropan-2-one Chemical compound C1=C(OC2CCCC2)C(OC)=CC=C1CC(=O)CC1=CC=CC=C1 BFQYBNXJQBXNSS-UHFFFAOYSA-N 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
KTQNWVIHYKDPEV-UHFFFAOYSA-N 1-[3-(3-bicyclo[2.2.1]heptanyloxy)-4-methoxyphenyl]ethanone Chemical compound COC1=CC=C(C(C)=O)C=C1OC1C(C2)CCC2C1 KTQNWVIHYKDPEV-UHFFFAOYSA-N 0.000 claims 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
STTRYQAGHGJXJJ-LICLKQGHSA-N filaminast Chemical compound COC1=CC=C(C(\C)=N\OC(N)=O)C=C1OC1CCCC1 STTRYQAGHGJXJJ-LICLKQGHSA-N 0.000 claims 1
239000012948 isocyanate Substances 0.000 claims 1
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150000002431 hydrogen Chemical class 0.000 abstract 2
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UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 1
108010044467 Isoenzymes Proteins 0.000 abstract 1
125000001475 halogen functional group Chemical group 0.000 abstract 1
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YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 189
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
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VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
239000008346 aqueous phase Substances 0.000 description 8
RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 8
230000000694 effects Effects 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
239000011734 sodium Substances 0.000 description 7
238000012360 testing method Methods 0.000 description 6
KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 5
229910004298 SiO 2 Inorganic materials 0.000 description 5
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QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
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WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 4
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239000000047 product Substances 0.000 description 4
ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 4
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229960005305 adenosine Drugs 0.000 description 1
102000030621 adenylate cyclase Human genes 0.000 description 1
108060000200 adenylate cyclase Proteins 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
201000009961 allergic asthma Diseases 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000001088 anti-asthma Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
229940033687 beuthanasia Drugs 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
208000030303 breathing problems Diseases 0.000 description 1
BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
230000007883 bronchodilation Effects 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
230000006020 chronic inflammation Effects 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
210000002808 connective tissue Anatomy 0.000 description 1
230000008602 contraction Effects 0.000 description 1
239000012043 crude product Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000006471 dimerization reaction Methods 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229940029575 guanosine Drugs 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000005457 ice water Substances 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
201000010659 intrinsic asthma Diseases 0.000 description 1
239000008101 lactose Substances 0.000 description 1
238000002386 leaching Methods 0.000 description 1
210000000265 leukocyte Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
YSMZEMQBSONIMJ-UHFFFAOYSA-M magnesium;2-methanidylpropane;chloride Chemical compound [Mg+2].[Cl-].CC(C)[CH2-] YSMZEMQBSONIMJ-UHFFFAOYSA-M 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
150000004712 monophosphates Chemical class 0.000 description 1
229940105631 nembutal Drugs 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
MSHFRERJPWKJFX-UHFFFAOYSA-N para-methoxybenzyl alcohol Natural products COC1=CC=C(CO)C=C1 MSHFRERJPWKJFX-UHFFFAOYSA-N 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
239000012071 phase Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000004033 plastic Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
210000003019 respiratory muscle Anatomy 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
238000012552 review Methods 0.000 description 1
HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
229950005741 rolipram Drugs 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910052814 silicon oxide Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
230000001300 stimulation of adenylate cyclase Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
239000000196 tragacanth 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
230000009466 transformation Effects 0.000 description 1
UVDTXTAXFIUJCQ-UHFFFAOYSA-N uranium tetrahydrate Chemical compound O.O.O.O.[U] UVDTXTAXFIUJCQ-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/62—Oximes having oxygen atoms of oxyimino groups esterified
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/32—Oximes
- C07C251/34—Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/24—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a ring other than a six-membered aromatic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/60—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups having oxygen atoms of carbamate groups bound to nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/36—Systems containing two condensed rings the rings having more than two atoms in common
- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Pulmonology (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Polyesters Or Polycarbonates (AREA)
Reinforced Plastic Materials (AREA)
Quinoline Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Medicinal Preparation (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

NO913065A 1990-08-08 1991-08-07 Analogifremgangsmåte for fremstilling av terapeutisk aktive oksimkarbamater og oksim-karbonater NO174805B (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US07/564,263 US5124455A (en)	1990-08-08	1990-08-08	Oxime-carbamates and oxime-carbonates as bronchodilators and anti-inflammatory agents

Publications (4)

Publication Number	Publication Date
NO913065D0 NO913065D0 (no)	1991-08-07
NO913065L NO913065L (no)	1992-02-10
NO174805B true NO174805B (no)	1994-04-05
NO174805C NO174805C (cs)	1994-07-13

Family

ID=24253782

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO913065A NO174805B (no)	1990-08-08	1991-08-07	Analogifremgangsmåte for fremstilling av terapeutisk aktive oksimkarbamater og oksim-karbonater

Country Status (24)

Country	Link
US (1)	US5124455A (cs)
EP (1)	EP0470805B1 (cs)
JP (1)	JP2651292B2 (cs)
KR (1)	KR920004335A (cs)
CN (1)	CN1029613C (cs)
AT (1)	ATE111076T1 (cs)
AU (1)	AU640251B2 (cs)
CA (1)	CA2048518A1 (cs)
CS (1)	CS245091A3 (cs)
CY (1)	CY2057B1 (cs)
DE (1)	DE69103846T2 (cs)
DK (1)	DK0470805T3 (cs)
ES (1)	ES2060307T3 (cs)
FI (1)	FI913738A7 (cs)
GB (1)	GB2246777B (cs)
HU (3)	HU207289B (cs)
IE (1)	IE66049B1 (cs)
IL (1)	IL99081A (cs)
MX (1)	MX9100549A (cs)
NO (1)	NO174805B (cs)
NZ (1)	NZ239279A (cs)
PT (1)	PT98596B (cs)
RU (1)	RU2051145C1 (cs)
ZA (1)	ZA916154B (cs)

Families Citing this family (94)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5430176A (en) *	1990-07-06	1995-07-04	The Upjohn Company	Intermediate used for the preparation of deferoxamine
US5698711A (en)	1991-01-28	1997-12-16	Rhone-Poulenc Rorer Limited	Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group
GB9311281D0 (en) *	1993-06-01	1993-07-21	Rhone Poulenc Rorer Ltd	Novel composition of matter
GB9204808D0 (en) *	1992-03-04	1992-04-15	Rhone Poulenc Rorer Ltd	Novel compositions of matter
GB9212673D0 (en) *	1992-06-15	1992-07-29	Celltech Ltd	Chemical compounds
CZ14795A3 (en) *	1992-07-28	1996-07-17	Rhone Poulenc Rorer Ltd	Benzene derivative containing phenyl group bound to aryl or heteroaryl fraction through an aliphatic or hetero atom containing group, process of its preparation and pharmaceutical composition containing thereof
US5679696A (en) *	1992-07-28	1997-10-21	Rhone-Poulenc Rorer Limited	Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic-or heteroatom-containing linking group
GB9222253D0 (en) *	1992-10-23	1992-12-09	Celltech Ltd	Chemical compounds
US5622977A (en) *	1992-12-23	1997-04-22	Celltech Therapeutics Limited	Tri-substituted (aryl or heteroaryl) derivatives and pharmaceutical compositions containing the same
GB9226830D0 (en) *	1992-12-23	1993-02-17	Celltech Ltd	Chemical compounds
GB9304920D0 (en) *	1993-03-10	1993-04-28	Celltech Ltd	Chemical compounds
GB9304919D0 (en) *	1993-03-10	1993-04-28	Celltech Ltd	Chemical compounds
GB9312853D0 (en)	1993-06-22	1993-08-04	Euro Celtique Sa	Chemical compounds
US5665754A (en) *	1993-09-20	1997-09-09	Glaxo Wellcome Inc.	Substituted pyrrolidines
US5502072A (en) *	1993-11-26	1996-03-26	Pfizer Inc.	Substituted oxindoles
GB9326173D0 (en) *	1993-12-22	1994-02-23	Celltech Ltd	Chemical compounds and process
EP0738268B1 (en) *	1993-12-22	2004-03-03	Celltech R&D Limited	Trisubstituted phenyl derivatives, processes for their preparation and their use as phosphodiesterase (type iv) inhibitors
US5786354A (en) *	1994-06-21	1998-07-28	Celltech Therapeutics, Limited	Tri-substituted phenyl derivatives and processes for their preparation
US6245774B1 (en)	1994-06-21	2001-06-12	Celltech Therapeutics Limited	Tri-substituted phenyl or pyridine derivatives
GB9412571D0 (en)	1994-06-22	1994-08-10	Celltech Ltd	Chemical compounds
GB9412573D0 (en) *	1994-06-22	1994-08-10	Celltech Ltd	Chemical compounds
GB9412672D0 (en) *	1994-06-23	1994-08-10	Celltech Ltd	Chemical compounds
US5591776A (en) *	1994-06-24	1997-01-07	Euro-Celtique, S.A.	Pheynl or benzyl-substituted rolipram-based compounds for and method of inhibiting phosphodiesterase IV
US5922751A (en)	1994-06-24	1999-07-13	Euro-Celtique, S.A.	Aryl pyrazole compound for inhibiting phosphodiesterase IV and methods of using same
US6514949B1 (en)	1994-07-11	2003-02-04	University Of Virginia Patent Foundation	Method compositions for treating the inflammatory response
US6448235B1 (en)	1994-07-11	2002-09-10	University Of Virginia Patent Foundation	Method for treating restenosis with A2A adenosine receptor agonists
US5665737B1 (en) *	1994-10-12	1999-02-16	Euro Celtique Sa	Substituted benzoxazoles
US6025361A (en) *	1994-12-13	2000-02-15	Euro-Celtique, S.A.	Trisubstituted thioxanthines
DE69531506T2 (de)	1994-12-13	2004-06-24	Euroceltique S.A.	Arylthioxanthine
US6268373B1 (en)	1995-06-07	2001-07-31	Euro-Celtique S.A.	Trisubstituted thioxanthines
CA2227237C (en)	1995-07-26	2005-12-13	Pfizer Inc.	N-(aroyl)glycine hydroxamic acid derivatives and related compounds
GB9523675D0 (en) *	1995-11-20	1996-01-24	Celltech Therapeutics Ltd	Chemical compounds
GB9526245D0 (en) *	1995-12-21	1996-02-21	Celltech Therapeutics Ltd	Chemical compounds
GB9526243D0 (en) *	1995-12-21	1996-02-21	Celltech Therapeutics Ltd	Chemical compounds
GB9526246D0 (en) *	1995-12-21	1996-02-21	Celltech Therapeutics Ltd	Chemical compounds
US6075016A (en)	1996-04-10	2000-06-13	Euro-Celtique S.A.	6,5-fused aromatic ring systems having enhanced phosphodiesterase IV inhibitory activity
GB9608435D0 (en) *	1996-04-24	1996-06-26	Celltech Therapeutics Ltd	Chemical compounds
US5864037A (en)	1996-06-06	1999-01-26	Euro-Celtique, S.A.	Methods for the synthesis of chemical compounds having PDE-IV inhibitory activity
JP4373497B2 (ja)	1996-06-19	2009-11-25	ローン−プーラン・ロレ・リミテツド	置換されたアザビシクロ化合物、ならびにｔｎｆおよびサイクリックａｍｐホスホジエステラーゼ産生の阻害剤としてのそれらの使用
GB9619284D0 (en) *	1996-09-16	1996-10-30	Celltech Therapeutics Ltd	Chemical compounds
US5744473A (en) *	1996-09-16	1998-04-28	Euro-Celtique, S.A.	PDE IV inhibitors: "bis-compounds"
GB9622363D0 (en)	1996-10-28	1997-01-08	Celltech Therapeutics Ltd	Chemical compounds
GB9625184D0 (en) *	1996-12-04	1997-01-22	Celltech Therapeutics Ltd	Chemical compounds
EP0946523A1 (en)	1996-12-23	1999-10-06	Celltech Therapeutics Limited	Fused polycyclic 2-aminopyrimidine derivatives, their preparation and their use as protein tyrosine kinase inhibitors
US5981549A (en) *	1997-02-14	1999-11-09	Synapse Pharmaceutical International	Method for controlling or alleviating the symptoms of respiratory disease and allergies
GB9705361D0 (en)	1997-03-14	1997-04-30	Celltech Therapeutics Ltd	Chemical compounds
GB9713087D0 (en) *	1997-06-20	1997-08-27	Celltech Therapeutics Ltd	Chemical compounds
CN1130363C (zh)	1997-11-12	2003-12-10	三菱化学株式会社	嘌呤衍生物以及含有其作为有效成分的药物
US6117878A (en) *	1998-02-24	2000-09-12	University Of Virginia	8-phenyl- or 8-cycloalkyl xanthine antagonists of A2B human adenosine receptors
KR100479019B1 (ko) *	1998-05-22	2005-08-29	씨제이 주식회사	캐테콜히드라존유도체,이의제조방법및그를함유한약제학적조성물
KR100578425B1 (ko) *	1998-10-16	2007-01-11	씨제이 주식회사	캐테콜 히드라진 유도체, 이의 제조 방법 및 이를 함유한 약제학적 조성물
US6232297B1 (en)	1999-02-01	2001-05-15	University Of Virginia Patent Foundation	Methods and compositions for treating inflammatory response
US7378400B2 (en) *	1999-02-01	2008-05-27	University Of Virginia Patent Foundation	Method to reduce an inflammatory response from arthritis
US7427606B2 (en) *	1999-02-01	2008-09-23	University Of Virginia Patent Foundation	Method to reduce inflammatory response in transplanted tissue
WO2000068231A1 (en) *	1999-05-11	2000-11-16	Mitsubishi Chemical Corporation	Purine derivative dihydrate, drugs containing the same as the active ingredient and intermediate in the production thereof
GB9914258D0 (en)	1999-06-18	1999-08-18	Celltech Therapeutics Ltd	Chemical compounds
US6322771B1 (en)	1999-06-18	2001-11-27	University Of Virginia Patent Foundation	Induction of pharmacological stress with adenosine receptor agonists
CA2715683A1 (en)	1999-08-21	2001-03-01	Nycomed Gmbh	Synergistic combination
GB9924862D0 (en)	1999-10-20	1999-12-22	Celltech Therapeutics Ltd	Chemical compounds
CA2402384A1 (en) *	2000-03-16	2001-09-20	Inflazyme Pharmaceuticals Ltd.	Benzylated pde4 inhibitors
BR0209774A (pt) *	2001-05-29	2004-06-01	Schering Ag	Pirimidinas inibidoras de cdk, sua preparação e aplicação como medicamento
AU2002322720B2 (en)	2001-07-25	2008-11-13	Raptor Pharmaceutical Inc.	Compositions and methods for modulating blood-brain barrier transport
NZ556354A (en) *	2001-10-01	2008-10-31	Univ Virginia	2-Propynyl adenosine analogs having A2A agonist activity and compositions thereof
US7772188B2 (en)	2003-01-28	2010-08-10	Ironwood Pharmaceuticals, Inc.	Methods and compositions for the treatment of gastrointestinal disorders
US7153824B2 (en)	2003-04-01	2006-12-26	Applied Research Systems Ars Holding N.V.	Inhibitors of phosphodiesterases in infertility
FR2861069B1 (fr) *	2003-10-17	2005-12-09	Galderma Res & Dev	NOUVEAUX LIGANDS ACTIVATEURS DES RECEPTEURS RARs, UTILISATION EN MEDECINE HUMAINE AINSI QU'EN COSMETIQUE
US7122705B2 (en) *	2004-04-08	2006-10-17	Wyeth	Method for preparing 3-cyclopentyloxy-4-methoxybenzaldehyde
ATE413398T1 (de) *	2004-04-08	2008-11-15	Wyeth Corp	Thioamidderivate als progesteronrezeptormodulatoren
US7576069B2 (en) *	2004-08-02	2009-08-18	University Of Virginia Patent Foundation	2-polycyclic propynyl adenosine analogs having A2A agonist activity
WO2006023272A1 (en) *	2004-08-02	2006-03-02	University Of Virginia Patent Foundation	2-polycyclic propynyl adenosine analogs having a2a agonist activity
AU2005267706B2 (en) *	2004-08-02	2011-12-08	University Of Virginia Patent Foundation	2-propynyl adenosine analogs with modified 5'-ribose groups having A2A agonist activity
CA2789262C (en)	2005-04-28	2016-10-04	Proteus Digital Health, Inc.	Pharma-informatics system
JP2009514969A (ja)	2005-11-09	2009-04-09	コンビナトアールエックスインコーポレーティッド	医学的状態を治療するための方法、組成物、およびキット
US8178509B2 (en) *	2006-02-10	2012-05-15	University Of Virginia Patent Foundation	Method to treat sickle cell disease
US8188063B2 (en) *	2006-06-19	2012-05-29	University Of Virginia Patent Foundation	Use of adenosine A2A modulators to treat spinal cord injury
EP2063905B1 (en)	2006-09-18	2014-07-30	Raptor Pharmaceutical Inc	Treatment of liver disorders by administration of receptor-associated protein (rap)-conjugates
MX354786B (es)	2007-06-04	2018-03-21	Synergy Pharmaceuticals Inc	Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos.
US8969514B2 (en)	2007-06-04	2015-03-03	Synergy Pharmaceuticals, Inc.	Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases
EP2022783A1 (en)	2007-08-08	2009-02-11	CHIESI FARMACEUTICI S.p.A.	"Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as phosphodiesterase inhibitors"
US8058259B2 (en) *	2007-12-20	2011-11-15	University Of Virginia Patent Foundation	Substituted 4-{3-[6-amino-9-(3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid esters as A2AR agonists
ES2522968T3 (es)	2008-06-04	2014-11-19	Synergy Pharmaceuticals Inc.	Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos
AU2009270833B2 (en)	2008-07-16	2015-02-19	Bausch Health Ireland Limited	Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders
TR201908314T4 (tr)	2009-02-20	2019-06-21	2 Bbb Medicines B V	Glutatyon bazlı ilaç dağıtım sistemi.
KR101909711B1 (ko)	2009-05-06	2018-12-19	라보라토리 스킨 케어, 인크.	활성제-칼슘 포스페이트 입자 복합체를 포함하는 피부 전달 조성물 및 이들을 이용하는 방법
US9616097B2 (en)	2010-09-15	2017-04-11	Synergy Pharmaceuticals, Inc.	Formulations of guanylate cyclase C agonists and methods of use
US20120077778A1 (en)	2010-09-29	2012-03-29	Andrea Bourdelais	Ladder-Frame Polyether Conjugates
DK2681236T3 (en)	2011-03-01	2018-04-16	Synergy Pharmaceuticals Inc	PROCEDURE FOR MANUFACTURING GUANYLATE CYCLASE-C-AGONISTS
WO2014131024A2 (en)	2013-02-25	2014-08-28	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase and their uses
AU2014235209B2 (en)	2013-03-15	2018-06-14	Bausch Health Ireland Limited	Guanylate cyclase receptor agonists combined with other drugs
AU2014235215A1 (en)	2013-03-15	2015-10-01	Synergy Pharmaceuticals Inc.	Agonists of guanylate cyclase and their uses
BR112015030326A2 (pt)	2013-06-05	2017-08-29	Synergy Pharmaceuticals Inc	Agonistas ultrapuros de guanilato ciclase c, método de fabricar e usar os mesmos
AU2014305843B2 (en)	2013-08-09	2019-08-29	Ardelyx, Inc.	Compounds and methods for inhibiting phosphate transport
CN106146350B (zh) *	2016-07-21	2017-10-20	华南理工大学	一种合成氨基甲酸肟酯衍生物的新方法
EP4706758A3 (en)	2019-05-21	2026-05-06	Ardelyx, Inc.	Methods for inhibiting phosphate transport

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3466316A (en) *	1964-09-23	1969-09-09	Union Carbide Corp	Alpha-cyano carbamoyloxime compounds
FR1575544A (cs) *	1967-11-09	1969-07-25
US3923833A (en) *	1968-05-01	1975-12-02	Hoffmann La Roche	N-{8 (1-cyano-2-phenyl)ethyl{9 carbamates
US3647861A (en) *	1970-08-25	1972-03-07	Du Pont	Substituted o-carbamylhydroxamates
DE2111156C3 (de) *	1971-03-09	1975-11-06	Hoechst Ag, 6000 Frankfurt	Oximcarbamatverbindungen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende insektizide Mittel
FR2201885A1 (en) *	1972-10-10	1974-05-03	Delalande Sa	4-Aryl carbonyl methyl pyrimidine oxime carbamates - prepd. by treatment of the oxime with an isocyanate, used as sedatives, analgesics, vasodilators, diuretics
FR2202689B1 (cs) *	1972-10-17	1975-10-31	Delalande Sa
FR2204406A1 (en) *	1972-10-26	1974-05-24	Delalande Sa	1-Phenyl-3-aminocarbonylpropan-1-one oxime carbamates - with analgesic, antiinflammatory, hypotensive and sedative activities etc.
FR2244499A1 (en) *	1973-06-07	1975-04-18	Delalande Sa	Indol-3-ylformaldoxime carbamates - for treating anxiety epilepsy, cardiac arrhythmias, asthma, intestinal spasm, peptic ulcer, cardiac insufficiency
DE2655369A1 (de) *	1976-12-03	1978-06-08	Schering Ag	5-(subst. phenyl)-oxazolidinone und deren schwefelanaloga sowie verfahren zu deren herstellung
HU179019B (en) *	1978-11-01	1982-08-28	Gyogyszekutato Intezet	Process for preparing 4-//3,4-dialkoxy-phenyl/-alkyl/- 2imidazolidinone derivatives
US4475945A (en) *	1980-01-14	1984-10-09	Ciba-Geigy Corporation	Aminoglyoxyloitrile oximino carboxylic acid esters and thio esters for the protection of crops against injury by herbicides
DE3438839A1 (de) *	1984-10-19	1986-04-24	Schering AG, 1000 Berlin und 4709 Bergkamen	Pharmazeutische praeparate
EP0186817B1 (en) *	1984-12-10	1989-08-02	Nissan Chemical Industries Ltd.	3(2h)pyridazinone, process for its preparation and anti-allergic agent containing it
FI875724A0 (fi) *	1986-04-29	1987-12-28	Pfizer	Av kalcium oberoende camp fosfodiesteras-inhibitordepressant.
GB8711802D0 (en) *	1987-05-19	1987-06-24	Fujisawa Pharmaceutical Co	Dithioacetal compounds
RU2104306C1 (ru) *	1989-11-13	1998-02-10	Пфайзер Инк.	Способ получения оптически активного (2s)- или (2r)-эндо-бицикло[2.2.1]гептан-2-ола, способ получения 5-(3-[(2r)-экзо-бицикло[2.2.1]гепт-2-илокси]-4-метоксифенил)-3,4,5,6-тетрагидропиримидин-2(1н)-она, оптически активный 5-(3-[экзо-бицикло[2.2.1]гепт-2-илокси]4-метоксифенил)-3,4,5,6-тетрагидропиримидин-2(1н)-он, оптически активные промежуточные соединения и способ их получения

1990
- 1990-08-08 US US07/564,263 patent/US5124455A/en not_active Expired - Fee Related
1991
- 1991-08-05 JP JP3195183A patent/JP2651292B2/ja not_active Expired - Lifetime
- 1991-08-05 ZA ZA916154A patent/ZA916154B/xx unknown
- 1991-08-05 IL IL9908191A patent/IL99081A/en unknown
- 1991-08-05 AU AU81623/91A patent/AU640251B2/en not_active Ceased
- 1991-08-06 FI FI913738A patent/FI913738A7/fi unknown
- 1991-08-06 KR KR1019910013552A patent/KR920004335A/ko not_active Abandoned
- 1991-08-06 DK DK91307197.3T patent/DK0470805T3/da active
- 1991-08-06 NZ NZ239279A patent/NZ239279A/xx unknown
- 1991-08-06 DE DE69103846T patent/DE69103846T2/de not_active Expired - Fee Related
- 1991-08-06 MX MX9100549A patent/MX9100549A/es unknown
- 1991-08-06 GB GB9116950A patent/GB2246777B/en not_active Expired - Fee Related
- 1991-08-06 ES ES91307197T patent/ES2060307T3/es not_active Expired - Lifetime
- 1991-08-06 AT AT91307197T patent/ATE111076T1/de active
- 1991-08-06 EP EP91307197A patent/EP0470805B1/en not_active Expired - Lifetime
- 1991-08-07 HU HU912634A patent/HU207289B/hu not_active IP Right Cessation
- 1991-08-07 HU HU9202417A patent/HU215159B/hu not_active IP Right Cessation
- 1991-08-07 RU SU915001278A patent/RU2051145C1/ru active
- 1991-08-07 NO NO913065A patent/NO174805B/no unknown
- 1991-08-07 IE IE279491A patent/IE66049B1/en not_active IP Right Cessation
- 1991-08-07 CA CA002048518A patent/CA2048518A1/en not_active Abandoned
- 1991-08-07 CN CN91105530A patent/CN1029613C/zh not_active Expired - Fee Related
- 1991-08-07 PT PT98596A patent/PT98596B/pt not_active IP Right Cessation
- 1991-08-07 CS CS912450A patent/CS245091A3/cs unknown
1995
- 1995-06-28 HU HU95P/P00483P patent/HU211643A9/hu unknown
1998
- 1998-04-30 CY CY9802057A patent/CY2057B1/xx unknown

Also Published As

Publication number	Publication date
MX9100549A (es)	1992-04-01
ES2060307T3 (es)	1994-11-16
NO174805C (cs)	1994-07-13
ZA916154B (en)	1993-04-28
JPH04253945A (ja)	1992-09-09
CY2057B1 (en)	1998-04-30
DK0470805T3 (da)	1994-10-17
HUT61273A (en)	1992-12-28
DE69103846D1 (de)	1994-10-13
KR920004335A (ko)	1992-03-27
HU211643A9 (en)	1995-12-28
HU912634D0 (en)	1992-01-28
FI913738A0 (fi)	1991-08-06
AU640251B2 (en)	1993-08-19
GB2246777A (en)	1992-02-12
IE912794A1 (en)	1992-02-12
HK1000103A1 (en)	1997-11-28
ATE111076T1 (de)	1994-09-15
EP0470805A1 (en)	1992-02-12
US5124455A (en)	1992-06-23
JP2651292B2 (ja)	1997-09-10
FI913738A7 (fi)	1992-02-09
CN1029613C (zh)	1995-08-30
NZ239279A (en)	1993-09-27
HUT58694A (en)	1992-03-30
RU2051145C1 (ru)	1995-12-27
NO913065D0 (no)	1991-08-07
GB2246777B (en)	1994-08-17
GB9116950D0 (en)	1991-09-18
NO913065L (no)	1992-02-10
PT98596B (pt)	1999-03-31
IL99081A0 (en)	1992-07-15
IE66049B1 (en)	1995-12-13
DE69103846T2 (de)	1995-01-12
IL99081A (en)	1995-05-26
CA2048518A1 (en)	1992-02-09
PT98596A (pt)	1992-07-31
CS245091A3 (en)	1992-03-18
HU215159B (hu)	1998-12-28
HU207289B (en)	1993-03-29
AU8162391A (en)	1992-02-13
CN1058771A (zh)	1992-02-19
EP0470805B1 (en)	1994-09-07

Publication	Publication Date	Title
NO174805B (no)	1994-04-05	Analogifremgangsmåte for fremstilling av terapeutisk aktive oksimkarbamater og oksim-karbonater
US5459151A (en)	1995-10-17	N-acyl substituted phenyl piperidines as bronchodilators and antiinflammatory agents
US4665074A (en)	1987-05-12	6-(polyfluoroalkoxyphenyl) pyridazinones, their compositions, synthesis and use
US4346094A (en)	1982-08-24	3-Aryl-5-isothiazolecarboxylic acids and related compounds used to lower uric acid levels
JPH07110850B2 (ja)	1995-11-29	窒素含有複素環化合物のフルオロアルコキシベンジルアミノ誘導体
US4069223A (en)	1978-01-17	4-Aminomethyl-1-(3,3,3-triarylpropyl)-4-arylpiperidine and derivatives thereof
JPS5916875A (ja)	1984-01-28	新規アリ−ルピペリジン誘導体の製造方法
EP0290211A1 (en)	1988-11-09	Dihydropyridines
EP0051917B1 (en)	1986-02-19	Benzofuran ethanolamine derivatives, processes for their preparation, and their use in medicine
EP0091749A2 (en)	1983-10-19	Ethanolamine derivatives, process for their preparation and pharmaceutical compositions containing them
EP0089154A2 (en)	1983-09-21	Ethanolamine derivatives, their preparation and use in pharmaceutical compositions
US4137325A (en)	1979-01-30	Antisecretory oxamic acid esters
US4544752A (en)	1985-10-01	3-Aryl-5-isothiazolecarboxylic acids and related compounds used to lower uric acid levels
CA1325430C (en)	1993-12-21	Di-t-butylphenyl alkyl and benzyl ethers
EP0060176B1 (fr)	1985-01-02	Trifluorométhylphényltétrahydropyridines substituées à activité anorexigène, un procédé de préparation et compositions pharmaceutiques
NO753718L (cs)	1976-05-10
US6022968A (en)	2000-02-08	Processes for the synthesis of 5-(3-[exo-bicyclo[2.2.1]hept-2-yloxy]-4-methoxyphenyl)-3,4,5,6-tetrahydr opyrimidin-2(1H)-one
US4287212A (en)	1981-09-01	2-Aryl-1,2-dialkylcycloalkylamines
US4228280A (en)	1980-10-14	Pyrano[4,3-e]-as-triazines and corresponding 4-oxides
US4935548A (en)	1990-06-19	1.4-dihydropyridines
AU2003268868B2 (en)	2006-12-14	Novel antihistaminic piperidine derivatives and intermediates for the preparation thereof
MXPA98004820A (en)	1999-01-11	Procedures and intermediates for preparing 1-bencil-4 - ((5,6-dimetoxi-1-indanon) -2-il) metilpiperid
JP2003505374A (ja)	2003-02-12	硫酸モノ−［３−（｛１−［２−（４−フルオロ−フェニル）−エチル］−ピペリジン−４−イル｝−ヒドロキシ−メチル）−２−メトキシ−フェニル］エステル
HK1054744A (en)	2003-12-12	5-phenylbenzylamine compounds, process for their production and intermediates for their synthesis
GB1594914A (en)	1981-08-05	Thioxanthene compounds